To explore the application value of whole exome sequencing (WES) in the diagnosis of prenatal and postnatal neurodevelopmental disorders (NDDs). A total of 70 patients diagnosed with NDDs who underwent WES at the Medical Genetics Center of the Maternal and Child Health Hospital of Hubei Province between June 2020 and July 2021 were retrospectively analyzed. Genomic DNA was extracted from peripheral blood samples and amniotic fluid. WES-based copy number variant (CNV) analysis was integrated into the routine WES data analysis pipeline. The results showed that a molecular diagnosis rate could be made in 21/70 (30%) cases. Of 21 positive cases, 14 (23%) cases were detected by single-nucleotide variant/small insertion/deletion (SNV/Indel) analysis, of which 12 variants were novel, 6 (9.8%) cases were detected by WES-based CNV analysis, and 1 (1.6%) case was detected by a combination of both. The diagnostic yield of WES combined with CNV analysis was higher than that of SNV/Indel analysis alone (30%, 21/70 vs. 20%, 14/70). Of the 28 prenatally diagnosed cases, 6 cases were found to have inherited parental variation for NDDs, 10 cases were found not to have the same pathogenic variation as the proband, and the remaining 12 cases were found to have no pathogenic or likely pathogenic variation that could explain the NDDs phenotype. Clinical follow-up showed that 5 families opted for abortion and the remaining had no current abnormalities. In conclusion, WES may be an effective method to clarify the genetic etiology and prenatal diagnosis of NDDs, which is helpful in assessing the prognosis to aid clinical management and reproductive guidance.
Pregnancy ; Humans ; Female ; Exome Sequencing ; Retrospective Studies ; Prenatal Diagnosis ; Amniotic Fluid ; Phenotype

ObjectiveTo explore the mechanism of Dendrobium huoshanense in the treatment of gastric ulcer （GU） based on network pharmacology and in vivo experiment. MethodThe active components of D. huoshanense were searched from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and literature， and the targets of the components were screened from TCMSP and SwissTargetPrediction. GU-related genes were retrieved from GeneCards， Online Mendelian Inheritance in Man （OMIM）， and DisGeNET. Thereby， the common targets of the disease and the medicinal were yielded and the protein-protein interaction （PPI） network was constructed， followed by Gene Ontology （GO） term enrichment and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment. According to the predicted results， hematoxylin-eosin （HE） staining， immunohistochemistry， enzyme-linked immunosorbent assay （ELISA）， Western blot， and real-time fluorescent quantitative polymerase chain reaction （Real-time PCR） were used to validate the effects of D. huoshanense on acetic acid-induced GU in rats. ResultA total of 63 active components of D. huoshanense and 37 target genes of D. huoshanense for the treatment of GU were screened out. PPI network analysis yielded several possible core anti-GU targets of D. huoshanense. They influenced the development of GU by acting on signaling pathways such as phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， hypoxia inducible factor-1 （HIF-1）， tumor necrosis factor （TNF）， and nuclear factor-κB （NF-κB）， and various biological processes. The in vivo experiment showed that D. huoshanense significantly reduced the levels of inflammatory factors such as interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and TNF-α in the serum of model rats （P<0.05， P<0.01）， increased gastric blood flow （GBF） at the ulcer margin， raised the expression of epidermal growth factor （EGF） and epidermal growth factor receptor （EGFR） at the ulcer margin （P<0.01）， significantly down-regulated protein and mRNA expression of PI3K and Akt， and up-regulated protein and mRNA expression of phosphatase and tensin homolog deleted on chromosome ten （PTEN） in the gastric tissues of GU rats （P<0.01）. ConclusionThrough regulating EGFR/PI3K/Akt signaling pathway， D. huoshanense can inhibit tissue inflammation， increase gastric microcirculatory blood flow at the ulcer margin， and promote cell proliferation and repair of damaged gastric mucosa.

Objective:To investigate the effects of preoperative nutritional status on postoperative functional prognosis in elderly patients with proximal humerus fracture.Methods:From January 2020 to December 2020, 103 elderly patients (≥65 years old) were treated for proximal humerus fractures by open reduction and internal fixation at Department of Traumatology, Honghui Hospital Affiliated to Xi'an Jiaotong University. Upon admission, according to the Geriatric Nutrition Risk Index (GNRI), they were assigned into a normal nutrition group (55 cases, with GNRI≥92) and a malnutrition group (48 cases, with GNRI<92). The baseline data, preoperative hemoglobin level, time from injury to operation, intraoperative blood transfusion, postoperative complications, 1-year mortality, and Neer shoulder functional scores at 3 months, 6 months and the last follow-up were compared between the 2 groups.Results:The 2 groups were comparable because there were no significant differences in gender, injury side, Neer fracture classification, injury cause, or American Society of Anesthesiologists (ASA) grading ( P>0.05). The age of the malnutrition group was significant older than that of the normal nutrition group ( P<0.05). All patients were followed up for 9 to 16 months (mean, 13.6 months) after surgery. In the normal nutrition group and the malnutrition group, respectively, the preoperative hemoglobin level was (10.24±0.68) g/dL and (8.94±0.89) g/dL, the time from injury to operation (3.9±1.3) d and (5.8±1.2) d, the rate of intraoperative blood transfusion 14.5%(8/55) and 60.4%(29/48), the rate of postoperative complications 20.0%(11/55) and 39.6%(19/48), the 1-year mortality 1.8%(1/55)、4.2%(2/48), and the Neer shoulder function score (46.7±8.8) points and (43.2±5.6) points at 3 months after operation, (67.6±6.2) points and (76.3±5.5) points at 6 months after operation, and (80.4±5.0) points and (76.3±5.5) points at the last follow-up. Comparisons of all the above items showed significant differences between the 2 groups (all P<0.05). Conclusions:Preoperative malnutrition in elderly patients with proximal humerus fracture has adverse effects on preoperative waiting time, intraoperative blood transfusion, complications and postoperative shoulder function. Therefore, perioperatively, attention should be paid to the nutritional status of elderly patients to reduce their stress responses to fracture, surgery and anesthesia, and to improve their postoperative function and quality of life.

Salviae Miltiorrhizae Radix et Rhizoma is a Chinese herbal medicine that promotes blood circulation to remove blood stasis, nourishes blood to tranquilize the mind, and cools blood to disperse carbuncles. Salviae Miltiorrhizae Radix et Rhizoma has microcirculation-improving, blood vessel-dilating, atherosclerosis-preventing, anti-inflammatory, anti-tumor, and blood pressure-and blood lipid-lowering activities. As research progresses, the chemical composition, pharmacological effect, and clinical application of Salviae Miltiorrhizae Radix et Rhizoma have attracted much attention. We reviewed the research progress in this field. Based on the concept of quality marker(Q-marker) in traditional Chinese medicine, the Q-markers of Salviae Miltiorrhizae Radix et Rhizoma were predicted and analyzed from the aspects of quality transfer, traceability, ingredient specificity, association between ingredients and pharmacological effects, ingredient predictability, and compounding environment. This review provides a scientific basis for the quality control of Salviae Miltiorrhizae Radix et Rhizoma and its preparations.
Drugs, Chinese Herbal/pharmacology* ; Medicine, Chinese Traditional ; Plant Roots ; Rhizome ; Salvia miltiorrhiza

Objective:To explore the effects of anti-microbial compound （T1） from Bacillus （Phylum Firmicutes） and anti-microbial compound （T2） from Pseudomonas and Rhizobium， two growth-promoting agents， on the physiological characteristics and growth of Fritillaria przewalskii， in order to lay a foundation for the development of functional microbial agents and the promotion of ecological planting. Method:The endophytic bacteria of F. przewalskii were isolated and identified using conventional methods. The leaves of three-year-old F. przewalskii were sprayed with T1 and T2， followed by yield determination. The enzyme activities and physiological and biochemical indexes in the plant and microorganisms were measured using the corresponding assay kits， and the contents of related hormones by liquid chromatography-mass spectrometry （LC-MS）. Result:The isolated endophytic bacteria were classified into Firmicutes，Proteobacteria， and Actinomycetes. The activities of superoxide dismutase（SOD） and peroxidase（POD） and auxin content after T2 treatment were significantly higher than those after T1 treatment， while the contents of siderophore，salicylic acid， and gibberellin were lower. Compared with the blank （CK） group， T1 and T2 increased the contents of endogenous gibberellin，cytokinin， and auxin in F. przewalskii leaves，but did not significantly change jasmonic acid and abscisic acid. T1 promoted the accumulation of endogenous salicylic acid in F. przewalskii leaves， but there was no significant change after T2 treatment. Compared with CK，T1 and T2 enhanced the activities of SOD， POD， and catalase （CAT） and decreased the content of malondialdehyde. T2 promoted the accumulation of hydrogen peroxide in F. przewalskii leaves， but no significant difference was observed after T1 treatment. Compared with CK，both T1 and T2 increased chlorophyll，average iron content in rhizosphere soil， and 100-plant weight. Conclusion:T1 and T2 treatments help to increase the yield，and their specific mechanisms differ from each other. T1 exhibits better effect than T2.

Objective:To explore the relationship between electrocardiogram QRS wave duration and pathological parameters of acute myocardial infarction and its prognosis.Methods:The patients with acute myocardial infarction treated in Hunan Brain Hospital from January 2018 to June 2019 were divided into normal group (≤110 ms, NG group) and extended group (>110 ms, EG group) according to the time limit of QRS wave group of electrocardiogram (ECG). The clinicopathological data of the two groups were collected, and the differences of relevant pathological parameters between the two groups were compared. The correlation between ECG QRS complex time limit and pathological parameters of acute myocardial infarction and the independent risk factors affecting the occurrence of malignant cardiovascular events after acute myocardial infarction were analyzed.Results:A total of 134 patients were enrolled, 73 in the EG group, and 61 in the NG group. The plasma levels of N-terminal pro-brain natriuretic peptide (N-proBNP) in EG group were significantly higher than those in NG group ( P<0.05), and left ventricular ejection fraction (LVEF) was significantly lower than that in NG group ( P<0.05). The time limit of QRS wave group in EG group was positively correlated with the plasma levels of N-proBNP ( r=0.981, P<0.001) and negatively correlated with LVEF ( r=-0.979, P<0.001). The ratio of Killip grade Ⅰ patients in EG group were lower than those in NG group ( P<0.05), while the ratio of grade Ⅱ and Ⅲ patients were significantly higher than those in NG group ( P<0.05), and there was no significant difference between the two groups in grade Ⅳ patients ( P>0.05). The incidence of malignant cardiovascular events (cardiogenic shock, malignant arrhythmia, acute pulmonary edema, cardiogenic death and re-infarction) in EG group was significantly higher than that in NG group ( P<0.05). Multivariate logistic regression analysis showed that elevated serum N-proBNP, decreased LVEF, prolonged QRS wave duration and high Killip cardiac function were independent risk factors for malignant cardiovascular events after acute myocardial infarction. Conclusions:After acute myocardial infarction, EG patients have worse cardiac function, higher incidence of malignant cardiovascular events and worse prognosis than NG patients.

OBJECTIVE: To observe the clinical effect of high suspension and low incision (HSLI) surgery on mixed haemorrhoids, compared with Milligan-Morgan haemorrhoidectomy. METHODS: A multi-centre, randomized, single-blind, non-inferiority clinical trial was performed. Participants with mixed haemorrhoids from Xiyuan Hospital of China Academy of Chinese Medical Sciences, Beijing Rectum Hospital, Air Force Medical Center of People's Liberation Army of China, and Puyang Hospital of Traditional Chinese Medicine were enrolled from September 2016 to March 2018. By using a blocked randomization scheme, participants were assigned to two groups. The experimental group was treated with HSLI, while the control group was treated with Milligan-Morgan haemorrhoidectomy. The primary outcome was the clinical effect evaluated at 12 weeks after operation. The secondary outcomes included the number of haemorrhoids treated during the operation, pain scores, use of analgesics, postoperative oedema, wound healing, incidence of anal stenosis, anorectal manometry after operation, as well as surgical duration, length of stay and total hospitalization expenses. A safety evaluation was also conducted. RESULTS: In total, 246 eligible participants were enrolled, with 123 cases in each group. There was no significant difference in the clinical effect between the two groups (100.00% vs. 99.19%, P>0.05). Compared with the control group, the number of external haemorrhoids treated during the operation and the pain scores after operation were significantly reduced in the experimental group (P<0.05 or P<0.01); the patient number with wound healing at 2 weeks after operation and the functional length of anal canal at 12 weeks after operation were significantly increased in the experimental group (P<0.05). There was no significant difference in the incidence of anal stenosis, the numbers of patients using analgesics and patients with postoperative oedema between the two groups after operation (P>0.05). The surgical duration and length of stay in the experimental group were significantly longer than those in the control group, and the total hospitalization expense was significantly higher than that in the control group (all P<0.05). No adverse events were reported in either group during the whole trial or follow-up period. CONCLUSION HSLI had the advantages of preserving the skin of anal canal completely, alleviating postsurgical pain and promoting rapid recovery after operation. (Registration No. ChiCTR1900022883).

BACKGROUND: Shenyankangfu Tablet (SYKFT) is a Chinese patent medicine that has been used widely to decrease proteinuria and the progression of chronic kidney disease. OBJECTIVE: This trial compared the efficacy and safety of SYKFT, for the control of proteinuria in primary glomerulonephritis patients, against the standard drug, losartan potassium. DESIGN, SETTING, PARTICIPANTS AND INTERVENTION: This was a multicenter, double-blind, randomized, controlled clinical trial. Primary glomerulonephritis patients, aged 18-70 years, with blood pressure ≤ 140/90 mmHg, estimated glomerular filtration rate (eGFR) ≥ 45 mL/min per 1.73 m MAIN OUTCOME MEASURES: The primary outcome was change in the 24-hour proteinuria level, after 48 weeks of treatment. RESULTS: A total of 735 participants were enrolled. The percent decline of urine protein quantification in the SYKFT group after 48 weeks was 8.78% ± 2.56% (P = 0.006) more than that in the losartan 50 mg group, which was 0.51% ± 2.54% (P = 1.000) less than that in the losartan 100 mg group. Compared with the losartan potassium 50 mg group, the SYKFT plus losartan potassium 50 mg group had a 13.39% ± 2.49% (P < 0.001) greater reduction in urine protein level. Compared with the losartan potassium 100 mg group, the SYKFT plus losartan potassium 100 mg group had a 9.77% ± 2.52% (P = 0.001) greater reduction in urine protein. With a superiority threshold of 15%, neither was statistically significant. eGFR, serum creatinine and serum albumin from the baseline did not change statistically significant. The average change in TCM syndrome score between the patients who took SYKFT (-3.00 [-6.00, -2.00]) and who did not take SYKFT (-2.00 [-5.00, 0]) was statistically significant (P = 0.003). No obvious adverse reactions were observed in any group. CONCLUSION: SYKFT decreased the proteinuria and improved the TCM syndrome scores of primary glomerulonephritis patients, with no change in the rate of decrease in the eGFR. SYKFT plus losartan potassium therapy decreased proteinuria more than losartan potassium therapy alone. TRIAL REGISTRATION NUMBER NCT02063100 on ClinicalTrials.gov.

Objective: This study explored the thromboembolism risk of low-risk atrial fibrillation (AF) patients (CHA₂DS₂-VASc score of 0 or 1 for male and 1 or 2 for female) with different clinical characteristics to provide the basis for anticoagulation decision-making in these patients. Methods: We prospectively enrolled consecutive 2 862 nonvalvular low-risk AF patients between August 2011 to December 2018 in China-AF (China Atrial Fibrillation Registry) Study, their CHA₂DS₂-VASc score was 0 or 1 for male and 1 or 2 for female. According to their age, sex, presence or absence of hypertension, diabetes mellitus, congestive heart failure, and vascular disease at the time of enrolling, patients were divided into CHA₂DS₂-VASc score 0 score group, 1 score group, and 2 score group. Patients were followed up every 6 months by outpatient clinic visit or telephone interview. The outcome was a thromboembolic event, including ischemic stroke and systemic embolism. Univariate Cox regression analysis was used to compare the thromboembolism risk between the patients with different risk factors and CHA₂DS₂-VASc score 0 group. Results: A total of 2 862 low-risk atrial fibrillation patients were enrolled in this study. 915 patients (32.0%) were female, and age was (55.0±10.7) years old. There were 933 patients (32.6%) in CHA₂DS₂-VASc score 0 group, 1 401 patients (49.0%) in score 1 group and 528 patients (18.5%) in score 2 group. During follow-up (median 1.5 years, 5 811.82 person-years), 33 cases of thromboembolic events were recorded, the annual rate of thromboembolism was 0.57% (95%CI 0.40%~0.80%). The number of thromboembolic events in patients with CHA₂DS₂-VASc score 0, 1 and 2 were 8, 11 and 14, respectively, and the annual thromboembolism event rates were 0.40% (95%CI 0.20%-0.81%), 0.39% (95%CI 0.22%-0.71%) and 1.34% (95%CI 0.80%-2.27%), respectively. The risk of thromboembolism of CHA₂DS₂-VASc score 2 group (HR=3.53, 95%CI 1.48-8.44; P=0.005), especially female patients aged 65-74 years in CHA₂DS₂-VASc score 2 group (HR=2.67, 95%CI 1.63-4.38; P<0.000) was significantly higher than that in patients of CHA₂DS₂-VASc score 0 group. Conclusion: Low-Risk Atrial Fibrillation patients with CHA₂DS₂-VASc score 2, especially female patients aged 65-74 years old with CHA₂DS₂-VASc score 2 are at higher risk of thromboembolism in low-risk AF patients. For such patients, intensified oral anticoagulant therapy might be helpful to reduce the risk of thrombolism.
Adult ; Aged ; Anticoagulants ; Atrial Fibrillation ; China ; Female ; Humans ; Male ; Middle Aged ; Risk Assessment ; Risk Factors ; Stroke ; Thromboembolism