Objective To use a simple bedside technique to verify the pathophysiological mechanism of pulmonary hypertension (PH) in different races. Method The Valsalva maneuver (VM) was performed in patients referred to a specialty PH clinic. The blood pressure response of patients to VM was in different fashions. The blood pressure (BP) was measured by using cuff and stethoscope. When the cuff was inflated to 15 mmHg above the systolic pressure, sound could be heard by auscultation during VM and when the cuff was deflated the sound disappeared over 3 heart beats which was considered as abnormal BP response, and less than 3 heart beats defined as normal BP response. The right heart catheterization in patients with PH as a part of the standard evaluation. Results This study included 84 patients with a mean age of (63 ± 16) years. Those with abnormal BP response to VM had higher pulmonary artery wedge pressure (PAWP) [(22.5±6.6) vs. (11.9±4.3) mmHg, P ＜0.0001] and lower pulmonary vascular resistance [(5.8 ± 4.0) vs. (8.1 ± 4.6 ) WU, P = 0.01]. Blood pressure response to VM did not correlate with mean pulmonary artery (PA) pressure [(46.2 ± 9.9) vs. (43.4 ±10.4) mmHg, P =0.20] or cardiac index (both 2.4 ± 0.6 L/min/m2). The abnormal BP response to VM had high sensitivity (89.4%), specificity (86.1%) and accuracy (86.9%) for determining PAWP＞ 15 mmHg.Conclusions BP response to Valsalva maneuver provides important information about left heart filling pressures in patients with PH.

Objective To discuss the effectiveness of anterolateral thigh propeller flaps for treatment of inguinal skin and soft tissue defects.Methods From June,2009 to October,2014,12 patients with inguinal skin and soft tissue defects were treated with anterolateral thigh propeller flaps pedicled with perforator of descending branch of lateral circumflex femoral artery.Of them there were 8 males and 4 females,aged from 22 to 51 years.The left side was involved in 3 cases and right side 9 cases.Defects were caused by traffic accident injury in 5 cases,crash injury of heavy object in 7 cases.There were mere skin and soft tissue in 2 cases,combined with bone fractures,nerves,vessels and muscles injury in 10 cases.The area of defects ranged from 9.0 cm×5.0 cm to 22.0 cm×9.0 cm.During operation,anterolateral thigh propeller flaps ranging from 11.0 cm×7.0 cm to 24.0 cm×1 1.0 cm were used to repair the wounds.Results All flaps and skingrafts survived after operation and the wounds obtained primary healing.After 8-24 months follow-up,all flaps were characterized by soft texture,good color,and satisfactory appearance.According to the Britain's Medical Research Council at 8 months after operation,the sensation of the flaps were recovered to S2 ～ S3+,No obvious scar contracture and chromatosis were observed at donor site.Conclusion Anterolateral thigh propeller flaps pedicled with artery descending branch of lateral circumflex femoral perforator is an ideal choice for the reconstruction for inguinal skin and soft tissue defects.

Proton is formed after hydrogen atom loses an electron with a positive charge of particle (H+ ). After the proton is accelerated, it possesses significant advantages in terms of the distribution of physical dose compared with the photon. Currently, proton radiation has captivated extensive attention and has been actively applied in clinical practice. Nevertheless, due to the small amount of proton facilities and lack of clinical trials, the proton therapy, especially the radiobiological characteristics and biological effect of photon radiotherapy has been poorly understood. In this article, these issues were summarized as below.

Objective To investigate whether simple visual assessment of FVERVOT(the right ventricular outflow tract Doppler flow velocity envelop) graphs aids in hemodynamic differentiation. Method The hemodynamics, echocardiography, and clinical data of 88 patients with pulmonary hypertension (PH) were reviewed. The FVERVOTgraphs were categorized into normal pattern (no notch; NN), late systolic notch pattern (LSN) or mid-systolic notch pattern (MSN). Results The pulmonary vascular resistance (PVR) was highest in the MSN pattern (9.2±3.5 WU; P＜0. 001), in comparison with LSN (5,7 ±3. 1 WU) and NN (3.3±2.4 WU) patterns. The ratio of stroke volume to pulse pressure (compliance) also varied with different patterns of FVERVOr graph (MSN = 1.2 ± 0. 5; LSN = 1.7 ± 0.8; NN = 2.6 ± 1. 7, P = 0.001 and 0.04 respectively compared with NN). The specificity and sensitivity of MSN were 96% and 71%, respectively in case of a PVR ＞ 5 WU (PPV 98%). In the patients with PH, any notching pattern of FVERVOT graph was highly associated with PVR ＞ 3 WU (OR = 22.3, 95 % CI: 5.2 ～ 96.4), whereas the NN pattern predicted a PVR ≤3 WU and pulmonary artery wedge pressure (PAWP) ＞ 15 mmHg (OR =30.2, 95%CI: 6.3 ～ 144.9). Conclusions Visual inspection of the shape of the FVERVOT graphs provides insight into the hemodynamic status of patients with PH.

Objective To investigate the detection rate,clinical indications and pregnancy outcomes of pregnancies with prenatally diagnosed small supernumerary marker chromosome (sSMC) to provide a theoretical foundation for prenatal diagnosis and genetic counseling of sSMC.Methods This study retrospectively analyzed the clinical data of 20541 cases who underwent prenatal diagnosis at the Prenatal Diagnostic Center in the Department of Obstetrics and Gynecology in Peking University First Hospital from January 2007 to May 2018.The detection rate,diagnostic indications and pregnancy outcomes of the cases with sSMC were analyzed after cell culture and karyotyping.Array comparative genomic hybridization (aCGH) was used to analyze the origin of fetal abnormal chromosome in some cases.Results Prenatal diagnostic samples of 20486 cases were successfully cultured,among which 20 (sSMC) were detected giving an detection rate of 0.98‰,while the figures in samples obtained through chorionic villus sampling,amniocentesis and umbilical cord blood sampling were 2.20 ‰ (2/910),0.74 ‰ (14/18824) and 5.32 ‰ (4/752),respectively.Twelve cases of mosaic karyotype were also found.In gravidas for prenatal diagnosis indicated by maternal or paternal chromosomal abnormality,fetal structural anomalies on ultrasonography,adverse pregnant history,advanced maternal age and high risk of Down's syndrome,the detection rates of sSMC were 10.42 ‰ (1/96),2.65 ‰ (4/1507),1.89 ‰ (5/2 643),0.83‰ (8/9 624) and 0.49‰ (2/4013),respectively.Eleven cases were further analyzed with aCGH,four of which showed pathogenic copy number variants involving 2q11.1-q12.1,2p12-p11.1 and 2q11.1-q12.1,7q 11.21-q 11.23 and 15q11.1-q 13.3 dup1ications and terminated the pregnancies.Seven cases carried nonpathogenic marker chromosomes,of which one terminated the pregnancy,while the other six continued to fullterm with uneventful outcomes until follow-ups.Conclusions sSMC is hard to detect in prenatal diagnosis,but maternal or paternal chromosomal abnormalities,fetal structural anomalies on ultrasonography and adverse pregnancy and childbirth history are strong indications.Cytogenetics and molecular diagnosis combined can clarify the character,origin and pathogenicity of sSMC,and is of great clinical importance in prenatal genetic counseling and maternal decision making.

Objective: To investigate the value and safety of first-trimester chorionic villus sampling (CVS) in prenatal diagnosis. Methods: This study retrospectively analyzed the clinical data of 985 cases undergoing CVS and prenatal diagnosis with karyotyping and fluorescence in situ hybridization (FISH) in the Department of Obstetrics and Gynecology of Peking University First Hospital from January 2012 to December 2017. The success rate of cell culture, indications for prenatal diagnosis, karyotyping results, and complications of CVS were described. Results: Among the 985 cases, 970 (98.48%) underwent FISH and 893 (90.66%) received karyotyping, and 878 (89.14%) accepted both. After CVS, the success rate of cell culture was 96.64% (863/893). Abnormal ultrasonographic findings (42.64%, 420/985) were the most common indications for prenatal diagnosis. In this study, 181 cases of chromosomal abnormalities were detected, including numerical and structural abnormalities, accounting for 18.38% of all 985 cases. Those cases with abnormal ultrasonographic images had the highest detection rate of chromosomal abnormalities (31.90%, 134/420), followed by those with adverse pregnant history (11.83%, 20/169) and advanced maternal age (8.21%, 11/134). In addition, there was a discrepancy between karyotyping and FISH results, which might due to 16 cases of placental mosaicism and 13 cases of maternal cell contamination (MCC). Embryonic demises were reported in six cases (0.61%, 6/985), including four with chromosomal numerical abnormalities within four weeks after CVS. No other short- or long-term postoperative complications were found in the rest 979 cases (99.39%). Conclusions CVS in the first trimester is a safe and reliable invasive method for prenatal diagnosis, which can help to obtain an earlier diagnosis in a certain population such as those with abnormal ultrasonographic findings, thus improve the pertinence and efficiency of prenatal diagnosis. However, the potential influences of placental mosaicism and MCC on the diagnostic results should not be ignored.

Central nervous system (CNS) injuries, including stroke, traumatic brain injury, and spinal cord injury, are essential causes of death and long-term disability and are difficult to cure, mainly due to the limited neuron regeneration and the glial scar formation. Herein, we apply extracellular vesicles (EVs) secreted by M2 microglia to improve the differentiation of neural stem cells (NSCs) at the injured site, and simultaneously modify them with the injured vascular targeting peptide (DA7R) and the stem cell recruiting factor (SDF-1) on their surface via copper-free click chemistry to recruit NSCs, inducing their neuronal differentiation, and serving as the nanocarriers at the injured site (Dual-EV). Results prove that the Dual-EV could target human umbilical vascular endothelial cells (HUVECs), recruit NSCs, and promote the neuronal differentiation of NSCs in vitro. Furthermore, 10 miRNAs are found to be upregulated in Dual-M2-EVs compared to Dual-M0-EVs via bioinformatic analysis, and further NSC differentiation experiment by flow cytometry reveals that among these miRNAs, miR30b-3p, miR-222-3p, miR-129-5p, and miR-155-5p may exert effect of inducing NSC to differentiate into neurons. In vivo experiments show that Dual-EV nanocarriers achieve improved accumulation in the ischemic area of stroke model mice, potentiate NSCs recruitment, and increase neurogenesis. This work provides new insights for the treatment of neuronal regeneration after CNS injuries as well as endogenous stem cells, and the click chemistry EV/peptide/chemokine and related nanocarriers for improving human health.

Humans ; Severe Acute Respiratory Syndrome ; diagnosis ; therapy

Existing traditional Chinese medicine (TCM)-related databases are still insufficient in data standardization, integrity and precision, and need to be updated urgently. Herein, an Encyclopedia of Traditional Chinese Medicine version 2.0 (ETCM v2.0, http://www.tcmip.cn/ETCM2/front/#/) was constructed as the latest curated database hosting 48,442 TCM formulas recorded by ancient Chinese medical books, 9872 Chinese patent drugs, 2079 Chinese medicinal materials and 38,298 ingredients. To facilitate the mechanistic research and new drug discovery, we improved the target identification method based on a two-dimensional ligand similarity search module, which provides the confirmed and/or potential targets of each ingredient, as well as their binding activities. Importantly, five TCM formulas/Chinese patent drugs/herbs/ingredients with the highest Jaccard similarity scores to the submitted drugs are offered in ETCM v2.0, which may be of significance to identify prescriptions/herbs/ingredients with similar clinical efficacy, to summarize the rules of prescription use, and to find alternative drugs for endangered Chinese medicinal materials. Moreover, ETCM v2.0 provides an enhanced JavaScript-based network visualization tool for creating, modifying and exploring multi-scale biological networks. ETCM v2.0 may be a major data warehouse for the quality marker identification of TCMs, the TCM-derived drug discovery and repurposing, and the pharmacological mechanism investigation of TCMs against various human diseases.