BACKGROUND: Long-term remote ischemic conditioning (RIC) has been proven to be beneficial in multiple diseases, such as cerebral and cardiovascular diseases. However, the hyperacute and acute effects of a single RIC stimulus are still not clear. Quantitative proteomic analyses of plasma proteins following RIC application have been conducted in preclinical and clinical studies but exhibit high heterogeneity in results due to wide variations in experimental setups and sampling procedures. Hence, this study aimed to explore the immediate effects of RIC on plasma proteome in healthy young adults to exclude confounding factors of disease entity, such as medications and gender. METHODS: Young healthy male participants were enrolled after a systematic physical examination and 6-month lifestyle observation. Individual RIC sessions included five cycles of alternative ischemia and reperfusion, each lasting for 5 min in bilateral forearms. Blood samples were collected at baseline, 5 min after RIC, and 2 h after RIC, and then samples were processed for proteomic analysis using liquid chromatography-tandem mass spectrometry method. RESULTS: Proteins related to lipid metabolism (e.g., Apolipoprotein F), coagulation factors (hepatocyte growth factor activator preproprotein), members of complement cascades (mannan-binding lectin serine protease 1 isoform 2 precursor), and inflammatory responses (carboxypeptidase N catalytic chain precursor) were differentially altered at their serum levels following the RIC intervention. The most enriched pathways were protein glycosylation and complement/coagulation cascades. CONCLUSIONS One-time RIC stimulus may induce instant cellular responses like anti-inflammation, coagulation, and fibrinolysis balancing, and lipid metabolism regulation which are protective in different perspectives. Protective effects of single RIC in hyperacute and acute phases may be exploited in clinical emergency settings due to apparently beneficial alterations in plasma proteome profile. Furthermore, the beneficial effects of long-term (repeated) RIC interventions in preventing chronic cardiovascular diseases among general populations can also be expected based on our study findings.
Young Adult ; Humans ; Male ; Proteome ; Cardiovascular Diseases ; Proteomics ; Ischemia ; Blood Coagulation

Objective Bushen-Qingxin decoction combined conjugated estrogen tablets of modulation perimenopausal women osteoporosis patients, explore the impact of bone mineral density and bone metabolic markers. Methods A total of 160 female patients were recruited in our hospital by the random number table method, and were divided into the control group 80 cases and the observation group 80 cases. The control group was treated with standard dose of conjugated estrogen tablets, while the observation group was treated with Bushen Qingxin decoction on the basis of the control group. Both groups were treated 3 period with 28 days per period. The enzyme-linked immunity analyzer was used to detect serum bone-specific alkaline phosphatase (BALP), C-terminal cross linked peptide (CTX-Ⅰ), tartrate resistant acid phosphatase -5b (TRACP-5b) level, and the dual-energy X-ray absorptiometry measurement method was used to detect bone mineral density values. The clinical curative effect was compared between two groups. Results The total effective rate of the observation group was 91.3%, while the control group was 78.8%, which showed the difference was statistically significant (χ 2=3.971, P=3.971). After treatment, the serum BALP levels (88.55 ± 10.33 U/L vs. 80.47 ± 8.67 U/L, t=5.399) of the observation group were significantly higher than this of the control group (P<0.01). After treatment, the serum TRACP-5b (501.31 ± 35.77 pg/L vs. 538.51 ± 37.69 pg/L, t=6.498), CTX- (130.09 ±Ⅰ17.55 ng/ml vs. 164.71 ± 19.45 ng/ml, t=11.928) of the observation group were significantly lower than those of the control group (P<0.01). After treatment, the bone mineral density of the observation group rose up from the baseline (t=3.396, P=0.010). Conclusions The Bushen-Qingxin decoction combined conjugated estrogen tablets can increase on women in the menopausal transition of osteoporosis in patients with bone mineral density values and serum BALP levels, reduce serum TRACP-5b, CTX-Ⅰ level.

Objective: To explore the association between the efficacy of peg-IFN and the complexity of TP and RT regions of hepatitis B virus (HBV) in chronic hepatitis B. Methods: Patients with HBeAg positive, HBV DNA positive chronic hepatitis B were given peg-interferon 180 μg once a week for subcutaneous injection, and baseline information was collected from baseline and after 12 weeks’ treatment. The baseline HBV DNA TP and RT fragments were amplified, database, high-throughput sequencing, and the average genetic distance calculation. Results: Data of 108 patients were analyzed by logistic regression. RT area fragment Markov distance and TP area fragment Shannon quotient for HBV DNA response were calculated. ALT level is good for HBeAg response. HBsAg level is bad for HBsAg response. Conclusions The complexity of the baseline TP and RT regions may be associated with the efficacy of peg-interferon therapy for CHB.

Objective To investigate the correlation between quantitative parameters derived from iodine overlay images and the monochromatic images of dual‐energy CT and the differentiation degree of laryngeal and hypopharyngeal squamous cell carcinoma(LHSCC). Methods Retrospective analysis of clinical and imaging data of eighty patients with different differentiation degree of LHSCC who underwent dual‐energy CT enhanced scan in the arterial and venous phase from March 2016 to January 2017 (20, 42 and 18 patients with well, moderately and poorly differentiation, respectively) was performed.Among them, twenty‐eight cases were stage T1, twenty‐four cases were stage T2, twenty cases were stage T3 and eight cases were stage T4. All patients were not treated with radiotherapy and chemotherapy before operation. Iodine overlay images and the monochromatic images of arterial and venous phases were acquired from Syngo MultiModality Workplace dual‐energy post‐processing software of Siemens, respectively. The mean iodine concentration (IC), standardized iodine concentration (SIC), and the slope of spectral curve(λ) of different differentiation degrees of LHSCC were calculated and compared. The correlation between quantitative parameters of LHSCC and its differentiation degree was performed by Spearman rank sum test. One‐way analysis of variance was used to compare the quantitative parameters of different differentiation degree of LHSCC. Receiver operating characteristic (ROC) curve was used for analyzing diagnostic efficiency. Results The IC, SIC, and λ in the arterial phase, and IC in the venous phase correlated positively with differentiation degree in LHSCC (r=0.258, 0.350, 0.262 and 0.275, respectively; P<0.05) in this group. The IC, SIC, and λ of poorly differentiated LHSCC in the arterial phase [(3.13 ± 0.54) mg/ml, (0.38±0.10), (5.40±0.92)] were higher than those of well differentiated LHSCC [(2.38±1.02) mg/ml, (0.25± 0.09) and (4.19 ± 1.18); t=2.73, 3.36 and 2.75 respectively; P<0.05] and moderately differentiated LHSCC [(2.56±0.85) mg/ml, (0.28±0.16) and (4.56±1.41); t=2.38, 3.06 and 2.21, P<0.05]. IC of poorly differentiated LHSCC in the venous phase [(2.59 ± 0.62) mg/ml] was significantly higher than that of well differentiated LHSCC [(1.96±0.56) mg/ml,t=2.45,P<0.05] and moderately differentiated [(2.02±0.93) mg/ml,t=2.56,P<0.05] LHSCC. There was no significant difference in the SIC and λ between different differentiation degrees of LHSCC (P>0.05) in the venous phase. The standardized iodine concentration in the arterial phase was the best in distinguishing poorly and moderately differentiated LHSCC, and poorly and well differentiated LHSCC with the area under the receiver operating curve 0.77 and 0.81, respectively, the sensitivity 88.2% and 70.0%, respectively, and the specificity 69.0% and 70.0%, respectively. Conclusions Quantitative parameters derived from dual‐energy CT might be useful in the evaluation of different differentiated degrees of LHSCC. In addition, the standardized iodine concentration of LHSCC in the arterial phase was the best in the estimation of different differentiated degrees of LHSCC.

Objective To observe the clinical efficacy of Bushen-Qingxin decoction for the patients with premature ovarian failure (POF) with kidney deficiency type. Methods A total of 120 POF patients were randomly divided into the observation group and the control group. The observation group were treated with Bushen-Qingxin decoction. The control group were treated with hormone replacement therapy (HRT). After continuous treatment for 3 courses, the clinical efficacy, clinical symptoms and the levels of estrogen (E2), luteotropic hormone (LH), follicle-stimulating hormone (FSH) were comparedbefore and after treatment. Results The total effective rate in the observation group was 86.7% (52/60), and the control group was 60.0% (36/60). The difference was statistically significant (x2=9.588, P=0.002) between two groups. The symptoms aversion to cold, and cold limbs, depressed mood, night sweats were improved significantly better than those in the control group(x2=16.464,16.214,11.525,9.938,P<0.001).After treatment,the serum E2(88.32 ± 9.35 pmol/L vs. 62.10 ± 7.22 pmol/L, t=17.848) in the observation group was significantly higher than this in the control group,while the serum FSH(32.33 ± 4.60 U/L vs.46.82 ± 5.47 U/L,t=15.704),LH(24.80 ± 3.37 U/L vs.32.16 ± 4.02 U/L, t=10.868) in the observation group were significantly lower than those in the control group (P<0.01). In the follow-up of 3 months, the recurrence rate in the observation group was 3.8% (2/52), but 16.7% (6/36) in the control group. The difference was statistically significant between two groups (x2=4.231, P=0.040).Conclusions The Bushen-Qingxin decocation can significantly improve the clinical symptoms and restore ovarian function.The Bushen-Qingxin decocation is an effective method for the treatment of premature ovarian failure.

Objective: To investigate the differences in frequency and function of natural killer cells (NK) between chronic hepatitis B (CHB) and acute hepatitis B (AHB). Methods: Patients with AHB and those with CHB in immune active (IA) phase were enrolled. The frequencies of NK, CD56^dimNK, CD56^brightNK and the expression of functional molecules IFNAR2 and NKp46 on the surface of NK cells were detected respectively among patients with CHB in IA phase, patients with AHB, and those recovered from AHB. At the same time, their correlations with ALT, HBV DNA and HBV markers were analyzed. Results: Between IA and AHB, the frequencies of NK cells and NKp46^dim NK cells in AHB cases were significantly lower than those in IA cases, but the frequency of NKp46^high NK cells in AHB was higher than that in IA. For patients who recovered from AHB, the frequency of NK cells and NKp46^dim NK cells increased; the varied ranges of frequencies of CD56^dimNK, IFNAR2⁺ NK and NKp46⁺ NK cells were on the rise, while the frequency of NKp46^high NK cells decreased after the recovery from AHB, and the varied ranges of CD56^brightNK and IFNAR2MFI, NKp46MFI decreased. In AHB, HBVDNA loads were positively correlated with ALT levels. Before and after the recovery of AHB: ΔHBV DNA and ΔALT, Δ NK/LY (%) were positively correlated; ΔALT and ΔNKp46^highNK/NK(%), ΔNKp46MFI, ΔIFNAR2MFI were positively correlated. Conclusions In CHB immune active phase, the activity of peripheral blood NK cells was too weak to remove the virus, but NK cells play an important role in eliminating the viruses and mediating liver tissue inflammation in AHB.

Objective: To explore the persistent viral response rate (SVR) in patients with refractory chronic hepatitis C after interferon (IFN) (peginterferon 360 μg qw) and ribavirin (PR) therapy failure. The SVR of patients with refractory chronic hepatitis C was improved by PR combined with direct antiviral agents (DAA) and proper extension of the course of therapy was applied. Methods: Seventeen cases of refractory chronic hepatitis C after IFN(peginterferon 360 μg qw) and ribavirin therapy failure were given PR combined with DAA treatment. The side effects were observed and corresponding adjustments were made on drug dosage, and SVR was recorded. Results: The 17 cases completed the whole course of treatment with PR combined with DAA for 24 weeks. All the 17 patients obtained rapid viralogical response (RVR) and SVR. After treatment, the SVR rate was 100% in patients including those with virologic relapse, retreated or previously non-responsive patients with refractory chronic hepatitis C. The adverse reaction of PR combined with DAA 24 weeks was generally mild. Conclusions The use of PR combined with DAA re-treatment in patients with refractory chronic hepatitis C can achieve SVR and shorten the treatment time. PR combined with DAA re-therapy is one of effective treatments to improve the rate of sustained viral response in patients with refractory chronic hepatitis C.

Objective: To investigate the change of hepatitis B surface antibody (HBsAb) titer and its long-term protection and infection rates between 1 and 3-year-old children whose mothers were chronic hepatitis B pregnant woman with HBeAg positive and high viral load after successful blocking of mother-to-child transmission. Methods: One-year-old children whose mothers were hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive, with HBV DNA≥10⁶IU/ml were enrolled, then were followed up till 3 years old, and tested the five serological markers of hepatitis B and biochemical parameters at the age of one and three years respectively, and analyzed HBsAb titer, positive rate, negative rate and infection rate of 1 to 3-year-old children without enhanced vaccination; meanwhile, data of HBsAb titers at the age of 7 months were collected HBsAb titer, positive rate, and negative rate were analyzed. Results: Totally 264 1-year-old children were enrolled into the study, including 178 children without enhanced vaccination between seven months and 1 year of age, and 114 children without enhanced vaccination between 1 year and 3 years of age. Our result showed that there were no infected children at the age between 1 and 3 years. HBsAb titer decreased from 7 months to 1 year old and dropped from 1 000 IU/L to 509.43 IU/L (P<0.05), and the antibody was still protective. From 1 year to 3 years old, HBsAb titer dropped from 466.72 IU/L to 67.3 IU/L (P< 0.05); at the age of 3 years, 60.52 % children were either weakly positive or negative, but still protective, but significantly less than those who had the reinforced vaccination. As a result , the children without the enhanced vaccination between 1 and 3 years of age were still at high risk. Conclusions If the antibody was protective at 7 months, children were not easily infected between 1 year and 3 years of age. At the age of 3, the antibody dropped to low or no responsive levels, and the children were still at high risk. It is necessary to take protective measures and supplement the vaccine.

Objective: To observe the changes of peripheral blood picture of CHB with Peg-IFN, and explored the relationship between the changes and decline of HBV DNA, clearance of HBsAg. Methods: Patients with CHB treated with Peg-IFN α-2 a in the Second Division of Liver Disease in Beijing Ditan Hospital were monitored for blood routine examination and Liver function, kidney function, thyroid function of baseline and weeks 2, 4, 8, 12, 24, 36, 48, and weeks 12, 24, and 48 after the end of treatment for chronic hepatitis B, and HBV DNA, HBsAg. Results: The decrease of peripheral blood cells began to occur at week 2 of treatment. For CHB with HBeAg negative patients, white blood cells, lymphocyte, neutrophils, hemoglobin and platelets significantly decreased at 2 weeks, while a minimum value occurred at 48 weeks. The recovery was obvious at the end of treatment (48 weeks), and reached pre-treatment levels at 48 weeks after the end of treatment. For CHB with HBeAg positive patients, white blood cells, neutrophils, hemoglobin and platelets significantly decreased at 2 weeks, while a minimum value was found at 36-48 weeks. The recovery was obvious at the end of treatment (48 weeks), and reached pre-treatment levels at 48weeks after the end of treatment. For patients with CHB, hemoglobin declined by more than13.64% at 36th week, which means that the patient would have a predictive significance for decrease of HBV DNA, and drops of more than 0.33% at 2nd week means that the patient would have a predictive significance for clearance of HBsAg. Conclusions During the treatment with interferon, the variation regularity of blood picture for predicting result have a certain effect, which may help predict and monitor the change of blood picture in clinical work.

Objective: To investigate the differences in function of plasmacytoid dendritic cells (pDC) and CD4⁺ T helper cells (CD4⁺ Th cells) between acute hepatitis B (AHB) and chronic hepatitis B (CHB). Methods: In this study, patients with AHB and those with CHB in immune active (IA) phase were enrolled. The frequencies of pDC, CD86⁺ pDC, CD4⁺ T cells and their subsets, surface functional molecules were detected respectively among patients with chronic HBV infection in IA phase, patients with AHB, those recovered from AHB. Meanwhile, their correlations with ALT, HBV DNA and HBV markers were analyzed. Results: The ALT level in AHB was significantly higher than that in IA, and inflammation was more obvious in AHB. Between IA and AHB, CD86⁺ pDC frequency and the mean fluorescence intensity of functional molecule CD86 (CD86MFI) were higher in IA than those in AHB, but the frequency of CD4⁺ T cells in AHB was higher than that in IA. For patients who got over AHB, the frequency of CD86⁺ pDC increased; Th1 were on the rise, while the frequencies of CD4⁺ T and Th2 decreased after the recovery of AHB, and Th2 / Th1 ratio decreased..In AHB, HBVDNA loads were positively correlated with ALT levels and Th2 frequencies. Conclusions In CHB immune active phase, CD86⁺ pDC with stimulating function played an important role, but the cellular immune response of CD4⁺ T cells decreased. In AHB inflammatory stage, CD4⁺ T cells played a strong cellular immune response, which result ed in viral clearance. Th2 cells regulation of CD4⁺ T cells played a dominant role, which was involved in the inflammatory response, and the cytotoxic role of Th1 cells during the recovery period was dominant, playing a strong cellular immune response, then the virus were completely eliminated.