Bioactive compounds derived from herbal medicinal plants modulate various therapeutic targets and signaling pathways associated with cardiovascular diseases (CVDs), the world's primary cause of death. Ginkgo biloba, a well-known traditional Chinese medicine with notable cardiovascular actions, has been used as a cardio- and cerebrovascular therapeutic drug and nutraceutical in Asian countries for centuries. Preclinical studies have shown that ginkgolide B, a bioactive component in Ginkgo biloba, can ameliorate atherosclerosis in cultured vascular cells and disease models. Of clinical relevance, several clinical trials are ongoing or being completed to examine the efficacy and safety of ginkgolide B-related drug preparations in the prevention of cerebrovascular diseases, such as ischemia stroke. Here, we present a comprehensive review of the pharmacological activities, pharmacokinetic characteristics, and mechanisms of action of ginkgolide B in atherosclerosis prevention and therapy. We highlight new molecular targets of ginkgolide B, including nicotinamide adenine dinucleotide phosphate oxidases (NADPH oxidase), lectin-like oxidized LDL receptor-1 (LOX-1), sirtuin 1 (SIRT1), platelet-activating factor (PAF), proprotein convertase subtilisin/kexin type 9 (PCSK9) and others. Finally, we provide an overview and discussion of the therapeutic potential of ginkgolide B and highlight the future perspective of developing ginkgolide B as an effective therapeutic agent for treating atherosclerosis.

Objective:To investigate the epidemiological characteristics, diagnosis, treat-ment and prognosis of gallbladder cancer in China from 2010 to 2017.Methods:The single disease retrospective registration cohort study was conducted. Based on the concept of the real world study, the clinicopathological data, from multicenter retrospective clinical data database of gallbladder cancer of Chinese Research Group of Gallbladder Cancer (CRGGC), of 6 159 patients with gallbladder cancer who were admitted to 42 hospitals from January 2010 to December 2017 were collected. Observation indicators: (1) case resources; (2) age and sex distribution; (3) diagnosis; (4) surgical treatment and prognosis; (5) multimodality therapy and prognosis. The follow-up data of the 42 hospitals were collected and analyzed by the CRGGC. The main outcome indicator was the overall survival time from date of operation for surgical patients or date of diagnosis for non-surgical patients to the end of outcome event or the last follow-up. Measurement data with normal distribu-tion were represented as Mean±SD, and comparison between groups was conducted using the t test. Measurement data with skewed distribution were represented as M( Q1, Q3) or M(range), and com-parison between groups was conducted using the U test. Count data were described as absolute numbers or percentages, and comparison between groups was conducted using the chi-square test. Univariate analysis was performed using the Logistic forced regression model, and variables with P<0.1 in the univariate analysis were included for multivariate analysis. Multivariate analysis was performed using the Logistic stepwise regression model. The life table method was used to calculate survival rates and the Kaplan-Meier method was used to draw survival curves. Log-rank test was used for survival analysis. Results:(1) Case resources: of the 42 hospitals, there were 35 class A of tertiary hospitals and 7 class B of tertiary hospitals, 16 hospitals with high admission of gallbladder cancer and 26 hospitals with low admission of gallbladder cancer, respectively. Geographical distribution of the 42 hospitals: there were 9 hospitals in central China, 5 hospitals in northeast China, 22 hospitals in eastern China and 6 hospitals in western China. Geographical distribution of the 6 159 patients: there were 2 154 cases(34.973%) from central China, 705 cases(11.447%) from northeast China, 1 969 cases(31.969%) from eastern China and 1 331 cases(21.611%) from western China. The total average number of cases undergoing diagnosis and treatment in hospitals of the 6 159 patients was 18.3±4.5 per year, in which the average number of cases undergoing diagnosis and treatment in hospitals of 4 974 patients(80.760%) from hospitals with high admission of gallbladder cancer was 38.8±8.9 per year and the average number of cases undergoing diagnosis and treatment in hospitals of 1 185 patients(19.240%) from hospitals with low admission of gallbladder cancer was 5.7±1.9 per year. (2) Age and sex distribution: the age of 6 159 patients diagnosed as gallbladder cancer was 64(56,71) years, in which the age of 2 247 male patients(36.483%) diagnosed as gallbladder cancer was 64(58,71)years and the age of 3 912 female patients(63.517%) diagnosed as gallbladder cancer was 63(55,71)years. The sex ratio of female to male was 1.74:1. Of 6 159 patients, 3 886 cases(63.095%) were diagnosed as gallbladder cancer at 56 to 75 years old. There was a significant difference on age at diagnosis between male and female patients ( Z=-3.99, P<0.001). (3) Diagnosis: of 6 159 patients, 2 503 cases(40.640%) were initially diagnosed as gallbladder cancer and 3 656 cases(59.360%) were initially diagnosed as non-gallbladder cancer. There were 2 110 patients(34.259%) not undergoing surgical treatment, of which 200 cases(9.479%) were initially diagnosed as gallbladder cancer and 1 910 cases(90.521%) were initially diagnosed as non-gallbladder cancer. There were 4 049 patients(65.741%) undergoing surgical treatment, of which 2 303 cases(56.878%) were initially diagnosed as gallbladder cancer and 1 746 cases(43.122%) were initial diagnosed as non-gallbladder cancer. Of the 1 746 patients who were initially diagnosed as non-gallbladder cancer, there were 774 cases(19.116%) diagnosed as gallbladder cancer during operation and 972 cases(24.006%) diagnosed as gallbladder cancer after operation. Of 6 159 patients, there were 2 521 cases(40.932%), 2 335 cases(37.912%) and 1 114 cases(18.087%) undergoing ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI) examination before initial diagnosis, respec-tively, and there were 3 259 cases(52.914%), 3 172 cases(51.502%) and 4 016 cases(65.205%) undergoing serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis, respectively. One patient may underwent multiple examinations. Results of univariate analysis showed that geographical distribution of hospitals (eastern China or western China), age ≥72 years, gallbladder cancer annual admission of hospitals, whether undergoing ultrasound, CT, MRI, serum carcinoembryonic antigen, CA19-9 or CA125 examination before initially diagnosis were related factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.45, 1.98, 0.69, 0.68, 2.43, 0.41, 1.63, 0.41, 0.39, 0.42, 95% confidence interval as 1.21-1.74, 1.64-2.40, 0.59-0.80, 0.60-0.78, 2.19-2.70, 0.37-0.45, 1.43-1.86, 0.37-0.45, 0.35-0.43, 0.38-0.47, P<0.05). Results of multivariate analysis showed that geographical distribution of hospitals (eastern China or western China), sex, age ≥72 years, gallbladder cancer annual admission of hospitals and cases undergoing ultrasound, CT, serum CA19-9 examination before initially diagnosis were indepen-dent influencing factors influencing initial diagnosis of gallbladder cancer patients ( odds ratio=1.36, 1.42, 0.89, 0.67, 1.85, 1.56, 1.57, 0.39, 95% confidence interval as 1.13-1.64, 1.16-1.73, 0.79-0.99, 0.57-0.78, 1.60-2.14, 1.38-1.77, 1.38-1.79, 0.35-0.43, P<0.05). (4) Surgical treatment and prognosis. Of the 4 049 patients undergoing surgical treatment, there were 2 447 cases(60.435%) with complete pathological staging data and follow-up data. Cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb were 85(3.474%), 201(8.214%), 71(2.902%), 890(36.371%), 382(15.611%), 33(1.348%) and 785(32.080%), respectively. The median follow-up time and median postoperative overall survival time of the 2 447 cases were 55.75 months (95% confidence interval as 52.78-58.35) and 23.46 months (95% confidence interval as 21.23-25.71), respectively. There was a significant difference in the overall survival between cases with pathological staging as stage 0, stage Ⅰ, stage Ⅱ, stage Ⅲa, stage Ⅲb, stage Ⅳa and stage Ⅳb ( χ2=512.47, P<0.001). Of the 4 049 patients undergoing surgical treatment, there were 2 988 cases(73.796%) with resectable tumor, 177 cases(4.371%) with unresectable tumor and 884 cases(21.833%) with tumor unassessable for resectabi-lity. Of the 2 988 cases with resectable tumor, there were 2 036 cases(68.139%) undergoing radical resection, 504 cases(16.867%) undergoing non-radical resection and 448 cases(14.994%) with operation unassessable for curative effect. Of the 2 447 cases with complete pathological staging data and follow-up data who underwent surgical treatment, there were 53 cases(2.166%) with unresectable tumor, 300 cases(12.260%) with resectable tumor and receiving non-radical resection, 1 441 cases(58.888%) with resectable tumor and receiving radical resection, 653 cases(26.686%) with resectable tumor and receiving operation unassessable for curative effect. There were 733 cases not undergoing surgical treatment with complete pathological staging data and follow-up data. There was a significant difference in the overall survival between cases not undergoing surgical treatment, cases undergoing surgical treatment for unresectable tumor, cases undergoing non-radical resection for resectable tumor and cases undergoing radical resection for resectable tumor ( χ2=121.04, P<0.001). (5) Multimodality therapy and prognosis: of 6 159 patients, there were 541 cases(8.784%) under-going postoperative adjuvant chemotherapy and advanced chemotherapy, 76 cases(1.234%) under-going radiotherapy. There were 1 170 advanced gallbladder cancer (pathological staging ≥stage Ⅲa) patients undergoing radical resection, including 126 cases(10.769%) with post-operative adjuvant chemotherapy and 1 044 cases(89.231%) without postoperative adjuvant chemo-therapy. There was no significant difference in the overall survival between cases with post-operative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.23, P=0.629). There were 658 patients with pathological staging as stage Ⅲa who underwent radical resection, including 66 cases(10.030%) with postoperative adjuvant chemotherapy and 592 cases(89.970%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemotherapy and cases without postoperative adjuvant chemotherapy ( χ2=0.05, P=0.817). There were 512 patients with pathological staging ≥stage Ⅲb who underwent radical resection, including 60 cases(11.719%) with postoperative adjuvant chemotherapy and 452 cases(88.281%) without postoperative adjuvant chemotherapy. There was no significant difference in the overall survival between cases with postoperative adjuvant chemo-therapy and cases without post-operative adjuvant chemo-therapy ( χ2=1.50, P=0.220). Conclusions:There are more women than men with gallbladder cancer in China and more than half of patients are diagnosed at the age of 56 to 75 years. Cases undergoing ultrasound, CT, serum CA19-9 examination before initial diagnosis are independent influencing factors influencing initial diagnosis of gallbladder cancer patients. Preoperative resectability evaluation can improve the therapy strategy and patient prognosis. Adjuvant chemotherapy for gallbladder cancer is not standardized and in low proportion in China.

Eleven alkaloids were isolated from the twigs and leaves of Ervatamia pandacaqui using chromatographic methods of silica gel, Sephadex LH-20, ODS, and HPLC.Their structures were elucidated by physical,chemical and spectroscopic methods and determined as voacristine 7-hydroxyindolenine (1),iboxygaine (2), 19S-hydroxyibogamine (3), 3-oxotabersonine (4), perivine (5), pericyclivine (6), rhazinalinol (7), geissoschizol (8), 3, 14-dihydroolivacine (9), vallesamine (10), and conolobine A (11), respectively.All compounds were isolated from this plant for the first time.

Objective:Unidentified filling objects (UFO) can cause adverse results including infections, overfilling, asymmetry, foreign body granulomas, dislocation or psychological panic. To remove UFO accurately, it is important to locate and identify the injected substances preoperatively. This study investigated the viability of using MRI to correctly locate and identify injected substances by relating MRI to gross and pathological microscopic examination.Methods:Eighty-two facial UFO patients from 2013 to 2017 were studied by the experts of the Department of Image, Xinhua Hospital of Dalian University. Five of the patients were male and seventy-seven were female. The age ranged from 17 to 58 years with average 29.4 years. They came to our hospital for removal of UFO after they had facial injective fillers in the illegal medial offices. The injected sites involved in the forehead, temple, malar, cheek, nose, nasolabial folds, and chin. All the patients＇ faces were examined with MRI preoperatively, using T1W, T2W and fat-suppressed sequences. Based on the guides of MRI, UFOs were removed with their capsules by open approach. Samples were recorded with digital pictures and then were fixed in 10% formalin solution for microscopic examination of HE stained slices.Results:Based on MRI, gross and microscopic examination, UFO were classified into 3 types, gel-like fillers, solid particles, and growth factors. Gel-like fillers appeared strongly hyperintense on T2 W and STIR sequences and hypointense on T1 W sequences. Grossly, they looked like gruel covered by altered soft tissue. Under the light microscope, many pieces of blue-stained material were dispersed in subcutaneous tissue infiltrated with a large number of mononuclear cells and foreign-body giant cells. Solid particles had low to intermediate signal intensity on T1 W and T2 W images. Grossly, they were like sand merging in soft tissue. The biopsy showed crowed bubbles surrounded by tissue filled with a large number of mononuclear cells and foreign-body giant cells. For growth factors affected tissue, it was hard to differentiate between normal and abnormal on MRI. The affected tissue appeared as somehow hypointense on T1 W sequences and hyperintense on T2 W fat suppressed sequences. During the operation, the affected region was easy bleeding and full of fibrofatty tissue. Under the microscope, there were increased small blood vessels and collagens.Conclusions:Based on MRI, gross and microscopic examination, UFO can be classified into 3 types, gel-like fillers, solid particles, and growth factors. MRI is very important for doctors to assess the patient＇s conditions and make the plan of operation. MRI is also useful for doctors to locate UFO and understand the relationship between UFO and their nearby organs.

The aim of this study was to evaluate the fatigue property
Heart Valve Prosthesis ; Heart Valves ; Materials Testing ; Prosthesis Design ; Stents

Objective:To study the diagnostic clues and significance in serous effusion cytology associated with lymphoblatic lymphoma/acute lymphoblastic leukemia (LBL/ALL).Methods:Forty-five serous effusion specimens with final diagnosis of LBL/ALL were collected from August 2011 to December 2019 at the First Affiliated Hospital of Zhengzhou University. All cases were reviewed for their clinical profiles, cytomorphologic features and ancillary studies. Cell blocks and immunocytochemistry were prepared in 22 cases; flow cytometric immunophenotyping was performed in three cases and gene rearrangement analysis (T-cell recepter, TCR and immunoglobulin, Ig) was performed in five cases.Results:Among the 45 cases, there were 35 males and 10 females with male to female ratio of 3.5∶1.0. The median age was 15 years. Mediastinal mass was the initial presentation in 39 patients (86.7%) and high LDL level were observed in 34 patients (75.6%). Microscopically, the majority of the specimens (86.7%) were hypercellular. The smears demonstrated dispersed lymphoblasts that were predominantly small to intermediate in size with scanty basophilic cytoplasm and irregular or convoluted nuclei with fine chromatin condensation and inconspicuous nucleoli. Mitoses were frequently observed. Karyorrhexis and apoptosis were seen in all cases. By immunophenotyping, TdT was expressed in 19 cases (86.4%) and CD99 in 20 cases (90.9%). Ki-67 expression varied from 65% to 95%. Flow cytometry in three cases demonstrated positivity for TdT, CD2, CD3 and CD7. Monoclonal TCR gene rearrangement was found in 4 of 5 cases, and both monoclonal TCR and Igκ gene were found in 1 case.Conclusions:In LBL/ALL, primary diagnosis could be made basing on clinical features (younger male patients with a mediastinum mass) and cytomorphology (monotonous, small to medium sized lymphoid cells with prominent irregular nuclei, fine chromatin and frequent mitoses, karyorrhexis and apoptosis). If immunocytochemistry and other ancillary studies are performed, the accuracy and reliability of the results could be improved.

Objective To study the characteristics of fluid intake and central venous pressure (CVP) within 4 days after birth in very low birth weight (VLBW) premature infants complicated with bronchopulmonary dysplasia (BPD).Method From February 2015 to March 2019,VLBW preterm infants without serious complications were enrolled in two hospitals.Their CVP were measured every 4 ～ 6 hours after birth.They were assigned into BPD group and non-BPD group,and the fluid intake and CVP within 4 days after birth were compared between these two groups.Result A total of 45 VLBW preterm infants were included,including 17 in the BPD group and 28 in the non-BPD group.The fluid intake in the BPD group showed no significant difference with the non-BPD group within 4 days after birth (P ＞ 0.05).No significant correlation existed between the mean liquid intake and the mean CVP in 1 ～ 4 days after birth (r =0.093,P=0.542).From day1 to day4,the CVPs of the BPD group were (3.97 ± 0.68),(4.49 ± 0.75),(4.55 ± 0.66),(4.02 ± 1.05) cmH2O,and the non-BPD group were (3.66 ± 1.09),(3.96 ±0.76),(3.81 ± 0.69),(3.91 ± 0.65) cmH2O.The differences between the BPD group and the nonBPD group were statistically significant (P ＜ 0.05).The CVP of the BPD group was increasing from day 2 to day 3 (P ＜ 0.05).Conclusion VLBW premature infants complicated with BPD may have higher CVP at the early stage of life,which may not be related with the fluid intake.

Objective:To investigate differences in stratum corneum components between sensitive skin and normal skin by attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy, and to evaluate the value of ATR-FTIR spectroscopy in the study of pathogenesis of sensitive skin.Methods:From December 2018 to February 2019, 148 volunteers were recruited, who had lived in Shanghai for ≥ 6 years. Through questionnaire survey, lactic acid sting test and capsaicin test, the subjects were divided into normal skin group and sensitive skin group; meanwhile, total sting score and total burning score of the subjects were recorded in the lactic acid sting test and capsaicin test respectively. ATR-FTIR spectroscopy was performed to detect stratum corneum components, including natural moisturizing factor (NMF), stratum corneum lipids, free fatty acids (FFA) and β-sheet/α-helix (β/α) ratio; moreover, other non-invasive techniques were used to measure skin physiological parameters, including transepidermal water loss (TEWL), stratum corneum hydration (SCH) levels, stratum corneum lipids, skin pH, current perception thresholds of 3 peripheral sensory nerve fibers, and superficial skin blood flow perfusion. Spearman correlation coefficients between stratum corneum components and the total sting score as well as total burning pain score were analyzed, so were Pearson correlation coefficients between the stratum corneum components and skin physiological parameters.Results:A total of 73 volunteers completed all tests, including 15 males and 19 females aged 41.8 ± 8.9 years in the sensitive skin group, and 19 males and 20 females aged 42.8 ± 9.4 years in the normal skin group. Compared with the normal skin group, the sensitive skin group showed significantly decreased levels of stratum corneum NMF (30.90 ± 7.38 vs. 37.01 ± 8.77, t = 3.193, P < 0.01) and FFA (14.90 ± 6.75 vs. 20.45 ± 11.76, t = 2.422, P < 0.05), but significantly increased β/α ratio (3.17 ± 1.03 vs. 2.67 ± 0.56, t = -2.595, P < 0.05) ; there was no significant difference in stratum corneum lipid content between the two groups ( t = 1.458, P > 0.05). As far as the skin physiological parameters were concerned, the sensitive skin group showed significantly increased TEWL ( t = -3.496, P < 0.001), but significantly decreased current perception thresholds at a frequency of 5 Hz and epidermal density (both P < 0.05) compared with the normal skin group; no significant difference in stratum corneum lipid content was observed between the two groups ( P > 0.05). Correlation analysis revealed that NMF, FFA and β/α ratio were significantly correlated with TEWL ( r = -0.405, -0.562, 0.503, respectively, all P < 0.01) and total sting score ( rs = -0.401, -0.285, 0.316, respectively, P < 0.01 or 0.05) ; meanwhile, epidermal density was also significantly correlated with NMF ( r = 0.402, P < 0.01) and β/α ratio ( r = -0.369, P < 0.05). However, none of NMF, FFA and β/α ratio was correlated with stratum corneum lipid content, current perception thresholds of the 3 sensory nerve fibers, superficial skin blood flow perfusion or epidermal thickness (all P > 0.05) . Conclusions:NMF, FFA and β/α ratio in the stratum corneum significantly differed between the sensitive skin and normal skin, and were significantly correlated with some physiological parameters related to stratum corneum barrier function. ATR-FTIR spectroscopy is an effective method for evaluating barrier function of sensitive skin.

TSCI have dyskinesia and sensory disturbance that can cause various life-threaten complications. The patients with traumatic spinal cord injury (TSCI), seriously affecting the quality of life of patients. Based on the epidemiology of TSCI and domestic and foreign literatures as well as expert investigations, this expert consensus reviews the definition, injury classification, rehabilitation assessment, rehabilitation strategies and rehabilitation measures of TSCI so as to provide early standardized rehabilitation treatment methods for TSCI.

Objective:To investigate the clinicopathological features of pulmonary epithelioid hemangioendothelioma (PEHE).Methods:Eighteen cases of PEHE were collected from August 2011 to December 2018 at the First Affiliated Hospital of Zhengzhou University. All cases were retrospectively studied by hematoxylin and eosin staining and immunohistochemistry (IHC). The clinicopathological features were reviewed; the status of CAMTA1 and TFE3 gene was analyzed and patients′ outcome was followed up.Results:Of the 18 cases, there were 11 males and 7 females with a male to female ratio of 1.6 to 1.0. The patients′ age ranged from 36 to 68 years (mean 52 years). Twelve cases (12/18) showed a single nodule and six cases (6/18) showed multiple bilateral nodules. Seven cases (7/18) involved other organs besides lung. Seventeen (17/18) patients presented with respiratory symptoms and one patient (1/18) presented with abdominal pain. Grossly, the tumors were greyish-white nodules with indistinct borders. Microscopically the tumor cells were epithelioid and arranged in strands and nests, and cytoplasmic vacuoles were commonly noted. The stroma was myxochondroid or hyaline. By IHC, the tumor cells were positive for CD31(18/18), CD34 (16/18), ERG (18/18) and Fli-1 (18/18); CKpan was focally positive in 5 cases (5/18). TFE3 was positive in 3 cases (3/18), and Ki-67 index ranged from 5% to 30%. FISH analysis showed seventeen cases (17/18) had CAMAT1 rearrangement, one case had TFE3 rearrangement displaying a split signal. Eight patients (8/18) had surgical excision, three patients (3/18) had surgery and chemotherapy, and seven patients (7/18) had chemotherapy only. Four patients (4/18) died of the disease.Conclusions:Patients with PEHE have non-specific symptoms, and correct diagnosis depends on pathologic biopsy and the exclusion of other tumors with epithelioid morphology. Some patients with PEHE have poor prognosis, particularly in those who have multiple nodules, peripheral invasion or metastasis.