Objective To investigate the mid- to long-term follow-up results of ascending aorta (AAO)-descending thoracic aorta (DTA) bypass grafting via median sternotomy incision for the treatment of complex aortic arch coarctation. Methods A retrospective analysis was conducted on the clinical data of patients with complex aortic arch coarctation who underwent AAO-DTA bypass grafting via median sternotomy incision at the First Hospital of Tsinghua University from August 2004 to May 2017. Results A total of 7 patients were enrolled, including 4 males and 3 females, aged (13.3±4.6) years, and weighted (40.2±12.2) kg. Six (85.7%) patients had concomitant upper limb hypertension. Four patients were aortic arch coarctation combined with intracardiac malformations, two were post-operative restenosis, and 1 was post-operative restenosis combined with intracardiac malformation. All patients underwent surgery under cardiopulmonary bypass. There were no perioperative deaths or major complications. The pre-operative upper-lower limb pressure difference was (39.3±19.2) mm Hg, which decreased to (2.9±2.7) mm Hg post-operatively (P<0.01). The follow-up period was (14.9±5.9) years. There were no long-term deaths or artificial graft-related complications. Except for one patient who still had mild hypertension, the blood pressure of the remaining patients returned to normal. Conclusion AAO-DTA bypass grafting via median sternotomy incision for the treatment of complex aortic arch coarctation can effectively reduce upper limb blood pressure and the upper-lower limb arterial pressure difference, has fewer complications, and demonstrates satisfactory mid- to long-term efficacy.

Objective To study the correlation between red blood cell distribution width(RDW)and intradialytic hypotension(IDH)as well as arteriovenous fistula thrombosis.Methods A total of 110 patients who received hemodialysis treatment at the Blood Purification Center of Beijing Aerospace General Hospital from January 1,2021,to June 1,2022,were selected as the study subjects.According to whether intradialytic hypotension(IDH)occurred,the patients were divided into the IDH group(n=40)and the non-IDH group(n=70).The occurrences of arteriovenous fistula thrombosis during dialysis,baseline data,laboratory indica-tors,and IDH event records of the two groups were recorded to analyze the relationship between RDW and IDH as well as arteriovenous fistula thrombosis.Results The average age of the IDH group was(66.05±12.42)years,higher than that of the non-IDH group at(50.96±14.50)years(P<0.05).The RDW in the IDH group was 16.24%±1.36%,higher than that in the non-IDH group at 14.17%±1.04%(P<0.05).Be-fore IDH correction,RDW levels increased progressively from the mild,moderate,to severe hypotension groups,with statistically significant differences between groups(P<0.05);12 weeks after IDH correction,there were no statistically significant differences in RDW levels among the groups(P>0.05).Logistic regres-sion analysis showed that RDW and IDH events were independent risk factors for arteriovenous fistula throm-bosis(HR>1,P<0.05).The AUC for RDW in predicting IDH events was 0.880(95%CI:0.816 to 0.944).Con-clusion Patients with higher RDW levels have a higher probability of developing IDH,and RDW and IDH events are independent risk factors for arteriovenous fistula thrombosis.

Objective    To investigate the clinical efficacy of minimally invasive Ivor-Lewis esophagectomy (MIILE) with reverse-puncture anastomosis. Methods    Clinical data of the patients with lower esophageal carcinoma who underwent MIILE with reverse-puncture anastomosis in our department from May 2015 to December 2020 were collected. Modified MIILE consisted of several key steps: (1) pylorus fully dissociated; (2) making gastric tube under laparoscope; (3) dissection of esophagus and thoracic lymph nodes under artificial pneumothorax with single-lumen endotracheal tube intubation in semi-prone position; (4) left lung ventilation with bronchial blocker; (5) intrathoracic anastomosis with reverse-puncture anastomosis technique. Results     Finally 248 patients were collected, including 206 males and 42 females, with a mean age of 63.3±7.4 years. All 248 patients underwent MIILE with reverse-puncture anastomosis successfully. The mean operation time was 176±35 min and estimated blood loss was 110±70 mL. The mean number of lymph nodes harvested from each patient was 24±8. The rate of lymph node metastasis was 43.1% (107/248). The pulmonary complication rate was 13.7% (34/248), including 6 patients of acute respiratory distress syndrome. Among the 6 patients, 2 patients needed endotracheal intubation-assisted respiration. Postoperative hemorrhage was observed in 5 patients and 2 of them needed hemostasis under thoracoscopy. Thoracoscopic thoracic duct ligation was performed in 1 patient due to the type Ⅲ chylothorax. TypeⅡ anastomotic leakage was found in 3 patients and 1 of them died of acute respiratory distress syndrome. One patient of delayed broncho-gastric fistula was cured after secondary operation. Ten patients with type Ⅰ recurrent laryngeal nerve injury were cured after conservative treatment. All patients were followe up for at least 16 months. The median follow-up time was 44 months. The 3-year survival rate was 71.8%, and the 5-year survival rate was 57.8%. Conclusion    The optimized MIILE with reverse-puncture anastomosis for the treatment of lower esophageal cancer is safe and feasible, and the long-term survival is satisfactory.

Objective:To explore the impact of baseline remnant cholesterol levels at a single time point and cumulative remnant cholesterol exposure on the progression trajectories of arterial stiffness.Methods:This prospective cohort study included 2 401 eligible participants from the Beijing Health Management Cohort who consecutively attended health examinations in 2010-2011, 2012-2013, and 2014-2015. The remnant cholesterol value measured in 2014-2015 served as the baseline remnant cholesterol level at a single time point. The cumulative exposure indices were calculated based on remnant cholesterol values from three health examinations from 2010 to 2015, including cumulative exposure, cumulative exposure burden, and duration of high remnant cholesterol exposure. Arterial stiffness was assessed by brachial-ankle pulse wave velocity (baPWV). The follow-up continued until December 31, 2019, with annual check-ups. During the follow-up period, a group-based trajectory model was employed to construct the progression trajectories of baPWV. The associations between the baseline remnant cholesterol level, cumulative exposure indices of remnant cholesterol and baPWV trajectories were examined using ordinal logistic regression models, adjusting for traditional cardiovascular risk factors and low-density lipoprotein cholesterol (LDL-C) levels.Results:The age of the 2 401 participants was 61 (54, 69) years, with 1 801 (75.01%) being male. The group-based trajectory model indicated that the best-fit model categorized the participants into three subgroups: low-rising group (1 036 individuals, 43.15%), moderate-rising group (1 137 individuals, 47.36%), and high-rising group (228 individuals, 9.50%). After adjusting for traditional cardiovascular risk factors, baseline remnant cholesterol levels at a single point ( OR=1.170, 95% CI: 1.074-1.274), cumulative remnant cholesterol exposure ( OR=1.194, 95% CI: 1.096-1.303), cumulative remnant cholesterol exposure burden ( OR=1.270, 95% CI: 1.071-1.507), and high-remnant cholesterol exposure duration (6 years: OR=1.351, 95% CI: 1.077-1.695) were significantly associated with the risk of developing a poor baPWV progression trajectory. These results remained significant after adjusting for cumulative average LDL-C levels. The association between baseline remnant cholesterol levels and baPWV progression became insignificant after adjusting for cumulative remnant cholesterol levels ( OR=1.053, 95% CI: 0.923-1.197), while the association between cumulative remnant cholesterol exposure and baPWV progression remained significant after adjusting for baseline remnant cholesterol levels ( OR=1.145, 95% CI: 1.008-1.305). Conclusions:Higher levels of baseline remnant cholesterol and cumulative remnant cholesterol are independent risk factors for the progression of arterial stiffness. These associations remain significant even after adjusting for traditional cardiovascular risk factors and LDL-C levels. Furthermore, the effect of cumulative remnant cholesterol levels on the progression of arterial stiffness was stronger than the effect of baseline remnant cholesterol levels.

Background Evidence about the association between air pollution and carotid intima-media thickness (CIMT) is inconsistent, and limited studies have explored the relationship between gaseous pollutants and CIMT. Additionally, personal activity patterns and infiltrated ambient pollution are not comprehensively considered to estimate individual exposure to air pollutants. Objective To investigate the relationship between long-term time-weighted individual exposure to ambient pollutants [fine particulate matter (PM_2.5), inhalable particulate matter (PM₁₀), nitrogen dioxide (NO₂), sulfur dioxide (SO₂), ozone (O₃), and carbon monoxide (CO)] and the progression of CIMT. Methods This study was performed among 554 participants in the Beijing Health Management Cohort who were free of atherosclerotic lesions on carotid artery at baseline. Daily concentrations of pollutants were predicted at both residential and work addresses based on land-use regression model. With additional consideration of personal indoor and outdoor activity patterns at both addresses and exposure to ambient pollutants from traffic transportation, individual time-weighted concentration was calculated. Indoor exposure was estimated by infiltrated ambient pollutants (based on infiltration factors and land-use regression model). Personal activity patterns included type, time, location, and frequency. Exposure to ambient pollutants from different traffic transportations was estimated by the average outdoor pollutant concentrations at both residential and work addresses combined within filtration factors and time spent on commuting. Multiple linear regression was conducted to assess the association of time-weighted individual pollutant exposure and the central position of CIMT progression. Quantile regression was applied to explore the relationship between time-weighted individual pollutant exposure and the progression of CIMT on different percentiles. Results The median value of CIMT progression was 369.49 μm·year⁻¹. PM_2.5, PM₁₀, SO₂, and O₃ were associated with CIMT progression in the multiple linear regression model. The largest effect sizes of PM_2.5, PM₁₀, and SO₂ were obtained for one-year exposure (regression coefficient: 66.910, 64.077, and 191.070, respectively), and two-year exposure for O₃ (regression coefficient: 62.197). The results of quantile regression demonstrated different effect sizes for pollutants among different percentiles on CIMT progression. Significant associations between CIMT progression and PM_2.5 from P₃₀ to P₅₀, CO from P₁₀ to P₄₀, and PM₁₀ from P₃₀ to P₆₀ were observed. Two-year and three-year exposures to NO₂ (P₁₀, P₂₀ and P₄₀) were also associated with CIMT progression. The association between SO₂ and the progression of CIMT was proved on all percentiles, and larger effect sizes of one-year and two-year exposures to SO₂ (except P₉₀) were demonstrated with increasing percentiles. The upward trend for the coefficients was clearly presented from P₅₀ to P₈₀. Specifically, the coefficient of two-year exposure to SO₂ ranged from 136.583 (P₅₀) to 277.330 (P₈₀). No statistically significant association was observed between O₃ and CIMT progression on any percentile (P>0.05), and the results were inconsistent with those of the multiple linear regression. Conclusion Individual time-weighted exposures to PM_2.5, PM₁₀, SO₂, NO₂, and CO have the potential to promote the progression of CIMT, and the adverse effect of ambient pollution on atherosclerotic lesion is identified.

Humans ; Asthma/drug therapy* ; Biological Therapy

The global COVID-19 coronavirus pandemic has infected over 109 million people, leading to over 2 million deaths up to date and still lacking of effective drugs for patient treatment. Here, we screened about 1.8 million small molecules against the main protease (M^pro) and papain like protease (PL^pro), two major proteases in severe acute respiratory syndrome-coronavirus 2 genome, and identified 1851M^pro inhibitors and 205 PL^pro inhibitors with low nmol/l activity of the best hits. Among these inhibitors, eight small molecules showed dual inhibition effects on both M^pro and PL^pro, exhibiting potential as better candidates for COVID-19 treatment. The best inhibitors of each protease were tested in antiviral assay, with over 40% of M^pro inhibitors and over 20% of PL^pro inhibitors showing high potency in viral inhibition with low cytotoxicity. The X-ray crystal structure of SARS-CoV-2 M^pro in complex with its potent inhibitor 4a was determined at 1.8 Å resolution. Together with docking assays, our results provide a comprehensive resource for future research on anti-SARS-CoV-2 drug development.
Humans ; Antiviral Agents/chemistry* ; COVID-19 ; COVID-19 Drug Treatment ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Protease Inhibitors/chemistry* ; SARS-CoV-2/enzymology* ; Viral Nonstructural Proteins

Background Few studies have investigated the association between air pollution and arterial stiffness in Chinese population, and the findings are inconsistent. The problem of multicollinearity exists when modeling multiple air pollutants simultaneously. Objective To investigate potential association between air quality index (AQI) and population brachial-ankle pulse wave velocity (baPWV) in Beijing. Methods This study retrieved medical examination data of 2971 participants from the Beijing Health Management Cohort, who were under 60 years old and not yet retired, from January 1, 2015 to December 31, 2019. The most recent medical examination data available were utilized for this analysis. AQI data from 35 air pollution monitoring sites in Beijing and meteorological data (including atmospheric pressure, air temperature, wind speed, and relative humidity) from 16 meteorological monitoring stations from January 1, 2014 to December 31, 2019 were collected. An average AQI exposure level for 365 d before the date of physical examination for each participant was computed using inverse distance weighting. Multiple linear regression analysis was employed to investigate the relationship between AQI and baPWV in Beijing, after adjusting for confounding variables including age, gender, body mass index, mean arterial pressure, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, fasting blood glucose, atmospheric pressure, temperature, wind speed, relative humidity, medication history of diabetes, medication history of hypertension, cardiovascular disease, education, smoking status, drinking status, and physical activity intensity. Subgroup analysis was performed by age, sex, presence of diabetes, and presence of hypertension. Results AQI demonstrated an overall decreasing trend during the study period and was lower in the northern regions and higher in the southern regions of Beijing. After adjusting the confounding variables, each 10 unit increase in AQI was associated with 6.18 (95%CI: 1.25, 11.10) cm·s⁻¹ increase in baPWV in all participants, 8.05 (95%CI: 2.32, 13.79) cm·s⁻¹ increase in the participants <50 years, 15.82 (95%CI: 8.33, 23.31) cm·s⁻¹ increase in the female group, 10.10 (95%CI: 4.66, 15.55) cm·s⁻¹ increase in the participants without diabetes, and 9.41 (95%CI: 4.21, 14.62) cm·s⁻¹ increase in the participants without hypertension. However, there was no statistically significant association observed between AQI and baPWV in the age group ≥50 years, the male group, the diabetic group, and the hypertensive group (P>0.05). Conclusion An increase in long-term AQI levels is associated with an elevation in the degree of arterial stiffness. Individuals under 50 years old, females, without hypertension or diabetes are susceptible populations to arterial stiffness when being exposed to air pollution. Improving air quality may contribute to prevent arterial stiffness.

Objective:To explore the clinical values of PICaSSO histological remission index (PHRI) in evaluation of ulcerative colitis (UC) .Methods:A cross-sectional study was conducted. Clinical data of UC patients diagnosed in the Department of Gastroenterology of Peking Union Medical College Hospital from June 2018 to October 2019 were collected, including demography characteristics, Montreal classification, serological indicatiors, Mayo score and Mayo endoscopic score (MES), ulcerative colitis endoscopic index of severity (UCEIS), Robarts histopathology index (RHI) and PHRI. Mayo score was used to evaluate the clinical activity of the disease. MES = 0 or UCEIS ≤1 point was defined as endoscopic remission (ER), and RHI ≤3 points or PHRI<1 point as histological remission (HR). Spearman correlation analysis was used to evaluate the correlations of PHRI with serological indicators, endoscopic scores, and RHI. Kappa test was used to analyze the consistency between scores. Results:A total of 60 UC patients (31 men, 29 women; mean age, 40.5±13.7 years) were enrolled. The lesion located in the rectum (E1) in 11 patients, left colon (E2) in 14 and extensive colon (E3) in 35. According to the Mayo score, clinical remission occurred in 20 patients, mild activity in 20, moderate activity in 12 and severe activity in 8. A total of 15 patients with PHRI<1 point were assigned to PHRI-HR group, while 45 patients with PHRI≥1 point were assigned to non-HR group. Spearman correlation analysis showed that there was a negative correlation between PHRI and serum albumin level ( r s = -0.327, P = 0.011) ; there were strong positive correlations of PHRI with MES and UCEIS scores ( r s = 0.698, 0.735, both P<0.001) and there was an extremely strong positive correlation of PHRI with RHI ( r s = 0.868, P<0.001). The difference in serum albumin levels between the PHRI-HR group and the non-HR group was statistically significant ( Z = -2.364, P = 0.018). Kappa consistency test showed that the results of MES-ER and PHRI-HR were moderately consistent ( κ = 0.535, P<0.001), and the specificity and accuracy of PHRI-HR judged by MES-ER were 91.1% and 83.3%, respectively. The results of UCEIS-ER and PHRI-HR were also moderately consistent ( κ = 0.542, P<0.001), and the specificity and accuracy of PHRI-HR judged by UCEIS-ER were 90.5% and 81.7%, respectively. The results of RHI-HR and PHRI-HR were strongly consistent ( κ = 0.644, P<0.001), and the specificity and accuracy of PHRI-HR judged by RHI-HR were 73.3% and 86.7%, respectively. Conclusion:PHRI is strongly correlated with RHI and endoscopic scores and may be a potential optimal histopathological score in evaluation of UC disease activities.

A case of 22 year-old man with Cronkhite-Canada syndrome who responded to adequate glucocorticoids and azathioprine was reported. The pathogenesis, diagnosis, treatment and prognosis of Cronkhite-Canada syndrome were also discussed in details in order to provide clinical experience for clinicians.