ObjectiveBased on transcriptomics， to explore the mechanism of Hei Xiaoyaosan regulating the phosphatidylinositol 3-kinase/protein kinase B （PI3K/Akt） signaling pathway to improve the learning and memory ability of insomnia rats with liver depression syndrome. MethodsSixty 8-week-old male SD rats were randomly divided into the blank group， model group， eszopiclone group （0.09 mg·kg^-1）， and low， medium， and high dose groups of Hei Xiaoyaosan （3.82， 7.65， 15.30 g·kg^-1）， with ten rats in each group. Except for the blank group， the other groups were induced insomnia rat model with liver depression by chronic restraint， tail clamping stimulation and intraperitoneal injection of p-chlorophenylalanine （PCPA）. Each treatment group received intragastric administration according to the specified dosage， once a day for 14 consecutive days. The pentobarbital sodium cooperative sleep test， open field test， and Morris water maze test were used to test the sleep quality， depressive-like behavior， and learning and memory abilities of rats. Additionally， enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of 5-hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， brain-derived neurotrophic factor （BDNF）， glial cell line-derived neurotrophic factor （GDNF） and nitric oxide （NO） in hippocampus. Hematoxylin-eosin （HE） staining was performed to observe pathological changes of the hippocampal tissue， while terminal deoxynucleotidyl transferase deoxyuridine triphosphate （dUTP） nick end labeling （TUNEL） was used to evaluate apoptosis of hippocampal neurons. Transcriptomic sequencing technology was employed to identify differentially expressed genes in hippocampus between the model group and the blank group， as well as between the medium-dose group of Hei Xiaoyaosan and the model group. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis were performed on the intersecting genes. Subsequently， the enriched key genes and signaling pathways were analyzed and verified. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was utilized to assess the mRNA expression levels of phosphatase and tensin homolog （PTEN）， B-cell lymphoma-2 （Bcl-2）-like protein 11 （BCL2L11）， and mitogen-activated protein kinase 1 （MAPK1） in hippocampus， and Western blot was employed to evaluate the protein expressions of PI3K， phosphorylation （p）-PI3K， Akt， p-Akt， Bcl-2， Bcl-2-associated X protein （Bax）， and cleaved Caspase-3 in the same tissue. ResultsCompared with the blank group， the model group exhibited a reduction in body weight， an increase in sleep latency， and a decrease in sleep duration （P<0.01）. Additionally， rats showed obvious depression-like behavior， and their learning and memory abilities decreased. Furthermore， the contents of 5-HT， GABA， NO， BDNF and GDNF in hippocampus decreased （P<0.01）. Histological examination revealed a disorganized cell arrangement in the CA1 region of the hippocampus， characterized by irregular cell shapes， a reduced cell count， deeply stained and pyknotic nuclei， increased vacuolar degeneration， and an elevated apoptosis rate （P<0.01）. Compared with the model group， the body weight of the high and medium dose groups of Hei Xiaoyaosan increased， the sleep latency shortened and the sleep time prolonged （P<0.05， P<0.01）. Additionally， depression-like behavior and learning and memory abilities of rats were significantly improved， the levels of 5-HT， GABA， NO， BDNF and GDNF in the hippocampus increased （P<0.05， P<0.01）. These interventions also ameliorated pathological damage in the hippocampal CA1 area and reduced the apoptosis of hippocampal neurons （P<0.01）. Transcriptomic sequencing results indicated that Hei Xiaoyaosan might exert a therapeutic effect by regulating PI3K/Akt pathway through key mRNAs such as PTEN， BCL2L11， and MAPK1. The roles of these key mRNAs and proteins within PI3K/Akt pathway were further validated. In comparison to the blank group， the expression levels of PTEN， BCL2L11 and MAPK1 mRNA in the hippocampus of rats in the model group were increased （P<0.01）， while the protein expression levels of p-PI3K， p-Akt and Bcl-2 were decreased （P<0.01）， and the protein expression levels of PTEN， Bax and cleaved Caspase-3 were increased （P<0.01）. Compared with the model group， the high-dose and medium-dose groups of Hei Xiaoyaosan could down-regulate the expressions of PTEN， BCL2L11 and MAPK1 mRNAs （P<0.01）， up-regulate the expressions of p-PI3K， p-Akt and Bcl-2 proteins （P<0.01）， and down-regulate the protein expressions of PTEN， Bax and cleaved Caspase-3 （P<0.05， P<0.01）. ConclusionHei Xiaoyaosan may regulate PI3K/Akt signaling pathway by down-regulating expressions of key genes such as PTEN， BCL2L11 and MAPK1， and thus improve the learning and memory abilities of insomnia rats with liver depression syndrome.

Objective To investigate the effect of circFOXK2 on the proliferation,migration and invasion of lung cancer cells and its possible mechanism.Methods The cancer tissues and adjacent tissues of 45 patients with lung cancer were collect-ed,and the expression of circFOXK2 and miR-409-3p in the tissues were detected by qRT-PCR.Lung cancer cell A549 and H1299 was cultured in vitro,and the dual-luciferase reporter assay was used to verify the regulatory relationship between circ-FOXK2 and miR-409-3p.The CCK-8,clone formation and Transwell assays were used to detect cell proliferation,migration and invasion.Western blot was used to detect the protein expression of E-cadherin and N-cadherin in cells.Results The expression of circFOXK2 was significantly higher(P＜0.05),but the expression of miR-409-3p was significantly lower(P＜0.05)in lung cancer tissues.circFOXK2 could target miR-409-3p and negatively regulate its expression in lung cancer cells.The proliferation,migration and invasion were reduced in circFOXK2(all P＜0.05),N-cadherin level was decreased(P＜0.05),but E-cadherin level was increased(P＜0.05)in circFOXK2 knockdown or miR-409-3p overexpressed A549 and H1299 cells.The inhibitory effects of circFOXK2 knockdown on the proliferation,migration and invasion of lung cancer cells could be reversed by miR-409-3p inhibitor.Conclusion The circFOXK2 was upregulated in lung cancer,which promoted the proliferation,migration and inva-sion of lung cancer cells by targeting miR-409-3p.

2019 Novel coronavirus (2019-nCoV) infection caused a pandemic in the world. From the reported cases in the literatures, the level of D-dimer in patients with coronavirus disease 2019 (COVID-19) is positively correlated with the severity of illness, which needs the attention of clinical workers. According to Western medicine, the increase of D-dimer is related to the hyperactivity of fibrinolytic system and the shortening of prothrombin time (PT), resulting in excessive production and degradation of plasma fibrin and hypercoagulable state of blood, while traditional Chinese medicine (TCM) believes that the above syndromes belong to the pathogenesis of "blood stasis" according to TCM theories. Over the years, TCM has a significant effect on promoting blood circulation, removing blood stasis and improving microcirculation. This article reviews the mechanism, clinical significance, understanding of TCM and common methods of promoting blood circulation and removing blood stasis caused by 2019-nCoV, in order to provide ideas for the prevention and treatment of impaired blood coagulation in patients with COVID-19.

Objective:To analyze the dosimetric differences between CT-guided free-hand intracavity/interstitial brachytherapy[image-guided adaptive brachytherapy (IGABT)] and conventional point-A plan (CP) in the treatment of cervical cancer.Methods:Twenty-six cervical cancer patients who received four cycles of IGABT in Sun Yat-sen University Cancer Center were enrolled in this study. Two sets of CT images were obtained before and after applicator adjustment to aid in the design of CP and IGABT plans. The high-risk clinical target volume (HRCTV), point A, and organs at risk (bladder, rectum, and sigmoid colon) were defined on CT images. CP and IGABT plans were designed on CT images. Parameter differences between CP and IGABT plans were analyzed with paired t-test and Wilcoxon test. Results:According to the coverage index (CI) of CP, plans were divided into two groups: in group A (CI≥0.90), 20 CP and corresponding IGABT plans were included, and 84 CP and corresponding IGABT plans in group B (CI<0.90). The mean volume of HRCTV and mean tumor diameter in group A were significantly smaller than those in group B (46.7 cm 3vs. 62.1 cm 3, P<0.001 and 3.1 cm vs. 4.4 cm, P<0.001). Compared with CP, IGABT significantly improved the value of D 90% in all plans and group B, whereas lowered the bladder dose. IGABT also reduced the dose of sigmoid colon in group A. IGABT significantly improved conformal index and dose homogeneity index. Conclusions:IGABT can significantly improve the target coverage, conformal index and dose homogeneity index, protect organs at risk. Compared with CP, IGABT has advantages in the treatment of patients with bulky tumor.

The lung is the second most common site of neuroendocrine tumors (NETs). Typical and atypical carcinoids are low-grade NETs of the lung. These rare tumors have received little attention and education is needed for treating physicians. The article describes the classifcation of lung NETs, the epidemiology and pathological characteristics. When lung NETs are diagnosed at an early stage, surgical intervention is often curative. For advanced lung NETs patients, different treatment methods including chemotherapy, somatostatin analogs, m-TOR inhibition, peptide receptor radioligand therapy, and biologic systemic therapy are discussed. The conclusions are generally extrapolated from the outcome of extra-pulmonary carcinoids. Prospective randomized well-designed trials are urgently needed to inform current recommendations on systemic treatment.
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Disease-Free Survival ; Drug Therapy ; methods ; Humans ; Lung ; drug effects ; radiation effects ; surgery ; Lung Neoplasms ; pathology ; surgery ; therapy ; Neoplasm Grading ; Neuroendocrine Tumors ; pathology ; surgery ; therapy ; Outcome Assessment (Health Care) ; Radiotherapy ; methods

Objective: To study the antiseptic effect of compound lysostaphin disinfectant and its preventive effect on infection of artificial dermis after graft on full-thickness skin defect wound in rats. Methods: (1) Each one standard strain of Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus were selected. Each 20 clinical strains of Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus were collected from those isolated from wound exudates of burn patients hospitalized in our wards from January 2014 to December 2016 according to the random number table. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of compound lysostaphin disinfectant to above-mentioned strains were detected. The experiment was repeated 3 times. Compared with the corresponding standard strain, the clinical strain with higher MIC and/or MBC was considered as having decreased sensitivity to the disinfectant. The percentage of strains of each of the three kinds of bacteria with decreased sensitivity was calculated. (2) Artificial dermis pieces were soaked in compound lysostaphin disinfectant for 5 min, 1 h, 2 h, and 4 h, respectively, with 21 pieces at each time point. After standing for 0 (immediately), 12, 24, 36, 48, 60, 72 h (with 3 pieces at each time point), respectively, the diameters of their inhibition zones to standard strains of Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus were measured. The experiment was repeated 3 times. The shortest soaking time corresponding to the longest standing time, after which the disinfectant-soaked artificial dermis could form an effective inhibition zone (with diameter more than 7 mm), was the sufficient soaking time of the disinfectant to the artificial dermis. (3) Forty Sprague-Dawley rats were divided into post injury day (PID) 3, 7, 14, and 21 sampling groups according to the random number table, with 10 rats in each group. A full-thickness skin defect wound with a diameter of 20 mm was made on both sides of the spine on the back of each rat. Immediately after injury, the artificial dermis without any treatment was grafted on the wound on left side of the spine (hereinafter referred to as control wound), while the sufficiently soaked artificial dermis with compound lysostaphin disinfectant was grafted on the wound on right side of the spine (hereinafter referred to as disinfectant wound). On PID 3, 7, 14, and 21, the gross condition of wounds of all the surviving rats was observed, and the new infection rates of control wounds and disinfectant wounds were calculated. Then, the rats in the sampling group with corresponding time were killed, and the full-thickness wound tissue containing artificial dermis was collected for quantitative analysis of bacteria. Bacteria content of the uninfected control wounds and that of the uninfected disinfectant wounds were compared. Data were processed with chi-square test and Wilcoxon rank sum test. Results: (1) The MIC of compound lysostaphin disinfectant to standard strains of Staphylococcus aureus, Klebsiella pneumoniae, and Acinetobacter baumannii were 1/32, 1/32, and 1/512 of the original concentration of the disinfectant, respectively, and the MBC were 1/32, 1/16, and 1/512 of the original concentration of the disinfectant, respectively. The percentages of clinical strains of Klebsiella pneumoniae, Acinetobacter baumannii and Staphylococcus aureus with decreased sensitivity to compound lysostaphin disinfectant were 15% (3/20), 20% (4/20), and 10% (2/20), respectively. (2) After being soaked in compound lysostaphin disinfectant for 2 and 4 h, the longest standing time, after which the artificial dermis could form an effective inhibition zone against Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus, were 24, 36, and 48 h respectively, longer than 12, 24, and 24 h of soaking for 5 min and 24, 24, and 36 h of soaking for 1 h. The sufficient soaking time of compound lysostaphin disinfectant to artificial dermis was 2 h. (3) On PID 3, no infection symptom was observed in all the wounds, and so both the new infection rate of control wounds and that of disinfectant wounds were 0. The artificial dermis was transparent but not well connected with the wound. On PID 7, the new infection rate of control wounds was 20.00% (6/30), which was obviously higher than 3.33% (1/30) of disinfectant wounds, χ²=4.043, P<0.05. On the infected wound, a large amount of purulent exudates were observed, and the artificial dermis was not connected with the wound and degraded partially. On the uninfected wound, artificial dermis was transparent and had a partial connection with the wound. On PID 14 and 21, no new infected wound was observed, and so both the new infection rate of control wounds and that of disinfectant wounds were 0. There was no obvious improvement on the infected wounds. The collagen layers of artificial dermis in the uninfected wound established a good connection with the wound and were separating from the silica gel layer gradually. Infection occurred in 2, 3, 1 control wound (s) in PID 7, 14, and 21 sampling groups, respectively, and in 1 disinfectant wound in PID 14 sampling group. The bacteria content of the infected wounds tissue was 0.79×10⁶ to 7.22×10⁹ colony-forming unit (CFU)/g. The bacteria content of uninfected control wounds tissue in PID 3, 7, and 14 sampling groups were (3.43±1.88)×10^2, (2.37±0.43)×10^3, and (8.40±1.03)×10³ CFU/g, respectively, which were significantly higher than (0.33±0.12)×10^2, (0.43±0.17)×10^3, (2.16±0.52)×10³ CFU/g of uninfected disinfectant wounds tissue (Z=-3.780, -3.554, -3.334, P<0.05). The bacteria content of uninfected control wounds tissue and that of uninfected disinfectant wounds tissue in PID 21 sampling group were similar (Z=-0.490, P>0.05). Conclusions Compound lysostaphin disinfectant has quite strong antibacterial ability against Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus. Clinical strains of the three kinds of bacteria were highly sensitive to compound lysostaphin disinfectant. Saturation of absorption of compound lysostaphin disinfectant achieves in artificial dermis after 2 hours′ soaking. After 24, 36, and 48 hours′ standing, the soaked artificial dermis still has the antibacterial effect on Klebsiella pneumoniae, Acinetobacter baumannii, and Staphylococcus aureus, respectively. The infection rate and the bacteria content of full-thickness skin defect wound in rats are all decreased when grafted with soaked artificial dermis.

Objective To observe the effects of obesity on dose-response curve of rocuronium in female patients and calculate ED9 5 of rocuronium.Methods Eighty female patients,aged 18-45 years, falling into ASA grade Ⅰ or Ⅱ,schedualed for elective surgery under general anesthesia,undergoing surgery less than 1.5 h,were included in the study.The patients with body mass index of 20-25 kg/m2 as group N were randomized to divided group N1,group N2,group N3 and group N4.Anoth-er 40 patients with body mass index of 30-35 kg/m2 as group B were randomized to divided group B1, group B2,group B3 and group B4.When the first twitch height of TOF (T1)was 100%,groups N1-N4 and groups B1-B4 patients were injected rocuronium 0.075,0.1,0.1 5,0.3 mg/kg respectively. The first dose of rocuronium in each group,T1 maximum inhibition degree and onset time were re-corded.The relationship between probit-transformed depression of T1 and the logarithm dose of rocu-ronium was analyzed by linear regression.ED50 and ED9 5 of rocuronium in obese and normal body weight patients were calculated.Results Dose-response curve equation of each group were Y1 =3.464X1 -2.23 and Y2 = 3.843X2 - 2.750 respectively(P < 0.05 ).The ED50 and ED9 5 (95% CI)of rocuronium were 0.122 (0.092-0.1 65 )mg/kg and 0.324 (0.242-0.433 )mg/kg in group N,and were 0.103 (0.078-0.133)mg/kg and 0.25 1 (0.1 93-0.326)mg/kg in group B.Conclusion Obesity significantly affects the dose-response curve of young women and can enhance the sensitivity of them to the rocuronium.The ED9 5 of obese patients is 0.25 1 mg/kg.

Objective To explore the application value of endoscopic ultrasonography (EUS) in the diagnosis of suspected obstructive jaundice in acute biliary pancreatitis and its effect on treatment outcomes. Methods Clinical data were retrospectively collected in 96 patients with acute biliary pancreatitis (ABP) who were suspected obstructive jaundice. Patients were divided into early EUS scanning group (EES) and delay EUS scanning group (DES). Clinical treatment results and test results were compared between the two groups. Results The diagnosis sensitivity, specificity, accuracy, positive predictive value and negative predictive value of EUS were 96.43 %, 82.5 %, 90.63 %, 88.52 % and 96.29 %. Early EUS scan with 72 h could identify the etiology of ABP and subsequent treatment based on the EUS can easily decrease the white blood cell count, percentage of neutrophils, total bilirubin and serum amylase (P < 0.05). The pain relief rate in EEI group after 1 week treatment was significantly higher than that in the DES group (87.50 % vs 66.67 %, P = 0.027) and average length of hospitalization was shorter [(12.70 ±2.10) d vs (14.10 ± 3.00) d, P = 0.006]. Delay EUS scan were likely to have higher white blood cell count and total bilirubin, meanwhile seemed to increase the organ failure rate and necrotic infection of the pancreas. Conclusion ABP with suspected obstructive jaundice should be considered to have endoscopy intervention. Results of EUS are the basis for treatment decision, which can avoid the unnecessary endoscopy treatment.

Objective To explore the effect of functional electrical stimulation combined with treadmill training and botulinum toxin type A injection on foot-drop and strephenopodia among stroke survivors.Methods Sixty-seven stroke survivors with foot-drop and strephenopodia were randomly divided into an electrical stimulation group (n=23),a conventional treatment group (n =22) and a combined treatment group (n =22).All 3 groups received a 400 U injection of BTX-A and electrical stimulation.After 24 hours,the patients in the conventional treatment group received conventional treatment including a brain protection agent,limb function exercises,gait training,balance training and training in the activities of daily living.The patients in the combined treatment group received that conventional treatment,plus functional electrical stimulation and weight loss training on a treadmill.The patients in the electrical stimulation group received functional electrical stimulation treatment supplementing the conventional treatment.Therapeutic effects were evaluated before and after six weeks of treatment using integral electromyography (iEMS) of the anterior tibial muscle and the lateral head of the gastrocnemius muscle,the co-contraction ratio (CR) during ankle dorsiflexion,the modified Ashworth Scale (MAS),the Berg balance scale (BBS),a functional walking score (FAC),and the active range of motion (AROM) of the ankle in dorsiflexion and eversion.Results After the treatment,significant improvement was observed in all three groups in the average iEMS value of the anterior tibial muscle and the lateral head of the gastrocnemius muscle,the CR in ankle dorsiflexion,and in their MAS,BBS,FAC and AROM results.There was no significant difference among the three groups after treatment in their average iEMS values at the lateral head of the gastrocnemius.The average values of the other indicators were,however,significantly better in the combined treatment group than in the other 2 groups.Conclusion Functional electrical stimulation combined with treadmill training and botulinum toxin type A injection can significantly improve foot-drop,strephenopodia and the walking function of stroke survivors.This combined treatment deserves popularization and application in clinical practice.

Objective To observe the intervention effects of Xintongfang on the expression of P-selectin (PS), P-selectin glycoprotein ligand-1 (PSGL-1), platelet-leukocyte aggregates (PLA) and platelet-monocyte aggregates (PMA) in patients of coronary heart disease with carotid artery plaque. Methods Sixty patients were randomly divided into Xintongfang group and the control group, with 30 cases in each group. Xintongfang group was given Xintongfang, the control group was given aspirin and atorvastatin calcium for two months. The expression of PS, PSGL-1, PLA and PMA were tested by flow cytometry before and after treatment. Results The expression of PS, PSGL-1, PLA and PMA in two groups were reduced (P<0.01). Xintongfang group had more obvious effects on the expression of PLA and PMA than the control group (P<0.05). Conclusion Xintongfang can reduce the degree of inflammatory in patients of coronary heart disease with carotid artery plaque by inhibiting platelet-leukocyte interaction.