Experimental study on treatment of severe limb ischemia with Ad-hVEGF-hHGF gene / 实用医学杂志

Objective To explore the role and efficacy of VEGF and HGF gene adenovirus vector in promoting angiogenesis in ischemic tissue.Methods 84 Kunming mice were randomly divided into sham group,control group,VEGF group,HGF group and VEGF+HGF group,and the left lower limb ischemia model was established.The blood supply of ischemic tissue was observed by rheometer,and the expression levels of VEGF and HGF in each group were detected by Western Blot and ELISA.Immunohistochemical staining was used to detect angiogenesis(CD31,SMA)in ischemic tissues.Safety was assessed by side effects during treatment in mice.Results After the successful modeling,the blood flow velocity of the left lower limb in each group decreased significantly.On the 7th day after operation,the blood flow of the left lower limb in each group was significantly better than that on the 0th day after operation(P<0.05),and the blood flow of the left lower limb in Ad-VEGF-HGF group was significantly better than that in other groups(P<0.05).On the 28th day after operation,the blood flow of the left lower limb in Ad-VEGF-HGF group gradually stabilized,the blood flow in Ad-VEGF-HGF group was significantly better than that in other groups,and both VEGF group and HGF group were significantly better than the control group(P<0.05).On the 7th,14th,and 28th days following surgery,HGF and VEGF protein levels in the Ad-HGF,Ad-VEGF,and Ad-VEGF-HGF groups were substantially greater than those in the control group(P<0.05).The expression level in the Ad-VEGF-HGF group peaked on the 14th day(all P<0.001)and subsequently declined to preoperative levels on the 28th day after operation.Conclusion Ad-VEGF-HGF gene injection can effectively boost VEGF and HGF protein expression and rapidly reach the relative peak level,encour-aging angiogenesis after lower limb ischemia,increasing blood flow,and improving lower limb circulation.

Targeting microRNA-125b inhibited the metastasis of Alisertib resistance cells through mediating p53 pathway / 中华肿瘤杂志

Objective: To clarify the mechanisms involvement in Alisertib-resistant colorectal cells and explore a potential target to overcome Alisertib-resistance. Methods: Drug-resistant colon cancer cell line (named as HCT-8-7T cells) was established and transplanted into immunodeficient mice. The metastasis in vivo were observed. Proliferation and migration of HCT-8-7T cells and their parental cells were assessed by colony formation and Transwell assay, respectively. Glycolytic capacity and glutamine metabolism of cells were analyzed by metabolism assays. The protein and mRNA levels of critical factors which are involved in mediating glycolysis and epithelial-mesenchymal transition (EMT) were examined by western blot and reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR), respectively. Results: In comparison with the mice transplanted with HCT-8 cells, which were survival with limited metastatic tumor cells in organs, aggressive metastases were observed in liver, lung, kidney and ovary of HCT-8-7T transplanted mice (P<0.05). The levels of ATP [(0.10±0.01) mmol/L], glycolysis [(81.77±8.21) mpH/min] and the capacity of glycolysis [(55.50±3.48) mpH/min] in HCT-8-7T cells were higher than those of HCT-8 cells [(0.04±0.01) mmol/L, (27.77±2.55) mpH/min and(14.00±1.19) mpH/min, respectively, P<0.05]. Meanwhile, the levels of p53 protein and mRNA in HCT-8-7T cells were potently decreased as compared to that in HCT-8 cells (P<0.05). However, the level of miRNA-125b (2.21±0.12) in HCT-8-7T cells was significantly elevated as compared to that in HCT-8 cells (1.00±0.00, P<0.001). In HCT-8-7T cells, forced-expression of p53 reduced the colon number (162.00±24.00) and the migration [(18.53±5.67)%] as compared with those in cells transfected with control vector [274.70±40.50 and (100.00±29.06)%, P<0.05, respectively]. Similarly, miR-125b mimic decreased the glycolysis [(25.28±9.51) mpH/min] in HCT-8-7T cells as compared with that [(54.38±12.70)mpH/min, P=0.003] in HCT-8-7T cells transfected with control. Meanwhile, in comparison with control transfected HCT-8-7T cells, miR-125b mimic also significantly led to an increase in the levels of p53 and β-catenin, in parallel with a decrease in the levels of PFK1 and HK1 in HCT-8-7T cells (P<0.05). Conclusions: Silencing of p53 by miR-125b could be one of the mechanisms that contributes to Alisertib resistance. Targeting miR-125b could be a strategy to overcome Alisertib resistance.

Course and characteristics of neonatal chaotic atrial tachycardia: a retrospective analysis of 30 cases / 中华围产医学杂志

Objective:To summarize the arrhythmic characteristics, clinical course, and prognosis of chaotic atrial tachycardia (CAT) in neonates.Methods:The researchers retrospectively analyzed and described the clinical data obtained from 30 neonates diagnosed with CAT and treated at the Maternal and Child Health Hospital of Hubei Province from January 2019 to August 2022. Prenatal and postnatal data were collected to analyze the electrocardiogram characteristics, clinical manifestations, treatment, and prognosis of CAT. Statistical analysis was performed using Mann-Whitney U and Chi-square (or Fisher's exact) tests. Results:(1) Among the 30 newborns with CAT, 19 were male infants (63%). The diagnosis age [ M(min-max)] was 11 days (1-28 days). Among them, 20 (67%) were born with full term, six (20%) had low birth weight, and 15 (50%) had abnormal cardiac structures. (2) The incidence of postnatal complex arrhythmias (coexisting with atrial fibrillation, flutter, supraventricular tachycardia, etc.) in fetuses with abnormalities, including fetal arrhythmias and fetal distress, was higher than those without abnormalities (9/14 vs 3/16, Fisher's exact, P=0.024). The median maximum atrial rate in incessant-type CAT patients (8 cases) was higher than that of paroxysmal-type CAT patients (22 cases) [400 bpm (300-700 bpm) vs 300 bpm (200-460 bpm), Z=－2.41, P=0.02]. There was no statistically significant difference in the maximum ventricular rate between the two groups [250 bpm (190-350 bpm) vs 270 bpm (180-350 bpm), Z=－0.26, P=0.800]. There were 19 cases (63%) complicated with diseases that seriously affected the respiratory or circulatory system, or infectious diseases. (3) Antiarrhythmic drugs were used in 23 cases (77%), including six cases treated with one drug, 12 cases with two drugs, and five cases with more than two drugs, mainly propafenone (20 cases, 67%). Seven cases (23%) with no complex arrhythmia turned to normal rhythm spontaneously without using antiarrhythmic drugs. Among all cases, 16 (53%) achieved clinical cures after complete cardioversion during hospitalization, while 14 cases (47%) were not cured. (4) The children who were cured during hospitalization were followed up for 1.5 months (2 weeks to 8 months) after discharge, and no recurrence was observed, indicating good growth and development. Untreated patients were followed up for 1.9 years (3.5 months to 4.4 years), of which seven cases completely recovered within six months, and the other seven cases continued to recur. However, no adverse outcomes, such as death, occurred. Conclusions:The overall prognosis of neonatal CAT is favorable. A history of fetal arrhythmia and intrauterine distress may increase the risk of CAT. Active drug treatment should be considered for children of CAT with complex arrhythmia.

Effect of Plasmacytoid Dendritic Cell Dose in Grafts on CMV Infection after Allogeneic Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To investigate the correlation between plasmacytoid dendritic cell (pDC) dose in grafts and the occurrence of cytomegalovirus (CMV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT).@*METHODS@#The clinical data of 80 children who received allo-HSCT in Children's Hospital of Soochow University from August 20, 2020 to June 11, 2021 were retrospectively analyzed. Proportions of DC subsets and T-cell subsets in grafts were detected by flow cytometry in order to calculate infused cell dose of each cell. Weekly monitoring of CMV-DNA copies in peripheral blood for each child were performed after transplantation. The last follow-up date was December 31, 2021.@*RESULTS@#All the children gained hematopoietic reconstitution. CMV infection was observed in 51 children (63.8%±5.4%) within the first 100 days after transplantation, including 2 cases developing CMV disease. Univariate analysis indicated that infused doses of DC and pDC were significantly associated with CMV infection within 100 days after allo-HSCT (P <0.05). Multivariate analysis indicated that a high dose infusion of pDC was an independent protective factor for CMV infection within 100 days after allo-HSCT (P <0.05). By the end of follow-up, 7 children died of transplantation-related complications, including 2 deaths from CMV disease, 2 deaths from extensive chronic graft-versus-host disease, and 3 deaths from capillary leak syndrome. The overall survival rate was 91.2%.@*CONCLUSION@#The pDC in grafts may be associated with early infection of CMV after allo-HSCT, while a high infused pDC dose may serve as a protective factor for CMV infection after transplantation.

Preliminary study on coronary artery interventional procedure assisted by guide wire and balloon assisted 360° twisting radial artery straightening technique / 中国介入心脏病学杂志

Objective Coronary arteriography(CAG)and percutaneous coronary intervention(PCI)are the most effective methods for the treatment of coronary atherosclerotic heart disease(CAD),but radial artery vascular variation,especially the presence of 360° tortuous(annular tortuous)radial artery seriously affects the success rate of trans-radial artery approach(TRA)interventional operation.This article provides a preliminary exploration of CAG and PCI through the annular tortuous radial artery.Methods We retrospectively analyzed 15 patients with annular tortuous right radial artery who successfully completed CAG or PCI by annular tortuous radial artery,and summarized the procedures performed through the annular tortuous radial artery.Results We found that the annular tortuous radial artery could be passed through by the catheter with the assistance of percutaneous transluminal coronary angioplasty(PTCA)guide wire or combined with a diameter of 2.0 mm balloon(6-8 atm dilatation state),and then the PTCA wire and the balloon can be replaced with a coronary angiography guide wire after the catheter passed through annular tortuous radial artery,and finally the annular tortuous radial artery could be straightened by fixing the coronary angiography guide wire and rotating and pulling the catheter.Finally,the catheter could be advanced to the coronary orifice and subsequent CAG or PCI could be performed while the annular tortuous radial artery was kept straightening.Both the left and right coronary arteries could perform coronary intervention using this technique,and there were no complications such as forearm hematoma or vascular rupture after this operation.Conclusions It is possible to successfully complete the coronary interventional therapy through annular tortuous radial artery by using the technique with the help of PTCA wire combined with balloon.

Correlation analysis between the expression of cannabinoid 2 receptor and the related indicators of pyroptosis in sepsis / 中华急诊医学杂志

Objective:To explore the correlation between cannabinoid 2 receptor (CB2R) and pyroptosis-related indicators in mice with septic lung injury.Methods:Mice were randomly (ramdon number) divided into four groups ( n=6 per group): sham operation group (sham), mild sepsis group (ALIMi), moderate sepsis group (ALIMo) and severe sepsis group (ALIS). The model of septic lung injury was established by cecal ligation and puncture. The wet-dry weight ratio of lung tissues and lung injury scores were measured 12 hours after operation. The expression of CB2R protein was measured by western blot, and the expression of mRNA of CB2R, NLRP3, caspase-1/11, GSDMD were detected by RT-PCR. Meanwhile ELISA was used to measure the level of inflammatory factor IL-6 and TNF-α. SPSS 22.0 software was used for data analysis. Multiple comparison was analyzed by one-way analysis of variance (one-way ANOVA) and comparison between two groups was performed by LSD test or Games-Howell test. Then, the correlation between the expression of CB2R mRNA and the level of inflammatory cytokines as well as the expression of the pyroptosis-related indicators mRNA was analyzed by pearson correlation analysis, respectively. Results:The statistical value F was obtained by one-way ANOVA and comparison between two groups was performed. Compared to sham group, all above indicators increased with the aggravation of inflammation in the sepsis groups ( P<0.05). Compared to ALIMi group, the concentrations of IL-6 [(277.31±41.07) vs.(140.09±27.56), P<0.05] and TNF-α [(501.09±73.91) vs. (261.36±40.73), P<0.05] in lung tissue homogenate increased in ALIMo group. And the level of CB2mRNA [(2.99±0.28) vs. (2.02±0.19), P<0.05], the expression of CB2 protein [(0.44±0.08) vs.(0.23±0.05), P<0.05] and the level of NLRP3 [(2.53±0.26) vs.(1.61±0.15), P<0.05], caspase-1 [(6.02±0.35) vs.(3.60±0.38), P<0.05], caspase-11 [(11.43±0.83) vs.(6.30±0.65), P<0.05] and GSDMD [(10.46±0.62) vs. (5.67±0.54), P<0.05] mRNA also increased. Compared to ALIMo group, the concentrations of IL-6 [(475.90±67.65) vs. (277.31±41.07), P<0.05] and TNF-α [(713.93±58.85) vs. (501.09±73.91), P<0.05] in lung tissue homogenate increased in ALIS group. And the level of CB2mRNA [(4.00±0.19) vs.(2.99±0.28), P<0.05], the expression of CB2 protein [(0.61±0.05) vs.(0.44±0.08), P<0.05] and the level of NLRP3 [(4.75±0.40) vs.(2.53±0.26), P<0.05], caspase-1 [(8.76±0.72) vs.(6.02±0.35), P<0.05], caspase-11 [(16.31±1.13) vs.(11.43±0.83), P<0.05] and GSDMD [(16.46±1.22) vs. (10.46±0.62), P<0.05] mRNA also increased. Furthermore, correlation analysis showed that there was a highly positive correlation between the expression of CB2R mRNA and the expression of mRNA of NLRP3, caspase-1/11, and GSDMD respectively ( r>0.9, P<0.01). Conclusion:The correlation between the aggravation of inflammation, the indicators of pyroptosis and CB2R mRNA was highly positive in different degrees of septic lung injury. Consequently, CB2R may play a role in the regulatory process of inflammation.

Digital analysis of the correlation between gingival thickness and alveolar bone thickness in the maxillary anterior teeth region / 中华口腔医学杂志

Objective: To measure the labial gingival thickness and bone lamella thickness in the maxillary anterior area using digital method, and to analyze the correlation between the two, so as to provide a reference for esthetic restoration and implantation treatment of the upper anterior area. Methods: Fifty-seven patients [23 males, 34 females, (25.8±4.5) years old] who planned to receive posterior dental implant restoration were recruited randomly with the inclusion and exclusion criteria in Department of Prosthodontics, School of Stomatology, The Fourth Military Medical University from May 2020 to October 2020. The 3Shape software was used to perform oral scanning, and cone beam CT (CBCT) was taken for each patient. The image data was fitted and registered by the 3Shape software. The gingival thickness at 2 mm below the gingival margin, bone thickness and gingival thickness at 2 and, 4 mm below the crest of the labial alveolar crest in maxillary central incisors, lateral incisors and canines, were measured. Results: The gingival thickness at 2 mm below the gingival margin of maxillary central incisors, lateral incisors and canines was (1.42±0.21), (1.19±0.17) and (1.23±0.20) mm respectively (F=12.47, P<0.001). The gingival thickness at 2 mm below gingival margin and 4 mm below crest of residual ridge in the male patients were (1.31±0.21) and (0.67±0.22) mm, and those in the female patients were (1.26±0.22) and (0.58±0.19) mm respectively, and there were statistically significant differences in the gingival thickness between the "2 mm below gingival margin" group and the "4 mm below crest of residual ridge" group (t=2.01 and 3.97, P<0.05). There was a positive correlation between gingival thickness and alveolar bone thickness at 2 mm and 4 mm below the crest of residual ridge in maxillary anterior region, and the correlation coefficients (r) were 0.387 and 0.344 respectively (P<0.05). Conclusions: Gingival thickness of maxillary anterior area is related to the tooth position and gender. The gingival thickness of men is greater than that of women.The gingival thickness at 2 and 4 mm below the crest of the alveolar crest is positively correlated with the thickness of the alveolar bone.

One-year follow-up results of atrial fibrillation patients who undergoing transcatheter aortic valve implantation / 中华心血管病杂志

Objective: To investigate whether atrial fibrillation (AF) before transcatheter aortic valve implantation (TAVI) will affect the prognosis of patients post TAVI. Methods: This is a single center retrospective study. A total of 115 patients with severe aortic stenosis (AS) who were admitted to General Hospital of Northern Theater Command from May 2016 to November 2020 and successfully received TAVI treatment were included. According to absence or accompaniment of AF pre-TAVI, they were divided into AF group (21 cases) and non-AF group (94 cases). The patients were followed up for postoperative antithrombotic treatment and the occurrence of the net adverse clinical and cerebrovascular events (NACCE) at 12 months post TAVI, including cardiogenic death, readmission to hospital for heart failure, nonfatal myocardial infarction, ischemic stroke and severe bleeding (BARC levels 3-5). Univariate logistic regression was used to analyze the related factors of NACCE. Results: Among the 115 selected patients, age was (73.8±6.9) years, there were 63 males. And 21 cases (18.2%) were diagnosed as AFbefore TAVI. In terms of postoperative antithrombotic therapy, 48.9% (46/94) of the patients in the non-AF group received monotherapy and 47.9% (45/94) received dual antiplatelet therapy. In the AF group, 47.6% (10/21) received anticoagulants and 33.3% (7/21) received dual antiplatelet therapy. The proportion of patients in the AF group taking non-vitamin K antagonist oral anticoagulants (NOAC) was higher than that in the non-AF group (38.1% (8/21) vs. 2.1% (2/94), P<0.001). Patients in both groups were followed up to 12 months after TAVI. During the 12 months follow-up, the incidence of NACCE after TAVI was 14.3% (3/21) in the AF group, which was numerically higher than that in the non-AF group (6.4% (6/94)), but the difference was not statistically significant (P=0.441). The incidence of severe bleeding was significantly higher in the AF group than in the non-AF group (9.5% (2/21) vs. 0, P=0.032). Univariate logistic regression analysis showed that hypertension was associated with the risk of NACCE (OR=8.308, P=0.050), while AF was not associated with the risk of NACCE (P=0.235). Conclusion: The incidence of severe bleeding after TAVI is higher in patients with AF than in patients without AF prior TAVI, and there is a trend of increased risk of NACCE post TAVI in AF patients.

Radiation-induced Hierarchical Topologically Associated Domain Change and Its Role in Cellular Responses to Radiation / 中国生物化学与分子生物学报

The three-dimensional (3D) genome organization plays an important role in gene regulation. As a basic functional unit of the genome, topologically associated domain (TAD) regulates multiplebiological processes such as gene expression and DNA replication and plays a role in radiation-inducedDNA damage repair. Recent studies showed that TAD is not a completely independent domain butcontains hierarchical internal domains, which could be a new mechanism of gene regulation. To explorethe role of hierarchical TAD in cellular responses to radiation, we apply the OnTAD algorithm, anoptimized nested TAD caller from Hi-C data, to identify hierarchical TAD in 26 Hi-C data from Geneexpression omnibus (GEO) database. These data were from irradiated fibroblasts, lymphoblasts andfibroblasts deficient in the ataxia telangiectasia mutated (ATM) gene with 5 Gy X-ray. We observe thatX-ray can regularly affect the hierarchy of TAD in which high-level TAD is prone to change and low-levelTAD is more conservative. We propose that radiation-induced TAD hierarchy change can regulate cellularresponses to radiation by regulating gene expression, and ATM is a necessary factor for radiation-inducedTAD hierarchy change and recovery. This study provides new insights into the role of the 3D genome inradiation-induced cellular responses from the perspective of hierarchical TAD structures.

Real-world outcomes of niraparib treatment in patients with ovarian cancer: the first observational multicenter study in China / 부인종양

Objective@#The objective of this study was to present the real-world patients’ portrait, and the results of niraparib treatment in China. @*Methods@#This study included 142 patients treated with niraparib from 8 hospitals in China between December 2018 and September 2021. Patients’ characteristics were summarized. The efficacy and safety in first-line maintenance (1L-M), platinum-sensitive recurrence maintenance (PSR-M), and treatment for ovarian cancer were evaluated. Survival outcomes and the factors influencing progression-free survival (PFS) were estimated. @*Results@#The 93 patients received Niraparib as 1L-M, 31 as PSR-M and 18 as salvage. BRCA status was wild type or unknown in 87.3% of patients. With a median follow-up time of 8.7 months, the median PFS (mPFS) for 1L-M has not yet been reached, and the mPFS for PSR-M and salvage therapy was 10.5 and 5.7 months, respectively. Responses to last chemotherapy and cancer antigen 125 value before taking niraparib were 2 important factors affecting PFS among 1L and PSR patients. The 12.7% (18/142) of patients experienced grade ≥3 hematologic adverse events and 23.2% experienced dose adjustment. It was noteworthy that when the interval of chemotherapy and niraparib <21 days, the incidence of grade ≥3 adverse events increased significantly (p=0.0355). @*Conclusion@#Generally, niraparib was effective and well tolerated, which was consistent with the results of prospective trials. However, in real world, it was more inclined to use niraparib in late-line treatment without genetic testing.

Role of the LRP1-pPyk2-MMP9 pathway in hyperoxia-induced lung injury in neonatal rats / 中国当代儿科杂志

OBJECTIVES@#To study the role of the low-density lipoprotein receptor-related protein 1 (LRP1)-proline-rich tyrosine kinase 2 phosphorylation (pPyk2)-matrix metalloproteinases 9 (MMP9) pathway in hyperoxia-induced lung injury in neonatal rats.@*METHODS@#A total of 16 neonatal rats were randomly placed in chambers containing room air (air group) or 95% medical oxygen (hyperoxia group) immediately after birth, with 8 rats in each group. All of the rats were sacrificed on day 8 of life. Hematoxylin and eosin staining was used to observe the pathological changes of lung tissue. ELISA was used to measure the levels of soluble LRP1 (sLRP1) and MMP9 in serum and bronchoalveolar lavage fluid (BALF). Western blot was used to measure the protein expression levels of LRP1, MMP9, Pyk2, and pPyk2 in lung tissue. RT-PCR was used to measure the mRNA expression levels of LRP1 and MMP9 in lung tissue.@*RESULTS@#The hyperoxia group had significantly higher levels of sLRP1 and MMP9 in serum and BALF than the air group (@*CONCLUSIONS@#The activation of the LRP1-pPyk2-MMP9 pathway is enhanced in hyperoxia-induced lung injury in neonatal rats, which may be involved in the pathogenesis of bronchopulmonary dysplasia.

Perioperative serious complications in patients undergoing transcatheter aortic valve replacement: a single-center experience / 中华心血管病杂志

Objective: To observe the incidence of perioperative severe complications in aortic stenosis (AS) patients undergoing transcatheter aortic valve implantation (TAVR), and to explore the influence of the accumulated experience of the operators on the incidence of complications. Methods: This is a single-center retrospective study. Patients with AS who underwent TAVR from May 2016 to November 2020 in General Hospital of Northern Theater Command were included. The occurrence of severe complications during perioperative period was recorded. Severe complications included all-cause death, surgical transfer to thoracotomy, coronary artery occlusion, peripheral vascular approach complications, severe cerebrovascular events, moderate or above perivalvular leakage, valve displacement (implanted valve middle valve), pacemaker implantation, etc. In order to observe the influence of the accumulated experience of the operators on the occurrence of postoperative complications, the complications in each stage of the patients were counted and the bar chart was drawn with interval of every 30 patients. Results: A total of 119 patients were included, including 64 males and 55 females, the mean age was (73.9±6.9) years. The valve implantation was unsuccessful in 3 out of 119 patients (2.5%). There were 39 cases of severe complications during perioperative period, including 1 death (0.8%), 2 cases of thoracotomy (1.7%), 2 cases of coronary artery occlusion (1.7%), 8 cases of peripheral vascular approach complications (6.7%), and 1 case of new severe cerebrovascular event (0.8%), 3 cases of moderate or higher perivalvular leakage (2.5%), 8 cases of valve displacement leads to midvalvular implantation (6.7%), 14 cases of permanent pacemaker implantation due to new atrioventricular block (11.8%). The bar chart showed that the incidence of permanent pacemaker implantation and in-valve implantation did not significantly decrease with the accumulation of experience, while the incidence of other complications showed a decreasing trend after 30 cases. Conclusions: Most serious complications occurred in the early stage of TAVR in our center. The incidence of all cause death, coronary artery occlusion and peripheral vascular approach complications in the perioperative period post TAVR could be reduced in the TAVR center in the learning stage through the accumulation of procedure-related experience, but the incidence of pacemaker placement and the implanted valve within the valve dose not significantly decrease over time.

Analysis of Chemical Constituents in Violae Herba and Investigation of Its Antioxidant Activity in Vitro / 中国实验方剂学杂志

Objective:To investigate the chemical constituents and antioxidant activities of Violae Herba from the Violaceae. Method:The 5 kg of Violae Herba was refluxing extracted with 3 times the amount of 95% ethanol for three times， then the extracting solution was combined， filtrated， concentrated under vacuum to get the total extract. Seven corresponding fractions were eluted with petroleum ether， dichloromethane， dichloromethane-methanol （50∶1， 10∶1， 5∶1， 2∶1） and methanol by silica gel column chromatography （60-100 mesh） on the total extract. Each fraction was isolated and purified by normal phase silica gel column chromatography， octadecylsilane chemically bonded silica （ODS） column chromatography， Sephadex LH-20 column chromatography and preparative high performance liquid chromatography （HPLC）， respectively. The structures of the obtained compounds were identified by spectroscopic methods of nuclear magnetic resonance （NMR）， mass spectroscopy （MS） and infrared spectroscopy （IR）. Meanwhile， some of these compounds isolated from Violae Herba were carried on the 1，1-diphenyl-2-picrylhydrazyl （DPPH） free radical scavenging experiment. Result:Fourteen compounds were isolated from the 95% ethanol extract of Violae Herba， including <italic>N</italic>-acetyl-1-ethyl ester glutamic acid （<bold>1</bold>）， <italic>N</italic>-acetyl glutamic acid-1-ethyl-5-methyl ester （<bold>2</bold>）， aurantiamide （<bold>3</bold>）， <italic>rel</italic>-（2<italic>α</italic>，3<italic>β</italic>）-7-<italic>O</italic>-methylcedrusin （<bold>4</bold>）， oleanolic acid （<bold>5</bold>）， <italic>α</italic>-tocopherol-quinone （<bold>6</bold>）， tectochrysin （<bold>7</bold>）， isoscopoletin （<bold>8</bold>）， esculetin （<bold>9</bold>）， 24-ethylcholesta-4，24（28）<italic>Z</italic>-dien-3-one （<bold>10</bold>）， stigmasta-4，25-dien-3-one （<bold>11</bold>）， <italic>β</italic>-sitostenone （<bold>12</bold>）， <italic>β</italic>-sitosterol （<bold>13</bold>）， （24<italic>R</italic>）-3<italic>β</italic>-hydroxy-ethylcholest-5-en-7-one （<bold>14</bold>）. Conclusion:Compound <bold>2</bold> is a new natural product， compounds <bold>1</bold>， <bold>4</bold>， <bold>6</bold>， <bold>7</bold>， <bold>10</bold>-<bold>12 </bold>are isolated from the genus <italic>Viola</italic> for the first time. Compound <bold>9</bold> has significant antioxidant activity， while compounds <bold>2</bold>， <bold>6 </bold>and<bold> 8</bold> have certain DPPH free radical scavenging activity.

Curative effect of antibiotic de-escalation therapy on severe pneumonia / 中国基层医药

Objective:To investigate the clinical efficacy and safety of antibiotic de-escalation therapy in the treatment of severe pneumonia.Methods:Sixty patients with severe pneumonia who received treatment in The First People's Hospital of Yongkang,China from January 2015 to January 2018 were included in this study.They were randomly assigned to receive either conventional antibiotic therapy (control group, n = 30) or antibiotic de-escalation therapy (observation group, n = 30).The clinical efficacy,symptom relief time,antibiotic treatment time,length of hospital stay,pulmonary ventilation function index,serum levels of inflammatory factors and the incidence of adverse reactions were compared between the control and observation groups. Results:Total effective rate in the observation group was significantly higher than that in the control group [93.33% (28/30) vs.73.33% (22/30), χ2 = 4.320, P < 0.05].The time to disappearance of cough,fever and abnormal lung sounds in the observation group was (2.10 ± 1.25) d,(2.19 ± 1.24) d,(2.01 ± 0.56) d,respectively,which was significantly shorter than that in the control group [(3.73 ± 1.92) d,(3.68 ± 1.70) d,(3.36 ± 0.78) d, t = 3.897,3.878,7.701,all P < 0.05].The antibiotic treatment time and length of hospital stay in the observation group were (2.89 ± 1.06) d and (4.08 ± 1.23) d,respectively,which were shorter those in the control group [(4.27 ± 1.45) d and (5.76 ± 1.69) d, t = 4.208 and 4.402,both P < 0.05].The forced expiratory volume in one second (FEV 1) and the ratio of FEV 1 to forced vital capacity (FVC) in the observation group were (2.09 ± 0.69) L and (58.94 ± 15.67)%,respectively,which were significantly higher than those in the control group [(1.43 ± 0.57) L,(43.12 ± 11.03)%, t = 4.039 and 4.522,both P < 0.05).Serum levels of C-reactive protein,interleukin-6 and procalcitonin in the observation group were (5.84 ± 2.09) mg/L,(20.05 ± 2.76) ng/L,(2.18 ± 0.78) ng/L respectively,which were significantly lower than those in the control group [(8.50 ± 2.67) mg/L,(23.24 ± 3.07) ng/L,(3.11 ± 0.97) ng/L, t = 4.297,4.232,4.092,all P < 0.05].There was no significant difference in the incidence of adverse reactions between the observation and control groups (6.67% vs.10.00%, χ2 = 0.218, P > 0.05). Conclusion:Antibiotic de-escalation therapy for the treatment of severe pneumonia can shorten the time of disappearance of clinical symptoms,improve pulmonary ventilation function,and inhibit systemic inflammatory reaction without increasing adverse reactions.

Critical quality attribute assessment of big brand traditional Chinese medicine: quality control method of Huangjing Zanyu Capsules based on chemical properties of characteristic components / 中国中药杂志

The chemical properties of characteristic components are significant to the manufacturing quality control of big brand traditional Chinese medicine. In this study, the Huangjing Zanyu Capsules were used as the research carrier to determine the content of five characteristic components including icraiin, emodin, schisandrin A, 2,3,5,4'-tetrahydroxystilbene-2-O-β-D-glucoside, and osthole simultaneously by high-performance liquid chromatography(HPLC). The results showed that the chemical properties of five cha-racteristic components had a good linear relationship(r>0.999 9) within the quantitative range; the relative standard deviations(RSD) was 0.11%-2.0% and 0.25%-2.8% respectively for intra-day and inter-day precision; the RSD of repeatability was 1.8%-2.6%; the RSD of stability within 48 hours was 0.19%-2.8%, and the average recovery rate was 95.52%-100.1%, all meeting the requirements of pharmaceutical quantitative analysis. Additionally, the interval estimation method was used to directly reflect the distribution of samples with abnormal chemical properties of characteristic components, and the results showed ten samples were detected beyound the 95% control line of confidence level. Multivariate statistical process control(MSPC) method was used to monitor the abnormal samples of Huangjing Zanyu Capsules collectively, and the results showed that two samples were beyond the 95% control line of Hotelling's T~2 and three samples beyond the 95% control line of squared prediction error(SPE), indicating consistent quality control of Huangjing Zanyu Capsules. In conclusion, the proposed method is not only accurate and efficient but also a compensation for the traditional single-component quality control method, providing a scientific basis for the quality control in manufacturing process of Huangjing Zanyu Capsules. Furthermore, it could also serve as a reference method for the quality control in manufacturing big brand traditional Chinese medicine.

Effects of different depths of anesthesia on postoperative cognitive function in patients undergoing minimally invasive McKeown esophagectomy / 肿瘤研究与临床

Objective:To analyze the effects of different anesthesia depths on serum S100β protein level and postoperative cognitive function in patients undergoing minimally invasive McKeown esophagectomy with bispectral index (BIS) monitoring.Methods:A total of 120 patients who received minimally invasive McKeown esophagectomy in the Second Hospital of Shanxi Medical University from April 2018 to April 2019 were selected, and they were divided into light anesthesia group (L group, 40 cases, BIS 46-60), deep anesthesia group (D group, 40 cases, BIS 35-45) and control group (C group, 40 cases, no BIS monitoring) by using the random number table method. Elbow venous blood was taken from each group to detect serum S100β protein levels before induction (T 0), 10 minutes after extubation (T 3), the first day after surgery (T 4), and the third day after surgery (T 5). The mini-mental state examination scale (MMSE) score and the monterey cognitive assessment scale (MoCA) score were performed before surgery and on day 1, 3, and 7 after surgery to count the incidence of postoperative cognitive dysfunction(POCD). Results:There was no statistical difference in serum S100β protein levels between the three groups at T 0 (F = 0.083, P = 0.920). The level of serum S100β protein in D group [(1.08±0.05) μg/L] was significantly higher than that in C group and L group [(0.98±0.10) μg/L and (0.84±0.09) μg/L] at T 3, and the level of serum S100β protein in L group was lower than that in C group, the differences between the three groups were statistically significant (P < 0.05). There was no statistical difference in the incidence of POCD among the three groups on day 7 after surgery (χ 2 = 2.914, P = 0.233). The incidence rates of POCD in D group on day 1 and 3 after surgery (57.1% and 37.1%) were significantly higher than those in C group (41.7% and 38.9%) and L group (20.0% and 14.3%), and the incidence of POCD in L group were lower than those in C group, the differences among the three groups were statistically significant (χ 2 = 10.187, P = 0.006; χ 2 = 6.296, P = 0.043). Conclusions:For patients undergoing minimally invasive McKeown esophagectomy, intraoperative BIS monitoring maintains a light anesthetic state, which can effectively reduce serum S100β protein level and POCD. The mechanism may be related to reducing serum S100β protein level and improving brain damage.

Effect of Paiteling on HeLa Cell Proliferation and Metastasis Ability and PI3K/Akt Signal Transduction Pathway / 中国实验方剂学杂志

Objective:To explore the effect of Paiteling on the proliferation，metastasis and invasion of HeLa cells and relevant proteins of phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. Method:① HeLa cells were divided into blank group and Paiteling concentration gradient groups (3.906，2.604，1.953，1.563，1.302，1.116，0.977 g·L-1). After drug intervention for 24 h，the cell morphological changes were observed under microscope. The cell viability was measured by thiazole blue (MTT) colorimetry，and the half inhibitory concentration (IC50) of Paiteling on HeLa cells was calculated. ② HeLa cells were divided into blank group，cisplatin group (0.01 g·L-1)，Paiteling high-dose group (2.974 g·L-1)，Paiteling medium-dose group (1.487 g·L-1) and Paiteling low-dose group (0.991 g·L-1). Cell proliferation and toxicity test (CCK-8) method was used to detect the effect of Paiteling on the proliferation ability of HeLa cells，scratch test was used to detect cell migration，and invasion test (Transwell) was used to detect changes in cell invasion ability. ③ Inhibitor LY294002 group (0.006 g·L-1) was added. Western blot (WB) was used to detect the expressions of Paiteling on PI3K，Akt，recombinant human B-cell lymphoma factor-xl (Bcl-xl)，and B-cell lymphoma/leukemia associated D protein (Bad). Result:① Compared with the blank group，microscopic observation showed that the number of cells in the treatment group was significantly reduced, and the cell morphology was incomplete. MTT experiments showed that Paiteling has a significantly inhibitory effect on HeLa cell proliferation (P<0.01). The IC50 of Paiteling on HeLa cells was calculated as 2.974 g·L-1. ② The CCK-8 experiment showed that compared with the blank group，all the drug-treated groups had an inhibitory effect on HeLa cell proliferation at 24，36，48 h (P<0.01), compared with the cisplatin group，middle and low-dose Paiteling groups showed a reduced inhibitory effect on HeLa cell proliferation at each time point (P<0.01). The scratch test showed that，compared with the blank group，each drug-added group could inhibit the migration ability of HeLa cells (P<0.01)，and the cell migration rate of the high-dose Paiteling group was lower than that of the cisplatin group (P<0.05). Transwell experiments showed that compared with the blank group，the number of membranes permeated by HeLa cells in each drug-treated group was decreased (P<0.01)，and the number of membranes permeated in the middle and low-dose Paiteling groups was increased compared with the cisplatin group (P<0.01). ③ Western blot showed that compared with the blank group，the expression levels of PI3K，Bcl-xl，and Akt in the high，medium，and low-dose Paiteling groups and the LY294002 group decreased (P<0.05，P<0.01)，while the expression of Bad increased (P<0.01). Compared with the high-dose Paiteling group，the PI3K，Akt，and Bcl-xl protein expressions were increased in the low-dose Paiteling group (P<0.01)，whereas Bad expression was decreased (P<0.01). Conclusion:Paiteling can inhibit HeLa cell proliferation，metastasis and invasion ability in a dose-dependent and time-dependent manner，which may be related to its effect on the expressions of PI3K/Akt signaling pathway-related proteins.

Isolation and Identification of Chemical Constituents from Paeonia veitchii / 中国实验方剂学杂志

Objective::To investigate the chemical constituents from Paeonia veitchii. Method::P. veitchii samples (30 kg) were extracted with 95% ethanol for four times and then filtrated, and the combined filtrates were concentrated under vacuum to get the extracts. After suspension with water, exaction was conducted with petroleum ether, dichloromethane, ethyl acetate, n-butanol and water successively to obtain five corresponding fractions. The compounds were isolated and purified by silica gel, Sephadex LH-20, ODS column chromatography and prep-HPLC, and the structures of these compounds were determined by such spectrum technologies as infrared spectroscopy (IR), mass spectroscopy (MS), and nuclear magnetic resonance (NMR). Result::Sixteen compounds were isolated and their structures were identified as follows (1S, 5R, 6R)-1, 8-dihydroxypin-2-en-4-one (1), (2-hydroxyl)-phenyl-methyl-β-D-xylopyranoside (2), flufuran (3), 6′-O-vanillylpaeoniflorin (4), methyl 2, 5-dihydroxycinnamate (5), (1S, 2S, 5R, 6R)-1, 8-dihydroxypin-4-one (6), palbinone (7), 4-O-methylpaeoniflorin (8), 4-O-ethylpaeoniflorin (9), benzoyloxypaeoniflorin (10), benzoic acid (11), gallic acid (12), methyl gallate (13), ethyl gallate (14), β-sitosterol (15), and 1, 2, 3, 4, 6-penta-O-galloyl-β-D-glucopyranose (16). Conclusion::Compounds 1, 2 were new natural compounds; compound 3 was isolated from genus Paeonia for the first time, and compounds 4-7 were isolated from this plant for the first time.

Chemical Constituents from Stems of Zanthoxylum bungeanum / 中国实验方剂学杂志

Objective::To isolate and identify the chemical constituents from the 95%, 75%ethanol extracts of the stems of Zanthoxylum bungeanum. Method::The 25 kg stems of Z. bungeanum were extracted with 95%, 75%ethanol for three times, and the combined filtrates were concentrated under vacuum to get the extracts. The 95%extracts were then extracted by petroleum ether, dichloromethane, ethyl acetate and n-butanol successively to obtain corresponding fractions. Such fractions and 75%extracts were isolated and purified by silicagel, Sephadex LH-20, ODS, preparation HPLC and recrystallization to obtain compounds. Their structures were identified by mass spectroscopy (MS), and nuclear magnetic resonance (NMR). Result::Sixteen compounds were isolated from the stems of Z. bungeanum and identified as dictamnine(1), decarine(2), zanthobungeanine(3), pseudocolumbamine(4), skimmianine(5), norchelerythrine(6), osthenol(7), dimethylfraxetin(8), 3, 4, 5-trimethoxycinnamylalcohol(9), asarinin(10), yangambin(11), syringaresinol(12), ashantin(13), bis(2-ethylhexyl) benzene-1, 2-dicarboxylate(14), 24-propylcholesterol(15), and sucrose(16). Conclusion::Compounds pseudocolumbamine(4), 3, 4, 5-trimethoxycinnamylalcohol(9), and 24-propylcholesterol(15)were isolated from the genus of Zanthoxylum for the first time and compounds dictamnine(1), osthenol(7), dimethylfraxetin(8), asarinin(10), yangambin(11), syringaresinol(12), ashantin(13), and bis(2-ethylhexyl) benzene-1, 2-dicarboxylate(14)were isolated from this plant for the first time.

Effect of electroacupuncture on rehabilitation of knee joint movement after anterior cruciate ligament reconstruction / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) on the rehabilitation of knee joint function after anterior cruciate ligament (ACL) reconstruction.@*METHODS@#A total of 140 patients with ACL reconstruction were randomly divided into an observation group (58 cases recruited, 12 cases dropped out) and a control group (65 cases recruited, 5 cases dropped out). The patients in the control group were treated with routine rehabilitation treatment. The patients in the observation group, on the basis of the treatment in the control group, were treated with EA at Fengshi (GB 31), Futu (ST 32), Zusanli (ST 36), Shangjuxu (ST 37), Fenglong (ST 40), Xuanzhong (GB 39), Diji (SP 8) and Sanyinjiao (SP 6) on the affected side (2 Hz/100 Hz of dilatational wave, 2-5 mA). Each EA treatment lasted 20-30 min, twice a day for 7 days. The swelling degree (d), pain visual analogue scale (VAS), knee joint range of motion (ROM), scores of International Knee Documentation Committee (IKDC) subjective short form and scores of Lysholm were observed in the two groups 1 day, 1 month, 3 months, 6 months and 1 year after operation.@*RESULTS@#One month and 3 months after operation, the swelling degree (d) and VAS scores in the observation group were lower than those in the control group (0.05). One month, 3 months, 6 months and 1 year after operation, the ROM of the knee joint in the observation group was higher than that in the control group (<0.05), the IKDC score and Lysholm score were higher than those in the control group (<0.05). Within one year, there were no relaxations, fractures and other related complications in the two groups. The pivot shift test, anterior drawer test and the Lachman test were all negative.@*CONCLUSION@#EA combined with routine rehabilitation training could obviously reduce the pain of knee joint, improve the swelling degree, increase the ROM of knee joint, promote the functional recovery in patients with ACL reconstruction, which are superior to rehabilitation training alone.