Historical Evolution and Modern Research Progress of Processing of Scutellariae Radix / 中国实验方剂学杂志

By consulting ancient herbal books and modern literature， this paper systematically sorted out and researched the processing history， relevant processing norms in recent years， modern processing technology， chemical composition changes of processed products and their pharmacological mechanism of Scutellariae Radix， in order to provide a basis for the further development of Scutellariae Radix decoction pieces. According to the textual research of ancient books， there were many kinds of processing auxiliary materials of Scutellariae Radix， such as wine， vinegar， salt， honey， pig bile and so on， among which the wine processing was the most diverse and detailed， and the processed products such as raw products， stir-fried products， wine-processed products， fried charcoal products were still in use. The modern processing techniques of Scutellariae Radix mainly focus on the processing aspects of softening and slicing， wine processing and charcoal frying， and the research methods are relatively unified. At present， it is found that the changed chemical constituents of Scutellariae Radix after processing are flavonoids， polysaccharides， volatile oils and trace elements， etc. Pharmacological effects of processed products are hemostasis， antibacterial， anti-inflammatory， antioxidant， analgesic and antipyretic， treatment of lung diseases， treatment of colitis， etc. However， in the studies of Scutellariae Radix processing， there is a lack of research on the structural changes of chemical components caused by processing and a comprehensive comparative study on the pharmacological effects of various processed products. Based on this， it is suggested to carry out systematic research on the processing technology to processing mechanism， further explore the relationship between the change rule of material basis and pharmacological action before and after processing of Scutellariae Radix， and deepen the exploration of molecular mechanism and clinical application of processed products of Scutellariae Radix， in order to clarify the scientific connotation of the processing mechanism of Scutellariae Radix， and lay a foundation for the subsequent expansion of the application of Scutellariae Radix decoction pieces and the formulation of processing standards.

Effect of Linggui Zhugantang on Mitochondrial Fusion-fission and Sirt3/ AMPK Signaling Pathway in Chronic Heart Failure Rats After Myocardial Infarction / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Linggui Zhugantang on mitochondrial fission and fusion and silencing information regulator 3（Sirt3）/adenosine monophosphate dependent protein kinase （AMPK） signaling pathway in chronic heart failure （CHF） rats after myocardial infarction （MI）. MethodSD rats randomly divide into sham operation group （normal saline ，thread only without ligature）， model group （normal saline， ligation of the left anterior descending coronary artery proximal to the heart）， Linggui Zhugantang group （4.8 g·kg-1） and Captopril group （0.002 57 g·kg-1）， with 10 rats in each group. Administere drug continuously for 28 days. Echocardiography detected cardiac function parameters. Hematoxylin eosin （HE） staining observed the pathological changes of the heart. Immunofluorescence detected the levels of reactive oxygen species （ROS）. JC-1 detect mitochondrial membrane potential. Colorimetry measure adenosine triphosphate （ATP）， superoxide dismutase （SOD）， malondialdehyde （MDA）， mitochondrial respiratory chain complex activity （Ⅰ-Ⅳ）. TdT-mediated dUTP nick end labeling （TUNEL） staining detected the apoptosis rate of myocardial tissue. Western blot detected protein expression levels of Sirt3， phosphorylated AMPK （p-AMPK）， phosphorylated dynamic-related protein 1（p-Drp1）， mitochondrial fission protein 1（Fis1）， mitochondrial fission factor （MFF）， optic atrophy protein 1（OPA1）. ResultCompared to the sham group， the left ventricular end diastolic diameter （LVIDd） and left ventricular end systolic diameter （LVIDs） were significantly increased in model group （P<0.01）， while the left ventricular short axis shortening rate （LVFS） and left ventricular ejection fraction （LVEF） were significantly decreased （P<0.01）. There were inflammatory cell infiltration and obvious pathological injury in myocardial tissue. ROS， MDA levels and myocardial cell apoptosis rate were significantly increased （P<0.01）， SOD level， ATP content， and membrane potential were significantly decreased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） was significantly decreased （P<0.01）. Levels of p-Drp1， Fis1， MFF proteins were significantly up-regulated （P<0.01）， while Sirt3， p-AMPK， OPA1 proteins level were significantly down-regulated （P<0.01）. Compared with model group， LVIDd and LVIDs were significantly decreased （P<0.01）， LVEF and LVFS were significantly increased （P<0.01）. Inflammatory cell infiltration and pathological damage of myocardial tissue were significantly relieved. ROS， MDA levels and myocardial cell apoptosis rate were significantly decreased in Linggui Zhugantang group and Captopril group （P<0.01）， SOD level， ATP content， and membrane potential significantly increased （P<0.01）. The activity of mitochondrial respiratory chain complexes （Ⅰ-Ⅳ） increased significantly （P<0.01），and p-Drp1， Fis1， MFF protein levels were significantly down-regulated （P<0.01）， Sirt3， p-AMPK， OPA1 protein were significantly up-regulated （P<0.01）. ConclusionLinggui Zhugantang can alleviate oxidative stress and apoptosis damage of myocardial cells， maintain mitochondrial function stability， and its effect may be related to mitochondrial mitosis fusion and Sirt3/AMPK signaling pathway.

Neuroprotection of Natural Products Based on Keap1/Nrf2/ARE Signaling Pathway： A Review / 中国实验方剂学杂志

The pathological manifestations of neurodegenerative diseases， such as Alzheimer's disease， Parkinson's disease， and multiple sclerosis， are abnormal protein aggregation and accumulation， microglia activation， and mitochondrial dysfunction， which eventually lead to the gradual loss of neuronal structure or function and deteriorate over time. These pathological processes are related to the production of reactive oxygen species （ROS）， which can cause oxidative stress and damage proteins， lipids， and DNA， leading to cell and tissue injuries. The Kelch-like ECH-associated protein 1 （Keap1）/nuclear factor E2-related factor 2 （Nrf2）/antioxidant response element （ARE） signaling pathway is the main mechanism to maintain the redox balance of the body and defend against oxidative stress injury. Nrf2 activates the expression of a series of antioxidant genes related to ARE through the dissociation of Keap1 and nuclear transfer in the cytoplasm to protect the body from oxidative damage. Therefore， the discovery and study of the Keap1/Nrf2/ARE signaling pathway activator is of great significance for the prevention and treatment of neurodegenerative diseases. Because of the remarkable biological activity and slight side effects， natural products are a treasure trove for new drug research and development. Studies have shown that a variety of natural products can activate the Keap1/Nrf2/ARE signaling pathway and play a neuroprotective role. According to the structural characteristics， natural products can be divided into flavonoids， terpenoids， volatile oils， polyphenols， and phenylpropanoids. This study summarized the underlying mechanism of the Keap1/Nrf2/ARE signaling pathway in regulating diseases and reviewed the research progress on natural products based on this signaling pathway in neuroprotection to provide references for the development of clinical drugs for the prevention and treatment of neurodegenerative diseases.

Echocardiographic diagnosis of sinus of Valsalva aneurysm / 中山大学学报(医学科学版)

ObjectiveTo summarize the echocardiographic features of sinus of Valsalva aneurysm （SVA）， analyze the causes of missed diagnosis， thus explore the diagnostic skills and improve the diagnostic accuracy for SVA. MethodsThe echocardiographic features and clinical data of 52 SVA patients who underwent surgery in the First Affiliated Hospital of Sun Yat-sen University from January 2014 to March 2022 were retrospectively reviewed. The patients were divided into 5 types according to modified Sakakibara classification system. ResultsThere were 32 male and 20 female patients with their age of 18~66 （36.1±11.6） years. Of the 52 aneurysms， 44 originated from the right coronary sinus （RCS）， 8 from noncoronary sinus （NCS） and none from left coronary sinus （LCS）. Among the 35 SVAs protruding into the right ventricle， including type I， type Ⅱ and type Ⅲv， 32 （91.4%） were associated with ventricular septal defect （VSD）. There were 2 （17.6%） associated with VSD among the 17 SVAs protruding into the right atrium or other sites of the heart， including type Ⅲa， type Ⅳ and type Ⅴ. SVA was frequently associated with aortic valve disease， 27 cases （51.9%） of which needed surgical valve replacement or valvoplasty. SVA was missed in 4 patients and VSD in 8， with the misdiagnosis rates of 7.7% and 23.5%， respectively. The most commonly missed VSD diagnosis was subarterial VSD with type I SVA. Of the 19 SVAs associated with infective endocarditis （IE）， 2 were missed， with the misdiagnosis rate of 10.5%. ConclusionThe ultrasound images of SVA are diverse and complex. SVA protruding into the right atrium is rarely associated with VSD， while SVA protruding into the right ventricle is frequently associated with VSD. SVA is also prone to be associated with aortic valve disease and IE， which makes the diagnosis more challenging. Therefore， during ultrasound examination， we must vigilantly and flexibly make use of the multiple scan slices so as to decrease the rate of missed diagnosis and improve the diagnostic accuracy for SVA.

Prognostic value of combined detection of three indexes in patients with advanced cervical squamous cell carcinoma / 中华放射肿瘤学杂志

Objective:To evaluate the prognostic value of combined detection of platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and squamous cell carcinoma antigen (SCC) for patients with advanced cervical squamous cell carcinoma undergoing radical radiotherapy.Methods:Clinical data of 127 patients with advanced cervical squamous cell carcinoma who received radical radiotherapy in the Affiliated Tumor Hospital of Nantong University from January 2016 to February 2019 were analyzed retrospectively. The enrolled cases were divided into the survival group and death group according to the survival at the end of 3 years after treatment. The laboratory indexes of peripheral blood were collected before treatment, PLR and NLR were calculated, and the differences of clinical parameters were compared between two groups. The prediction model was established, and the prediction efficiency of PLR, NLR and SCC alone and combined prediction models for 3-year overall survival (OS) in patients with advanced cervical squamous cell carcinoma was compared through the ROC curve. Univariate and multivariate analyses of prognosis were carried out by binary logistic regression model.Results:A total of 127 patients with advanced cervical squamous cell carcinoma were included in the study. There were 96 cases in the survival group and 31 cases in the death group. There were significant differences between two groups in FIGO stage, longest diameter of tumor, lymph node metastasis, PLR, NLR and SCC (all P<0.05). The area under ROC curve (AUC) of PLR, NLR and SCC was 0.660, 0.712 and 0.700, respectively. The AUC of PLR+NLR+SCC combined prediction model was increased to 0.784. Logistic multivariate analysis showed that FIGO Ⅲ, FIGO Ⅳ, lymph node metastasis, PLR≥205.555, NLR≥3.060 and SCC≥6.950 ng/ml were the independent risk factors for 3-year OS in patients with advanced cervical squamous cell carcinoma (all P<0.05). Conclusions:PLR, NLR and SCC have good value in predicting the 3-year OS of patients with advanced cervical squamous cell carcinoma, and the combined prediction model of PLR+NLR+SCC has higher prediction value.

Protective Effect of Linggui Zhugantang Medicated Serum Against H2O2-induced Injury in H9c2 Cells by Regulating PI3K/Akt Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the protective effect of Linggui Zhugantang （LGZGT）-medicated serum against H2O2-induced injury in H9c2 cells and its relationship with the phosphatidylinositol 3- kinase/protein kinase B （PI3K/Akt） signaling pathway. MethodThe LGZGT-medicated serum and blank serum were prepared based on serum pharmacology. H9c2 cells were cultured in vitro and divided into a normal group， an H2O2 group， a 20% blank serum group， and a 20% LGZGT-medicated serum group. The cells were treated with corresponding drugs for 12 h and cultured with 100 μmol·L-1 H2O2 for another 6 h. The effect of 20% LGZGT-medicated serum on the proliferation activity of H9c2 cells induced by H2O2 was detected by cell counting kit-8 （CCK-8） assay. Mitochondrial reactive oxygen species （ROS） level was detected by the fluorescence probe. The levels of malondialdehyde （MDA）， lactate dehydrogenase （LDH）， catalase （CAT）， and glutathione peroxidase （GSH-Px） were detected by colorimetry. Western blot was used to detect the protein expression levels of phosphoinositide 3-kinase （PI3K）， phosphorylated-PI3K （p-PI3K）， protein kinase B （Akt）， and phosphorylated-Akt （p-Akt）. Real-time fluorescence-based quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression of PI3K and Akt. Flow cytometry was used to detect the apoptosis rate. After the addition of PI3K inhibitor LY294002， the levels of mitochondrial ROS， LDH， and GSH-Px， protein expression of PI3K， p-PI3K， Akt， and p-Akt， and cell apoptosis rate were detected. ResultCompared with the normal group， the H2O2 group showed blunted cell viability （P<0.01）， increased levels of mitochondrial ROS， MDA， and LDH （P<0.01）， decreased levels of CAT and GSH-Px （P<0.01）， reduced phosphorylation and mRNA expression of PI3K and Akt （P<0.05， P<0.01）， and increased apoptosis rate （P<0.01）. Compared with the H2O2 group， the 20% LGZGT-medicated serum group showed potentiated cell viability， reduced levels of mitochondrial ROS， MDA， and LDH （P<0.01）， increased levels of CAT and GSH-Px （P<0.01）， up-regulated phosphorylation and mRNA expression of PI3K and Akt （P<0.05， P<0.01）， and decreased apoptosis rate （P<0.01）. The combined use of LGZGT-medicated serum and inhibitor LY294002 reversed the above-mentioned effects of LGZGT-medicated serum on H9c2 cells （P<0.05， P<0.01）. ConclusionThe protective effect of LGZGT-medicated serum on H2O2-induced H9c2 cell injury may be related to the regulation of the PI3K/Akt signaling pathway to reduce oxidative stress and apoptosis.

Material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood:based on computer-aided drug design / 中国中药杂志

Angelicae Sinensis Radix excels in activating blood, but the scientific mechanism has not been systematically analyzed, thus limiting the development of the medicinal. This study employed the computer-aided drug design methods, such as structural similarity-based target reverse prediction, complex network analysis, molecular docking, binding free energy calculation, cluster analysis, and ADMET(absorption, distribution, metabolism, excretion, toxicity) calculation, and enzyme activity assay in vitro, to explore the components and mechanism of Angelicae Sinensis Radix in activating blood. Target reverse prediction and complex network analysis yielded 40 potential anticoagulant targets of the medicinal. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis indicated that the targets mainly acted on the complement and coagulation cascade signaling pathway to exert the anticoagulant function. Among them, the key enzymes thrombin(THR) and coagulation factor Xa(FXa) in coagulation cascade and thrombosis were the drug targets for thromboembolic diseases. At the same time, molecular docking and cluster analysis showed that the medicinal had high selectivity for FXa. According to binding free energy score, 8 potential active components were selected for enzyme activity assay in vitro. The results demonstrated that 8 components inhibited THR and FXa, and the inhibition was stronger on FXa than on THR. The pharmacophore model of 8 active compounds was constructed, which suggested that the components had the common pharmacophore AAHH. The ADMET calculation result indicated that they had good pharmacokinetic properties and were safe. Based on target reverse prediction, complex network analysis, molecular docking and binding free energy calculation, anticoagulant activity in vitro, spatial binding conformation of molecules and targets, pharmacophore model construction, and ADMET calculation, this study preliminarily clarified the material basis and molecular mechanism of Angelicae Sinensis Radix in activating blood from the perspective of big data, and calculated the pharmacology and toxicology parameters of the active components. Our study, for the first time, revealed that the medicinal had obvious selectivity and pertinence for different coagulation proteins, reflecting the unique effect of different Chinese medicinals and the biological basis. Therefore, this study can provide clues for precision application of Angelicae Sinensis Radix and the development of the blood-activating components with modern technology.

Effect of self-made Qingyuan Shenghua decoction on coagulation dysfunction in patients with sepsis / 中华危重病急救医学

Objective:To observe the effects of self-made Qingyuan Shenghua decoction on coagulation dysfunction in patients with sepsis, and to explore its possible mechanism.Methods:Eighty patients with sepsis and coagulation dysfunction admitted to the department of critical care medicine of Chengdu First People's Hospital from March 2018 to April 2020 were enrolled. The patients were divided into control group and observation group according to random number table method, with 40 cases in each group. Patients in both groups received basic treatment for sepsis. On this basis, the observation group was administrated with self-made Qingyuan Shenghua decoction, one dose a day, 100 mL in the morning and 100 mL in the evening; the control group was given the same amount of normal saline. Both groups were treated for 7 days. Prothrombin time (PT), activated partial thromboplastin time (APTT), international normalized ratio (INR), fibrinogen (Fib), D-dimer, platelet count (PLT), white blood cell count (WBC), C-reactive protein (CRP), and procalcitonin (PCT) were measured before and after treatment, and acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) and sequential organ failure assessment (SOFA) were calculated. The length of intensive care unit (ICU) stay, the incidence of multiple organ dysfunction syndrome (MODS) and 28-day mortality was recorded.Results:The indexes of coagulation function and inflammation in the two groups were significantly improved after treatment, the improvement of various indexes in the observation group were better than those in the control group [PT (s): 16.01±1.08 vs. 19.21±1.38, APTT (s): 55.33±15.29 vs. 79.41±12.69, INR: 1.30±0.21 vs. 1.65±0.22, Fib (g/L): 2.87±0.89 vs. 5.44±1.13, D-dimer (mg/L): 2.56±1.67 vs. 6.41±2.42, PLT (×10 9/L): 125.79±18.51 vs. 95.46±18.50, WBC (×10 9/L): 7.50±0.78 vs. 12.75±4.09, CRP (mg/L): 21.27±9.32 vs. 65.44±13.40, PCT (μg/L): 1.15±0.58 vs. 6.31±1.29], and the differences were statistically significant (all P < 0.05). After treatment, APACHEⅡ and SOFA scores in the two groups decreased significantly compared with those before treatment, and the decrease in the observation group were more obvious than those in the control group (APACHEⅡ score: 10.29±1.86 vs. 15.35±2.06, SOFA score: 5.51±1.08 vs. 7.65±1.58, both P < 0.05). The length of ICU stay was shortened in the observation group than that in the control group (days: 12.22±9.48 vs. 20.22±15.35, P < 0.05). The incidence of MODS [35.0% (14/40) vs. 47.5% (19/40)] and the 28-day mortality [45.0% (18/40) vs. 47.5% (19/40)] was lower than that of the control group, but there was no statistical difference (both P > 0.05). Conclusion:Self-made Qingyuan Shenghua decoction can effectively improve the prognosis of patients with coagulation dysfunction and sepsis, and its mechanism may be related to inhibition of inflammatory reaction and improvement of coagulation function.

Analysis of pathogenic variants of USH2A gene in a child with Usher syndrome type II / 中华医学遗传学杂志

OBJECTIVE@#To detect pathogenic variant in a child featuring Usher syndrome type II.@*METHODS@#Peripheral blood samples of the child and his parents were collected for the analysis of variants of hearing impairment-related genes. The findings were verified in 100 individuals with normal hearing.@*RESULTS@#The child was found to harbor compound heterozygous variants of the USH2A gene, namely c.8224-1G>C in intron 41 and c.5678C>G(p.Ser1893X) in exon 28, which were inherited respectively from his mother and father. Based on the American College of Medical Genetics and Genomics standards and guidelines, both c.8224-1G>C and c.5678C>G(p.Ser1893X) variants of USH2A gene were predicted to be pathogenic(PVS1+PM2+PM3).@*CONCLUSION@#The compound heterozygous variants c.8224-1G>C and c.5678C>G of the USH2A gene probably underlay the disease in this child. Above finding has enriched the spectrum of USH2A gene variants.

Prenatal diagnosis of a fetus with chromosome 18p deletion and duplication / 中华医学遗传学杂志

OBJECTIVE@#To assess the value of chromosomal microarray analysis (CMA) to verify a fetus with partial 18p deletion signaled by non-invasive prenatal testing.@*METHODS@#G-banding chromosomal karyotyping analysis was carried out on amniotic fluid sample of the fetus and peripheral blood samples from the parents. Amniotic DNA was also subjected to CMA analysis. The fetus was also subjected to systematic ultrasound scan.@*RESULTS@#The fetus was found to have a karyotype of 46,XX,18p+. CMA has revealed a 5 Mb deletion at 18p11.32-p11.31, a 2.9 Mb duplication at 18p11.31-p11.23, and a 2.5 Mb duplication at 18p11.23-p11.22. No chromosomal aberration or microdeletion/microduplication was detected in either parent.@*CONCLUSION@#Non-invasive prenatal testing and CMA are both sensitive for the detection of chromosomal microdeletions and microduplications. CMA can help with clarification of genotype-phenotype correlation and facilitate prenatal diagnosis and genetic counseling for the family.

Quantitative evaluation of magnetic resonance T2 mapping in Brucella spondylitis / 中华地方病学杂志

Objective:To analyze the characteristics and quantitative evaluation of Brucella spondylitis patients by magnetic resonance T2 mapping. Methods:A prospective clinical study was conducted to analyze the MRI data of 23 patients with brucellosis spondylitis diagnosed in the First Affiliated Hospital of Xinjiang Medical University from January 2016 to September 2018, and 25 healthy volunteers were selected as the control group. MRI was used to examine the vertebral bodies of the subjects, and T2 mapping map was automatically generated. Regions of interest (ROI) were selected on the T2 mapping map to generate T2 mapping values automatically. The T2 mapping values of diseased vertebrae, adjacent unaffected vertebrae, paravertebral abscess and healthy volunteers were analyzed.Results:Among 48 MRI examinees, 23 cases were Brucella spondylitis, including 17 males and 6 females, aged (38.5 ± 13.4) years; 25 healthy volunteers, including 15 males and 10 females, aged (35.1 ± 12.7) years. In 23 patients with Brucella spondylitis, 5 thoracic vertebrae, 40 lumbar vertebrae and 7 sacral vertebrae were involved, with a total of 52 vertebral bodies. Among them, 11 (21.2%) vertebral bodies showed bone marrow edema on MRI, 41 (78.8%) vertebral bodies showed bone marrow edema and vertebral bone destruction. T2 mapping values of the diseased vertebrae, adjacent unaffected vertebrae and paravertebral abscess in Brucella spondylitis patients and normal vertebrae in healthy volunteers were (115.62 ± 11.37), (75.21 ± 5.57), (240.26 ± 30.67) and (77.29 ± 4.19) ms, respectively. There were significant differences between the diseased vertebrae in Brucella spondylitis and adjacent unaffected vertebrae in Brucella spondylitis, and there were significant differences between the diseased vertebrae in Brucella spondylitis and normal vertebrae in healthy volunteers ( t = 26.78, 19.42, P < 0.05). Conclusion:Magnetic resonance T2 mapping can be used to evaluate the pathological tissues in Brucella spondylitis patients, and it has certain guiding significance for the quantitative description and qualitative diagnosis.

The value of MRI in differentiating Brucella spondylitis from tuberculosis spondylitis / 中华地方病学杂志

Objective:To evaluate the value of magnetic resonance imaging (MRI) in differentiating Brucella spondylitis from tuberculosis spondylitis. Methods:A retrospective analysis method was used to include Brucella spondylitis patients and tuberculous spondylitis patients who had undergone MRI examination at the First Affiliated Hospital of Xinjiang Medical University from January 2015 to December 2017. All patients data of MRI examination (all had T1WI, T2WI, STIR images) were collected and compared. The differences in lesion location, MRI signal, vertebral body destruction, vertebral wedge, kyphosis deformity, attachment destruction, dead bone, bone hyperplasia, intervertebral space change, abscess location, and abscess range were analyzed. Results:A total of 91 patients with brucella spondylitis were selected, including 36 women and 55 men, with an average age of 49.40 years old; 112 patients with tuberculous spondylitis selected in the same examination, including 48 women and 64 men, with an average age of 47.15 years old. There was no statistically significant difference in gender and age between the two groups (χ 2 = 0.225, t = 1.387, P > 0.05). Brucella spondylitis was more common in lumbar spine [72.53% (66/91)], and tuberculosis spondylitis was more common in thoracic spine [47.32% (53/112)]. Brucella spondylitis patients showed higher T2WI hyperintensity than tuberculosis spondylitis patients [51.65% (47/91) vs 24.11% (27/112), P <0.05]; and showed lower T2 hyperlipidemia than patients with tuberculosis spondylitis [59.34% (54/91) vs 72.32% (81/112), P < 0.05]; the incidence rates of mild destruction of vertebral body, bone hyperplasia, normal intervertebral space, paravertebral abscess, and abscess not exceeding the range of vertebral body were higher than those of patients with tuberculosis spondylitis [81.32% (74/91), 93.41% (85/91), 37.36% (34/91), 71.43% (65/91), 38.46% (35/91) vs 20.54% (23/112), 28.57% (32/112), 1.79% (2/112), 30.36% (34/112), 1.79% (2/112), P < 0.01]; the incidence rates of vertebral body severe destruction, vertebral wedge less than 1/2, kyphosis deformity, dead bone, inter vertebral space narrowing, inter vertebral space vanishing, psoas abscess, abscess beyond the range of vertebral body were lower than those of patients with tuberculous spondylitis [12.09% (11/91), 18.68% (17/91), 2.20% (2/91), 2.20% (2/91), 61.54% (56/91), 1.10% (1/91), 2.20% (2/91), 1.10% (1/91) vs 75.89% (85/112), 72.32% (81/112), 29.46% (33/112), 46.43% (52/112), 79.46% (89/112), 18.75% (21/112), 66.96% (75/112), 74.11% (83/112), P < 0.01]. Conclusions:MRI signs can be used to differentiate Brucella spondylitis from tuberculosis spondylitis through analysis of bone hyperplasia, vertebral body destruction, vertebral wedge, kyphosis deformity, dead bone, abnormal intervertebral space, and paravertebral abscess and psoas abscess.

Training system of scientific research ability of medical undergraduates guided by literature reading / 中华医学教育探索杂志

At present, a common lack of basic scientific research training in the undergraduate education is one of the reasons restricting the innovation ability of undergraduates. Cultivating scientific research ability of undergraduates is one of the effective ways to improve the undergraduate professional education as well as the innovation ability. Therefore, after exploration and summary for years, we have formed a relatively mature new mode that cultivates the undergraduates' comprehensive abilities in scientific research, namely, the training system of scientific research ability of medical undergraduates guided by literature reading. It has improved the basic scientific quality and innovation ability of medical undergraduates in our university, and trained a group of outstanding undergraduates who have obtained various achievements, contributing to the construction of excellent postgraduate talents in our university. In addition, it is also an effective and feasible new teaching mode.

Genetic analysis and prenatal diagnosis of a pregnant woman with Sheldon-Hall syndrome / 中华医学遗传学杂志

OBJECTIVE@#To provide genetic testing and prenatal diagnosis for a woman with Sheldon-Hall syndrome.@*METHODS@#The woman was subjected to targeted capture and next-generation sequencing for variant of genes associated with skeletal disorders. And the result was verified in her parents and fetus.@*RESULTS@#The woman was found to harbor a c.188G>A variant of the TNNT3 gene, which was also found in her affected mother and the fetus. Her grandmother and grandmother's brother had similar manifestations, which was in line with an autosomal dominant inheritance. The same variant was not found in her father.@*CONCLUSION@#The c.188G>A variant of the TNNT3 gene probably underlay the distal joint contracture in this pedigree, based on which prenatal diagnosis was attained.

Prenatal diagnosis of three fetuses with small supernumerary marker chromosomes / 中华医学遗传学杂志

OBJECTIVE@#To explore the origin and mechanism of small supernumerary marker chromosomes (sSMC) in three fetuses.@*METHODS@#The three fetuses were predicted to have carried chromosomal abnormalities by non-invasive prenatal testing (NIPT). G-banding chromosomal karyotyping analysis were carried out on amniotic fluid samples of the fetuses and peripheral blood samples from their parents. Single nucleotide polymorphism array (SNP-array) was used to determine the origin, size and genetic effect of sSMCs.@*RESULTS@#In fetus 1, SNP array has detected two microduplications respectively at 4p16.3p15.2 (24.7 Mb) and 18p11.32q11.2 (20.5 Mb) which, as verified by fluorescence in situ hybridization (FISH), have derived from a balanced 46,XY,t(4;18)(p15.2q11.2) translocation carried by its father. Fetus 2 has carried a de novo microduplication of 15q11.2-q13.3 (9.7 Mb). The sequence of SMC in fetus 3 has derived from 21q11.2-q21.1 (8.3 Mb), which was inherited from its mother.@*CONCLUSION@#Both NIPT and SNP-array are highly accurate for the detection of sSMC. SNP-array can delineate the origin and size of abnormal chromosomes, which in turn can help with clarification of sSMC-related genotype-phenotype correlation and facilitate prenatal diagnosis and genetic counseling for the family.

Study on pain control of continuous adductor block analgesia after primary knee replacement / 中国骨伤

OBJECTIVE@#To investigate the effect of continuous adductor block on pain control after bilateral knee joint Ⅰ stage replacement.@*METHODS@#A retrospective analysis was made of the data of 24 patients with bilateral knee joint I stage replacement who were treated in our hospital from January 2018 to January 2019, and who underwent continuous adductor block analgesia. There were 6 males and 18 females, aged 60 to 72 (65.05±5.82) years old. The patients underwent continuous block of adductor canal with patient-controlled analgesia system. At 4, 6, 12, 24, 36 and 48 hours after operation, visual analogue score(VAS) of resting state and passive motion state was performed;the knee joint activity was followed up for 1 week, 1, 3 and 6 months after operation;the knee joint function was scored at 6 months after operation, using the knee joint scoring standard of American Special Surgery Hospital(HSS);adverse reactions and complications were recorded.@*RESULTS@#The VAS scores under resting state and passive motion state at each time point were less than 3 points in patients with continuous adductor block. The patients had better postoperative exercise of knee joint activity. The score of HSS was excellent in 20 cases, good in 2 cases, fair in 1 case and poor in 1 case. There were only 4 cases of nausea and vomiting, none of them had serious adverse reactions and complications such as bradycardia and deep vein thrombosis.@*CONCLUSION@#Continuous adductor block has a significant effect on pain control and less adverse reactions after bilateral knee jointⅠ -stage replacement.

Advances in small molecule inhibitors of ACK1 / 药学学报

ACK1 (activated Cdc42-associated kinase) is a non-receptor tyrosine kinase, originally identified by its binding to the GTP-binding small GTPase Cdc42. It is widely expressed in human tissues and activated by various extracellular growth factors such as EGF, PDGF and TGF-β. The activated ACK1 mediates the signaling cascade by interacting with downstream effectors followed by their phosphorylation. In recent years, researchers have investigated the biological functions of ACK1 and its roles in cancer research. The gene amplification and overexpression of ACK1 is associated with a poor prognosis and metastasis in a variety of cancers including lung, ovarian and prostate cancers. Therefore, the development of small molecule inhibitors of ACK1 provides promising opportunities for cancer-targeted therapy. In this review, we briefly describe recent advances in understanding the activation and biological function of ACK1 and introduce its novel inhibitors with potential therapeutic activities in preclinical studies.

Current status of cytomegalovirus infection in pregnant women and its correlation with pregnancy outcomes in Huzhou / 中华实验和临床病毒学杂志

Objective@#To understand the current situation of human cytomegalovirus(HCMV) infection in local pregnant women and its impact on pregnancy outcomes, so as to provide reference for strengthening health care during pregnancy and promoting the policy of "fewer and better children"@*Methods@#A total of 2 000 pregnant women underwent prenatal examination who had delivery in the Maternal and Child Health Hospital of Huzhou from July 2017 to December 2018. HCMV IgM, IgG and IgG- avidity index (AI) were detected by enzyme-linked immunosorbent assay (ELISA), and HCMV DNA was detected by real-time polymerase chain reaction (PCR) -fluorescent probe. We also analyzed the positive status of HCMV and its relationship with pregnancy outcome.@*Results@#Among the 2 000 pregnant women, 1 941 cases (97.05%) were positive for HCMV IgG, 26 cases (1.30%) had active infection with HCMV, of whom 5 cases (0.25%) were serum HCMV IgM/IgG dual positive, 24 cases (1.20%) were urine HCMV DNA positive. HCMV IgG AI test result showed that 3 cases of AI ≤30%, which means that they had primary infections. The detection rates of HCMV DNA positive and HCMV IgM/IgG dual positive were 12.12%, 4.54% in 66 pregnant women with adverse pregnancy and 0.83%, 0.10% in 1 934 pregnant women with normal pregnancy. The difference was significant (χ2=68.663, 50.499, P<0.01). Logistic regression analysis showed that HCMV IgM/IgG dual positive (OR=12.743, 95%CI: 1.202-135.100, P=0.035), HCMV-DNA positive (OR=10.426, 95%CI: 3.635-29.909, P<0.01) were independent risk factors for adverse pregnancy outcomes. In addition, low education level, living in rural areas and having a history of adverse pregnancy also increased the incidence of adverse pregnancy outcomes.@*Conclusions@#HCMV infection is prevalent in pregnant women in this area, but only a few of them had active infection. HCMV active infection is a risk factor for adverse pregnancy outcomes.

Downregulation of miR-4772-3p promotes enhanced regulatory T cell capacity in malignant pleural effusion by elevating Helios levels / 中华医学杂志(英文版)

Background@#Malignant pleural effusion (MPE) is a complicated condition of patients with advanced tumors. Further dissecting the microenvironment of infiltrated immune cells and malignant cells are warranted to understand the immune-evasion mechanisms of tumor development and progression.@*Methods@#The possible involvement of microRNAs (miRNAs) in malignant pleural fluid was investigated using small RNA sequencing. Regulatory T cell (Treg) markers (CD4, CD25, forkhead box P3), and Helios (also known as IKAROS Family Zinc Finger 2 [IKZF2]) were detected using flow cytometry. The expression levels of IKZF2 and miR-4772-3p were measured using quantitative real-time reverse transcription polymerase chain reaction. The interaction between miR-4772-3p and Helios was determined using dual-luciferase reporter assays. The effects of miR-4772-3p on Helios expression were evaluated using an in vitro system. Correlation assays between miR-4772-3p and functional molecules of Tregs were performed.@*Results@#Compared with non-malignant controls, patients with non-small cell lung cancer had an increased Tregs frequency with Helios expression in the MPE and peripheral blood mononuclear cells. The verified downregulation of miR-4772-3p was inversely related to the Helios+ Tregs frequency and Helios expression in the MPE. Overexpression of miR-4772-3p could inhibit Helios expression in in vitro experiments. However, ectopic expression of Helios in induced Tregs reversed the effects induced by miR-4772-3p overexpression. Additionally, miR-4772-3p could regulate Helios expression by directly targeting IKZF2 mRNA.@*Conclusion@#Downregulation of miR-4772-3p, by targeting Helios, contributes to enhanced Tregs activities in the MPE microenvironment.

Study on optogenetics technology and the design of its script for virtual simulation experiment / 中华医学教育探索杂志

Optogenetics is one of the biggest breakthroughs in neurobiology in recent decades,which is a revolutionary approach to precise intervention of specific cell functions through the combination of optical and genetic engineering techniques.However,this technique involves the interdisciplinary theoretical knowledge and methods,and it requires expensive equipments and long experimental period.Thus,it is not convenient to carry out widely in experiment teaching for undergraduates except the virtual simulation teaching.In present virtual simulation experiment,we aim to learn the basic principle,operation and application of optogenetics and achieve the desired teaching effects by simulating the process of the virus package,simulating the process of the animal selection,surgery and virus stereotactic microinjection,simulating the expression process of photosensitive channel,the extracellular verification process of photosensitive channel function in vivo,and simulating the observation process that optogenetic inhibition of glutamate neurons in the amygdala affect animal fear behavior.In this paper,the content design of the script making of the virtual experiment has been discussed in the above ways.