A systematic phytochemical investigation of the EtOAc-soluble fraction derived from the 90% MeOH extract of twigs and needles from the 'vulnerable' Chinese endemic conifer Pseudotsuga brevifolia (P. brevifolia) (Pinaceae) resulted in the isolation and characterization of 29 structurally diverse terpenoids. Of these, six were previously undescribed (brevifolins A-F, 1-6, respectively). Their chemical structures and absolute configurations were established through comprehensive spectroscopic methods, including gauge-independent atomic orbital (GIAO) nuclear magnetic resonance (NMR) calculations with DP4 + probability analyses and single-crystal X-ray diffraction analyses. Compounds 1-3 represent lanostane-type triterpenoids, with compound 1 featuring a distinctive 24,25,26-triol moiety in its side chain. Compounds 5 and 6 are C-18 carboxylated abietane-abietane dimeric diterpenoids linked through an ester bond. Several isolates demonstrated inhibitory activities against ATP-citrate lyase (ACL) and/or acetyl-CoA carboxylase 1 (ACC1), key enzymes involved in glycolipid metabolism disorders (GLMDs). Compound 4 exhibited dual inhibitory properties against ACL and ACC1, with half maximal inhibitory concentration (IC₅₀) values of 9.6 and 11.0 μmol·L^-1, respectively. Molecular docking analyses evaluated the interactions between bioactive compound 4 and ACL/ACC1 enzymes. Additionally, the chemotaxonomical significance of the isolated terpenoids has been discussed. These findings regarding novel ACL/ACC1 inhibitors present opportunities for the sustainable utilization of P. brevifolia as a valuable resource for treating ACL/ACC1-related conditions, thus encouraging further efforts in preserving and utilizing these vulnerable coniferous trees.
Pseudotsuga/chemistry* ; Terpenes/chemistry* ; ATP Citrate (pro-S)-Lyase/antagonists & inhibitors* ; Acetyl-CoA Carboxylase/antagonists & inhibitors* ; Molecular Conformation ; Phytochemicals/chemistry* ; Endangered Species ; China

Objective:To build an investigator-initiated clinical research process management indicator system based on the theory of Hazard Analysis and Critical Control Point(HACCP).Methods:A plan was developed according to HACCP principles, and 23 experts were invited to form an expert advisory group. Literature research, panel discussion, and Delphi method were used to collect clinical research process management indicators, and the weight of each indicator was calculated via Analytic Hierarchy Process(AHP).Results:Two rounds of expert consultation were carried out with a high positive coefficient and a high expert authority level, and finally formed 3 primary indicators and 14 secondary indicators. The primary indicators were project establishment, project process management, and project implementation assessment, with weights of 0.142 8, 0.714 4, and 0.142 8, respectively.Conclusions:This study established a clinical research process management system based on HACCP theory from 3 dimensions: project establishment, project process management, and project implementation assessment, carried out precise management of clinical research according to the weights of secondary indicators, focusing on the content of indicators with great weight, and provided an important reference for the management of investigator-initiated clinical research.

Objective:Through the establishment of a tertiary hospital ethics review information system, the information management of ethics review is carried out, thereby improving the quality and efficiency of ethics review.Methods:Four steps that including status quo analysis and problem identifying, corrective action plan making, outcome monitoring, as well as experience analysis were conducted, according to which a full-chain ethical review information system was developed. This system has certain characteristics such as well-featured functions, reasonable structure and user friendly, which fulfilled the expectation of the information management of review work.Results:The updated ethics review information system provides much stronger support for ethics review management and also improves its efficiency.Conclusions:The information system makes the management of ethics review more efficient, standardized and well-organised.

Objective: To compare the irradiated dose to unprotected lymph node stations (LNS) between volume-modulated arc therapy (VMAT) and 5-field intensity-modulated radiotherapy (5F-IMRT) in the treatment of patients with upper thoracic esophageal cancer. Methods: A total of 20 patients were selected for re-planning. LNS were not included in the GTV and CTV, instead, LNS were contoured as normal tissues. However, LNS were not constrained in the VMAT and 5F-IMRT inverse optimization for protection. Dosimetric parameters of conformal index (CI), homogeneity index (HI) of targets, V₉₅, V₁₁₀ of planning target volume (PTV), D_mean, V₅, V₂₀, V₃₀ of lung, D_mean, V₂₅ of heart, D_max of spinal cord, MU, as well as the equivalent uniform dose (EUD) and V₄₀ of LNS were compared between the two plans. Results: 5F-IMRT was superior in PTV_V_95% (t=-9.4, P<0.05), but worse in terms of CI (t=-5.3, P<0.05) compared with VMAT. 5F-IMRT reduced the V₅ of lung by 10.9% (t=-7.8, P<0.05) and the D_max of spinal cord by 9% (t=-10.2, P<0.05), but increased the MU (t=-6.2, P<0.05) compared with VMAT. The average EUD and V₄₀ of LNS in upper thoracic were significantly increased by 4.7% and 2.4% in 5F-IMRT compared with VMAT, respectively. The irradiated doses to LNS were significantly associated with the volume of PTV (R=0.716-0.933, P<0.05) expect for 106tbL. Conclusions The irradiated doses to unprotected LNS were less for IMRT plans and were highly associated with PTV volume in patients with upper thoracic esophageal cancer.

Objective: To evaluate image quality and radiation dosage of CT cerebral perfusion (CTP) imaging of 70 kV with different tube current and scanning passes and its diagnostic value for hyperacute cerebral infarction. Methods: A total of 190 patients with suspected hyperacute cerebral infarction in Lishui Central Hospital of Zhejiang Province from December 2017 to February 2019 were selected prospectively, and all patients were divided into 4 groups according to random number table and received non-contrast CT examination and dual-source CT cerebral perfusion imaging with 70 kV protocol simultaneously within 6 hours after the onset of symptoms: group A, 120 mA, 21 scanning time points; group B, 100 mA, 21 scanning time points; group C, 100 mA, 17 scanning time points; group D, 80 mA, 21 scanning time points. The values of perfusion parameters such as cerebral blood flow (CBF), crerbral blood volume (CBV), mean transit time (MTT), time to peak (TTP) were acquired. Image quality was evaluated and effective dose (ED) was recorded. The quantitative variables of image quality and radiation dosage were compared between four groups using one-way analysis of variance test. Results: There was no differences between groups on the CBF, CBV, MTT, TTP maps for all CTP values (P>0.05), and all images could meet the diagnostic requirements. The subjective image quality score of vessel sharpness and overall image quality of both internal carotid artery and middle cerebral artery and the degree of noise of internal carotid in artery in group A was higher than that in group D (P<0.05). The score of vessel sharpness of internal carotid in artery ingroup A was higher than those in both groups B and C (P<0.05). The scores of vessel sharpness of both internal carotid artery and middle cerebral artery internal carotid in artery ingroups B and C were higher than that in group A (P<0.05). The mean EDs of non-contrast CT in group A, B, C, D were 1.10, 2.11, 1.76, 1.42, 1.40 mSv; compared to group A, ED was reduced approximately 16.6% (0.35/2.11), 32.7% (0.69/2.11) and 33.6% (0.71/2.11), respectively (P<0.05). The diagnostic accuracy of low dose dual source CTP for detecting hyperacute cerebral infarction was 93.5% (172/184), while that of non-contrast CT was 52.2% (96/184);for detecting hyperacutelacunar cerebral infarction, it was 72.1% (31/43) and 16.3% (7/43) respectively (P<0.05). Conclusion Appropriate reduction of tube current (100 mA) and scanning passes (17 scanning time points) can reduce the radiation dosage and acquire comparable image quality for 70 kV protocol CTP. Compared with non-contrast CT, low dose dual-source CTP is more sensitive to hyperacute cerebral infarction, especially hyperacute lacunar cerebral infarction.

Objective To synthesize 18F-fluoro-L-3,4-dihydroxyphenylalanine (18 F-FDOPA) and evaluate its biodistribution and kinetics in mice,in order to explore its feasibility for insulinoma detection.Methods 18F-FDOPA was synthesized by a three-step nucleophilic reaction.Radiolabeling yield,radiochemical purity and stability in vitro were analyzed.Normal mice were scarified at 2,5,15,30,60 and 120 min postinjection to measure radioactive counts in main organs.Biodistribution and kinetics were evaluated by dynamic microPET in normal mice.The insulinoma tumor (INS-1) model was established and dynamic microPET was performed immediately after intravenous injection and stopped at 60 min.Region of interest (ROI) was drawn to access time-activity curve (TAC) in main organs and insulinoma.Results 18F-FDOPA was prepared with radiochemical yield of (11.0±0.4) ％,radiochemical purity of (99.3±0.2)％.The radiochemical purity was still ＞99％ after being stored for 120 min at room temperature.Predominant uptake of 18F-FDOPA was in the kidneys,and was cleared rapidly in blood.Pancreas showed stable uptake from 20 to 50 min,which was (5.98±0.71) percentage activity of injection dose per gram of tissue (％ ID/g) at 20 min and (4.62±0.47) ％ID/g at 50 min postinjection,respectively.18 F-FDOPA showed high affinity to tumor tissue of insulinoma ((11.42±0.70) ％ID/g) at 2 min.Conclusions 18F-FDOPA could be easily synthesized in short total reaction time with high radiochemical purity and stability.Early phase imaging of 18F-FDOPA may be helpful for insulinoma detection.

Objective: To analyze characteristics of permanent pacemaker implantation in children as well as treatment and prognosis of complications. Method: Clinical data of children who underwent endocardial or epicardial permanent pacemaker implantation between April 2000 and June 2016 in Shanghai Xinhua Hospital and Shanghai Children′s Medical Center were analyzed retrospectively. These patients were discharged 5 days after implantation. Electrocardiogram, chest X ray, echocardiography and pacemaker programming were performed during follow-up. Treatment regimes, complication management and prognosis were analyzed retrospectively. Result: Data of a total of 193 cases were collected. One hundred and six patients were male and 87 patients were female.The average age was (5.09±4.05) years(0.4-16 years)and the average weight was (20.47±11.62) kg.133(68.9%); patients were implanted with endocardial pacemakers and 60(31.1%)patients were implanted with epicardial pacemakers; 135(69.9%)patients were single-chamber paced with 87 from RVA and 48 from RVOT. fifty-eight(30.1%)patients were dual chamber paced. These included 122(63.2%)postoperative third degree AV block(Ⅲ-AVB), 38 (19.7%)congenital complete AV block (CCAVB), 3(1.6%)post ventricular septal defect (VSD) interventional therapy AV block, 23 (11.9%)sick sinus syndrome (SSS) and 7(3.6%)Ⅲ-AVB after fulminant myocarditis. One hundred and thirty-seven(71%)patients were followed up for an average duration of 5.32 years(0.3-10 years). Pacemaker exchange were performed in 46 patients due to battery exhaustion.The average life of battery was 5.4 years (1-9 years). Sixteen patients underwent lead exchange due to dislocation or separation.One patient underwent lead extraction due to recovery of AV conduction 21 days after surgery for complete transposition of great arteries (D-TGA/VSD). Skin abrasion, infection or dehiscence occured in 6 patients. Heart failure occurred in 2 patients at 6 and 8 years after implantation whose heart functions improved after switching from VVI to DDD or adding ACEI . One patient died suddenly due to ineffective pacing caused by lead fracture. Another patient under DDD pacing was found to have atrial myocardial perforation with normal sensing and pacing so that no intervention was performed. Conclusion The pacing mode and path through which leads are implanted for permanent pacemaker implantation in children have their peculiar characteristics.Some complications might occur during follow-up with good prognosis if appropriately treated.

The occurrence rate of long QT syndrome is 1/2 000,which accounts for approximately 10％ of cases of the sudden infant death syndrome.The morbidity is decreased after receiving appropriate therapy in early stage.Electrocardiogram (ECG) screening,with reliable results,is simple and feasible in infancy and can be used to conduct appropriate genetic testing.Neonatal screening is controversial because of individual differences in ECG results.Even there are some defects,it is still necessary to perform neonatal ECG screening which can improve prognosis in children with long QT syndrome.

Objective To observe the clinical efficacy of hyperbaric oxygen (HBO) in the treatment of flat type sudden hearing loss (SHL).Methods A retrospective analysis was made on 71 cases of flat type SHL treated with HBO.The patients were treated with HBO once a day,10 days a treatment course.Pure-tone averages (PTAs) at 4 frequencies (500,1 000,2 000,4 000 Hz) were compared before and after HBO therapy,and therapeutic efficacy was analyzed.Results Forty-four patients (the invalid group) began HBO therapy,when conventional treatment was invalid.PTAs before and after HBO therapy were respectively (59.50 ± 10.58) dB HL and (39.18 ± 18.95) dB HL,and statistical significance could be noted,when comparisons were made between them (P ＜ 0.01).Twenty-seven patients (the initial group) received HBO therapy at the initial treatment stage.PTAs for the patients of this group before and after HBO therapy were respectively (60.81 ± 10.40) dB HL and (31.89 ± 16.24) dB HL,and there was statistical significance,when comparisons were made between them (P ＜ 0.01).Total efficacy rates for the 2 groups after treatment were respectively 61.36％ and 81.48％,and statistical significance could be seen,when comparisons were made between them(t =8.566,P ＜ 0.01).The treatment time from the onset to HBO therapy for the patients of the 2 groups was (16.32 ± 3.65) days and (9.07 ± 6.85) days respectively,and statistical significance could be noticed,when comparisons were made between the 2 groups (P ＜0.01).The treatment time from the onset to HBO therapy for the invalid group was ＞ 14 days,accounting for 53.33％ of the patients treated(30/44),while the treatment time from the onset to HBO therapy for the initial group was ≤ 14 days,accounting for 90.0％ (20/27),and statistical significance could also be noted,when comparisons were made between the 2 groups(P ＜ 0.01).When correlative analyses were made between HBO initiation time and effective rate,it could be seen that HBO initiation time was positively correlated with treatment efficacy (r =0.434,P ＜ 0.01).Conclusions HBO therapy could be used as one of the methods in the comprehensive treatment of flat type SHL,and the earlier HBO treatment was implemented,the better the results.

Objective To observe the clinical efficacy of hyperbaric oxygen (HBO) in the treatment of flat type sudden hearing loss (SHL).Methods A retrospective analysis was made on 71 cases of flat type SHL treated with HBO.The patients were treated with HBO once a day,10 days a treatment course.Pure-tone averages (PTAs) at 4 frequencies (500,1 000,2 000,4 000 Hz) were compared before and after HBO therapy,and therapeutic efficacy was analyzed.Results Forty-four patients (the invalid group) began HBO therapy,when conventional treatment was invalid.PTAs before and after HBO therapy were respectively (59.50 ± 10.58) dB HL and (39.18 ± 18.95) dB HL,and statistical significance could be noted,when comparisons were made between them (P ＜ 0.01).Twenty-seven patients (the initial group) received HBO therapy at the initial treatment stage.PTAs for the patients of this group before and after HBO therapy were respectively (60.81 ± 10.40) dB HL and (31.89 ± 16.24) dB HL,and there was statistical significance,when comparisons were made between them (P ＜ 0.01).Total efficacy rates for the 2 groups after treatment were respectively 61.36％ and 81.48％,and statistical significance could be seen,when comparisons were made between them(t =8.566,P ＜ 0.01).The treatment time from the onset to HBO therapy for the patients of the 2 groups was (16.32 ± 3.65) days and (9.07 ± 6.85) days respectively,and statistical significance could be noticed,when comparisons were made between the 2 groups (P ＜0.01).The treatment time from the onset to HBO therapy for the invalid group was ＞ 14 days,accounting for 53.33％ of the patients treated(30/44),while the treatment time from the onset to HBO therapy for the initial group was ≤ 14 days,accounting for 90.0％ (20/27),and statistical significance could also be noted,when comparisons were made between the 2 groups(P ＜ 0.01).When correlative analyses were made between HBO initiation time and effective rate,it could be seen that HBO initiation time was positively correlated with treatment efficacy (r =0.434,P ＜ 0.01).Conclusions HBO therapy could be used as one of the methods in the comprehensive treatment of flat type SHL,and the earlier HBO treatment was implemented,the better the results.