Mapping the modulating effect of transcutaneous auricular vagus nerve stimulation on voxel-based analyses in patients with first-episode major depressive disorder: a resting-state functional magnetic resonance imaging study

Introduction: Seed-based analysis has shown that transcutaneous auricular vagus nerve stimulation (taVNS) can modulate the dysfunctional brain network in patients with major depressive disorder (MDD). However, the voxel-based neuropsychological mechanism of taVNS on patients with first-episode MDD is poorly understood. The objective of this study was to assess the effects of an 8-week course of taVNS on patients with first-episode MDD. Methods: Twenty-two patients with first-episode MDD accepted an 8-week course of taVNS treatment. Resting-state functional magnetic resonance imaging (rs-fMRI) scans were performed before and after treatment. Voxel-based analyses were performed to characterize spontaneous brain activity. Healthy controls (n=23) were recruited to minimize test-retest effects. Analysis of covariance (ANCOVA) was performed to ascertain treatment-related changes. Then, correlations between changes in brain activity and the Hamilton Depression Rating Scale (HAM-D)/Hamilton Anxiety Scale (HAM-A) remission rate were estimated. Results: Significant group-by-time interactions on voxel-based analyses were observed in the inferior ventral striatum (VSi) and precuneus. Post-hoc analyses showed that taVNS inhibited higher brain activity in the VSi, while upregulating it in the precuneus. Functional connectivity (FC) between the VSi and precuneus decreased. Positive correlations were found between the HAM-D remission rate and changes in brain activity in the VSi. Conclusion: taVNS reduced the FC between VSi and precuneus by normalizing the abnormal spontaneous brain activity of VSi in first-episode MDD patients.

Efficacy and safety of various doses of hybutimibe monotherapy or in combination with atorvastatin for primary hypercholesterolemia: a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial / 中华心血管病杂志

Objective: To evaluate the efficacy and safety of hybutimibe monotherapy or in combination with atorvastatin in the treatment of primary hypercholesterolemia. Methods: This was a multicenter, randomized, double-blind, double-dummy, parallel-controlled phase Ⅲ clinical trial of patients with untreated primary hypercholesterolemia from 41 centers in China between August 2015 and April 2019. Patients were randomly assigned, at a ratio of 1∶1∶1∶1∶1∶1, to the atorvastatin 10 mg group (group A), hybutimibe 20 mg group (group B), hybutimibe 20 mg plus atorvastatin 10 mg group (group C), hybutimibe 10 mg group (group D), hybutimibe 10 mg plus atorvastatin 10 mg group (group E), and placebo group (group F). After a dietary run-in period for at least 4 weeks, all patients were administered orally once a day according to their groups. The treatment period was 12 weeks after the first dose of the study drug, and efficacy and safety were evaluated at weeks 2, 4, 8, and 12. After the treatment period, patients voluntarily entered the long-term safety evaluation period and continued the assigned treatment (those in group F were randomly assigned to group B or D), with 40 weeks' observation. The primary endpoint was the percent change in low density lipoprotein cholesterol (LDL-C) from baseline at week 12. Secondary endpoints included the percent changes in high density lipoprotein cholesterol (HDL-C), triglyceride (TG), apolipoprotein B (Apo B) at week 12 and changes of the four above-mentioned lipid indicators at weeks 18, 24, 38, and 52. Safety was evaluated during the whole treatment period. Results: Totally, 727 patients were included in the treatment period with a mean age of (55.0±9.3) years old, including 253 males. No statistical differences were observed among the groups in demographics, comorbidities, and baseline blood lipid levels. At week 12, the percent changes in LDL-C were significantly different among groups A to F (all P<0.01). Compared to atorvastatin alone, hybutimibe combined with atorvastatin could further improve LDL-C, TG, and Apo B (all P<0.05). Furthermore, there was no significant difference in percent changes in LDL-C at week 12 between group C and group E (P=0.991 7). During the long-term evaluation period, there were intergroup statistical differences in changes of LDL-C, TG and Apo B at 18, 24, 38, and 52 weeks from baseline among the statins group (group A), hybutimibe group (groups B, D, and F), and combination group (groups C and E) (all P<0.01), with the best effect observed in the combination group. The incidence of adverse events was 64.2% in the statins group, 61.7% in the hybutimibe group, and 71.0% in the combination group during the long-term evaluation period. No treatment-related serious adverse events or adverse events leading to death occurred during the 52-week study period. Conclusions: Hybutimibe combined with atorvastatin showed confirmatory efficacy in patients with untreated primary hypercholesterolemia, which could further enhance the efficacy on the basis of atorvastatin monotherapy, with a good overall safety profile.

Effect of transcutaneous auricular vagus nerve stimulation on functional connectivity in the related brain regions of patients with depression based on the resting-state fMRI / 中国针灸

OBJECTIVE@#To explore the brain effect mechanism and the correlation between brain functional imaging and cognitive function in treatment of depressive disorder (DD) with transcutaneous auricular vagus nerve stimulation (taVNS) based on the resting-state functional magenetic reasonance imaging (rs-fMRI).@*METHODS@#Thirty-two DD patients were included in a depression group and 32 subjects of healthy condition were enrolled in a normal group. In the depression group, the taVNS was applied to bilateral Xin (CO15) and Shen (CO10), at disperse-dense wave, 4 Hz/20 Hz in frequency and current intensity ≤20 mA depending on patient's tolerance, 30 min each time, twice daily. The duration of treatment consisted of 8 weeks. The patients of two groups were undertaken rs-fMRI scanning. The scores of Hamilton depression scale (HAMD), Hamilton anxiety scale (HAMA) and Wisconsin card sorting test (WCST) were observed in the normal group at baseline and the depression group before and after treatment separately. The differential brain regions were observed before and after treatment in the two groups and the value of degree centrality (DC) of fMRI was obtained. Their correlation was analyzed in terms of HAMD, HAMA and WCST scores.@*RESULTS@#The scores of HAMD and HAMA in the depression group were all higher than those in the normal group (P<0.05). After treatment, the scores of HAMD and HAMA were lower than those before treatment in the depression group; the scores of total responses, response errors and perseverative errors of WCST were all lower than those before treatment (P<0.05). The brain regions with significant differences included the left inferior temporal gyrus, the left cerebellar peduncles region 1, the left insula, the right putamen, the bilateral supplementary motor area and the right middle frontal gyrus. After treatment, the value of DC in left supplementary motor area was negatively correlated to HAMD and HAMA scores respectively (r=-0.324, P=0.012; r=-0.310, P=0.015); the value of DC in left cerebellar peduncles region 1 was negatively correlated to the total responses of WCST (r=-0.322, P=0.013), and the left insula was positively correlated to the total responses of WCST (r=0.271, P=0.036).@*CONCLUSION@#The taVNS can modulate the intensity of the functional activities of some brain regions so as to relieve depressive symptoms and improve cognitive function.

Clinical characteristics and risk factors of early septic patients complicated with bloodstream infection / 中华危重病急救医学

Objective:To analyze the clinical characteristics, risk factors and prognosis of early septic patients with bloodstream infection (BSI) in department of critical care medicine of Ningxia Medical University General Hospital.Methods:Patients with sepsis admitted to department of critical care medicine of Ningxia Medical University General Hospital from November 1, 2019 to August 31, 2021 were included in a prospective observational study. Blood samples were collected for culture within 24 hours of sepsis diagnosis. General information, laboratory test indicators and blood culture results within 24 hours of sepsis diagnosis were recorded. Patients were followed up and prognostic indicators [mechanical ventilation time, length of intensive care unit (ICU) stay, and 28-day survival] were observed. According to blood culture results, patients were divided into BSI group and non-BSI group. Univariate and multivariate Logistic regression analysis were performed on the general clinical characteristics of patients in the two groups to screen the risk factors of early BSI in septic patients. Receiver operator characteristic curve (ROC) was drawn to evaluate the predictive value of risk factors for early BSI in septic patients.Results:A total of 202 septic patients were included in this study, with 62 patients in BSI group and 140 patients in non-BSI group. The majority of patients in the BSI group were associated with abdominal infection (61.3%), and the majority of patients in the non-BSI group were associated with pulmonary infection (49.3%). A total of 76 strains were isolated from septic patients in BSI group, and the most common pathogens were Escherichia coli (26 strains, 34.2%), Klebsiella pneumoniae (11 strains, 14.4%), Enterococcus (7 strains, 9.2%), Bacteroides fragilis (6 strains, 7.9%) and Staphylococcus aureus (6 strains, 7.9%). There were no significant differences in mechanical ventilation time, the length of ICU stay and 28-day mortality between the BSI group and the non-BSI group. The difference of variables was statistically significant between two group according to Univariate analysis, which included body temperature, acute physiology and chronic health score Ⅱ (APACHEⅡ), use of antibiotics before admission to ICU, abdominal infection, hypersensitivity C-reactive protein (hs-CRP), serum creatinine (SCr), total bilirubin (TBil), platelet count (PLT), blood lactic acid (Lac) and hypercalcitonin (PCT). Multivariate analysis showed that low PLT [odds ratio ( OR) = 1.004, P = 0.019], high Lac ( OR = 1.314, P = 0.002), high body temperature ( OR = 1.482, P = 0.027), concomitant abdominal infection ( OR = 2.354, P = 0.040), no use of antibiotics before admission to ICU ( OR = 2.260, P = 0.049) were independent risk factors for early BSI in septic patients. The area under ROC curve (AUC) of PLT, Lac, body temperature, abdominal infection and no use of antibiotics before admission to ICU for predicting early BSI in septic patients were 0.711, 0.686, 0.594, 0.592 and 0.590, respectively. Youden index was used to calculate the optimal cut-off values, which was PLT 122.50×10 9/L, Lac 2.95 mmol/L, body temperature 39.45 ℃, respectively. The highest level of AUC was 0.754, the sensitivity was 75.8%, and the specificity was 68.8%, which were observed when the 5 items were combined. Conclusions:Early septic patients with BSI are more serious than those without BSI. Low PLT, high Lac, high temperature, concomitant abdominal infection and no use of antibiotics before admission to ICU are independent risk factors for early BSI in septic patients, and the combination of these five factors has good predictive value.

Effect of electroacupuncture at "Zusanli" (ST 36) on duodenal mast cells, NGF and NTRK1 in rats with functional dyspepsia / 中国针灸

OBJECTIVE@#To observe the effect of electroacupuncture (EA) at "Zusanli" (ST 36) on duodenal mast cells, nerve growth factor (NGF) and neurotrophic tyrosine kinase receptor type 1 (NTRK1), and to explore the mechanism of electroacupuncture at Zusanli (ST 36) on functional dyspepsia (FD).@*METHODS@#Sixty SPF-grade 10-day-old SD rats were randomly divided into a normal group, a model group, a ketotifen group and an EA group, 15 rats in each group. The FD model was prepared by iodoacetamide combined with rat tail clamping method in the model group, the ketotifen group and the EA group. The rats in the ketotifen group were injected intraperitoneally with ketotifen (1 mg•kg-1•d-1) for 7 days; the rats in the EA group were treated with EA at bilateral "Zusanli" (ST 36), with disperse-dense wave, frequency of 2 Hz/50 Hz and intensity of 0.5 mA, 20 min each time, once a day for 14 days. The gastric emptying rate and small intestinal propulsion rate in each group were observed; the morphology of duodenal mucosa was observed by HE staining; the toluidine blue staining was used to observe the number and degranulation of mast cells in duodenal mucosa; the protein and mRNA expressions of NGF, NTRK1 in duodenum were detected by Western blot and real-time PCR; the level of interleukin-1β (IL-1β) in duodenum was measured by ELISA.@*RESULTS@#Compared with the normal group, the gastric emptying rate and small intestinal propulsion rate in the model group were decreased (P<0.01); compared with the model group, the gastric emptying rate and small intestinal propulsion rate in the ketotifen group and the EA group were increased (P<0.01); the small intestinal propulsion rate in the EA group was higher than that in the ketotifen group (P<0.01). In the model group, local defects in duodenal mucosa were observed with a small amount of inflammatory cell infiltration; no obvious abnormality was found in duodenal mucosa of the other groups. Compared with the normal group, the mast cells of duodenal mucosa in the model group were increased significantly with significant degranulation; compared with the model group, the mast cells of duodenal mucosa in the ketotifen group and the EA group were decreased significantly, and the degranulation was not obvious. Compared with the normal group, the protein and mRNA expressions of NGF, NTRK1 as well as the level of IL-1β in duodenum in the model group were increased (P<0.01); compared with the model group, the protein and mRNA expressions of NGF, NTRK1 as well as the levels of IL-1β in duodenum in the ketotifen group and the EA group were decreased (P<0.01, P<0.05); compared with the ketotifen group, the mRNA expression of NGF, as well as the protein and mRNA expressions of NTRK1 in duodenum in the EA group were decreased (P<0.05, P<0.01).@*CONCLUSION@#EA at "Zusanli" (ST 36) could inhibit the activation of duodenal mast cells and regulate the expressions of NGF and its receptor to improve the low-grade inflammatory response of duodenum, resulting in treatment effect on FD.

Clinical observation on wrist-ankle acupuncture for shoulder-hand syndrome phaseⅠafter stroke / 中国针灸

OBJECTIVE@#To compare the clinical efficacy between wrist-ankle acupuncture and conventional acupuncture on shoulder-hand syndrome (SHS) phaseⅠafter stroke.@*METHODS@#A total of 64 patients with SHS phaseⅠafter stroke were randomized into a wrist-ankle acupuncture group and a conventional acupuncture group, 32 cases in each group. On the basis treatment of internal medicine and conventional rehabilitation, wrist-ankle acupuncture was applied at upper 4 area, upper 5 area and upper 6 area on the affected side in the wrist-ankle acupuncture group, while acupuncture was applied at Jianyu (LI 15), Quchi (LI 11), Shousanli (LI 10), etc. on the affected side in the conventional acupuncture group. The treatment was given 30 min each time, once a day, 5 days a week for 3 weeks in both groups. Before and after treatment, the visual analogue scale (VAS) score, degree of hand swelling, shoulder-hand syndrome scale (SHSS) score, Fugl-Meyer assessment for upper extremity (FMA-UE) score and modified Barthel index (MBI) score were observed, and the clinical therapeutic effect was evaluated in both groups.@*RESULTS@#After treatment, the VAS scores, degree of hand swelling and SHSS scores were decreased (P<0.05), and the FMA-UE scores and MBI scores were increased (P<0.05) compared before treatment in both groups; in the wrist-ankle acupuncture group, the VAS score, degree of hand swelling and SHSS score were lower (P<0.05), and the FMA-UE score and MBI score were higher (P<0.05) than those in the conventional acupuncture group. The total effective rate was 96.9% (31/32) in the wrist-ankle acupuncture group, which was superior to 90.6% (29/32) in the conventional acupuncture group (P<0.05).@*CONCLUSION@#Wrist-ankle acupuncture can effectively relieve pain and hand swelling, improve motor function of upper extremity and self-care ability of daily life in patients with shoulder-hand syndrome phaseⅠafter stroke, the therapeutic effect is superior to conventional acupuncture.

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.

An analysis on senior pupil's tobacco use and exposure in Shandong province in 2012 and 2019 / 中华流行病学杂志

Objective: To analyze the changes in tobacco use and exposure in primary school students in Shandong province in 2012 and 2019. Methods: A multi-stage stratified cluster random sampling method was used in the survey. In 2012 and 2019, 5 861 and 4 021 students from 3 different cities of Shandong province were selected as the study population. The questionnaire was filled anonymously by the subjects. χ2 test was conducted to compare the difference of groups. Results: In 2012 and 2019, the rate of attempting smoking among pupils under this study in Shandong province were 6.0％and 6.3%, respectively, while the current smoking rate were 1.2％and 2.3%, respectively. The sex ratio of male and female students attempting to smoke was 2.56∶1 in 2012 and 1.31∶1 in 2019. The sex ratio of current smoking rate was 2.43∶1 and 2.00∶1, respectively in 2012 and in 2019. The rate of tobacco exposure in the public places was 50.5％and 41.4%, respectively. The rate of tobacco exposure in family was 49.7% and 46.4%, respectively. Two rates of tobacco exposure decreased, but the reduction in family (3.3%) was far less than that in public places (9.1%). In 2019, the rate of tobacco exposure in family was higher than that in public places. Conclusions: The tobacco exposure rate declined in senior pupils in Shandong province. However, the situation is still grim for the current smoking rate, growth trend of girls tobacco use, and tobacco exposure in family.

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.

Prognostic value of coagulation function combined with acute physiology and chronic health evaluationⅡ and sequential organ failure assessment scores for patients with bloodstream infection / 中华危重病急救医学

Objective:To evaluate the prognostic value of platelet count (PLT), coagulation indexes, acute physiology and chronic health evaluationⅡ(APACHEⅡ), and sequential organ failure assessment (SOFA) in patients with bloodstream infection.Methods:A retrospective single center cohort study was conducted, patients with at least one positive blood culture bloodstream infection hospitalized in the intensive care unit (ICU) of Ningxia Medical University General Hospital from January 2016 to October 2020 were selected as the research objects, basic data and pathogen distribution, coagulation function, and prognosis at 28 days were collected, the APACHEⅡscore, SOFA score based on the results of laboratory examination within 24 hours of blood culture were calculated. Patients were divided into the survival group and the death group according to the 28-day prognosis, and the differences of the above indicators were compared. Multivariate Logistic regression analysis was used to screen out the risk factors for 28-day death of patients with bloodstream infection. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive efficacy of various risk factors for 28-day prognosis of patients with bloodstream infection.Results:A total of 215 patients with bloodstream infection were enrolled, of which 117 survived and 98 died within 28 days. The 256 strains of pathogenic bacteria were detected, including 161 (62.89%) Gram-negative bacteria (G -), 76 (29.69%) Gram-positive bacteria (G +), 17 fungi (6.64%), and 2 other strains (0.78%). The main pathogenic bacteria were Escherichia coli (53 strains, 20.70%), Enterococcus (37 strains, 14.45%), and Klebsiella pneumoniae (34 strains, 13.28%). Compared with the survival group, patients in the death group were older (years old: 60.98±16.08 vs. 55.64±16.35), had higher levels of body temperature, SOFA score, APACHEⅡ score, proportion of malignant tumor and pulmonary infection, blood lactic acid (Lac), and creatinine [Cr; body temperature (℃): 39.12±1.10 vs. 38.67±1.09, SOFA score: 13.05±4.40 vs. 7.85±3.74, APACHEⅡscore: 24.01±8.18 vs. 15.38±6.59, proportion of malignant tumor: 15.31% (15/98) vs. 12.82% (15/117), proportion of patients with pulmonary infection: 84.69% (83/98) vs. 72.65% (85/117), Lac (mmol/L): 7.13±6.04 vs. 4.31±2.98, Cr (μmol/L): 189.73±141.81 vs. 124.55±106.17, all P < 0.05]. The prothrombin time (PT), activated partial thrombin time (APTT), and thrombin time (TT) were significantly longer [PT (s): 19.51±15.16 vs. 14.94±2.86, APTT (s): 52.74±26.82 vs. 40.77±15.30, TT (s) : 21.59±18.46 vs. 17.38±2.59, all P < 0.05], PLT was significantly decreased [×10 9/L: 43.50 (18.75, 92.75) vs. 86.00 (36.00, 154.50), P < 0.05]. Logistic regression analysis showed that body temperature, age, SOFA score and APACHEⅡ score were independent risk factors [odds ratio ( OR) were 1.388, 1.023, 0.817 and 0.916, respectively, 95% confidence intervals (95% CI) were 1.001-1.926, 1.001-1.046, 0.730-0.913, 0.867-0.968, with respective P values of 0.046, 0.043, 0.000, 0.002]. ROC curve analysis showed that SOFA score, APACHEⅡ score, temperature, age had certain predictive values for the prognosis of patients with bloodstream infection, and area under ROC curve (AUC) was 0.815, 0.795, 0.625 and 0.594, respectively (all P < 0.05). The AUC predicted by the combination of the 4 variables was as high as 0.851, the specificity was 79.3%, and the sensitivity was 74.2%, suggesting that the combination variables could predict the death of patients with bloodstream infection with higher accuracy. Conclusions:PLT and coagulation indexes are helpful to evaluate the prognosis of patients with bloodstream infection in ICU. APACHEⅡscore and SOFA score are directly related to the prognosis of patients with bloodstream infection.

Analysis of correlation between fecal and alveolar lavage fluid flora of ventilator-associated pneumonia patients based on 16S rRNA sequencing technology / 中华危重病急救医学

Objective:To investigate the changes and correlation of intestinal and pulmonary microecological structures in patients with ventilator-associated pneumonia (VAP).Methods:A prospective observational study was conducted. Thirty-one patients with VAP admitted to the department of critical care medicine of General Hospital of Ningxia Medical University from May 1st 2019 to May 1st 2020 were enrolled. Feces and alveolar lavage fluid samples from patients with the same day, feces and alveolar lavage specimen flora composition and the structure of biological information analysis by 16S rRNA sequencing technologies, the comprehensive sequencing results, and clinical data of patients were analyzed.Results:① The diversity (abundance and diversity) of flora in the alveolar lavage fluid of VAP patients was higher than that of fecal flora. Among them, Ace index, Chao index and Shannon index describing the abundance of flora showed statistically significant differences [Ace index: 305.89 (214.39, 458.66) vs. 204.51 (165.15, 247.61), Chao index: 259.83 (194.20, 459.31) vs. 187.67 (153.28, 234.01), Shannon index: 3.01 (2.39, 3.54) vs. 2.55 (1.86, 2.95), all P < 0.05], but there was no significant difference in Simpson index describing diversity [0.14 (0.08, 0.27) vs. 0.19 (0.10, 0.33), P > 0.05]. ② In the sequencing results of feces and alveolar lavage fluid of VAP patients, there were some intestinal related bacteria groups with high abundance, such as Escherichia-Shigella, Faecalibacterium, Bacteroides, and Lachnospira, etc. ③ In 31 VAP patients, suspicious pathogenic bacteria was found in 20 cases (6 cases of Streptococcus viridans, 5 cases of Escherichia coli, 3 cases of Klebsiella pneumoniae, 3 cases of Acinetobacter baumannii, 2 cases of Staphylococcus aureus, 1 case of Pseudomonas aeruginosa), and the same suspected pathogens also existed in the 17 patients' alveolar lavage and waste sequencing. ④ Fourteen VAP patients combined with sepsis, 14 patients without sepsis were selected for sample size matching. The results showed that, Jaccard similarity index to describe lung-correlation of intestinal flora in VAP with sepsis group was significantly elevated, and the difference was statistically significant (0.24±0.08 vs. 0.19±0.06, P < 0.01). Conclusions:There is a certain correlation between pulmonary and intestinal flora in VAP patients. In addition to the exclusion of pulmonary infection caused by environmental and upper respiratory micro-inhalation, the lower digestive tract may also be source of infection.

Application prospect of common viral tracers in study on brain effect of acupuncture / 中国针灸

The feasibility and prospect of viral tracers and mediating functional components are explored in study on brain effect of acupuncture. In the paper, proceeding with viral tracers, the viral tracers used to analyze the structure of specific neural circuits are introduced, as well as their mediated probes, optical/chemical genetics techniques, Cre-LoxP systems, etc. The viral tracers and their functional components can not only mark specifically nerve cells or neural circuits, but also interfere with the function of specific types of neurons or nuclei. They solve some disadvantage of traditional nerve tracing method that only describes the morphology of neurons of one brain region and the simple projection among brain regions, and the indirect and non-specific absorption. The viral tracers and their functional components play the important approach to decoding the mechanism on brain effect of acupuncture when introduced in experimental acupuncture so as to provide an in vivo, real-time and intuitive novel method for a further analysis of neurobiological mechanism on brain effect of acupuncture.

Transcutaneous Auricular Vagus Nerve Stimulation: From Concept to Application / 神经科学通报·英文版

Whether in the West or the East, the connection between the ear and the rest of the body has been explored for a long time. Especially in the past century or more, the relevant theoretical and applied research on the ear has greatly promoted the development of ear therapy, and finally the concept of transcutaneous auricular vagus nerve stimulation (taVNS) has been proposed. The purpose of taVNS is to treat a disease non-invasively by applying electrical current to the cutaneous receptive field formed by the auricular branch of the vagus nerve in the outer ear. In the past two decades, taVNS has been a topic of basic, clinical, and transformation research. It has been applied as an alternative to drug treatment for a variety of diseases. Based on the rapid understanding of the application of taVNS to human health and disease, some limitations in the development of this field have also been gradually exposed. Here, we comprehensively review the origin and research status of the field.

Brain science promotes the development of acupuncture in treating brain diseases / 针刺研究

Brain science is the "ultimate territory" for human beings to understand the nature. In the present paper, the authors introduce the current state of brain science research projects in the USA, European countries, Japan and China. In recent years, with the continuous innovations of technologies in brain imaging, biosensors, human-computer interaction and big data, the brain science has become an important frontier field with interdisciplinarity and a focus of science and technology strategies in various countries. As a scientific and technological resource with original advantages in China, traditional Chinese medicine (TCM) is abundant in knowledge of brain, almost covering all kinds of encephalopathy in modern medicine. At present, TCM is increasingly becoming an effective tool to conquer mental and nervous diseases. With the intersection and penetration of multi-disciplines, an increasing close association between the traditional theory of TCM about prevention and treatment of encephalopathy and modern basic biological research appears, and new ideas, new technologies and new achievements have constantly been coming out, particularly in the field of acupuncture medicine. In the present historical juncture when the development of science and technology in China is changing from the "follower" to the "parallel runner", even the "top runner" in some fields, the progress of brain science research in TCM will make enormous contributions to explore brain disease and exploit cutting-edge technologies of TCM, as well as accelerate the modernization of TCM.

Pharmacokinetic Studies of Factor VIII in Chinese Boys with Severe Hemophilia A: A Single-Center Study / 中华医学杂志(英文版)

<p><b>Background</b>Although much attention has been paid to the pharmacokinetics (PKs) of different factor VIII (FVIII) concentrates in persons with hemophilia A (HA), limited information is available in young boys with severe HA. In this study, we aimed to assess the PK parameters of FVIII products in boys with severe HA in China.</p><p><b>Methods</b>A total of 36 boys (plasma-derived [pd]-FVIII, n = 15; recombinant [r] FVIII, n = 21) were enrolled between January 2015 and May 2016 in Beijing Children's Hospital. PK characteristics of FVIII products were studied according to a reduced 4-sampling time point design (1 h, 9 h, 24 h, and 48 h postinfusion).</p><p><b>Results</b>The mean FVIII half-life (t) was 10.99 ± 3.45 h (range 5.52-20.02 h), the mean in vivo recovery (IVR) was 2.01 ± 0.42 IU/dl per IU/kg (range 1.24-3.02 IU/dl per IU/kg) and mean clearance (CL) of FVIII is 4.34 ± 1.58 ml·kg·h (range 2.29-7.90 ml·kg·h). We also analyzed the influence of several parameters that potentially modulate FVIII PK. The age was closely associated with FVIII half-life (R = 0.32, P < 0.01). The tof FVIII increased by 0.59 h per year. Besides age, von Willebrand factor antigen (VWF:Ag) also was associated with FVIII half-life (R = 0.52, P < 0.01). Patients with blood Group O had a shorter FVIII half-life than patients with non-O blood group (9.40 ± 0.68 h vs. 12.3 ± 0.79 h, t = 2.70, P = 0.01). The FVIII IVR correlated with age (R = 0.21, P < 0.01) and VWF:Ag level (R = 0.28, P < 0.01). CL rates were faster in young patients and in those with low-VWF:Ag levels. CL rates of FVIII are higher in blood Group O versus non-blood Group O persons (5.02 ± 0.38 vs. 4.00 ± 0.32 ml·kg·h, t = 2.53, P = 0.02).</p><p><b>Conclusions</b>Chinese boys with severe HA have similar PK values to other ethnic groups and large differences in FVIII PK between individual patients. Age, blood group, and VWF:Ag levels are important determining factors for FVIII CL.</p>

Correlation between mild cognitive impairment and bone metabolism level in the elderly / 上海交通大学学报（医学版）

Objective·To investigate the correlation between mild cognitive impairment (MCI) and bone metabolism level in the elderly.Methods·Fifty patients with MCI and ninety controls with normal cognitive function were recruited from Department of Gerontology,Ruijin Hospital,Shanghai Jiao Tong University School of Medicine.Plasma levels of calcium and phosphorus metabolism indicators,bone resorption markers and bone formation markers were measured.Cognitive function was assessed by mini mental state examination (MMSE) and Montreal cognitive assessment (MoCA).Results·Plasma level of osteocalcin was elevated in patients with MCI (P=0.001) compared with controls,while plasma level of calcium was decreased in the MCI group (P=0.045).Among patients with MCI,the score of MMSE positively correlated with plasma level of 25-hydroxy vitamin D3 (r=0.290,P=0.041),while negatively correlated with plasma level of parathyroid hormone (r=-0.349,P=0.025).Conclusion·MCI may be correlated with bone metabolism level in the elderly.

Long-term Trends and Predictors of Smoking Behaviors among Men Following First-ever Ischemic Stroke / 华中科技大学学报（医学）（英德文版）

Continued smoking following stroke is associated with adverse outcomes including increased risk of mortality and secondary stroke.The aim of this study was to examine the long-term trends in smoking behaviors and factors associated with smoking relapse among men who survived their first-ever stroke.Data collection for this longitudinal study was conducted at baseline through face-to-face interviews and follow-up was completed every 3 months via telephone,beginning in 2010 and continuing through 2014.Cox proportional hazard regression models were used to identify predictors of smoking relapse behavior.At baseline,372 male patients were recruited into the study.Totally,155 (41.7％) of these patients stopped smoking for stroke,and 61 (39.3％) began smoking again within 57 months after discharge with an increasing trend in the number of cigarettes smoked per day.Exposure to environmental tobacco smoke at places outside of home and work (such as bars,restaurants) (HR,2.34;95％ CI,1.04-5.29,P=0.04),not having a spouse (HR,0.12;95％ CI,0.04-0.36;P=0.0002) and smoking at least 20 cigarettes per day before stroke (HR,2.42;95％ CI,1.14-5.14,P=0.02) were predictors of smoking relapse.It was concluded that environmental tobacco smoke is an important determinant of smoking relapse among men who survive their first stroke.Environmental tobacco smoke should be addressed by smoke-free policies in public places.

Somato stimulation and acupuncture therapy / 中国结合医学杂志

Acupuncture is an oldest somato stimulus medical technique. As the most representative peripheral nerve stimulation therapy, it has a complete system of theory and application and is applicable to a large population. This paper expounds the bionic origins of acupuncture and analyzes the physiological mechanism by which acupuncture works. For living creatures, functionally sound viscera and effective endurance of pain are essential for survival. This paper discusses the way in which acupuncture increases the pain threshold of living creatures and the underlying mechanism from the perspective of bionics. Acupuncture can also help to adjust visceral functions and works most effectively in facilitating the process of digestion and restraining visceral pain. This paper makes an in-depth overview of peripheral nerve stimulation therapy represented by acupuncture. We look forward to the revival of acupuncture, a long-standing somato stimulus medicine, in the modern medical systems.

Site-directed mutagenesis and protein expression of ABCA3 gene in A549 cells / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To study the protocol of construction of the mutation E292V and M723I of hABCA3 gene associated with neonatal respiratory distress syndrome, as well as their eukaryotic green fluorescent protein expression rectors, and to examine the expression of mutation proteins in human lung carcinoma epithelial cells (A549).</p><p><b>METHODS</b>Site-directed mutagenesis method based on overlap extension PCR was used to introduce mutations in the two sites which were E292V and M723I in the ABCA3. The PCR fragments were subcloned to PEGFP-C2 vectors to construct the eukaryotic green fluorescent protein expression rectors. A549 cells were transiently transfected with the recombinants using Lipofectamine 2000 and the transfection efficiency was confirmed through GFP signal. The expression and location of recombinants were detected by FV1000 laser scanning microscope.</p><p><b>RESULTS</b>Direct sequence analysis confirmed an A to T transition at position 875 in E292V and a G to A transition at position 2169 in M723I. Recombinants were transfected to A549 cells and both wild type and mutant ABCA3 proteins were expressed in the cytoplasm.</p><p><b>CONCLUSIONS</b>The eukaryotic green fluorescent protein expression rectors of wild type and mutant ABCA3 gene were constructed and they were successfully expressed in A549 cells. This experiment provides a basis for subsequent research.</p>

Auricular acupuncture and biomedical research--A promising Sino-Austrian research cooperation / 中国结合医学杂志

Treatment by auricular acupuncture has a long history. Ear-acupoint research has been advancing step by step in China and also in Europe. Auricles are rich in nerves, therefore a close relationship with different functions of the human body has been proved by the research teams of the two main authors of this article from China and Austria. In recent years, great progress has been made in the research of regulating human body functions through electroacupuncture at the auricular branch of the vagus nerve, which is part of auricular acupuncture therapy. It is well known that the auricular branch of the vagus nerve is the only peripheral pathway to the cerebral cortex. Studies of the Chinese team on hypertension, diabetes, epilepsy and depression have shown that the mechanism of auricular vagus nerve stimulation (VNS) may be comparable with cervical VNS in terms of pathways. Auricular VNS has a broad clinical application prospect.