Re-understanding of the mechanism of coagulation disorder in liver cirrhosis / 临床肝胆病杂志

The liver plays an important regulatory role in maintaining the dynamic balance of coagulation and anticoagulation in the body. Such dynamic balance is fragile in patients with liver cirrhosis， and the risk of bleeding can be increased due to reductions in coagulation factors and platelet count and excessive fibrinolysis； meanwhile， thrombus can be formed due to the increases in von Willebrand factor and coagulation factor Ⅷ， the reductions in anticoagulant protein C and anticoagulant protein S， the increase in thrombin-generating potential， and alterations in antifibrinolytic components. This article reviews the mechanisms of coagulation disorder in liver cirrhosis， so as to help clinicians with the prevention and treatment of bleeding or thrombotic disorders in patients with liver cirrhosis.

Inhibitory effect of berberine on morphine tolerance and hyperalgesia in mice.

OBJECTIVE: To evaluate the effect of berberine on morphine analgesia, tolerance, and hyperalgesia. METHODS: Morphine-induced acute tolerance model: mice received intraperitoneal berberine at doses of 2.5, 5.0, and 10 mg/kg; 30 min later, subcutaneous morphine 10 mg/kg was injected every hour for nine continuous h. Morphine 10 mg/kg alone was administered at 24 and 48 h. Morphine-induced chronic tolerance model: mice received intraperitoneal berberine 2.5, 5.0, and 10 mg/kg; 30 min later, 10 mg/kg morphine was injected subcutaneously for eight consecutive days. On the ninth day, morphine 10 mg/kg was given alone. Morphine-induced established tolerance model: mice were injected subcutaneously with morphine 10 mg/kg once a day for eight consecutive days. Berberine 2.5 mg/kg was administered on day one, four, and seven and morphine 10 mg/kg alone on day nine. The baseline latency (T0) and post-treatment latency (T1) were determined by the hot plate test, and the maximum possible analgesic effect (MPAE) was calculated. Nitric oxide synthase (NOS) activity and nitric oxide (NO) content in the spinal cord were measured by spectrophotometer. Verification of berberine analgesic effect by blocking N-methyl-D-aspartate (NMDA) receptor: HT-22 and HEK-293 cells transfected with NMDA plasmid were randomly divided into five groups: control group, NMDA group, berberine low-dose, medium-dose, and high-dose groups (5, 10, 20 µmol/L, respectively). Except for the control group, cells were treated with NMDA (HT-22 cells: 20 mmol/L; HEK-293 cells: 50 µmol/L). After 24 h, cell viability was detected by cell counting kit-8. The molecular mechanism between berberine and the NMDA receptor was studied by molecular docking. RESULTS: Berberine 2.5 and 5.0 mg/kg could prolong the analgesic time of morphine. In acute and chronic morphine tolerance models, berberine could inhibit the decrease of MPAE and baseline latency (0.05). In the established tolerance model, berberine could rapidly reverse the decreased MPAE (0.05). The combination of berberine and morphine on day one could effectively inhibit the morphine-induced increase of NOS activity and NO content in the spinal cord (0.05). Berberine significantly increased the cell viability of NMDA-induced nerve injury in HT-22 and HEK-293 cells (0.05). Molecular docking showed that berberine binds to the receptor pocket of NMDA. CONCLUSIONS: Berberine could effectively enhance and prolong the duration of morphine analgesia and inhibit the development of morphine-induced tolerance and hyperalgesia. Furthermore, berberine has a certain neuroprotective effect, which may be related to the inhibition of NMDA activity.

Whole-exome sequencing enables rapid and prenatal diagnosis of inherited skin disorders.

BACKGROUND: Genodermatoses are a broad group of disorders with specific or non-specific skin-based phenotypes, most of which are monogenic disorders. However, it's a great challenge to make a precise molecular diagnosis because of the clinical heterogeneity. The genetic and clinical heterogeneity brings great challenges for diagnosis in dermatology. The whole exome sequencing (WES) not only expedites the discovery of the genetic variations, but also contributes to genetic counselling and prenatal diagnosis. MATERIALS AND METHODS: Followed by the initial clinical and pathological diagnosis, genetic variations were identified by WES. The pathogenicity of the copy number variations (CNVs) and single-nucleotide variants (SNVs) were evaluated according to ACMG guidelines. Candidate pathogenic SNVs were confirmed by Sanger sequencing in the proband and the family members. RESULTS: Totally 25 cases were recruited. Nine novel variations, including c.5546G > C and c.1457delC in NF1, c.6110G > T in COL7A1, c.2127delG in TSC1, c.1445 C > A and c.1265G > A in TYR, Xp22.31 deletion in STS, c.908 C > T in ATP2A2, c.1371insC in IKBKG, and nine known ones were identified in 16 cases (64%). Prenatal diagnosis was applied in 6 pregnant women by amniocentesis, two of whom carried positive findings. CONCLUSIONS: Our findings highlighted the value of WES as a first-tier genetic test in determining the molecular diagnosis. We also discovered the distribution of genodermatoses in this district, which provided a novel clinical dataset for dermatologists.

Research on con-beam CT images segmentation method / 中华放射医学与防护杂志

Image-guided radiation therapy (IGRT) is a visual image-guided radiotherapy technique that has many advantages such as increasing the dose of tumor target area and reducing the dose of normal organ exposure. Cone beam CT (CBCT) is one of the most commonly used medical images in IGRT, and the rapid and accurate targeting of CBCT and the segmentation of dangerous organs are of great significance for radiotherapy. The current research method mainly includes partitioning method based on registration and segmentation method based on deep learning. This study reviews the CBCT image segmentation method, existing problems and development directions.

Effect of posaconazole combined with proton pump inhibitors on blood concentrations and invasive fungal infec-tion in patients with malignant hematological disorders / 中国药房

OBJECTIVE To explore the effects of posaconazole combined with proton pump inhibitors （PPI） on the blood concentration and the risk of invasive fungal disease （IFD） in patients with malignant hematological disorder. METHODS In accordance with the random number table method， 40 patients with malignant hematological disorders who were admitted to the hematology department of our hospital between December 2020 and December 2021 were chosen and divided into control group （20 cases） and observation group （20 cases）. The control group received Posaconazole oral suspension alone， while the observation group received Posaconazole oral suspension combined with PPI. The incidence of IFD， attainment rate of blood concentration， the time from the start of prophylaxis to IFD onset， the fatality associated with IFD， treatment of infected patients， and blood concentrations of posaconazole on 7th， 14th， 21st， and 28th day after posaconazole application were compared between 2 groups； the occurrence of adverse events during drug administration in the two groups was recorded. RESULTS The study was stopped because 2 patients in the observation group and 9 patients in the control group received hospital departures after taking posaconazole for fewer than 7 days. The incidence of IFD in the observation group was significantly higher than control group， and the attainment rate of blood concentration in the observation group was significantly lower than control group （P＜0.05）. There was no significant difference in the time from the start of prophylaxis to IFD onset， the fatality associated with IFD， treatment of infected patients and the incidence of adverse events （P＞ 0.05）. The blood concentration of posaconazole in the observation group was significantly lower than control group on 7th day of medication （P＜0.05）； there was no significant in blood concentration of posaconazole between 2 groups on the 14th day of medication （P＞0.05）. CONCLUSIONS Posaconazole combined with PPI can reduce the blood concentration of patients with malignant hematological disorders， increase the risk of IFD. Clinical practice should try to avoid the combination of the two or use them under the guidance of therapeutic drug monitoring.

Structural and computational insights into the SARS-CoV-2 Omicron RBD-ACE2 interaction

Since SARS-CoV-2 Omicron variant (B.1.1.529) was reported in November 2021, it has quickly spread to many countries and outcompeted the globally dominant Delta variant in several countries. The Omicron variant contains the largest number of mutations to date, with 32 mutations located at spike (S) glycoprotein, which raised great concern for its enhanced viral fitness and immune escape[1-4]. In this study, we reported the crystal structure of the receptor binding domain (RBD) of Omicron variant S glycoprotein bound to human ACE2 at a resolution of 2.6 [A]. Structural comparison, molecular dynamics simulation and binding free energy calculation collectively identified four key mutations (S477N, G496S, Q498R and N501Y) for the enhanced binding of ACE2 by the Omicron RBD compared to the WT RBD. Representative states of the WT and Omicron RBD-ACE2 systems were identified by Markov State Model, which provides a dynamic explanation for the enhanced binding of Omicron RBD. The effects of the mutations in the RBD for antibody recognition were analyzed, especially for the S371L/S373P/S375F substitutions significantly changing the local conformation of the residing loop to deactivate several class IV neutralizing antibodies.

Comparative study of quantitative methods based on intravenous enhancement of 3D-FLAIR sequence for evaluation of endolymphatic hydrops / 中华放射学杂志

Objective:To compare the diagnostic value of three quantitative evaluation methods based on three-dimensional rapid fluid attenuation inversion recovery sequence (3D-FLAIR) vein-enhanced labyrinth images in endolymphatic hydrops.Methods:From October 2017 to April 2019, a retrospective study was conducted on 86 patients with unilateral otogenic vertigo who were admitted to Beijing Tongren Hospital, Capital Medical University. MRI was performed 8 h after the single-dose Gd-DTPA intravenously injection in all patients. Three evaluation methods were used to calculate the ratio of the endolymphatic area to the total lymphatic area, the ratio of the saccule to utricle area, and the ratio of the endolymphatic volume to the total lymphatic volume, respectively. The paired t test was used to compare the three ratios between the affected and healthy ears. With clinical diagnosis as the gold standard, the receiver operating characteristic (ROC) curve analysis was used to analyze the efficacy of three methods in diagnosing endolymphatic hydrops. Results:Totally 65 cases were finally diagnosed endolymphatic hydrops clinically. There were statistically significant differences of all the 3 ratios between the affected and healthy ears ( t=9.93, 7.22, 8.20, all P<0.001). The ROC curve showed that the area under the curve (AUC) of endolymph/total lymph area ratio, saccule/utricle area ratio, endolymph/total lymph volume ratio for diagnosis of endolymphatic hydrops were 0.882, 0.768, 0.884 (all P<0.001). And there were no significant differences between each paired AUCs (all P>0.05). Conclusions:All three methods of endolymph/total lymph area ratio, saccule/utricle area ratio, endolymph/total lymph volume ratio can quantitatively evaluate endolymphatic hydrops. The endolymphatic/total lymphatic area ratio method is still the most convenient method at present.

Etiological analysis of acute respiratory tract infection in Taizhou of Zhejiang Province from 2020 to 2021 / 上海预防医学

ObjectiveWe examined the principal respiratory pathogens in patients with acute respiratory tract infection in Taizhou， Zhejiang Province during 2020‒2021 to provide evidence for prevention， diagnosis and treatment of acute respiratory tract infection. MethodsFrom September 2020 to August 2021， a total of 2 831 cases with acute respiratory tract infection were collected from two influenza sentinel surveillance hospitals in Taizhou， which had then received the examination of 22 respiratory pathogens by multiple fluorescence quantitative PCR. ResultsThe total positive rate of respiratory pathogens in 2 831 samples was 14.13%， among which enterovirus （7.77%） and respiratory syncytial virus （1.59%） were the principal pathogens. Except enterovirus， there was no significant difference in the positive rate of pathogens detected by gender（P>0.05）. Moreover， there was significant difference in pathogens by age （P<0.05）， with the highest positive rate in 0‒4 years（35.21%）. There was also significant difference in pathogens by seasons （P<0.05）， with the highest positive rate in summer（20.54%）. ConclusionThe positive rate of acute respiratory tract infection decreases significantly， compared with that before the COVID-19 epidemic. The differences in the positive rate differ significantly by age and seasons. Comprehensive consideration of diverse factors before diagnosis and the utilization of multiple fluorescent quantitative PCR can quickly and effectively determine the pathogens in the early stage of infection. Our findings may provide certain support for the diagnosis and treatment of acute respiratory infections in the context of COVID-19 in Taizhou.

Based on Theory of "Deficiency of Qi and Stagnation" to Explore Pathogenesis of Chronic Renal Failure "Micro-inflammatory State" and Progress of Traditional Chinese Medicine Prevention and Treatment / 中国实验方剂学杂志

Chronic renal failure （CRF） is generally characterized by micro-inflammatory state， which can aggravate the CRF process in severe cases， leading to the deterioration of renal function， malnutrition， anemia and other complications. Therefore， it is of great significance to improve the micro-inflammatory state of CRF. "Deficiency of Qi and stagnation" is the basic pathogenesis of the micro-inflammatory state of CRF， which runs through the whole process of the disease and affects the formation and outcome of CRF in different forms. Traditional Chinese medicine （TCM） has unique advantages in improving the micro-inflammatory state and enhancing the immunity of the body due to its advantages of syndrome differentiation and treatment， strengthening the righteousness and eliminating pathogenic factors. Therefore， the author systematically sorted out the relationship between micro-inflammatory state and CRF， understanding of micro-inflammatory state of CRF and its prevention and treatment of TCM by referring to relevant literature， based on the theory of "deficiency of Qi and stagnation"， and proposed that spleen and kidney failure （deficiency of Qi） is the origin of micro-inflammatory state of CRF， and blood stasis and poisonous evil （stagnation） is the target of its onset. Deficiency of Qi and stagnation adhered to each other， acted as cause and effect， and developed in a spiral manner throughout the development of the disease. TCM has the effects of nourishing the spleen and kidney， removing blood stasis and turbidity. By down-regulating C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor alpha （TNF-α） and other micro-inflammatory indicators， it can eliminate the pathological wastes derived from spleen and kidney deficiency， reduce the micro-inflammatory state， restore the balance of Yin and Yang in the body to achieve the purpose of eliminating pathogens and protecting renal function， providing guidance for the clinical treatment of CRF.

Exploration on Syndrome Types and Metabolic Markers of Rat Model with Heart Failure Caused by Transverse Aortic Constriction Based on Theory of Correspondence of Prescription and Syndrome / 中国实验方剂学杂志

ObjectiveTo observe the difference in the efficacy of three kinds of traditional Chinese medicine （TCM） injections on rat model of heart failure induced by transverse aortic constriction （TAC）， explore the TCM syndrome of the model based on the theory of correspondence of prescription and syndrome， and reveal the biological basis of prescription-syndrome from the perspective of metabolism. MethodRats were treated with TAC for modeling and were divided into Shenmai injection group （6.0 mL·kg-1）， model group， Danhong injection group （6.0 mL·kg-1）， Shenfu injection group （6.0 mL·kg-1） and trimetazidine group （10 mg·kg-1）， and sham operation group was set up as control. After drug intervention for 15 days， echocardiography， serum N-terminal pro-brain natriuretic peptide （NT-proBNP） and myocardial histopathological staining were performed for each group， so as to compare the efficacy to select the effective injection. Colorimetry was used to detect the serum glucolipid metabolism after the intervention of the effective injection， and ultra high performance liquid chromatography-mass spectrometry was used to observe the metabolites and related metabolic pathways in myocardial tissue. ResultCompared with the sham operation group， the left ventricular ejection fraction （LVEF） and left ventricular fractional shortening （FS） in the model group decreased （P<0.01）， while the left ventricular end-diastolic diameter （LVIDd）， left ventricular internal diameter at end-systole （LVIDs） and NT-proBNP level increased （P<0.01）. Compared with model group， LVEF and FS increased （P<0.01）， LVIDd， LVIDs and NT-proBNP level decreased （P<0.05， P<0.01） in Danhong injection group， NT-proBNP level in Shenfu injection group decreased （P<0.05）， LVIDd and NT-proBNP level increased （P<0.05， P<0.01） in Shenmai injection group， in trimetazidine group， LVEF and FS increased （P<0.01）， while LVIDs and NT-proBNP level decreased （P<0.05， P<0.01）. Serum glucose， low-density lipoprotein cholesterol and high-density lipoprotein cholesterol levels in Danhong injection group and trimetazidine group were adjusted by callbacks （P<0.01， P<0.05）. There were the callback of 9 myocardial metabolites in Danhong injection group， including glycine， serine and threonine metabolism， glyoxylate and dicarboxylate metabolism， glycerol phospholipid metabolism. There were the callback of 10 myocardial metabolites in trimetazidine group， including glycerol phospholipid metabolism. ConclusionThe efficacy of Danhong injection on heart failure model induced by TAC is significant and superior to Shenfu injection and Shenmai injection， suggesting that the model is closely related to heart-blood stasis. The biological mechanism of Danhong injection interfering with the model involves regulating the metabolic disorder of lipid， glucose， amino acid and butyric acid.

Role of Inflammation in Development of Chronic Heart Failure： Based on "Toxic Pathogen Theory" / 中国实验方剂学杂志

Chronic heart failure is a serious heart disease with dyspnea and limited activity tolerance as the main clinical manifestations. Activation of the inflammatory system can significantly stimulate cardiac fibrosis and remodeling and promote the progression of heart failure， playing a key role in the development of the disease. Studies have confirmed that inflammation is involved in the development of different types of heart failure. "Toxic pathogen theory" is an important basic theory of traditional Chinese medicine （TCM） to explain the occurrence of diseases. We concluded the similarities between TCM toxic pathogens and inflammation in concept， disease location， etiology， syndrome differentiation， and clinical characteristics. Chronic heart failure is manifested by the toxic pathogens of turbid phlegm， stagnated blood， and accumulated fluid. Heart vessel obstruction is the main pathological factor， and the inflammatory factors produced by necrotic cardiomyocytes are the microscopic manifestations of the obstruction. Therefore， based on the "toxic pathogen theory"， this study aimed to clarify the role of inflammation in the development of chronic heart failure from both macroscopic and microscopic perspectives. Moreover， this paper proposed that the stagnated blood has not been transformed into toxin in the early stage of the disease and thus the products of clearing heat and detoxification should not be used. At the development stage of the disease when the transformation tends to begin， treatment should be based on syndrome differentiation， and detoxifying Chinese medicine should be used in order to achieve the goal of "removing toxin without harming the healthy Qi". At the late stage of heart failure， toxins have been accumulated and detoxifying medicines and therapies should be applied to eliminate the toxic pathogens. This study is expected to lay a foundation for the modern research on the role of inflammation in the development of chronic heart failure with TCM theory and guide the diagnosis and treatment of this disease.

Role of Inflammation in Development of Chronic Heart Failure： Based on "Toxic Pathogen Theory" / 中国实验方剂学杂志

Chronic heart failure is a serious heart disease with dyspnea and limited activity tolerance as the main clinical manifestations. Activation of the inflammatory system can significantly stimulate cardiac fibrosis and remodeling and promote the progression of heart failure， playing a key role in the development of the disease. Studies have confirmed that inflammation is involved in the development of different types of heart failure. "Toxic pathogen theory" is an important basic theory of traditional Chinese medicine （TCM） to explain the occurrence of diseases. We concluded the similarities between TCM toxic pathogens and inflammation in concept， disease location， etiology， syndrome differentiation， and clinical characteristics. Chronic heart failure is manifested by the toxic pathogens of turbid phlegm， stagnated blood， and accumulated fluid. Heart vessel obstruction is the main pathological factor， and the inflammatory factors produced by necrotic cardiomyocytes are the microscopic manifestations of the obstruction. Therefore， based on the "toxic pathogen theory"， this study aimed to clarify the role of inflammation in the development of chronic heart failure from both macroscopic and microscopic perspectives. Moreover， this paper proposed that the stagnated blood has not been transformed into toxin in the early stage of the disease and thus the products of clearing heat and detoxification should not be used. At the development stage of the disease when the transformation tends to begin， treatment should be based on syndrome differentiation， and detoxifying Chinese medicine should be used in order to achieve the goal of "removing toxin without harming the healthy Qi". At the late stage of heart failure， toxins have been accumulated and detoxifying medicines and therapies should be applied to eliminate the toxic pathogens. This study is expected to lay a foundation for the modern research on the role of inflammation in the development of chronic heart failure with TCM theory and guide the diagnosis and treatment of this disease.

Deficiency of two-pore segment channel 2 contributes to systemic lupus erythematosus via regulation of apoptosis and cell cycle / 中华医学杂志(英文版)

BACKGROUND@#Systemic lupus erythematosus (SLE) is a complex autoimmune disease, and the mechanism of SLE is yet to be fully elucidated. The aim of this study was to explore the role of two-pore segment channel 2 (TPCN2) in SLE pathogenesis.@*METHODS@#Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression of TPCN2 in SLE. We performed a loss-of-function assay by lentiviral construct in Jurkat and THP-1 cell. Knockdown of TPCN2 were confirmed at the RNA level by qRT-PCR and protein level by Western blotting. Cell Count Kit-8 and flow cytometry were used to analyze the cell proliferation, apoptosis, and cell cycle of TPCN2-deficient cells. In addition, gene expression profile of TPCN2-deficient cells was analyzed by RNA sequencing (RNA-seq).@*RESULTS@#TPCN2 knockdown with short hairpin RNA (shRNA)-mediated lentiviruses inhibited cell proliferation, and induced apoptosis and cell-cycle arrest of G2/M phase in both Jurkat and THP-1 cells. We analyzed the transcriptome of knockdown-TPCN2-Jurkat cells, and screened the differential genes, which were enriched for the G2/M checkpoint, complement, and interleukin-6-Janus kinase-signal transducer and activator of transcription pathways, as well as changes in levels of forkhead box O, phosphatidylinositol 3-kinase/protein kinase B/mechanistic target of rapamycin, and T cell receptor pathways; moreover, TPCN2 significantly influenced cellular processes and biological regulation.@*CONCLUSION@#TPCN2 might be a potential protective factor against SLE.

SARS-CoV-2 hijacks neutralizing dimeric IgA for enhanced nasal infection and injury

Robust severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in nasal turbinate (NT) accounts for high viral transmissibility, yet whether neutralizing IgA antibodies can control it remains unknown. Here, we evaluated receptor binding domain (RBD)-specific monomeric B8-mIgA1 and B8-mIgA2, and dimeric B8-dIgA1 and B8-dIgA2 against intranasal SARS-CoV-2 challenge in Syrian hamsters. These antibodies exhibited comparably potent neutralization against authentic virus by competing with human angiotensin converting enzyme-2 (ACE2) receptor for RBD binding. While reducing viruses in lungs, pre-exposure intranasal B8-dIgA1 or B8-dIgA2 led to 81-fold more infectious viruses and severer damage in NT than placebo. Virus-bound B8-dIgA1 and B8-dIgA2 could engage CD209 as an alternative receptor for entry into ACE2-negative cells and allowed viral cell-to-cell transmission. Cryo-EM revealed B8 as a class II neutralizing antibody binding trimeric RBDs in 3-up or 2-up/1-down conformation. Therefore, RBD-specific neutralizing dIgA engages an unexpected action for enhanced SARS-CoV-2 nasal infection and injury in Syrian hamsters.

Endonuclease increases efficiency of osteoblast isolation from murine calvariae.

Bone is a highly dynamic organ that undergoes remodeling equally regulated by osteoblast-mediated bone formation and osteoclast-mediated bone resorption. To clarify the regulation of osteoblastogenesis, primary murine osteoblasts are required for an in vitro study. Primary osteoblasts are isolated from neonatal calvariae through digestion with collagenase. However, the number of cells collected from one pup is not sufficient for further in vitro experiments, leading to an increase in the use of euthanized pups. We hypothesized that the viscosity of digested calvariae and digestion solution supplemented with collagenase results in cell clumping and reduction of isolated cells from bones. We simply added Benzonase, a genetically engineered endonuclease that shears all forms of DNAs/RNAs, in order to reduce nucleic acid-mediated viscosity. We found that addition of Benzonase increased the number of collected osteoblasts by three fold compared to that without Benzonase through reduction of viscosity. Additionally, Benzonase has no effect on cellular identity and function. The new osteoblast isolation protocol with Benzonase minimizes the number of neonatal pups required for an in vitro study and expands the concept that isolation of other populations of cells including osteocytes that are difficult to be purified could be modified by Benzonase.

A case report of sporadic spinocerebellar ataxia type 23 / 中华神经科杂志

Spinocerebellar ataxias (SCAs), formerly known as autosomal dominant cerebellar ataxia, are a group of hereditary heterogeneous neurodegenerative disease that contains many subtypes. Spinocerebellar ataxia type 23 (SCA23), one type of SCAs, is caused by mutant prodynorphin (PDYN) gene. A 22-year-old patient was diagnosed with sporadic SCA23 due to gene detection, with a novel identified mutation, PDYN c.647C>T (p.P216L). Located in the dynorphin A-coding-region of PDYN gene, the pathogenic mechanism of the mutation may be relevant to the pathological changes caused by the variant including neurological dysfunction and death of cells. Mild improvement with the patient has been witnessed after active balance and speaking exercise.

Multi-parameter MRI signal analysis of labyrinth in patients with sudden deafness / 中华放射学杂志

Objective:To explore the clinical application value of each sequence by analyzing the characteristics of labyrinthine signal on MRI in patients with unilateral sudden deafness.Methods:Totally 52 patients of unilateral sudden deafness with inner ear MRI were analyzed retrospectively at Beijing Tongren Hospital, Capital Medical University from January 2016 to July 2019, all of which could find abnormalities in the labyrinth, including 17 cases of plain scan and 35 cases of enhanced scan, with sequences including plain T 1WI, enhanced T 1WI, plain and enhanced delayed 3D fluid attenuation inversion recovery (3D-FLAIR). The affected labyrinthine signal characteristics of each sequence were analyzed and the involvement sites were judged. The ability of each sequence to show labyrinthine abnormal signal was evaluated and scored. The Friedman test and Wilcoxon signed rank sum test were used to compare the subjective scores of the ability to show labyrinthine high signal in different sequences in plain and enhanced patients, respectively. Fisher′s exact probability method was used to analyze the relationship between the affected sites and the recovery of hearing, tinnitus and vertigo symptoms. Results:Fifty-two patients (100%, 52/52) showed labyrinthine high signal on T 1WI, 8 (15.4%, 8/52) showed higher signal and 3 (5.8%, 3/52) showed low signal on T 2WI. Thirty-five (100%, 35/35) showed high signal on enhanced T 1WI, among which 27 had enhancement (77.1%, 27/35). Fifty-two (100%, 52/52) showed significant high signal of the affected labyrinth on 3D-FLAIR (17 plain scan, 35 enhanced scan). The scores were 2 (2, 2), 3 (2, 3), 3 (3, 4) and 4 (4, 4) of T 1WI, enhanced T 1WI, plain and enhanced 3D-FLAIR respectively. The overall difference in subjective scores of plain T 1WI, enhanced T 1WI and enhanced 3D-FLAIR in enhanced patients was statistically significant (χ2=64.528, P<0.001), and the comparison between the two was statistically different (all corrected P<0.05). The plain 3D-FLAIR score was higher than the plain T 1WI in patients with a statistically significant difference ( Z=-3.729, P<0.001). Twenty-seven cases (51.9%, 27/52) exhibited high signal at the ampulla of semicircular canals, with a statistically significant difference in the distribution of hearing recovery or not ( P=0.001). Conclusions:Both T 1WI and 3D-FLAIR sequences can effectively identify the labyrinthine high signal, but the latter was better than the former of its ability to display, especially delayed enhanced 3D-FLAIR. The high signal at the ampulla of semicircular canals was a characteristic predictor of non-recovery of hearing.

Surgical approach for locally advanced hilar cholangiocarcinoma / 中华消化外科杂志

Hilar cholangiocarcinoma is a highly intractable malignancy, and most patients with this disease were diagnosed as a locally advanced stage at their initial presentation. Surgical resection remains as the only curative treatment for hilar cholangiocarcinoma. Hepatic surgeons focus on how to perform radical resection safely and effectively. For locally advanced hilar cholangio-carcinoma, aggressive surgical approach substantially increases the resectability of tumors which were initially regarded as unresectable. Hemihepatectomy or trisectionectomy combined with caudate lobectomy is the standard operation for radical resection of hilar cholangiocarcinoma, vascular resection and lymphadenectomy can be performed selectively. The safety and success of surgical approach is guaranteed by meticulous preoperative management such as preoperative biliary drainage and portal vein embolization, which prevent fatal postoperative complications. Multidisciplinary approach is required for the treatment of hilar cholangiocarcinoma. The combina-tion of aggressive surgical approach and adjuvant therapy remain a promising approach for further improving the resectability of tumors and the survival of patients.

Effects of decorin on proliferation, migration and invasion of bladder cancer cells / 国际肿瘤学杂志

Objective:To investigate the effects of decorin (DCN) on the proliferation, migration and invasion of bladder cancer cells.Methods:Bladder cancer T24 cell line was used as the research object. MTT assay was used to detect the inhibitory effect of DCN at different concentrations (0, 5, 10, 20, 30, 40, 50 mg/L) on T24 cell proliferation at 24, 48, 72 and 96 h. The effects of DCN on T24 cell cycle and apoptosis were analyzed by flow cytometry. MTT assay, Transwell migration and invasion experiments were used to detect the effects of DCN on the adhesion, migration and invasion ability of T24 cells. The effects of DCN on TGF-β1 and P21 protein expression were detected by ELISA and Western blotting.Results:T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN at 24, 48, 72 and 96 h, and there were statistically significant diffe-rences in cell proliferation activity ( F=168.64, P<0.001; F=165.81, P<0.001; F=291.02, P<0.001; F=148.93, P<0.001). T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN for 72 h, and the cell proliferation activities were (60.71±3.03)%, (40.82±2.09)%, (37.24±1.63)%, (25.65±2.55)%, (23.00±2.67)%, (10.78±1.17)%, (11.04±0.96)%, respectively, and there was a statistically significant difference. At the concentration of 40 mg/L, the proliferation activity reached the lowest level, and the inhibitory effect on cell proliferation was the strongest. At concentrations of 40 and 50 mg/L, the cells in G 1 phase reached the peak value, while the cells in S phase reached the lowest value, and the cells in G 2 phase remained unchanged throughout the treatment process. T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN for 72 h, and the apoptosis rates of cells were (12.18±1.17)%, (21.24±1.05)%, (19.80±1.20)%, (26.52±1.40)%, (30.86±1.40)%, (52.99±1.22)%, (43.04±2.16)%, respectively, and there was a statistically significant difference ( F=178.54, P<0.001). The differences between 5, 10, 20, 30, 40, 50 mg/L DCN and 0 mg/L DCN were all statistically significant (all P<0.001). When T24 cells were treated with 0, 40 mg/L DCN for 72 h, the cell adhesion rates were (37.14±1.35)% and (59.86±1.95)%, the numbers of migrated cells were 53.86±3.18 and 12.86±1.35, and there were statistically significant differences ( t=25.25, P<0.001; t=31.36, P<0.001). When DCN was applied to T24 cells for 48 h, the numbers of invasion at 0, 40 mg/L were 235.14±3.44 and 160.86±3.13, and there was a statistically significant difference ( t=2.27, P<0.001). When T24 cells were treated with 0, 5, 10, 20, 30, 40 and 50 mg/L DCN for 72 h, the relative expression levels of TGF-β1 were 85.67±3.35, 45.51±1.19, 49.93±4.15, 47.64±3.53, 46.05±3.18, 25.54±2.25, 33.44±4.05, and there was a statistically significant difference ( F=324.58, P<0.001). Compared with 0 mg/L DCN, 5, 10, 20, 30, 40 and 50 mg/L DCN could significantly inhibited the expression of TGF-β1 (all P<0.001). Compared with 0 mg/L DCN, P21 protein was upregulated 72 h after treatment with 40 mg/L DCN. Conclusion:DCN can inhibit proliferation and induce apoptosis of T24 cells in vitro, and has the effect of anti-metastasis of T24 cells.

Influence of physical activity patterns on academic performance in children and adolescents / 中国学校卫生

Abstract@#Physical activity promotes the physical and mental health of children and adolescents, and a growing body of research has demonstrated the positive effects of physical exercise, including better academic performance. This review presents a retrospective analysis of the existing literature in order to explore the relationship between physical activity patterns and academic performance in children and adolescents. This study analyzes the impact of differences in the duration, frequency, intensity, and type of physical activity on the academic performance of children and adolescents, which provides a basis for improving the quality and effect of such physical activities. High-quality evidence supports the view that long-term, high-frequency, aerobic physical activities of moderate-to-vigorous intensity have a positive impact on children and adolescents’ academic performance. This study provides a reference to help families, schools, and society to scientifically and rationally promote physical activity among children and adolescents.