Effect of thrombocytosis on prognosis of hepatocellular carcinoma after TACE / 中华肝胆外科杂志

Objective:To analyze the prognosis of hepatocellular carcinoma (HCC) patients with thrombocytosis (platelet count ≥350×10 9) after transcatheter arterial chemoembolization (TACE), and the effect of thrombocytosis on the prognosis of patients with HCC after TACE. Methods:Clinical data of 867 patients with HCC admitted to the Department of Interventional Radiology, the Affiliated Hospital of Xuzhou Medical University from January 2013 to May 2018 were retrospectively analyzed. After propensity score matching, 99 patients were enrolled, including 70 males and 29 females, aged (60.1±12.1) years. Patients were divided into the groups with thrombocytosis ( n=33) and without thrombocytosis ( n=66). The gender, maximum tumor diameter, Barcelona clinical liver cancer (BCLC) stage, and total bilirubin were compared between the two groups. The association of thrombocytosis with the prognosis of HCC after TACE treatment were analyzed using univariate and multivariate Cox regression. Results:After propensity score matching, the male proportion, maximum tumor diameter, BCLC stage, and serum level of total bilirubin were comparable between the groups (all P>0.05). Before TACE treatment, the platelet count of patients with thrombocytosis was (394.4±54.5)×10 9/L, which was higher than that after TACE [(278.2±86.4)×10 9/L, t=7.63, P<0.001]. The progression-free survival rates after TACE in without thrombocytosis group were 83.3%, 24.2%, and 7.6% at 3, 6 and 9 months, respectively, better than those in thrombocytosis group (51.5%, 3.0%, and 3.0%, respectively; χ2=31.24, P<0.001). The overall survival rates after TACE in without thrombocytosis group were 81.8%, 30.3%, and 4.5% at 1, 2 and 3 years, respectively, better than those in thrombocytosis group (15.2%, 9.1%, and 3.0%, respectively; χ2=27.89, P<0.001). Multivariate Cox regression analysis showed that patients of HCC with thrombocytosis had an increased risk of tumor progression ( HR=5.785, 95% CI: 3.291-10.168, P<0.001) and increased risk of death ( HR=4.090, 95% CI: 2.482-6.740, P<0.001) after TACE. Conclusion:The prognosis of TACE for HCC might be worse in patients with thrombocytosis. Thrombocytosis is a risk factor for cumulative survival and progression-free survival of HCC patients after TACE.

Correlation analysis of preoperative red blood cell distribution width and prognosis of patients undergoing TACE for hepatocellular carcinoma / 中华肝胆外科杂志

Objective:To evaluate the relationship between red blood cell distribution width (RDW) and prognosis of patients with hepatocellular carcinoma (HCC) andergoing transcatheter arterial chemoembolization (TACE).Methods:Clinical data of 212 patients with HCC andergoing TACE for the first time in Department of Interventional Radiology, the Affiliated Hospital of Xuzhou Medical University from January 2011 to May 2018 were retrospectively analyzed, including 184 males and 28 females, aged (56.8±11.2) years. Follow-up for survival. X-tile software was used to determine 13.1% as the optimal threshold for preoperative RDW prediction of prognosis, and enrolled patients were divided into a low level group (RDW<13.1%, n=70) and a high level group (RDW≥13.1%, n=142). Aspartate aminotransferase, total bilirubin, albumin, hemoglobin and lipoprotein a, Barcelona clinical liver cancer (BCLC) stage and other indexes were compared between the two groups. Survival analysis was performed by Kaplan-Meier method, survival rate was compared by log-rank test, and the effect of RDW on prognosis was analyzed by Cox regression. Results:The 1-year, 2-year and 3-year cumulative survival rates in RDW high level group were 34.5%, 14.1% and 6.3%, respectively, while those in RDW low level group were 64.3%, 38.6% and 21.4%, respectively, with significant difference ( χ2=23.09, P<0.001). Compared with the low level group, the levels of aspartate aminotransferase and total bilirubin were higher, the levels of albumin, hemoglobin and lipoprotein a were lower, the proportion of portal vein cancer thrombin was higher, and the stage of BCLC was later, with statistical significance (all P<0.05). Cox regression analysis showed that HCC patients with RDW≥13.1%( HR=1.732, 95% CI: 1.223-2.452, P=0.002) had poor survival prognosis after TACE. Conclusion:Preoperative RDW≥13.1% is an independent risk factor for survival after TACE in patients with HCC. RDW has potential predictive value for prognosis of patients with HCC.

Role of AQP4 in dexmedetomidine-induced reduction of blood-brain barrier permeability in mechanically ventilated mice: relationship with PKC / 中华麻醉学杂志

Objective:To evaluate the role of aquaporin 4 (AQP4) in dexmedetomidine-induced reduction of blood-brain barrier permeability in mechanically ventilated mice and the relationship with protein kinase C (PKC).Methods:One hundred and fifty clean-grade healthy male C57BL6 mice, weighing 20-25 g, aged 8-12 weeks, were divided into 5 groups ( n=30 each) using a random number table method: control group (group C), mechanical ventilation group (group V), LY317615 group (group L), dexmedetomidine group (group D), and dexmedetomidine+ PMA group (group DP). Group C spontaneously breathed air for 6 h. The animals were mechanically ventilated for 6 h in group V. PKC inhibitor LY3176 15 μg/kg was intraperitoneally injected at 30 min before mechanical ventilation in group L. Dexmedetomidine 50 μg/kg was intraperitoneally injected at 30 min before mechanical ventilation in D and DP groups. PKC activator PMA 15 μg/kg was intraperitoneally injected at 60 min before mechanical ventilation in group DP. Mice were anesthetized at 1 day after mechanical ventilation, then sacrificed and hippocampal tissues were taken for microscopic examination of pathological changes in the hippocampal CA1 and CA3 areas (with a light microscope). Brain tissues were also taken to measure the water content and content of Evans blue (EB) and to detect the expression of PKC and AQP4 (by Western blot). The cognitive function was evaluated using a novel object recognition task at 3 days after mechanical ventilation. Results:Compared with group C, the water content and EB content of brain tissues were significantly increased after mechanical ventilation, the expression of PKC and AQP4 in brain tissues was up-regulated, the percentage of novel object exploration and discrimination index were decreased ( P<0.05), and the histopathological damage in the hippocampal CA1 and CA3 areas was aggravated in group V and group DP. Compared with group V, the water content and EB content of brain tissues were significantly decreased after mechanical ventilation, the expression of PKC and AQP4 in brain tissues was down-regulated, the percentage of novel object exploration and discrimination index were increased ( P<0.05), and the histopathological damage in the hippocampal CA1 and CA3 areas was significantly attenuated in group D and group L. Compared with group D, the water content and EB content of brain tissues were significantly increased after mechanical ventilation, the expression of PKC and AQP4 in brain tissues was up-regulated, the percentage of novel object exploration and discrimination index were decreased ( P<0.05), and the histopathological damage in the hippocampal CA1 and CA3 areas was aggravated in group DP. Conclusions:AQP4 is involved in dexmedetomidine-induced reduction of blood-brain barrier permeability in mechanically ventilated mice, and the mechanism is related to inhibiting activation of PKC.

Comparative Study on Flexible Ureteroscope Guided Peritoneal Dialysis Catheter Placement / 中国微创外科杂志

Objective To explore the feasibility of peritoneal dialysis catheter placement assisted by flexible ureteroscope.Methods A retrospective analysis was conducted on clinical data of 54 cases of end-stage renal disease receiving peritoneal dialysis catheter placement from May 2019 to March 2023.The placement method was chosen by the patient.In the conventional group,23 cases were guided by a metal guide wire for insertion of the peritoneal dialysis catheter,while in the flexible ureteroscope group,31 cases were guided by flexible ureteroscope instead of guide wire for insertion of the peritoneal dialysis catheter.The success rate of catheterization,surgical time,use of postoperative analgesic,complications related to peritoneal dialysis catheter,and postoperative creatinine decrease were compared between the two groups.Results The catheter placement was successfully performed in both groups.The total incidence of complications related to peritoneal dialysis catheter in the flexible ureteroscope group was lower than that in the conventional group[6.5%(2/31)vs.30.4%(7/23),χ2 =3.878,P =0.049].Between the conventional group and the flexible ureteroscope group,there were no statistically significant differences in the surgical time,postoperative analgesic usage,and the decrease of creatinine at 2 weeks after surgery(P>0.05).The median postoperative follow-up period was10 months(range,3-24 months)in the two groups,and there were no complications such as peritoneal leakage,intestinal perforation,or intraperitoneal bleeding.Conclusion The placement of peritoneal dialysis catheter guided by the flexible ureteroscope instead of metal guide wire is a safe,visible,and accurate method,which can reduce complications related to peritoneal dialysis catheter,and detect and manage comorbidities in the abdominal cavity.

Focusing on timing selection and whole-course management of liver transplantation treatment for patients with acute-on-chronic liver failure / 中华肝脏病杂志

Acute-on-chronic liver failure (ACLF) is a clinical syndrome of acute decompensation accompanied by organ failure that occurs on the basis of chronic liver disease and has a high short-term mortality rate. Currently, there are still differences in relation to the definition of ACLF; thus, baseline characteristics and dynamic changes are important bases for clinical decision-making in patients with liver transplantation and others. The basic strategies for treating ACLF currently include internal medicine treatment, artificial liver support systems, and liver transplantation. Multidisciplinary active collaborative management throughout the whole course is of great significance for further improving the survival rate in patients with ACLF.

Phenolic derivatives from root bark of Schisandra sphenanthera / 中国中药杂志

This paper aimed to study the chemical constituents from the root bark of Schisandra sphenanthera. Silica, Sephadex LH-20 and RP-HPLC were used to separate and purify the 80% ethanol extract of S. sphenanthera. Eleven compounds were identified by ~1H-NMR, ~(13)C-NMR, ESI-MS, etc., which were 2-[2-hydroxy-5-(3-hydroxypropyl)-3-methoxyphenyl]-propane-1,3-diol(1), threo-7-methoxyguaiacylglycerol(2),4-O-(2-hydroxy-1-hydroxymethylethyl)-dihydroconiferylalcohol(3), morusin(4), sanggenol A(5), sanggenon I(6), sanggenon N(7), leachianone G(8),(+)-catechin(9), epicatechin(10), and 7,4'-dimethoxyisoflavone(11). Among them, compound 1 was a new compound, and compounds 2-9 were isolated from S. sphenanthera for the first time. Compounds 2-11 were subjected to cell viability assay, and the results revealed that compounds 4 and 5 had potential cytotoxicity, and compound 4 also had potential antiviral activity.

Scaffold protein MAPK8IP2 expression is a robust prognostic factor in prostate cancer associated with AR signaling activity / 亚洲男科学杂志(英文版)

Mitogen-activated protein kinase-8-interacting protein 2 (MAPK8IP2) is a scaffold protein that modulates MAPK signal cascades. Although MAPK pathways were heavily implicated in prostate cancer progression, the regulation of MAPK8IP2 expression in prostate cancer is not yet reported. We assessed MAPK8IP2 gene expression in prostate cancer related to disease progression and patient survival outcomes. MAPK8IP2 expression was analyzed using multiple genome-wide gene expression datasets derived from The Cancer Genome Atlas (TCGA) RNA-sequence project and complementary DNA (cDNA) microarrays. Multivariable Cox regressions and log-rank tests were used to analyze the overall survival outcome and progression-free interval. MAPK8IP2 protein expression was evaluated using the immunohistochemistry approach. The quantitative PCR and Western blot methods analyzed androgen-stimulated MAPK8IP2 expression in LNCaP cells. In primary prostate cancer tissues, MAPK8IP2 mRNA expression levels were significantly higher than those in the case-matched benign prostatic tissues. Increased MAPK8IP2 expression was strongly correlated with late tumor stages, lymph node invasion, residual tumors after surgery, higher Gleason scores, and preoperational serum prostate-specific antigen (PSA) levels. MAPK8IP2 upregulation was significantly associated with worse overall survival outcomes and progression-free intervals. In castration-resistant prostate cancers, MAPK8IP2 expression strongly correlated with androgen receptor (AR) signaling activity. In cell culture-based experiments, MAPK8IP2 expression was stimulated by androgens in AR-positive prostate cancer cells. However, MAPK8IP2 expression was blocked by AR antagonists only in androgen-sensitive LNCaP but not castration-resistant C4-2B and 22RV1 cells. These results indicate that MAPK8IP2 is a robust prognostic factor and therapeutic biomarker for prostate cancer. The potential role of MAPK8IP2 in the castration-resistant progression is under further investigation.

Efficacy of ultrasound-guided superior laryngeal nerve block combined with intravenous anesthesia for improving pediatric fiberoptic bronchoscopy / 中华麻醉学杂志

Objective:To evaluate the efficacy of ultrasound-guided superior laryngeal nerve block(SLNB) combined with intravenous anesthesia for improving pediatric fiberoptic bronchoscopy.Methods:Forty pediatric patients of either sex, aged 3-6 yr, of American Society of Anesthesiologists Physical Status classificationⅠor Ⅱ, with body mass index of 18-24 kg/m 2, undergoing fiberoptic bronchoscopy in Cangzhou Central Hospital in 2022, were divided into 2 groups ( n=20 each) by a random number table method: ultrasound-guided SLNB plus intravenous anesthesia group (group A) and topical anesthesia plus intravenous anesthesia group (group B). After sedation with dexmedetomidine and esketamine, ultrasound-guided bilateral SLNB was performed with 1% lidocaine 0.5 ml (for each side)in group A, and topical anesthesia was performed with 1% lidocaine in nasal and pharyngeal cavities in group B. After completion of the surgery procedure, propofol was continuously infused at 5 mg·kg -1·h -1 until completion of diagnosis and treatment. An increment of propofol 1 mg/kg was intravenously given if severe bucking or body movement occurred during operation. Mean arterial pressure (MAP), heart rate (HR) and SpO 2 were recorded on admission to the operating room (T 0), immediately after sedation (T 1), immediately after bronchoscopy entering the glottis (T 2), 5 min after start of treatment (T 3) and at the end of examination (T 4). The occurrence of intraoperative hypoxemia, HR <60 bpm, and MAP <50 mmHg were recorded, and the additional dose of propofol was recorded. The venous blood samples were collected at T 0 and T 4 to determine plasma cortisol concentrations by chemiluminescence.The surgeon′s satisfaction score was recorded. The complications of SLNB were also recorded within 2 h after operation in group A. Results:Compared with group B, HR was significantly decreased at T 2 and T 3, SpO 2 was increased, the intraoperative additional dosage of propofol and incidence of hypoxemia were decreased, and the surgeon′s satisfaction score was increased, and the concentrations of cortisol were decreased at T 4 in group A ( P<0.05). No HR<60 bpm and MAP<50 mmHg were found in two groups. No SLNB-related complications were observed after operation in group A. Conclusions:Ultrasound-guided SLNB combined with intravenous anesthesia is safer for pediatric fiberoptic bronchoscopy and can improve the analgesic effect and is more helpful in inhibiting intraoperative stress responses when compared with conventional anesthesia.

Correlation analysis between renin-angiotensin system and bone mineral density in children with glucocorticoid-induced osteoporosis / 中华内分泌外科杂志

Objective:To investigate the relationship between renin-angiotensin system (RAS) and bone mineral density in children with glucocorticoids-induced osteoporosis (GIOP) .Methods:From Apr. 2020 to May. 2021, 53 children with GIOP were recruited in the Children’s Hospital of Taiyuan Maternal and Child Health Hospital and included in the observation group, and 47 children who received glucocorticoid therapy but did not suffer from GIOP were included in the control group. The levels of serum RAS components and bone mineral density of the two groups of pediatric patients were detected and compared, and the risk clinical indicators affecting bone mineral density and GIOP were analyzed.Results:There were no significant differences between the observation group and the control group in terms of gender, age, BMI, disease type, type of glucocorticoid use, use of anti-osteoporosis (OP) drugs, expression levels of Angiotensin converting enzyme 2 (ACE2) or angiotensin II (Ang Ⅱ) (all P>0.05) . The bone density value of the observation group was lower than those of the control group, and the levels of angiotensin converting enzyme (ACE) (1.19±0.23) , angiotensin receptor 1 (AT1R) (1.24±0.24) , angiotensin receptor 2 (AT2R) (1.14±0.17) , and Mas receptor (MasR) (1.11±0.28) were significantly higher than those of the control group (1.00±0.23, 1.00±0.25, 1.00±0.21, 1.00±0.20) , and the differences were statistically significant (all P<0.05) . Pearson analysis showed that bone mineral density was negatively correlated with the levels of ACE ( r=-0.34, P=0.013) , AT1R ( r=-0.41, P=0.002) and AT2R ( r=-0.34, P=0.014) , and stepwise regression model showed that ACE ( t=-2.21, P=0.032) and AT1R ( t=-2.92, P=0.005) were the main factors affecting bone mineral density. Logistic regression model analysis showed that bone mineral density ( OR=0.85, P<0.001) , Ang Ⅱ ( OR=0.53, P=0.041) and AT2R ( OR=2.00, P=0.024) were independent clinical risk factors affecting GIOP (all P<0.05) . Conclusion:RAS components ACE and AT1R are independent risk factors affecting bone mineral density in children with GIOP, and are significantly correlated with bone mineral density in children.

Mechanism of Prunellae Spica Against Breast Diseases： A Review / 中国实验方剂学杂志

Prunellae Spica is the dry ear of the labiaceae plant Prunella vulgaris， which is a traditional medicine and food plant with many functions. Prunellae Spica can clear liver-fire， improve eyesight， disperse knot detumescence. It owns hot and bitter flavors and cold property. It goes to the liver， gallbladder meridian， and is a kind of commonly-used antifebric. Prunellae Spica has been used in the treatment of mammary gland diseases since ancient times.The mammary abscess， mammary nodules， mammary carcinoma of traditional Chinese medicine all belong to breast disease， and the liver meridian is most closely related to these diseases. With the development of social life， breast disease has gradually become the most primary health problem for women. Modern pharmacological studies show that Prunellae Spica contains terpenoids， phenolic acids， flavonoids and other biological active components， which have anti-inflammatory， antibacterial， hormone regulation， anti-tumor and other effects. Prunellae Spica inhibits the p38 mitogen-activated protein kinase （p38 MAPK）/nuclear factor kappa-B （NF-κB） pathway to play an anti-mastitis role， interferes with the effects of estrogen receptors or regulates lipid levels to treat breast hyperplasia， and treats breast cancer through promoting the apoptosis of breast cancer cells， inhibiting the migration of breast cancer cells， regulating the division of breast cancer cells and other ways. While referring to the relevant literature， it was found that Prunellae Spica often exerted pharmacological effects through multi-channels and multi-target regulation， but most of the studies did not specify the specific target of its effect， which needs further study. In this review， the effects and mechanisms of Prunellae Spica in the treatment of various breast diseases were summarized， so as to provide a reference for further research on the wider clinical therapeutic effects of Prunella subtilis and its therapeutic effects on breast diseases.

LPS stimulating neutrophils firmly adhered to ICAM-1 to form extracellular traps depends on integrin Mac-1 and cytoskeletal proteins / 生物医学工程学杂志

Neutrophil extracellular traps (NETs) play an important role in the formation of immunothrombosis. However, how vascular endothelial cells mediate the formation of NETs has not been fully understood. We stimulated neutrophils firmly attached on the endothelial cell surface intercellular adhesion molecule-1 (ICAM-1) with lipopolysaccharide (LPS) or phorbol-12-myristate-13-acetate (PMA) for 4 h, then labeled NETs-DNA with Sytox green dye and the formation of NETs was observed by fluorescent microscopy. The area and fluorescence intensity of NETs-DNA were analyzed to quantify the formation of NETs. The results showed that both PMA and LPS were able to induce firmly adhered neutrophils on ICAM-1 to produce NETs. NETs induced by PMA were independent of neither β2 integrin lymphocyte function-associated antigen-1 (LFA-1) nor macrophage antigen complex-1 (Mac-1). In contrast, LPS-stimulated NETs were mediated by Mac-1 integrin, but not by LFA-1. After inhibition of actin filaments or Talin-1, the formation of NETs irrespective of the stimulus was significantly reduced. This study reveals the mechanism of the direct interaction between neutrophils and endothelial cells to produce NETs under inflammatory conditions, providing a new theoretical basis for the treatment of related diseases and the development of new drugs.

Gene mining and efficient biosynthesis of a fungal peptidyl alkaloid / 中草药·英文版

Objective: Peptidyl alkaloids, a series of important natural products can be assembled by fungal non-ribosomal peptide synthetases (NRPSs). However, many of the NRPSs associated gene clusters are silent under laboratory conditions, and the traditional chemical separation yields are low. In this study, we aim to discovery and efficiently prepare fungal peptidyl alkaloids assembled by fungal NRPSs. Methods: Bioinformatics analysis of gene cluster containing NRPSs from the genome of Penicillium thymicola, and heterologous expression of the putative gene cluster in Aspergillus nidulans were performed. Isolation, structural identification, and biological evaluation of the product from heterologous expression were carried out. Results: The putative tri-modular NRPS AncA was heterologous-expressed in A. nidulans to give anacine (1) with high yield, which showed moderate and selective cytotoxic activity against A549 cell line. Conclusion: Heterologous expression in A. nidulans is an efficient strategy for mining fungal peptidyl alkaloids.

Arrhythmogenic right ventricular cardiomyopathy associated with arrhythmia-induced cardiomyopathy: A case report / 北京大学学报(医学版)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a kind of inherited cardio-myopathy, which is characterized by fibro-fatty replacement of right ventricular myocardium, leading to ventricular arrhythmia. However, rapid atrial arrhythmias are also common, including atrial fibrillation, atrial flutter and atrial tachycardia. Long term rapid atrial arrhythmia can lead to further deterioration of cardiac function. This case is a 51-year-old male. He was admitted to Department of Cardiology, Peking University Third Hospital with palpitation and fatigue after exercise. Electrocardiogram showed incessant atrial tachycardia. Echocardiography revealed dilation of all his four chambers, especially the right ventricle, with the left ventricular ejection fraction of 40% and the right ventricular hypokinesis. Cardiac magnetic resonance imaging found that the right ventricle was significantly enlarged, and the right ventricular aneurysm had formed; the right ventricular ejection fraction was as low as 8%, and the left ventricular ejection fraction was 35%. The patients met the diagnostic criteria of ARVC, and both left and right ventricles were involved. His physical activities were restricted, and metoprolol, digoxin, spironolactone and ramipril were given. Rivaroxaban was also given because atrial tachycardia could cause left atrial thrombosis and embolism. His atrial tachycardia converted spontaneously to normal sinus rhythm after these treatments. Since the patient had severe right ventricular dysfunction, frequent premature ventricular beats and non-sustained ventricular tachycardia on Holter monitoring, indicating a high risk of sudden death, implantable cardioverter defibrillator (ICD) was implanted. After discharge from hospital, physical activity restriction and the above medicines were continued. As rapid atrial arrhythmia could lead to inappropriate ICD shocks, amiodarone was added to prevent the recurrence of atrial tachycardia, and also control ventricular arrhythmia. After 6 months, echocardiography was repeated and showed that the left ventricle diameter was reduced significantly, and the left ventricular ejection fraction increased to 60%, while the size of right ventricle and right atrium decreased slightly. According to the clinical manifestations and outcomes, he was diagnosed with ARVC associated with arrhythmia induced cardiomyopathy. According to the results of his cardiac magnetic resonance imaging, the patient had left ventricular involvement caused by ARVC, and the persistent atrial tachycardia led to left ventricular systolic dysfunction.

Case report and literature review of vital pulp preservation by endodontic microsurgery at the distal buccal root of maxillary molar / 口腔疾病防治

Objective@#To investigate the diagnosis, treatment and prognosis of nonodontogenic periapical lesions and to provide a reference for clinical diagnosis and treatment.@*Methods@# A case of a patient with right upper molar pulp with apical penetration and local occlusion admitted to the West China Stomatological Hospital of Sichuan University was retrospectively analyzed, and the curative effect of microapical surgery and pith preservation was also analyzed.@*Results @#The imaging features of tooth 16 showed periradicular radiolucency combined with local radiopaque lesions around the distal buccal apical area. Endodontic microsurgery was performed under local anesthesia. Soft tissue coverage was observed in the distal buccal apical area during the surgery, and no radiopaque tissue was detected. The distal buccal root apex was cut by 3 mm, and mineral trioxide aggregate was used for root-end backfilling. The postoperative pathological results revealed fibrous connective tissue. One-week recall X-ray examination showed tight root-end backfilling and no periradicular radiolucency; an electrical test of pulp vitality showed positive results. The four-year follow-up showed that there was no discoloration in tooth 16 and no significant difference in thermal and electrical tests of pulp vitality compared with control teeth. Combining the clinical manifestations, imaging features, surgical exploration results and pathological reports, the case was most likely to be cemental hypoplasia. Through the literature review, the treatment and healthy pulp preservation of such cases by endodontic microsurgery under the premise of preserving teeth has not been reported.@*Conclusion@#For maxillary posterior teeth with periapical lesions but healthy pulp, accurate estimation of pulp status, endodontic microsurgical exploration and application of bioactive materials can achieve vital pulp preservation while removing the lesions.

Identification of Astragalus and its adulterants based on ITS2sequence and secondary structure / 药学学报

To effectively identify the Astragalus and its adulterants based on ITS2 sequence and secondary structure, in this study, 32 portions of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Beg.) Hsiao and Astragalus membranaceus (Fisch.) Bge. collected were conducted ITS2 sequence amplification and bidirectional sequencing, whose results were then spliced by CExpress software remove the 5.8S and 28S sequences at both ends to obtain a complete ITS2 sequence. In addition, 3 ITS2 sequences for each of the adulterants of Astragalus, respectively, Oxytropis coerulea, Caragana sinica, Hedysarum polybotrys, Althaea rosea were downloaded from GenBank. The intra-specific and inter-specific genetic distances were calculated by the software MEGA7 to analyze the difference of each sequence; the Neighbor-joining (NJ) method was used to construct the phylogenetic tree based on ITS2 sequence (primary structure) as well as joint ITS2 sequence and its secondary structure. The results showed that the average ITS2 sequence length of both A. mongolicus and A. membranaceus was 216 bp, and their average GC content was 50.00% and 50.46%, respectively. The similarity of ITS2 sequence length and GC content between the two kind of Astragalus and Oxytropis coerulea was the highest, while the ITS2 sequence length and GC content of Althaea rosea showed great differences with those of Astragalus. The inter-specific distance between Astragalus and Oxytropis coerulea was the smallest, while that between the medicinal Astragalus and Hedysarum polybotrys, Caragana sinica as well as Althaea rosea was great. The phylogenetic trees constructed based on the ITS2 sequence (primary structure) and joint ITS2 sequence and its secondary structure showed that the topological relations of the two phylogenetic trees were basically the same, and both could effectively identify the Astragalus and its adulterants. What’s more, the addition of secondary structure information made end branch of the phylogenetic tree become more in its construction, and the distinguish ability and approval rating were also improved, which further reflected the genetic relationship of Astragalus and its adulterants. This provides some scientific basis for classification and accurate identification of Astragalus and its adulterants.

Current status of the clinical practice and analysis on the ratioanl prescription of antiarrhythmic drugs in Chinese patients with atrial fibrillation: Results from the Chinese Atrial Fibrillation Registry (CAFR) trial / 中华心血管病杂志

Objective: To explore the practice patterns and the related factors of oral antiarrhythmic drug (AAD) treatment in Chinese patients with atrial fibrillation (AF), and to evaluate the compliance of AAD application to atrial fibrillation management guidelines. Methods: From August 2011 to August 2016, medical records from 18 014 patients with AF were analyzed based on data from the Chinese Atrial Fibrillation Registry trial. Patients were divided into AAD group (7 788 cases, 43.23%) and non-AAD group (10 226 cases, 56.77%) according to whether AAD was used at baseline or at the time of first use during follow-up. Amiodarone (4 129 cases, 53.02%) and propafenone (3 211 cases, 41.23%) were the mostly prescribed AAD and subgroup analysis was performed accordingly. Medical records were analyzed by random forest regression to evaluate the use of AAD and related factors in patients with AF, and the rationality of AAD was analyzed according to the guidelines for the management of atrial fibrillation. Result: A total of 18 014 patients were included in this study, of which 60.48% (10 895/18 014) were male patients, 22.65% (4 081/18 014) were elderly patients(≥75 years old), there were 7 788 patients (43.23%) in AAD group, and 10 226 patients(56.77%) in non-AAD group. Compared with the non-AAD group, the elderly patients (≥75 years old, 13.74%(1 070/7 788) vs. 29.44%(3 011/10 226)), persistent AF (28.95% (2 250/7 788) 45.80% (4 683/10 226)), heart failure(8.29% (646/7 788) vs. 21.95% (2 245/10 226)), stroke and (or) TIA(12.15% (946/7 788) vs. 19.95% (2 040/10 226)), renal dysfunction(16.36%(1 274/7 788) vs. 29.37% (3 003/10 226)), and high thromboembolism risk(60.17% (4 748/7 788) vs. 76.40% (7 813/10 226)) were less prevalent in the AAD subgroup (P<0.001). Multivariate analysis showed that patients in tertiary hospitals (OR=3.72, 95%CI 3.17-4.37) were more likely to use AAD, elderly patients (≥75 years old, OR=0.47, 95%CI 0.39-0.55), persistent atrial fibrillation (OR=0.66, 95%CI 0.60-0.72), and patients with heart failure (OR=0.54, 95%CI 0.47-0.63), stroke and (or) TIA (OR=0.77, 95%CI 0.68-0.87), renal dysfunction (OR=0.75, 95%CI 0.59-0.95) and high thromboembolism risk(OR=0.7, 95%CI 0.58-0.84) were more likely not to use AAD(P<0.05). In the AAD group, amiodarone and propafenone were the most commonly used AAD, accounting for 53.02% (4 129/7 788) and 41.23% (3 211/7 788), respectively. Multivariate analysis showed that patients with persistent atrial fibrillation (OR=4.57, 95%CI 3.94-5.29) and coronary heart disease (OR=4.14, 95%CI 3.03-5.64), heart failure (OR=2.07, 95%CI 1.48-2.89), non-ischemic cardiomyopathy (OR=4.84, 95%CI 2.41-9.73) were more likely to use amiodarone, and those with normal left ventricular ejection fraction (OR=0.31, 95%CI 0.15-0.65) and low thromboembolism risk (OR=0.78, 95%CI 0.63-0.97) were more likely to use propafenone (P<0.001). The overall incidence of AAD treatment, which was not indicated by the guidelines was 6.5% (480/7 340); 5.1% (212/4 129) in the amiodarone group and 8.3% (268/3 211) in the propafenone group, respectively. Compared with the rational AAD use group, the proportion of irrational drug use was higher in the elderly (≥75 years old) (20.4% (98/480) vs. 12.9% (887/6 860)), patients of high thromboembolism risk (77.1% (379/480) vs. 59.0% (4 047/6 860)), and in non-tertiary hospitals (7.1% (34/480) vs. 3.3% (299/6 860)), but lower in men(50.8% (244/480) vs. 64.5% (4 427/6 860)), P<0.001. Conclusions: The patients with paroxysmal atrial fibrillation, who were treated with AAD, were mostly patients with fewer complications, and the patients who were treated with amiodarone were mostly patients with persistent atrial fibrillation, patients were more likely to complicate with organic heart disease. The incidence of AAD that do not comply with the guidelines was low, and it was more common in non-tertiary hospitals and the elder patients with high thromboembolism risk.

Carfilzomib inhibits the growth of lung adenocarcinoma via upregulation of Gadd45a expression / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Proteasome inhibitors have shown remarkable success in the treatment of hematologic neoplasm. There has been a lot of attention to applying these drugs for solid tumor treatment. Recent preclinical study has signified the effectiveness on cell proliferation inhibition in lung adenocarcinoma treated by carfilzomib (CFZ), a second generation proteasome inhibitor. However, no insight has been gained regarding the mechanism. In this study, we have systematically investigated the CFZ functions in cell proliferation and growth, cell cycle arrest, and apoptosis in lung adenocarcinoma cells. Flow cytometry experiments showed that CFZ significantly induced G2/M cell cycle arrest and apoptosis in lung adenocarcinoma. MTS and colony formation assays revealed that CFZ substantially inhibited survival of lung adenocarcinoma cells. All results were consistently correlated to the upregulation expression of Gadd45a, which is an important gene in modulating cell cycle arrest and apoptosis in response to physiologic and environmental stresses. Here, upregulation of Gadd45a expression was observed after CFZ treatment. Knocking down Gadd45a expression suppressed G2/M arrest and apoptosis in CFZ-treated cells, and reduced cytotoxicity of this drug. The protein expression analysis has further identified that the AKT/FOXO3a pathway is involved in Gadd45a upregulation after CFZ treatment. These findings unveil a novel mechanism of proteasome inhibitor in anti-solid tumor activity, and shed light on novel preferable therapeutic strategy for lung adenocarcinoma. We believe that Gadd45a expression can be a highly promising candidate predictor in evaluating the efficacy of proteasome inhibitors in solid tumor therapy.

Isolation of Penicillium expansum WH-3 for the production of L(+)-tartaric acid / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The L(+)-form of tartaric acid (L(+)-TA) exists extensively in nature, and is widely used in the food, chemical, textile, building, and pharmaceutical industries (Su et al., 2001). The main method for L(+)-TA production is microbial transformation by cis-epoxysuccinate hydrolase (CESH), which can catalyze the asymmetric hydrolysis of cis-epoxysuccinic acid or its salts to TA or tartrate (Bao et al., 2019). Seventeen species containing CESH have been isolated so far. However, most species for L(+)-TA production have been reported from bacteria (Xuan and Feng, 2019). The only fungus isolated from soil by our lab recently, that could be used as catalyst for the process under acidic condition, is Aspergillus niger WH-2 (Bao et al., 2020). In order to find strains with new characteristics, this study attempted to isolate a new CESH source from fungi and investigate its application value.

Photosynthetic index and nitrogen assimilation in rapeseed seedlings transplanted in soil with ammonium glufosinate / Índice fotossintético e assimilação de nitrogênio em plântulas de colza transplantadas em resposta a resíduos de glufosinato presentes no solo

ABSTRACT: Herbicide application is an effective weed control method for mitigating crop yield loss; however, herbicide overuse can cause toxicity in non-target plants. The present study evaluated the effects of glufosinate at recommended dose for agricultural application (0.45 kg ha-1) and at overuse dose (0.90 kg ha-1) glufosinate application on photosynthetic performance and nitrogen assimilation of the rapeseed varieties D148 and Zhongshuang 11 (ZS11). Both glufosinate concentrations significantly decreased the content of chlorophyll and nitrogenous compounds, except free proline, and the activity of glutamine synthetase and glutamate synthase, and increased the activity of glutamic acid dehydrogenase in both varieties. When the concentration of glyphosate was 0.45kg ha-1, the nitrogen assimilation of the two varieties decreased, which indicated that the recommended dosage inhibited the nitrogen assimilation of the two varieties; however, the increase of net photosynthetic rate of D148 and the decrease of that of ZS11 mean that D148 is more tolerant to the recommended dose of glyphosate than ZS11. The 0.90 kg ha-1 dosage was toxic to both rapeseed varieties. Overall, our results indicated that herbicide overuse inhibited the photosynthetic rate and nitrogen assimilation in rapeseed seedlings, and it is essential to apply a suitable glufosinate dose based on the variety grown to minimize adverse effects on crops and environment.

RESUMO: A aplicação de herbicidas é um método eficaz de controle de ervas daninhas para mitigar a perda de produtividade das culturas. No entanto, o uso excessivo de herbicidas pode causar toxicidade em plantas não alvo. O presente estudo avaliou os efeitos da dose recomendada para aplicação agrícola (0.45 kg ha-1) e dose excessiva (0.90 kg ha-1) de glufosinato no desempenho fotossintético e assimilação de nitrogênio das variedades de colza D148 e Zhongshuang 11 (ZS11). Ambas as concentrações de glutamato diminuíram significativamente o teor de clorofila e compostos azotados, exceto a prolina livre, e a atividade de síntese da glutamina e de síntese de glutamato, e aumentaram a atividade de desidrogenase do ácido glutâmico em ambas as variedades. Quando a concentração de glifosato foi 0.45 kg ha-1, a assimilação de azoto das duas variedades diminuiu, o que indicou que a dosagem recomendada de glifosato inibiu a assimilação de azoto das duas variedades de colza. Entretanto, a taxa fotosintética líquida do D148 aumentou enquanto o do ZS11 diminuiu, o que significa que o D148 é mais tolerante a dose recomendada de glifosato do que o ZS11. A dose de 0.90 kg ha-1 de glifosato foi prejudicial para as mudas de duas variedades de colza. Em geral, os nossos resultados indicam que o uso excessivo de glufosinato inibe a taxa fotossintética e a assimilação de nitrogênio em mudas de colza, sendo essencial aplicar uma dose adequada deste herbicida com base na variedade cultivada para minimizar os efeitos adversos nas culturas e no meio ambiente.

Cloning and characterization of an oxiranedicarboxylate hydrolase from Labrys sp. WH-1 / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

OBJECTIVE@#This study aimed to clone and characterize the oxiranedicarboxylate hydrolase (ORCH) from Labrys sp. WH-1.@*METHODS@#Purification by column chromatography, characterization of enzymatic properties, gene cloning by protein terminal sequencing and polymerase chain reaction (PCR), and sequence analysis by secondary structure prediction and multiple sequence alignment were performed.@*RESULTS@#The ORCH from Labrys sp. WH-1 was purified 26-fold with a yield of 12.7%. It is a monomer with an isoelectric point (pI) of 8.57 and molecular mass of 30.2 kDa. It was stable up to 55 °C with temperature at which the activity of the enzyme decreased by 50% in 15 min (T5015) of 61 °C and the half-life at 50 °C (t1/2, 50 °C) of 51 min and was also stable from pH 4 to 10, with maximum activity at 55 °C and pH 8.5. It is a metal-independent enzyme and strongly inhibited by Cu2+, Ag+, and anionic surfactants. Its kinetic parameters (Km, kcat, and kcat/Km) were 18.7 mmol/L, 222.3 s-1, and 11.9 mmol/(L·s), respectively. The ORCH gene, which contained an open reading frame (ORF) of 825 bp encoding 274 amino acid residues, was overexpressed in Escherichia coli and the enzyme activity was 33 times higher than that of the wild strain.@*CONCLUSIONS@#The catalytic efficiency and thermal stability of the ORCH from Labrys sp. WH-1 were the best among the reported ORCHs, and it provides an alternative catalyst for preparation of L(+)-2,3-dihydrobutanedioic acid.