Effect of transcutaneous auricular vagus nerve stimulation on nocturnal autonomic nervous function in primary insomnia patients / 中国针灸

OBJECTIVE@#To observe the effect of transcutaneous auricular vagus nerve stimulation (taVNS) on the sleep quality and nocturnal heart rate variability (HRV) in patients with primary insomnia.@*METHODS@#Twenty-one patients with primary insomnia were included. Using SDZ-ⅡB electric acupuncture apparatus, Xin (CO15) and Shen (CO10) were stimulated with disperse-dense wave, 4 Hz/ 20 Hz in frequency, (0.2±30%) ms of pulse width and tolerable intensity. Electric stimulation was given once every morning and evening of a day, 30 min each time, for 4 weeks totally. Before and after treatment, the score of Pittsburgh sleep quality index (PSQI), objective sleep structure (total sleep time [TST], sleep latency [SL], wake after sleep onset [WASO], sleep efficiency [SE], the percentages of non-rapid eye movement period 1, 2, 3, and the percentage of rapid eye movement period to TST [N1%, N2%, N3%, REM%] ) and nocturnal HRV (high frequency [HF], low frequency [LF], the ratio of LF to HF [LF/HF], standard deviation for the normal RR intervals [SDNN], squared root of the mean sum of squares of differences between adjacent intervals RR [RMSSD], the percentage of adjacent RR intervals with differences larger than 50 ms in the entire recording [PNN50%], the mean of sinus RR intervals [NNMean] ) were compared in the patients separately.@*RESULTS@#After treatment, the score of each item and the total score of PSQI and SL were all reduced as compared with those before treatment (P<0.01, P<0.001); SE, N3%, LF, HF, LF/HF, SDNN, NNMean and RMSSD were all increased compared with those before treatment (P<0.001, P<0.01).@*CONCLUSION@#The taVNS improves the sleep quality and objective sleep structure in patients with primary insomnia, which is probably related to the regulation of autonomic nervous functions.

Integral theory-guided laparoscopic pelvic floor/ligament repair in the treatment of women's internal rectal prolapse / 中华普通外科杂志

Objective:To compare the clinical efficacy of laparoscopic integral pelvic floor/ligament repair (IPFLR) combined with a procedure for prolapse and hemorrhoids (PPH) and that laparoscopic IPFLR alone in the treatment of internal rectal prolapse (IRP) in women.Methods:Patients were divided into groups A in which 63 patients undergoing laparoscopic IPFLR alone, and group B of 67 patients reciving laparoscopic IPFLR combined with PPH. The degree of internal rectal prolapse (DIRP), Wexner constipation scale (WCS) score, Wexner incontinence scale (WIS) score, and Gastrointestinal Quality of Life Index (GIQLI) score were compared between these two groups and in each group those before surgery and 6 months, 2 years, and 5 years after surgery.Results:The number of bowel movements , DIRP, WCS score, WIS score, and GIQLI score before surgery were not significantly different between the two groups (all P>0.05). The DIRP, WCS score, WIS score, and GIQLI score in each group 6 months, 2 years, and 5 years after surgery in both two groups were significantly better than those before surgery (all P<0.001). The DIRP, WCS score, WIS score, and GIQLI score in group B were significantly better than those in group A at 6 months, 2 years, and 5 years after surgery (all P<0.05) except DIRP at 2 years after surgery (all P<0.05). There was a significant difference in the recurrence rate of IRP between the two groups when evaluated at 5 years after surgery ( P=0.001). Conclusions:Integral theory-guided laparoscopic IPFLR combined with PPH has a higher cure rate and a better clinical efficacy than laparoscopic IPFLR alone.

Genetic analysis of a case with mosaicism of a small supernumerary marker chromosome derived from idic(15) / 中华医学遗传学杂志

OBJECTIVE@#To determine the origin of a mosaicism small supernumerary marker chromosome (sSMC) by cytogenetic and molecular analysis.@*METHODS@#Karyotype analysis, fluorescence in situ hybridization (FISH) and SNP-array were carried out.@*RESULTS@#The karyotype of the patient was mos47,XX,+mar[45]/48,XX,+2mar[3]/46,XX[52]; the SNP-array result was arr[hg19]15q11.1q11.2 (20 161 372-24 314 675)×3, and the repeat fragment was about 4.15 Mb. FISH showed that approximately 50% of the cells have contained a sSMC with double D15Z1 probe site segments derived from abnormal idic(15). This sSMC did not contain SNRPN and PML probe fragments of Prader-Willi syndrome/Angelman syndrome.@*CONCLUSION@#When the patient's karyotype and phenotype are inconsistent, cytogenetic and molecular biology technologies should be combined to clarify the karyotype and gene location, so as to provide more accurate genetic consultation for the follow-up treatments.

Analysis of risk factors for readmission in elderly patients with hip fractures undergoing hip hemiarthroplasty / 中国骨伤

OBJECTIVE@#To explore the incidence and risk factors of readmission of elderly patients with hip fracture after hip hemiarthroplasty.@*METHODS@#A retrospective analysis of 237 elderly hip fracture patients who underwent hip hemiarthroplasty from February 2015 to October 2020 were performed. According to the readmission status of the patients at 3 months postoperatively, the patients were divided into readmission group (39 cases)and non-readmission group(198 cases). In readmission group, there were 7 males and 32 females with an average age of(84.59±4.34) years old, respectively, there were 34 males and 164 females with average age of (84.65±4.17) years old in non-readmission group. The general information, surgical status, hip Harris score and complications of patients in two groups were included in univariate analysis, and multivariate Logistic regression was used to analyze independent risk factors of patients' readmission.@*RESULTS@#The proportion of complications(cerebral infarction and coronary heart disease) in readmission group was significantly higher than that of non-readmission group (P<0.05), and intraoperative blood loss in readmission group was significantly higher than that of non-readmission group(P<0.05). Harris score of hip joint was significantly lower than that of non-readmission group(P<0.05). The proportion of infection, delirium, joint dislocation, anemia and venous thrombosis in readmission group were significantly higher than that of non-readmission group (all P<0.05). Multivariate Logistic regression analysis showed that the risk factors for readmission of elderly patients with hip fracture after hip hemiarthroplasty included cerebral infarction, infection, delirium, dislocation, anemia and venous thrombosis (all P<0.05).@*CONCLUSION@#The complications of the elderly patients who were readmission after hip hemiarthroplasty for hip fractures were significantly higher than those who were non-readmission. Cerebral infarction, infection, delirium, dislocation, anemia and venous thrombosis are risk factors that lead to patient readmission. Corresponding intervention measures can be taken clinically based on these risk factors to reduce the incidence of patient readmissions.

Discovery and confirmation of protein action site AK1 of ginsenosides in brain based on DARTS technology / 中国中药杂志

This study aims to explore the targets of ginsenosides in brain based on drug affinity responsive target stability(DARTS) technology. Specifically, DARTS technology was combined with label-free liquid chromatography tandem mass spectrometry(LC-MS) to screen out the proteins in the brain that might interact with ginsenosides. Based on the screening results, adenylate kinase 1(AK1) was selected for further confirmation. First, the His-AK1 fusion protein was yielded successively through the construction of recombinant prokaryotic expression vector, expression of target protein, and purification of the fusion protein. Biolayer interferometry(BLI) was employed to detect the direct interaction of Rg_1, Re, Rb_1, Rd, Rh_2, F1, Rh_1, compound K(CK), 25-OH-PPD, protopanaxa-diol(PPD), and protopanaxatriol(PPT) with AK1, thereby screening the ginsenoside monomer or sapogenin that had strong direct interaction with the suspected target protein AK1. Then, the BLI was used to further determine the kinetic parameters for the binding of PPD(strongest interaction with AK1) to His-AK1 fusion protein. Finally, molecular docking technology was applied to analyze the binding properties between the two. With DARTS and LC-MS, multiple differential proteins were screened out, and AK1 was selected based on previous research for target verification. Fusion protein His-AK1 was obtained by prokaryotic expression, and the response(nm) of Re, Rg_1, Rd, Rb_1, Rh_1, Rh_2, F1, PPT, PPD, 25-OH-PPD, and CK with His-AK1 was respectively 0.003 1, 0.001 9, 0.042 8, 0.022 2, 0.013 4, 0.037 3, 0.013 9, 0.030 7, 0.140 2, 0.016 0, and 0.040 8. The K_(on), K_(off), and K_D values of PPD and His-AK1 were determined by the BLI as 1.22×10~2 mol~(-1)·L·s~(-1), 1.04×10~(-2) s~(-1), 8.52×10~(-5) mol·L~(-1). According to the molecular docking result, PPD bound to AK1 with the absolute value of the docking score of 3.438, and hydrogen bonds mainly formed between the two. Thus, AK1 is one of the protein action sites of ginsenosides in the brain. The direct interaction between ginsenoside metabolite PPD and AK1 is the strongest.

Inhibition of Escherichia coli nitroreductase by the constituents in Syzygium aromaticum / 中国天然药物

Gut bacterial nitroreductases play an important role in reduction of various nitroaromatic compounds to the corresponding N-nitroso compounds, hydroxylamines or aromatic amines, most of which are carcinogenic and mutagenic agents. Inhibition of gut nitroreductases has been recognized as an attractive approach for reducing mutagen metabolites in the colon, so as to prevent colon diseases. In this study, the inhibitory effects of 55 herbal medicines against Escherichia coli(E. coli) nitroreductase (EcNfsA) were examined. Compared with other herbal extracts, Syzygium aromaticum extract showed superior inhibitory potency toward EcNfsA mediated nitrofurazone reduction. Then, the inhibitory effects of 22 major constituents in Syzygium aromaticum against EcNfsA were evaluted. Compared with other tested natural compounds, ellagic acid, corilagin, betulinic acid, oleanic acid, ursolic acid, urolithin M5 and isorhamnetin were found with strong to moderate inhibitory effect against EcNfsA, with IC50 values ranging from 0.67 to 28.98 mol·L-1. Furthermore, the inhibition kinetic analysis and docking simulation demonstrated that ellagic acid and betulinic acid potently inhibited EcNfsA (Ki < 2 μmol·L -1) in a competitively inhibitory manner, which created strong interactions with the catalytic triad of EcNfsA. In summary, our findings provide new scientific basis for explaining the anti-mutagenic activity of Syzygium aromaticum, where some newly identified EcNfsA inhibitors can be used for developing novel agents to reduce the toxicity induced by bacterial nitroreductase.

Influencing factors of adult thyroid volume in Lanzhou City / 中华地方病学杂志

Objective:To investigate the thyroid volume of adults in Lanzhou City, and analyze its influencing factors.Methods:In June 2016, according to the principle of multi-stage stratified cluster sampling, Han residents aged 18 and above in Chengguan, Xigu and Qilihe districts of Lanzhou City who had lived there for more than 5 years were selected as research subjects, and a portable B-ultrasound machine was used for thyroid examination. Morning urine samples of the subjects were collected to test urinary iodine; fasting venous blood samples of the subjects were collected to test serum thyroid stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), anti-thyroglobulin antibody (TgAb), blood lipids [triglycerides (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL)] and blood uric acid (Ua) levels. At the same time, body indexes systolic blood pressure (SP), diastolic blood pressure (DP), waist circumference, height and weight were measured, and the body mass index (BMI) was calculated. Multiple linear regression was used to analyze the influencing factors of thyroid volume.Results:A total of 1 009 subjects were included, aged (43.50 ± 15.16) years, and the thyroid volume was (8.74 ± 3.39) ml. Among them, 534 males had a thyroid volume of (9.46 ± 3.43) ml; 475 females had a thyroid volume of (7.93 ± 3.15) ml, the thyroid volume of males was larger than that of females ( t = 7.36, P < 0.01). Thyroid volume was positively correlated with age, height, weight, BMI, SP, waist circumference, LDL, Ua and TgAb ( r = 0.07, 0.23, 0.33, 0.27, 0.10, 0.27, 0.10, 0.08, 0.07, P < 0.05), and it was negatively correlated with thyroid nodules, TPOAb, TSH and urinary iodine ( r = - 0.16, - 0.07, - 0.10, - 0.08, P < 0.05). After multiple linear regression analysis, TSH, TPOAb, TgAb and thyroid nodules were included in the regression equation, and the standardized B values were - 0.135, - 0.065, 0.123 and - 0.197, respectively. Conclusions:The thyroid volume of males is larger than that of females in Lanzhou City. TSH, TPOAb, TgAb and thyroid nodules are influencing factors of thyroid volume.

Modulation of transcutaneous auricular vagus nerve stimulation on default mode network in patients with primary insomnia / 中国针灸

OBJECTIVE@#To explore the modulation of transcutaneous auricular vagus nerve stimulation (taVNS) on default mode network (DMN) in patients with primary insomnia (PI).@*METHODS@#A total of 22 PI patients (one patient dropped off and two patients were excluded) were included and treated with taVNS. The bilateral auricular points of Xin (CO15) and Shen (CO10) were selected and treated with disperse-dense wave at frequency of 4 Hz/20 Hz, the intensity was based on the patient's tolerance. taVNS was given once in the morning and once in the evening for 30 minutes each time. The treatment lasted for at least 5 days a week for 4 weeks. At the same time, 16 healthy subjects matched with gender and age were recruited. The Pittsburgh sleep quality index (PSQI) score was evaluated before and after treatment in PI patients. The resting-state functional magnetic resonance imaging (rs-fMRI) data of PI patients before and after treatment and healthy subjects at baseline period were collected to observe the effect of taVNS on the functional connection (FC) between posterior cingulate cortex (PCC) and whole brain.@*RESULTS@#After treatment, the total score of PSQI in PI patients was lower than that before treatment (P<0.01). Compared with healthy subjects, the FC of the left PCC was increased either with the left orbital superior frontal gyrus or with left middle frontal gyrus (P<0.001), and the FC between right PCC and left middle frontal gyrus was increased in PI patients before treatment (P<0.001). Compared before treatment, the FC between left PCC and left middle frontal gyrus was decreased (P<0.05), and the FC of the right PCC was decreased either with the right medial prefrontal cortex or with the left middle frontal gyrus in PI patients after treatment (P<0.001, P<0.01).@*CONCLUSION@#taVNS can modulate the FC between anterior and posterior DMN, and between DMN and cognitive control network of PI patients, which may be one of the brain effect mechanisms of taVNS in the treatment of PI patients.

Effect of general anesthesia guided by electroencephalography monitoring on postoperative delirium in elderly patients with non-acute fragile brain function / 中华麻醉学杂志

Objective:To evaluate the effect of general anesthesia guided by electroencephalography (EEG) monitoring on postoperative delirium (POD) in elderly patients with non-acute fragile brain function.Methods:Sixty patients of both sexes with non-acute fragile brain function, aged 65-85 yr, of American Society of Anesthesiologists physical status Ⅱ or Ⅲ, with body mass index of 18-30 kg/m 2, undergoing hip replacement, were divided into 2 groups ( n=30 each) by a random number table method: conventional general anesthesia group (group C) and general anesthesia guided by EEG monitoring group (group E). Anesthesia was maintained by intravenous infusion of propofol 50-150 μg·kg -1·min -1 and remifentanil 0.05-0.30 μg·kg -1·min -1 and intermittent intravenous boluses of rocuronium.In group E, the dose of anesthetic was reduced when the EEG burst-suppression ratio≥10% for more than 1 min or anesthesia index (AI) <40.If the situation mentioned above still existed after 1 min, the dose of anesthetic was continued to be reduced or norepinephrine was injected intravenously.In group C, the amount of intraoperative anesthesia was adjusted according to the changes in hemodynamics.Norepinephrine 4-10 μg or dopamine 1 mg was given intravenously in the light of the patients′ heart rates when intraoperative hypotension occurred.At 10 min after anesthesia induction, immediately after skin incision, immediately at the end of surgery and at 1 h after surgery, blood samples were obtained from the artery and jugular venous bulb for blood gas analysis and for calculation of jugular bulb blood oxygen content (CjvO 2), artery-jugular bulb blood oxygen content difference (Ca-jvO 2), cerebral oxygen uptake rate (CERO 2) and jugular-arterial blood lactate concentration difference (Djv-aLac). The emergence time, amounts of intraoperative anesthetics, use of noradrenaline, cumulative time of EEG burst inhibition and duration of AI<40 were recorded.The development of POD was assessed within 5 days after surgery by the confusion assessment method for the intensive care unit and the duration was recorded. Results:Compared with group C, recovery time, cumulative time of EEG burst inhibition and duration of AI<40 were significantly shortened, the intraoperative consumption of propofol and remifentanil was decreased, the requirement for intraoperative noradrenaline was increased, CjvO 2 was increased, Ca-jvO 2 and CERO 2 were decreased immediately at the end of surgery and at 1 h after surgery, the incidence of POD within 5 days after surgery was decreased, and POD duration was shortened in group E ( P<0.05). Conclusion:General anesthesia guided by EEG monitoring can reduce the development of POD in elderly patients with non-acute fragile brain function.

Detection of thyroid nodules in people with abnormal lipid metabolism and related factors / 中华地方病学杂志

Objective:To investigate the detection rate and related factors of thyroid nodules in people with abnormal lipid metabolism.Methods:From September 4, 2016 to February 1, 2017, community residents living in Lanzhou City, Longnan City, Dingxi City and Linxia City of Gansu Province for more than 5 years were selected as the respondents. General data were recorded, venous blood was collected, blood lipid related biochemical indexes were detected, and thyroid ultrasound was performed. By comparing the general data and biochemical indexes, the detection of abnormal lipid metabolism and thyroid nodules were analyzed, and the risk factors of thyroid nodules in people with abnormal lipid metabolism were analyzed by logistic regression.Results:Two thousand and fifty-nine residents were included in this study (1 049 males and 1 010 females). The total detection rate of thyroid nodules was 23.17% (477/2 059). The detection rate of thyroid nodules in people with abnormal lipid metabolism [34.16%(151/442)] was significantly higher than that in people with normal lipid metabolism [20.16% (326/1 617) , P < 0.01], and the detection rate of thyroid nodules of women [43.37% (85/196) ] was higher than that of men [26.83% (66/246) , P < 0.01]. Among the people with abnormal lipid metabolism, the highest detection rate of thyroid nodules was in mixed hyperlipidemia [57.14% (16/28)], followed by hypertriglyceridemia [34.59% (92/266)]. The detection rates of thyroid nodules in the groups with elevated total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels [35.16% (32/91), 34.85% (23/66)] were higher than those in the marginal elevated group [27.04%(86/318), 30.42% (73/240)] and the normal groups [21.76% (359/1 650), 21.73% (381/1 753), P < 0.05]. The results of logistic regression analysis showed that the risk factors of thyroid nodules in people with abnormal lipid metabolism were increased age, elevated fasting blood glucose (FPG), elevated blood glucose 2 hours (2 h PG) after oral glucose tolerance test (OGTT) load and elevated glycosylated hemoglobin [HbA1c, odds ratio ( OR)=1.065, 1.387, 1.866, 1.384, P < 0.05]. Conclusions:The prevalence of TN is higher in populations with abnormal lipid metabolism. The control of blood sugar and blood lipid levels may play a role in the prevention of thyroid nodules.

Construction and verification of an intelligent measurement model for diabetic foot ulcer / 中南大学学报(医学版)

OBJECTIVES@#The measurement of diabetic foot ulcers is important for the success in diabetic foot ulcer management. At present, it lacks the accurate and convenient measurement tools in clinical. In recent years, artificial intelligence technology has demonstrated the potential application value in the field of image segmentation and recognition. This study aims to construct an intelligent measurement model of diabetic foot ulcers based on the deep learning method, and to conduct preliminary verification.@*METHODS@#The data of 1 042 diabetic foot ulcers clinical samples were collected. The ulcers and color areas were manually labeled, of which 782 were used as the training data set and 260 as the test data set. The Mask RCNN ulcer tissue color semantic segmentation and RetinaNet scale digital scale target detection were used to build a model. The training data set was input into the model and iterated. The test data set was used to verify the intelligent measurement model.@*RESULTS@#This study established an intelligent measurement model of diabetic foot ulcers based on deep learning. The mean average precision@.5 intersection over union (mAP@.5IOU) of the color region segmentation in the training set and the test set were 87.9% and 63.9%, respectively; the mAP@.5IOU of the ruler scale digital detection in the training set and the test set were 96.5% and 83.4%, respectively. Compared with the manual measurement result of the test sample, the average error of the intelligent measurement result was about 3 mm.@*CONCLUSIONS@#The intelligent measurement model has good accuracy and robustness in measuring the diabetic foot ulcers. Future research can further optimize the model with larger-scale data samples.

Effect of electroacupuncture on serum melatonin and dopamine in aged insomnia / 中国针灸

OBJECTIVE@#To observe the clinical effect of electroacupuncture (EA) on aged insomnia, and explore its possible mechanism.@*METHODS@#A total of 60 patients with aged insomnia were randomly divided into an EA group (30 cases) and a sham EA group (30 cases, 1 case dropped off). The patients in the EA group were treated with acupuncture at Baihui (GV 20), Yintang (GV 29), Shenmen (HT 7), Sanyinjiao (SP 6), Xinshu (BL 15) and Shenshu (BL 23), and EA was used at Baihui (GV 20) and Yintang (GV 29), with intermittent wave, 2 Hz in frequency. In the sham EA group, the acupoints and the EA connection acupoints were the same as those in the EA group, 2-3 mm in depth, but no current was connected. The intervention was given 30 min each time, once every other day, 3 times a week for 4 weeks in the both groups. Before and after treatment, the Pittsburgh sleep quality index (PSQI) and Montreal cognitive assessment (MoCA) scale were used to assess sleep quality and cognitive function, and serum melatonin (MT) and dopamine (DA) levels were detected.@*RESULTS@#After treatment, the total score and sub-item scores of PSQI in the EA group were lower than those before treatment (@*CONCLUSION@#Electroacupuncture can improve sleep quality and cognitive function in aged insomnia patients, and its mechanism may be related to regulating serum MT and DA levels.

Anti-fatigue Analysis of Common Mechanisms of Interaction of Ginseng Radix et Rhizoma "Tonifying Qi" and Notoginseng Radix et Rhizoma "Enriching Blood" / 中国实验方剂学杂志

Objective:To analyze the common active ingredients， potential target genes and pathways of Ginseng Radix et Rhizoma "Tonifying Qi" and Notoginseng Radix et Rhizoma "Enriching blood" in alleviating fatigue based on the network pharmacology technology. And the compound ingredients of total Ginsenoside Ginseng Root and Notoginseng total Saponins were selected to verify the core target genes in vitro. Method:The main active ingredients and related targets of Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma were screened by traditional Chinese medicine systems pharmacology （TCMSP）. The data of fatigue genes were established by GeneCards comprehensive database and Human Mendelian Genetic Integrated Database（OMIM）. Depending， The data sets of fatigue-related genes are established based on the data bank of GeneCards and OMIM. The intersecting genes of drugs and disease were obtained by R software. Cytoscape software was used to establish the regulatory network among the active ingredients， drug targets and fatigue-related genes. PPI network of intersecting genes was constructed by STRING 11.0 software， and the core genes were screened by CytoHubba software and Matthews correlation coefficient （MCC） algorithm. Based on the results of network analysis， 24 male SPF ACR mice were randomly divided into control group， total Ginsenoside Ginseng Root group （0.08 g·kg-1） and Notoginseng total Saponins group （0.08 g·kg-1）. The corresponding drugs were given for 3 weeks. The expressions of core genes in muscle tissue were detected by real-time fluorescence quantitative PCR. Result:The 20 active components and 181 drug targets were screened from TCMSP. 33 intersecting genes of diseases and drugs were obtained when compared with GeneCards and OMIM comprehensive database using R software. 10 core genes including aryl hydrocarbon receptor （AHR）， androgen receptor （AR）， glutathione S-transferase P1 （GSTP1）， cysteine proteinase-3（Caspase-3）， cytochrome p450 enzyme 3A4 （CYP3A4）， intercellular adhesion molecule 1 （ICAM1） and nuclear factor kappa B inhibitor alpha （NFKBIA） were screened out by the algorithm of MCC. Total Ginsenoside Ginseng Root and Notoginseng total Saponins had no significant effect on GSTP1 and ICAM1 genes， but they could significantly inhibit the expressions of AHR， CYP3A4， Caspase-3， NFKBIA and AR （P<0.05，P<0.01）， and there were no significant difference in anti-fatigue effect between total Ginsenoside Ginseng Root and Notoginseng total Saponins groups. Conclusion:The mechanism of anti-fatigue of Ginseng Radix et Rhizoma and Notoginseng Radix et Rhizoma may be related to the regulation of AHR， CYP3A4 and Caspase-3 genes， and there is no significant difference in their anti-fatigue effects， through the analysis of network and experimental verification.

Analysis on Mechanisms of Modified Guipitang in Treatment of Yin-Fire Insomnia with Anxiety Based on Network Pharmacology / 中国实验方剂学杂志

Objective:To explore the mechanism of modified Guipitang in the treatment of Yin-Fire insomnia with anxiety with the help of network pharmacological analysis technology. Method:Traditional Chinese Medicine Systems Pharmacology (TCMSP) was used to screen the main components and target genes of modified Guipitang. GeneCards and Online Mendelian Inheritance in Man (OMIM) were used to establish the target gene sets of insomnia and anxiety. STRING 11.0 software was used to analyze the interaction between the overlapping genes, and Cytoscape_3.6.1 software analysis and Matthews correlation coefficient (MCC) algorithm were used to screen the core genes. Based on the results of network analysis, 48 SD female rats were randomly divided into blank control group, model group, eszopiclone tablets group (0.2 mg·kg-1·d-1), modified Guipitang low，medium，and high-dose groups (0.31，1.25，5 g·kg-1·d-1). The model of insomnia with anxiety was established by intraperitoneal injection of Para-chlorophenylalanine (PCPA) and these rats were treated with corresponding drugs for 7 days. Then the frequency, time and distance of the activities were observed in the experiment of autonomic activity. Real-time quantitative polymerase chain reaction (PCR) was used to detect the mRNA expressions of proactivated protein kinase 8 (MAPK8), RAC-alpha serine/threonine protein kinase (Akt1), mitogen-activated protein kinase 3 (MAPK3) and interleukin-6 (IL-6) in rat hippocampus. Result:A total of 228 active compounds were screened from TCMSP database and 181 intersecting genes of diseases and drugs were obtained by comparing with GeneCards and OMIM comprehensive database. 9 core genes, including MAPK3, MAPK8, Akt1 and IL-6 were identified by STRING software and MCC algorithm. Animal experiments showed that the number of activity times, time and distance of modified Guipitang in high and medium dose groups were significantly lower than those in the model group. The high and middle dose groups of modified Guipitang could significantly inhibit the mRNA expression of MAPK3, MAPK8, Akt1 and IL-6 in hippocampus（P<0.01）, while the low dose group had no significant effect. Conclusion:The mechanism of modified Guipitang in treating Yin-fire insomnia with anxiety may be related to the regulation of MAPK3, MAPK8, Akt1 and IL-6 genes.

Relationship Between Characters and Main Components of Chelidonii Herba Pieces / 中国实验方剂学杂志

Objective::To determine the relationship between the characters and the main components of Chelidonii Herba pieces. Method::The main components of the samples were determined by HPLC, and the characters of Chelidonii Herba Pieces were evaluated by sensory evaluation. The correlation between the characters and components was calculated by correlation formula. Result::The content of 6 components, such as chelidonine, was determined by HPLC. Based on the result of sensory evaluation, there was a certain correlation between the characters and the components. Character descriptions that " some have visible white powder, some have white pubescence, and sometimes they have visible yellow florets" had a very low similarity with total alkali, indicating that these characters and total alkali content was not related. The similarity between the description of " hollow stem" had a high similarity with total alkali content, indicating that the amount of stem was related to the total alkali content. The character description of " more broken leaves" was negatively correlated with total alkaloids in the similarity, which indicated that the content of total alkaloids was less when there were more leaves(or more broken leaves), otherwise, the content of total alkaloids was relatively higher. Conclusion::The established HPLC method is simple and feasible. This study objectively quantifies the descriptions of Chelidonii Herba pieces characters, correlates them with the main components of Chelidonii Herba pieces, and then preliminarily judges the quality of Chelidonii Herba pieces according to the appearance of the characters, which provides a theoretical basis for the identification of Chelidonii Herba pieces in the market by experience, and ideas for the study of the characters of other traditional Chinese medicines.

Changes of vessel density and macular perfusion measured by optical coherence tomography angiography in patients with non-diabetic end-stage renal disease undergoing peritoneal dialysis / 中华眼底病杂志

Objective:To observe the changes of blood flow density and perfusion density in the macula of non-diabetic peritoneal dialysis (PD) patients, and their correlation with blood pressure, total protein, albumin, prealbumin, serum creatinine, urea, and high-sensitivity C-reactive protein were preliminarily analyzed.Methods:A single-center, cross-sectional, clinical observational study. From January to December 2018, 63 eyes of 63 non-diabetic patients (non-diabetic PD group) and 75 eyes of normal healthy people (the normal control group) who underwent PD treatment at the PD Center of Peking University First Hospital were included in the study. All were monocular into the group. Among the 63 patients in the non-diabetic PD group, 24 were males and 39 were females. The duration of PD was 7 to 185 months, with the average duration of 67.87±48.36 months. There were 75 healthy persons in the normal control group. There was no significant difference in age ( t=-0.558), sex ratio ( χ2=0.492), axial length ( t=-1.197), and BCVA between the two groups ( P>0.05). OCT angiography was used to scan the macular area of 3 mm×3 mm and 6 mm×6 mm in the subject’s right eye. The blood flow density and perfusion density of superficial retinal capillaries in the macular area, as well as the area, circumference, and morphological index of the foveal avascular zone (FAZ) were measured. The blood flow density and perfusion density at different locations in the macular area of the two groups of eyes were compared by independent sample t test. The blood pressure, total protein, albumin, prealbumin, serum creatinine, urea, and high-sensitivity C-reactive protein was performed by Pearson correlation analysis. Results:Compared with the healthy control group, the blood flow density and perfusion density of superficial retinal capillaries in the macular area of the non-diabetic PD group decreased in different scanning ranges with the macular vessel 3×3 center ( t=-2.409), the macular vessel 3×3 macular ( t=-2.423), macular vessel 3×3 intact ( t=-2.759), macular vessel 6×6 intact ( t=-1.882), macular vessel 6×6 outer layer ( t=-2.188), macular perfusion 3×3 center ( t=-1.990), macular perfusion 3×3 complete ( t=-2.719), macular perfusion 6×6 complete ( t=-2.113), and macular perfusion 6×6 outer layer ( t=-2.205). The difference was statistically significant ( P<0.05). The comparison of the macular FAZ area of the two groups of eyes was statistically significant ( t=1.985, P <0.05). Correlation analysis showed that 3×3 macular blood vessels were intact and mean arterial pressure was positively correlated ( r=0.256, P=0.043). The macular blood vessels were 3×3 intact, macular perfusion was 3×3 intact, and macular blood was 6×6 intact, which the pre-white protein was positively correlated with ( r=0.468, 0.362, 0.333; P<0.001, P=0.004, 0.008). The macular vessel 3×3 was intact, the macular perfusion 6×6 was intact, which the hypersensitive C-reactive protein was negatively correlated with ( r=-0.370, -0.287, P=0.005, 0.030). Conclusion:The superficial retinal blood flow density and perfusion density in the macular area of non-diabetic PD patients are lower than those of normal healthy people.

Effect of Brucea javanica oil emulsion on proliferation inhibition of multi-drug resistant K562/VCR cell line of human leukemia / 中国医师进修杂志

Objective:To investigate the inhibitory effect of Brucea javanica oil emulsion on the proliferation of human leukemia multi-drug resistant K562/VCR cell line.Methods:Methyl thiazolyl tetrazolim (MTT) colorimetric method was used to detect the proliferation inhibition rate of K562/VCR cells in vitro after intervention with Brucea javanica oil emulsion.Results:With the increasing concentration of Brucea javanica oil emulsion (125,250,500,750,1 000 mg/L), the inhibition ratio to K562 cells continued to increase ( P<0.05), and with the increasing duration of Brucea javanica oil emulsion(24,48,72 h), the inhibition ratio to K562 cells continued to increase ( P<0.05). With the increasing concentration of Brucea javanica oil emulsion(500,750,1 000,1 500,2 000 mg/L), the inhibition ratio of K562/VCR cells continued to increase ( P<0.05), and with the increasing action time of Brucea javanica oil emulsion (24,48,72 h), the inhibition ratio of K562/VCR cells continued to increase ( P<0.05). With the increasing concentration of Brucea javanica oil emulsion(blank control group , Brucea javanica oil emulsion group for 500,750,1 000,1 500 mg/L), the G 0/G 1 ratio in K562/VCR cell cycle continued to increase, while the S ratio and G 2/M ratio continued to decrease ( P<0.05). After injection of Brucea javanica oil emulsion, ADM concentration (fluorescence intensity) in the cells increased significantly(161.4 ± 10.9 vs. 95.9 ± 8.1)( P<0.05). Conclusions:Brucea javanica oil emulsion can inhibit the proliferation of multi-drug resistant K562/VCR cell lines and induce the arrest of multi-drug resistant cell cycle. Brucea javanica oil emulsion increasesd the accumulation of chemotherapeutic agents in multi-drug resistant K562/VCR cell lines.

Protective Effect of Longxue Tongluo Capsule on H2O2-induced Injury of PC12 Cells / 中国实验方剂学杂志

Objective::To investigate the protective effect of Longxue Tongluo capsule (LTC) on H2O2-induced injury of PC12 cells and its potential mechanism. Method::An in vitro injury model in PC12 cells was established with 500 μmol·L-1 H2O2.The experiment was divided into control group, injury model group (H2O2 500 μmol·L-1), and Longxuetongluo capsule group (LTC, 1, 2, 4 mg·L-1). Cell counting kit-8 (CCK-8) assay, intracellular reactive oxygen species (ROS), mitochondrial membrane potential, apoptosis of PC12 cells, and Western blot were used to evaluate the protective effect of LTC on PC12 cells induced by H2O2. Result::Compared with the control group, the cell viability was significantly decreased in the injury model group (P<0.01), intracellular ROS level was significantly increased (P<0.01), mitochondrial membrane potential was decreased, while apoptosis of PC12 cells was significantly increased (P<0.01), and the expression of cleaved poly adenosine diphospho ribose polymerase (PARP) was also increased significantly (P<0.01). Compared with the injury model group, pretreatment with LTC at the concentrations of 2 and 4 mg·L for 6 h significantly increased cell viability in PC12 cells exposed to H2O2 (P<0.01). Moreover, pretreatment with LTC reduced intracellular ROS level (P<0.05), maintained mitochondrial membrane potential, and inhibited apoptosis of PC12 cells induced by H2O2 in a dose-dependent manner (P<0.01). The results of western blotting showed that pretreatment with LTC significantly reduced the expression of cleaved PARP (P<0.01). Conclusion::LTC exerts a significant protective effect against H2O2-induced PC12 cells injury through inhibition of neuronal apoptosis by suppressing intracellular oxidative stress, maintaining mitochondrial function, and promoting DNA repair.

Sputum Inflammometry to Manage Chronic Obstructive Pulmonary Disease Exacerbations: Beyond Guidelines / 결핵및호흡기질환

Quantitative sputum cytometry facilitates in assessing the nature of bronchitis associated with exacerbations of chronic obstructive pulmonary disease (COPD). This is not assessed in most clinical trials that evaluate the effectiveness of strategies to prevent or to treat exacerbations. While up to a quarter of exacerbations may be associated with raised eosinophil numbers, the vast majority of exacerbations are associated with neutrophilic bronchitis that may indicate airway infections. While eosinophilia may be a predictor of response to corticosteroids (oral and inhaled), the limited efficacy of anti–interleukin 5 therapies would suggest that eosinophils may not directly contribute to those exacerbations. However, they may contribute to airspace enlargement in patients with COPD through various mechanisms involving the interleukin 13 and matrix metalloprotease pathways. The absence of eosinophils may facilitate in limiting the unnecessary use of corticosteroids. The presence of neutrophiia could prompt an investigation for the specific pathogens in the airway. Additionally, sputum measurements may also provide insight into the mechanisms of susceptibility to airway infections. Iron within sputum macrophages, identified by hemosiderin staining (and by more direct quantification) may impair macrophage functions while the low levels of immunoglobulins in sputum may also contribute to airway infections. The assessment of sputum at the time of exacerbations thus would facilitate in customizing treatment and treat current exacerbations and reduce future risk of exacerbations.

Safety and Efficacy of Dexamethasone Intravitreal Implant in Secondary Macular Edema Patients: A Meta-analysis / 中国药学杂志

OBJECTIVE: To systematically review the safety and efficacy of dexamethasone intravitreal implant (DEX) in secondary macular edema (ME) patients. METHODS: Multiple databases were searched electronically for randomized controlled trials (RCTs) of DEX in secondary ME patients up to April 2019. Two reviewers independently screened literatures according to the inclusion and exclusion criteria, extracted data, and assessed the methodological quality of the included studies. Then Meta-analysis was performed using Rev Man 5.3 software. RESULTS: A total of nine randomized controlled trials involving 1 530 patients were included. There were 737 patients in the experimental group and 793 patients in the control group. DEX was retrieved. Anti-vascular endothelial growth factor (anti-VEGF) or sham injection were used to treat the patients in the control group. The efficacy analysis results showed that the improvement rate of best corrected visual acuity (BCVA) in DEX group was significant higher than the control group in retinal vein occlusion (RVO) patients [MD=-10.59, 95%CI: -13.96--7.23,P=0.01]. The CST/CRT decrease in DEX was significant lower than control group in diabetic macular edema(DME) patients [MD=-63.60, 95%CI: -114.83--12.37,P=0.01], but higher than the control group in RVO [MD=-114.89, 95%CI: -48.68--181.09,P=0.00]. The safty analysis results showed that the incidence of serious adverse events (SAEs) in DEX was significant higher than control group [9.36% (28/299) : 5.23%(19/363), RR=1.94, 95%CI: 1.05-3.59, P=0.04]in RVO. The cataractin DEX was significant higher in RVO [4.87%(22/452) : 0.97% (5/513), RR=5.06, 95%CI: 1.96-13.06, P=0.00] than the control group. CONCLUSION: DEX has better efficacy than anti-VEGF in DME patients. DEX is similar in efficacy but inferior in safety to anti-VEGF in patients with ME secondary to RVO.