[Efficacy of alcohol septal ablation in mildly symptomatic or severely symptomatic patients with hypertrophic obstructive cardiomyopathy].

Objective: To compare the prognosis of mildly or severely symptomatic patients with obstructive hypertrophic cardiomyopathy (OHCM) who underwent alcohol septal ablation (ASA). Methods: This retrospective study cohort consisted of patients with OHCM who received ASA treatment in Beijing Anzhen Hospital, Capital Medical University from March 2001 to August 2021. These patients were divided into mildly and severely symptomatic groups according to the severity of clinical symptoms. Long-term follow-up was conducted, and the following data were collected: duration of follow-up, postoperatire treatment, New York Heart Association (NYHA) classification, arrhythmia events and pacemaker implantation, echocardiographic parameters, and cause of death. Overall survival and survival free from OHCM-related death were observed, and the improvement of clinical symptoms and resting left ventricular outflow tract gradient (LVOTG) and the incidence of new-onset atrial fibrillation were evaluated. The Kaplan-Meier method and log-rank test were used to determine and compare the cumulative survival rates of the different groups. Cox regression analysis models were used to determine predictors of clinical events. Results: A total of 189 OHCM patients were included in this study, including 68 in the mildly symptomatic group and 121 in the severely symptomatic group. The median follow-up of the study was 6.0 (2.7, 10.6) years. There was no statistical difference in overall survival between the mildly symptomatic group (5-year and 10-year overall survival were 97.0% and 94.4%, respectively) and the severely symptomatic group (5-year and 10-year overall survival were 94.2% and 83.9%, respectively, P=0.405); there was also no statistical difference in survival free from OHCM-related death between the mildly symptomatic group (5-year and 10-year survival free from HCM-related death were 97.0% and 94.4%, respectively) and the severely symptomatic group (5-year and 10-year survival free from HCM-related death were 95.2% and 92.6%, respectively, P=0.846). In the mildly symptomatic group, NYHA classification was improved after ASA (P<0.001), among which 37 patients (54.4%) were in NYHA class Ⅰ, and the resting left ventricular outflow tract gradient (LVOTG) decreased from 67.6 (42.7, 90.1) mmHg (1 mmHg=0.133 kPa) to 24.4 (11.7, 35.6) mmHg (P<0.001). In severely symptomatic group, NYHA classification was also improved post ASA (P<0.001), among which 96 patients (79.3%) improved by at least one NYHA classification, and the resting LVOTG decreased from 69.6 (38.4, 96.1) mmHg to 19.0 (10.6, 39.8) mmHg (P<0.001). The incidence of new-onset atrial fibrillation was similar between the mildly and severely symptomatic groups (10.2% vs. 13.3%, P=0.565). Cox multivariate regression analysis showed that age was an independent predictor of all-cause mortality in OHCM patients post ASA (HR=1.068, 95%CI 1.002-1.139, P=0.042). Conclusions: Among patients with OHCM treated with ASA, overall survival and survival free from HCM-related death were similar between mildly symptomatic group and severely symptomatic group. ASA therapy can effectively relieve resting LVOTG and improve clinical symptoms in mildly or severely symptomatic patients with OHCM. Age was an independent predictor of all-cause mortality in OHCM patients post ASA.

[Therapeutic effects of alcohol septal ablation in mildly symptomatic patients with hypertrophic obstructive cardiomyopathy].

Objective: To observe the therapeutic effects of alcohol septal ablation (ASA) in mildly symptomatic patients (NYHA class Ⅱ) with hypertrophic obstructive cardiomyopathy(HOCM). Methods: This retrospective study included 150 mildly symptomatic patients with HOCM hospitalized in Beijing Anzhen Hospital affiliated to Capital Medical University from March 2001 to December 2017, consisting of medical therapy group (n=102) and ASA group (n=48). Baseline clinical data were collected, patients were followed up to a mean of 6.0 (3.5, 8.1) years. Overall and HCM-related mortality events (including chronic heart failure, atrial fibrillation related stroke, sudden cardiac death) were observed in the two groups. Moreover, the improvement of NYHA function classification and left ventricular outflow tract gradient (LVOTG) were also evaluated. Survival analysis was performed by Kaplan-Meier method. Results: Age of this cohort was (52.9±14.5)years, 92 cases(61.3%) were male. In the follow-up, LVOTG was reduced from (85.8±35.4)mmHg (1 mmHg=0.133 kPa) to (27.7±19.8)mmHg (P<0.001) in the ASA group, and from (66.3±35.0)mmHg to (56.5±27.7)mmHg in medical therapy group(P<0.01). At the last clinical follow-up, there were 32 patients (66.7%) whose LVOTG were<30 mmHg, septal thickness decreased from (20.3±3.8)mm to (16.1±3.4)mm (P<0.001), NYHA classification was also remarkably improved (P<0.001). New-onset atrial fibrillation tended to be lower in the ASA group compared to medical therapy group (9.3%(4/43) vs. 20.8%(20/96),P=0.096). Eleven patients (10.8%) in the medical therapy group and 2 patients (4.2%) in the ASA group died during the follow-up. One patient received pacemaker during the peri-procedural period, 1 patient was implanted with two-chamber pacemaker due to Ⅲ° atrioventricular block at 10 years after operation in the ASA group. Survival free of all-cause mortality of ASA group at 5 and 10 years was 97.9% and 97.9%, respectively, which was comparable to the medical therapy group (P=0.231). Survival free of HCM-related mortality was similar between the two groups (P=0.397). Conclusions: Compared with medical therapy in mildly symptomatic patients with HOCM, long-term survival rate is similar after ASA. Meanwhile, ASA can remarkably reduce LVOTG and improve the clinical status of the patients. Therefore, ASA may be used as an alternative therapy for mildly symptomatic HOCM patients.

[Epidemiology and influencing factors of human immunodeficiency virus and hepatitis B virus co-infected patients in Beijing].

Objective: To analyze the epidemiological characteristics of human immunodeficiency virus (HIV) and hepatitis B virus (HBV) co-infected patients in Beijing and investigate the associated factors. Methods: The clinical data of patients with HIV infection who were treated in HIV/AIDS designated hospitals (Peking Union Medical College Hospital, Beijing Ditan Hospital and Beijing Youan Hospital) were retrospectively analyzed. Results: A total of 11 572 patients were finally included in the study, among whom 532 patients (4.6%) were co-infected with HIV and HBV. Most of the co-infected patients were young male adults (28~48 years old), accounting for 85.9%. The main transmission route was homosexual behavior (74.8%). There were 87.4% co-infected patients treated with two anti-HBV drugs, including lamivudine (3TC) and tenofovir (TDF). From 2013 to 2018, the annual prevalence of HIV and HBV co-infection decreased gradually, with the rate of 6.37%, 4.55%, 3.92%, 4.68%, 4.24% and 2.74%, respectively. In our study, The main influencing factors of HIV and HBV co-infection were age older than 28 years old versus<28 years old (OR=2.807, 95%CI 1.241-6.345) and marriage status (married versus unmarried, OR=1.259, 95%CI 1.004-1.579). Conclusions: The proportion of HBV infection in HIV-infected patients is 4.60% (532) in our cohort. From 2013 to 2018, the prevalence of HIV and HBV co-infection in Beijing shows a decreasing trend. The risk of co-infection is higher in married young adults (28~48 years old).

Demographic and clinical factors associated with immune reconstitution in HIV/HBV co-infected and HIV mono-infected patients: a retrospective cohort study.

OBJECTIVES: To describe the clinical characteristics and factors associated with CD4 T-cell count and CD4/CD8 ratio restoration in HIV mono-infected and HIV/HBV co-infected individuals, and to explore liver and renal functional changes in both groups. METHODS: A retrospective cohort study was performed including 356 HIV/HBV co-infected and 716 HIV mono-infected participants who initiated antiretroviral therapy (ART) during 2013-2017 in Beijing Youan Hospital, China. Demographic and clinical characteristics were compared between the two groups, using χ2 and Mann-Whitney non-parametric tests. Bivariate and multivariate Cox regression models were used to test their association. RESULTS: Baseline HIV viral load and ART regimen were found to be significantly associated with CD4 T-cell restoration among HIV-infected participants, whereas baseline HIV viral load was the only significant factor associated with CD4 T-cell restoration in HIV/HBV co-infected participants. The final model showed that baseline HIV viral load and ART regimen were significantly associated with CD4/CD8 ratio restoration among HIV-infected participants, while baseline HIV viral load was the significant factor. Liver and renal functions were similar at the endpoint (P > 0.05). CONCLUSIONS: Baseline HIV viral load count was found to be the key factor affecting immune restoration in both HIV and HIV/HBV individuals. Future multi-wave prospective studies are needed to clarify the potential biological mechanism.

[Efficacy comparison between conservative therapy and septal ablation in patients with hypertrophic obstructive cardiomyopathy].

Objective: To compare the effects of septal ablation (SA) versus conservative medication (CM) on the hemodynamic, clinical status and survival in patients with hypertrophic obstructive cardiomyopathy (HOCM). Methods: This retrospective study included 350 consecutive patients with HOCM (mean age (51.3±13.5) years old) hospitalized in Anzhen Hospital between September 2002 to September 2014. The patients were followed up to 14 years and the follow up rate was 99.4% (348/350). Overall and cardiac-related mortalities were compared between SA group (n=184) and CM group (n=184). Moreover, SA related cardiac function and hemodynamics improvement were also evaluated, predictors for clinical events were evaluated by Cox regression analysis and Kaplan-Meier survival analysis was used to compare the total mortality between the two groups. The log-rank test was used to compare the survival curve differences between the two groups. Results: The median follow-up period was 4 years (1-14 years). The annual mortalities of SA and CM were 2.4% and 0.6% respectively (P<0.001) and cumulative sudden cardiac death (SCD)rates were 3.61% (6/166) and 0.54% (1/184) respectively (P=0.031). Multivariate regression analysis demonstrated that the age was the most important independent predictor for overall mortality(HR=1.259, 95%CI 1.101-1.438, P=0.001). In addition, left ventricular outflow tract (LVOT) gradient was significantly reduced post SA (peak velocity of LVOT: baseline (4.23±1.05) m/s, post SA: (1.83±0.79) m/s, P<0. 01) and heart function was also significantly improved post SA (NYHA at baseline: 2.97±0.29, post SA: 1.74±0.53, P<0.001). Conclusion: SA could significantly improve the hemodynamics and clinical status in drug-resistant patients with HOCM. In comparison to patients received CM, overall survival rate was significantly higher in SA group without extra risk of SCD.

Asparagine synthetase is an independent predictor of surgical survival and a potential therapeutic target in hepatocellular carcinoma.

BACKGROUND: Asparagine synthetase (ASNS) is associated with drug resistance in leukaemia, and the function of this enzyme in the context of hepatocellular carcinoma (HCC) is not clear. In this study, the relationship between ASNS expression and clinical outcomes after surgical resection was investigated, and the therapeutic value of ASNS was also evaluated. METHODS: The expression of ASNS was evaluated in HCC samples by real-time PCR and immunohistochemistry assays. The correlation between ASNS expression and clinicopathological features was investigated. Potential clinicopathological prognostic factors were examined by univariate and multivariate survival analysis. Asparagine synthetase was overexpressed and knocked down in HCC cell lines to assess the influence of the enzyme on cell proliferation, migration and tumourigenicity. L-asparaginase was used to treat HCC cells with high or low levels of ASNS in vitro and in vivo to examine the therapeutic efficacy. RESULTS: The expression of ASNS was higher in HCC tumour tissues and was closely correlated with the serum AFP level, tumour size, microscopic vascular invasion, tumour encapsulation, TNM stage and BCLC stage. Patients with low ASNS expression levels had a poor prognosis with respect to overall survival (OS). The multivariate survival analysis indicated that ASNS is an independent prognostic factor for OS. Furthermore, functional studies demonstrated that ASNS significantly inhibits the proliferation, migration and tumourigenicity of HCC cells. The knockdown of ASNS markedly increased sensitivity to L-asparaginase, indicating that cells with different ASNS protein levels have different sensitivities to L-asparaginase. CONCLUSION: The expression of ASNS is an independent factor affecting the survival of HCC patients, and low ASNS expression in HCC was correlated with worse surgical outcomes. The ASNS may be a promising therapeutic target for the treatment of HCC.

[Scientific and technological innovation and achievement transformation promote the medical development].

With the worldwide adoption of minimally invasive surgery, innovation again becomes the theme. In the past hundred years, molecular biology technology, minimally invasive surgery technology, pharmaceutical research and therapies have been constantly innovated to promote the development of medicine. As the subject of medical innovation, the innovative idea from medical staff is also very important. For surgeons, the invention and improvement of a new operation or surgical instrument directly depends on curiosity and exploration. Whether a novel idea or technology can be transformed and used in clinical practice depends on its commercial prospects and the adjustment of macro health policies. The protection of intellectual property and appropriate distribution of interests are the key to ensure sustainable innovation. We should put scientific and technological innovation and achievement transformation in the important position of the "healthy China" strategy, take scientific and technological innovation as the basis and achievements transformation as the means, promote the development of China's health protection, implement the healthy China strategy, and make our own contribution to provide people with all-round health services.

Changes and effects of plasma arginine vasopressin in traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a common disease accompanied by chronic morbidity and mortality. The pathological mechanism and effective pharmacological treatments of TBI remain undetermined. It is suggested that AVP is involved in TBI. It is thus interesting to investigate the changes and effects of plasma AVP in clinical trials. METHODS: The serum concentrations of AVP, serum electrolytes, and serum osmolarity in a total of 23 TBI patients were dynamically monitored (on admission, Day 1, Day 3, and Day 5). Relationship between AVP and severity of brain injury and functional outcome were evaluated, respectively. RESULTS: The mean AVP serum concentrations in the TBI group were significantly higher than those recorded in the control (CTRL) group on intensive care unit (ICU) admission and Day 1 (p<0.05). On Day 3 and Day 5, the differences between those groups were not significant (p>0.05). The negative correlations were found between sodium and AVP (r=-0.35; p<0.05) and between osmolarity and AVP (r=-0.42; p<0.05). In poor outcome group, the mean AVP serum concentrations were significantly higher than in good outcome group and CTRL group (p<0.05). A statistically significant correlation was also found between AVP on ICU admission and the initial Glasgow Coma Scale (r=0.47; p<0.05). CONCLUSION: We suggest that AVP is involved in the pathophysiology process of secondary brain damage after TBI. It seems that AVP antagonist is a promising target for the treatment of TBI, while further studies should be carried out.

In vitro cell culture model for anti-cataract drug penetration studies.

Immortalized human corneal epithelial cells (HCECs) and human lens epithelial cells (HLECs) were cultured in vitro. Cells were observed under a phase-contrast microscope and the integrity of cell monolayers was assayed by transepithelial electrical resistance (TEER) determination. The permeability of disulfiram (DSF) through a HCECs monolayer was compared with that of DSF through an excised rabbit cornea. The permeability coefficients of DSF through a HCECs monolayer and excised rabbit cornea were 29.5 +/- 4.8 x 10(-6) cm/s and 34.7 +/- 5.2 x 10(-6) cm/s, respectively. Diethyldithiocarbamate (DDC) had high permeability through HLECs monolayer with a permeability coefficient of 44.6 +/- 7.1 x 10(-6) cm/s. The cytotoxicity of DDC against HLECs was investigated using the trypan blue exclusion test. For a DDC concentration of 5 mmol/l, more than 85% cells were viable. DH3a1 mRNA was expressed in cultured HLECs. The expression of aldehyde dehydrogenase 3a1 (ALDH3a1), which may be be responsible for DSF-DDC conversion, was detected using RT-PCR and agarose gels electrophoresis. These results demonstrate that the permeability of DSF can be detected and intra-ocular drug action may be predicted using the cultured HCEC and HLEC monolayers as model.

RMP promotes venous metastases of hepatocellular carcinoma through promoting IL-6 transcription.

Hepatocellular carcinoma (HCC) is believed to arise from tumor-initiating cells (T-ICs), which are responsible for tumor relapse and metastases. Portal vein tumor thrombus (PVTT) is raised from HCC and strongly correlated to a poor prognosis. However, the mechanism underling the formation of PVTT is largely unknown. Herein, we provide evidence that RNA polymerase II subunit 5 (RPB5)-mediating protein (RMP) was progressively upregulated in PVTT and overexpressed RMP appeared to increase T-ICs self-renewal. Moreover, RMP promoted metastases of PVTT cells and HCC cells in vitro and in vivo. Knockdown of RMP attenuated T-ICs self-renewal and reversed epithelial-mesenchymal transition (EMT) in HCC and PVTT cells. The neutralizing assays suggested that interleukin-6 (IL-6) had an indispensable role in RMP regulating metastases and self-renewal of HCC cells. Furthermore, the transcription of IL-6 was verified to be modulated by RMP via interaction with p65 and RPB5, through which expanding the T-IC/cancer stem cell populations, as well as inducing EMT was promoted. These results suggested that RMP may promote PVTT formation by promoting IL-6 transcription. Thus, RMP serves as a potent factor contributed to develop PVTT and a promising therapeutic target for HCC patients.

[Isolation and identification of two new saponins from Bupleurum smithii Wolff].

Two new saikosaponins of oleanane type were isolated from the roots of Bupleurum smithii Wolff, collected in Minhe County, Qinghai, namely saikosaponin k (VIb) and saikosaponin 1 (VIII). Their structures were elucidated on the basis of spectral analysis of UV, IR, 1HNMR, 13CNMR and FAB-MS. Saikosaponin k (VIb) was identified as 3 beta, 16 beta, 23,28-tetrahydroxyoleana-11,13(18)-dien-3-O-beta-D-xylopyranosyl-(1-->2)-beta- D-glucopyranosyl-(1-->3)-beta-D-fucopyranoside, and saikosaponin 1 (VIII) as 3 beta, 16 alpha, 23,28,30-pentahydroxyoleana-11,13(18)-dien-3-O-beta-D- glucopyranosyl-(1-->3)-beta-D-fucopyranoside, respectively.

Remangilones A-C, new cytotoxic triterpenes from Physena madagascariensis.

Three new 24,28-dinorolean-3-one derivatives, the remangilones A-C (1-3), were isolated from the dried leaves of Physena madagascariensis using a human mammary carcinoma cell line to guide the isolation. The structures of 1-3 were deduced primarily from NMR studies. Compounds 1 and 3, remangilones A and C, respectively, were found to be cytotoxic against two human breast cancer cell lines and induced apoptosis at concentrations of 2.3 microM.

Synthesis of (3'-5'),(2'-5')-linked di- and tri-adenylyl methylphosphonate analogs.

Stereoselectivity was found during the coupling reaction, to form 2',5'- and 3',5'-linked di- and triadenylyl methylphosphonate. The configuration of phosphorus was determined by 1HNMR NOE.