Risk factors and predictive analysis of hyperkalemia after heart transplantation / 器官移植

Objective To analyze clinical prognosis, risk factors and predictive indexes of hyperkalemia in recipients after heart transplantation. Methods Clinical data of 158 recipients were retrospectively analyzed. According to the serum potassium levels within postoperative 1-year follow-up, all recipients were divided into the normal serum potassium level group (n=83), hyperkalemia group (n=43) and severe hyperkalemia group (n=32). The incidence and prognosis of hyperkalemia after heart transplantation were summarized. The risk factors and predictive indexes of hyperkalemia after heart transplantation were identified. Results The incidence of hyperkalemia and severe hyperkalemia within postoperative 1 year was 47.5%(75/158) and 20.3%(32/158), respectively. In the severe hyperkalemia group, the fatality was 16%(5/32), higher than 8%(7/83) in the normal serum potassium level group and 7%(3/43) in the hyperkalemia group. The mean serum creatinine (Scr) within 6 months before heart transplantation, the final total bilirubin level before heart transplantation, postoperative hemodialysis time, the Scr level and N-terminal pro-brain natriuretic peptide level at postoperative 1 d were the independent risk factors for hyperkalemia following heart transplantation (all P < 0.05). The mean Scr level within 6 months before heart transplantation, postoperative hemodialysis time, and Scr levels at postoperative 1 and 7 d could be used to predict postoperative severe hyperkalemia. Conclusions The recipients with severe hyperkalemia after heart transplantation obtain poor prognosis. The mean Scr level within 6 months before heart transplantation, the final total bilirubin level before heart transplantation, postoperative hemodialysis time, and the Scr level and N-terminal pro-brain natriuretic peptide level at postoperative 1 d are the independent risk factors for hyperkalemia after heart transplantation. Perioperative Scr level and postoperative hemodialysis time may be used to predict the incidence of severe hyperkalemia within 1 year after heart transplantation.

Progress and prospect of heart transplantation in children / 器官移植

Pediatric heart transplantation is the standard treatment for children complicated with refractory heart failure which is difficult to be treated by conventional surgery or drugs. At present, an increasing quantity of pediatric heart transplantation is being performed worldwide, whereas relevant experience is still lacking in China. In recent 10 years, significant progress has been achieved in pediatric heart transplantation. On one hand, the number of pediatric heart transplantation has been increased year by year. On the other hand, ABO-incompatible heart transplantation, application of ventricular assist device in children, and recipient-donor weight mismatch transplantation have been widely employed to resolve the shortage of donor heart in pediatric heart transplantation. However, relevant experience of pediatric heart transplantation is lacking in China, especially in understanding the indications of pediatric heart transplantation and the application of specific strategies for pediatric heart transplantation, etc. In this article, the development history, advances in therapeutic strategy and clinical prognosis of pediatric heart transplantation were reviewed.

Clinical immunologic analysis of 19 children with neuropsychiatric systemic lupus erythematosus / 中国医师杂志

Objective:To explore the clinical immune manifestations and high risk factors of children with neuropsychiatric systemic lupus erythematosus (NPSLE), so as to find the basis for early clinical differential diagnosis, prevention and treatment of NPSLE.Methods:Ninety-four children with systemic lupus erythematosus (SLE) admitted to Hunan Children′s Hospital from January 1, 2015 to April 30, 2022 were retrospectively selected. Among them, 19 children with NPSLE were in the NPSLE group, and 75 children without NPSLE were in the SLE group. The disease activity, immune system, lymphocyte subsets, inflammatory factors and autoantibodies were compared between the two groups.Results:Among 94 children with SLE, the incidence of NPSLE was 20.21%(19/94). The most common symptoms of 19 children with NPSLE were headache, epileptic seizure and cerebrovascular disease. The Systemic Lupus Erythematosus Disease Activity Index (SLEDAI)-2000 score was (19.89±8.33)points. Most of them had a good prognosis through hormone intervention. Compared with the SLE group, NPSLE group had higher SLEDAI-2000 score, white blood cell count, urine protein, erythrocyte sedimentation rate (ESR), interferon (IFN)-α, positive rate of anti-Sm antibody and anticardiolipin antibody, lower platelet count, interleukin-2 (IL-2), C 3, C 4 level (all P<0.05), while there was no significant difference in positive rate of anti-dsDNA antibody and anti-SSA antibody between the two group (both P>0.05). Conclusions:Compared with SLE children, children with NPSLE are often complicated with many kinds of abnormal immune function, mainly abnormal humoral immune function and many kinds of positive antibody, with increased inflammatory factors.

Characteristics of motor and non-motor symptoms in patients with rapid eye movement sleep behavior disorder and early Parkinson disease / 中华行为医学与脑科学杂志

Objective:To investigate the motor and non-motor symptoms and polysomnographic features in patients with rapid eye movement sleep behavior disorder (RBD), early Parkinson's disease (PD) with and without RBD.Methods:Patients with idiopathic RBD (IRBD) and early PD were collected from the clinics in West China Hospital of Sichuan University from August 2020 to May 2021.All the patients were divided into 3 groups including IRBD group (67 cases), PD with RBD (PD+ RBD) group (19 cases), and PD without RBD (PD-RBD) group (22 cases). Unified Parkinson's disease rating scale part 3 (UPDRS-Ⅲ), Hoehn-Yahr(H-Y) stage, Epworth sleepiness scale (ESS), REM sleep behavior disorder questionnaire-Hong Kong (RBDQ-HK), 17-item Hamilton depression scale(HAMD-17), mini-mental state examination(MMSE), Sniffin’Sticks olfactory function test, visual analogue scale (VAS), and scale for outcomes in Parkinson's disease-AUT(SCOPA-AUT) were used to assess the motor and non-motor symptoms including sleepiness, RBD, depression, cognitive function, olfactory function, pain and autonomic function respectively.All patients were performed to the polysomnography (PSG) examination.One-way ANOVA, Krukal-Wallis test, χ2 test and Fisher accurate test were used to analyze the data of motor and non-motor symptoms and sleep parameters among the 3 groups accordingly. Results:There were statistically significant differences in motor symptoms among the three groups ( F=57.009, P<0.05), and the scores of UPDRS Ⅲ and H-Y stage were higher in the PD+ /- RBD group than those in the IRBD group(both P<0.05). However, there was no significant difference in motor symptoms between PD+ RBD group and PD-RBD group ( P>0.05). There were no significant differences in the scores of ESS, MMSE, olfactory function test and VAS (all P>0.05). But the HAMD-17 score was significantly higher in the PD+ RBD group(2(1, 9)) than that in the IRBD group (0(0, 3)( P<0.05). The SCOPA-AUT scores of autonomic function were significant differences in the three groups, mainly in the digestive system, urinary system, and sexual function ( P<0.05). Notably, the IRBD group (8(4, 14)) and PD+ RBD group (11(7, 14)) had higher scores of SCOPA-AUT compared with PD-RBD group (4(4, 5.75)(all P<0.05), especially in the digestive dysfunction(all P<0.05). The PD+ RBD group(3.47±1.17) had higher scores of sexual function compared with IRBP group(1.78±0.60)( P<0.05), and the urinary system scores also higher than PD-RBD group( P<0.05). The PD-RBD group(21.30 (6.10, 34.00)/h) had a significantly higher oxygen desaturation index in REM sleep compared with that of IRBD group(5.90(2.70, 16.73)/h) ( P<0.05). Conclusions:Early PD with RBD has more severe non-motor symptoms, especially depression and autonomic dysfunction.RBD can be related with the earlier and more widely autonomic dysfunction.

Reconstruction of defects of distal-and-middle segments of finger pulps with striated wrist transverse flap carrying superficial palmar branch of radial artery with sensory nerve / 中华显微外科杂志

Objective:To evaluate the clinical effect of striated free wrist transverse flap pedicled with superficial palmar branch of radial artery carrying sensory nerve in repairing pulp defect of middle-and-distal segments of fingers.Methods:From February 2019 to March 2021, the data of 20 patients with defects of middle-and-distal finger segment were collected. The defects were repaired with striated free wrist transverse flaps pedicled with superficial palmar branch of radial artery. The defects sized were 2.0 cm×1.5 cm-4.0 cm×1.5 cm, and the flaps sized were 2.5 cm×2.0 cm-4.5 cm×2.0 cm. The flap carried metacarpal cutaneous branch of median nerve for the reconstruction of the sensation of finger pulps. The donor sites were directly sutured. After operation, the patients were evaluated according to the shape, sensation and functional recovery of the repaired fingers through outpatient visits and reviews via WeChat.Results:All 20 flaps survived and the wounds healed well. All patients entered regular follow-up for 6-12(average, 8) months. The colour of the flaps was close to the finger skin, without bloating flaps. The flaps were soft in good shapes and function. TPD were 6-11 mm, at 8 mm in average. The scars at the donor sites were hidden and the wrist function was not affected. According to the Trial Evaluation Standard of Upper Limb Function of Hand Surgery Society of Chinese Medical Association, 16 patients were classified as excellent and 4 as good.Conclusion:The striated transverse wrist flap with radial artery palmar superficial branch and sensory nerve offers many advantages, such as a good texture, hidden donor site, convenient flap harvesting, good recovery of sensation, etc. More clinical studies and the promotion of the technique are expected.

Effect of miltirone on proliferation and apoptosis of leukemia THP-1 cells / 中国中药杂志

To investigate the toxicity and related mechanism of miltirone to human acute myeloid leukemia THP-1 cells. To be specific, the active components and targets of miltirone were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP), and the target proteins were converted into standard gene names with UniProt. Acute leukemia-rela-ted target genes were screened from GeneCards and DisGeNET. Venn diagram was constructed with Venny 2.1 to yield the common targets of the disease and the drug. The protein-protein interaction(PPI) network was constructed by STRING and Cytoscape 3.8.2. THP-1 cells in the logarithmic growth phase were treated with dimethyl sulfoxide(DMSO), and 2.5, 5, 10, 15, and 20 μmol·L~(-1) miltirone for 24 h, respectively. The proliferation rate of cells was analyzed by carboxyfluorescein diacetate succinimidyl ester(CFSE), apoptosis rate by flow cytometry with Annexin V-PE/7 AAD staining, and cell morphology by acridine orange staining. Real-time quantitative PCR(qPCR) was employed to detect the mRNA levels of nuclear receptor coactivator 2(NCOA2), poly(ADP-ribose) polymerase-1(PARP1), B-cell lymphoma-2(Bcl-2)-associated X protein(Bax), Bcl-2, and cysteine aspartyl protease-3(caspase-3). The effect of miltirone on apoptosis was detected in presence of caspase inhibitor Z-VAD-FMK. A total of 26 targets of miltirone, 1 046 genes related to acute leukemia, and 6 common targets of the two were screened out. Flow cytometry result showed miltirone at 10 μmol·L~(-1) can inhibit proliferation and promote apoptosis of THP-1 cells. The typical manifestations of apoptosis, such as cell shrinkage, nuclear rupture, and chromatin agglomerate were displayed by acridine orange staining. The decreased mRNA levels of NCOA2 and PARP1 and increased Bax/Bcl-2 ratio and the activity of pro-apoptotic protein caspase-3 were observed. Z-VAD-FMK can attenuate the apoptosis-inducing effect of miltirone. This study indicates that miltirone can inhibit the proliferation and promote the apoptosis of THP-1 cells, by down-regulating NCOA2 and PARP1, raising Bax/Bcl-2 ratio, and activating caspase-3.

Application of three statistical models in association between polycyclic aromatic hydrocarbons exposure and cognitive level in workers / 环境与职业医学

Background As a complex organic pollutant, polycyclic aromatic hydrocarbons (PAHs) exposure shares the common exposure characteristics of multiple hydroxyl metabolites. Most studies have analyzed independent effect of each PAHs metabolite and have adjusted for the potential confounding effects induced by other metabolites concomitantly, without considering possible interactions among them. Proper statistical methods are needed to study their toxic effects. Objective To explore the applicability of logistic regression, weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR) in evaluating the correlation between mixed exposures to exogenous chemicals and health outcomes, compare the advantages and limitations of the three models, and propose analytical strategies for evaluating the health effects of mixed chemical exposure for application in the analysis of the association between PAHs exposure and cognition. Methods Urine samples were collected of workers from a coke oven plant and a water treatment plant in Shanxi Province, who participated in their routine employee healthexamination. Mono-hydroxylated PAHs were detected by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS), cognitive function was assessed using the Montreal Cognitive Assessment (MoCA). A cut-off value of MoCA less than 26 was considered mild cognitive impairment (MCI). According to a predetermined inclusion and exclusion criteria, 1 051 cases were included in the final data analysis. Logistic regression, WQS regression, and BKMR were used to analyze the relationship between PAHs metabolites and MCI. Results The prevalence rate of reporting MCI among the 1 051 workers was 21.7% (228/1 051). The concentration of 2-hydroxynathalene (2-OHNAP) was the highest among the 11 PAHs metabolites with a median concentration of 0.30 μg·L−1, followed by 9-hydroxyphenanthrene (9-OHPHE) (0.26 μg·L−1). There were significant differences between the two groups in 2-OHNAP, 1-hydroxynaphthalene (1-OHNAP), 2-hydroxyfluorene (2-OHFLU), 9-OHPHE, 1-hydroxyphenanthrene (1-OHPHE), and 1-hydroxypyrene (1-OHPYR) (all Ps<0.05). In the logistic regression, 2-OHNAP and 2-OHPHE were associated with MCI, and the OR (95%CI) for reporting MCI was 1.28 (1.01-1.67) and 1.27 (1.00-1.72) for each 10-fold increase in 2-OHNAP and 2-OHPHE concentrations, respectively. In the WQS regression analysis, the WQS index was positively correlated with the prevalence rate of reporting MCI (OR=1.37, 95%CI: 1.10-1.72). In the BKMR analysis, compared with the median exposure levels of all chemicals, the overall effect was statistically significant when all PAHs metabolites concentrations were at or above their 30th percentile; when all exposures were at the 75th percentile, the risk of reporting MCI increased by 6%. Conclusion Based on the results of these three models, 2-OHNAP and 2-OHPHE are the most important factors related to cognitive. It is recommended to use a combination of traditional logistic regression and either WQS or BKMR to study the association between PAHs and MCI.

Effects of inulin， resistant starch RS3 and their complexes on blood lipid levels and intestinal flora in mice / 上海预防医学

Objective To explore the effects of different dietary induction models of inulin， resistant starch RS3 and their complexes on the body weight and intestinal flora in mice. Methods A total of 64 C57BL/6 mice were randomly divided into low-fat control group， low-fat inulin group， low-fat resistant starch RS3 group， low-fat composite group and high-fat control group， high-fat inulin group， high-fat resistant starch RS3 group and high-fat composite group for dietary intervention. The mice were weighed and fresh feces were collected weekly. Diet intervention was continued until the weight of the high-fat control group was more than 14% higher than that of the low-fat control group. The mice were then sacrificed after overnight fasting. Liver and epididymal fat were weighed， and the colon contents were collected for 16S amplicon sequencing analysis. Results In low-fat diet fed mice， the combined induction of inulin and resistant starch RS3 caused a significant decrease in body weight gain. In high-fat diet fed mice， inulin alone and the combined induction both caused a significant reduction in weight gain， and there was no significant difference between the two methods. In the high-fat diet groups， inulin， resistant starch RS3， and the compound could be distinguished by Bacteroides， Bifidobacterium and Alloprevotella respectively. In the low-fat diet groups， inulin， resistant starch RS3， and the composite groups could be distinguished by Coriobacteriaceae_UCG_002， Bacteroides and Helicobacter， respectively. Conclusion Inulin and resistant starch RS3 diet induction can significantly reduce the weight gain of C57BL/6 mice， change the structure of intestinal flora， and show the difference between high-fat and low-fat diets. Inulin and resistant starch RS3 may reduce body weight and promote fat metabolism by changing the structure of intestinal flora.

Feasibility study of reducing the radiation dose on virtual non-contrast scanning in dual-layer spectral coronary CT angiography / 中华放射医学与防护杂志

Objective:To investigate the feasibility of reducing the radiation dose on coronary artery calcium score (CS) of virtual non-contrast (VNC) scanning in dual-layer spectral coronary CT angiography(CCTA).Methods:One hundred and twenty-two patients were examined on a dual-layer spectral detector CT scanner from March 2019 to August 2020. Volume CT dose index (CTDI vol), dose length product (DLP), effective dose ( E) were all evaluated for each patient. CS was calculated from both true non-contrast (TNC) and VNC images for left anterior descending (LAD), left circumflex (LCx), right coronary artery (RCA), and the total coronary artery (Total) by two radiologists independently. Pearson′s correlation coefficient was calculated for measuring the association between variables. The correction coefficients of each branch (λ LAD, λ LCx, and λ RCA) and the average correction coefficient (λ AVG) of the total coronary artery were obtained. The calibrated calcium score (CCS_VNC) was equal to λ multiplied by CS_VNC. The CS_TNC and CCS_VNC were compared using repeated oneway analysis of variance test. Correlation analyses for CS_TNC and CCS_VNC and agreement evaluation with Bland-Altman-Plots were performed. Results:The average effective doses in TNC, CCTA and total group were 0.69, 6.47 and 7.16 mSv, respectively. The effective dose was reduced by 10.6% and the scan time was reduced by 39% while using VNC images. There were significant differences among the CS_TNC and CS_VNC of LAD, LCx, RCA and Total ( t=6.75, 5.33, 4.99, 6.60, P< 0.05). Excellent correlations were observed between CS_VNC and CS_TNC ( R2 values were 0.929, 0.896, 0.958, and 0.918; λ values were 2.18, 1.18, 2.15, and 2.07, respectively). There were no significant statistically difference among the CS_TNC, CCS_VNC AVG, and CCS_VNC LAD/RCA of the LAD and RCA (all P> 0.05). The difference was statistically significant among the CS_TNC, CCS_VNC AVG, and CCS_VNC LCx of the LCx ( F=10.94, P<0.05). The paired comparison were performed in groups and the differences were statistically significant between the CS_TNC versus CCS_VNC AVGand CCS_VNC AVG versus CCS_VNC LCx ( t=3.31, 3.43, all P<0.05). There was no significant statistically difference between the CCS_VNC LCx and CCS_VNC AVG( P>0.05). Conclusions:It was feasible to accurately evaluate the CS_VNC from spectral data in comparison to TNC imaging, and to reduce the patient radiation dose and acquisition time.

Clinical application of the full-stack smart pelvic floor ultrasound to acquire and measure the minimal levator hiatus plane / 中华超声影像学杂志

Objective:To evaluate the feasibility of Full-stack Smart Pelvic Floor Ultrasound (FSPFU) software in the acquisition and measurement of the minimal levator hiatus (LH).Methods:Transperineal pelvic floor ultrasonography was performed in 119 women of 6-month postpartum from Nov.2020 to Jan.2021 of Shenzhen Second People′s Hospital. Mid-sagittal plane of pelvic floor was set as the initial plane, and the three-dimensional volume data was acquired. The dataset was stored in the machine. The offline volume data was manually adjusted to obtain the minimal LH images and measured by four physicians (two junior physicians as the D1 group and two senior physicians as the D2 group). For comparison, the results were also obtained using the fully automated method—the FSPFU software by a junior physician (the D3 group). The obtained parameters of minimal LH included area, circumference, anterioposterior diameter, transverse diameter, left and right levator-urethral gap distance. Analysis time was recorded for each group. The contours of minimal LH were outlined by three groups and the overlapping rate was calculated. The quality of the resulted images was evaluated and scored by another two senior physicians(A and B) independently.Results:The D3 group had a significant shorter analysis time compared with the other two groups, and the D1 group took a longer time than the D2 group, regardless of the cystocele severity (D1: 82.97 s, D2: 62.51 s, D3: 2.71 s, all P<0.05). The intergroup agreements and correlations of the minimum LH area were good (all ICC>0.85, rs>0.70, P<0.001) and the outlined contours were largely overlapped (>92%). There was no significant difference in image quality among the three groups(all P>0.05). Conclusions:FSPFU software can automatically obtain and measure the minimum LH in an efficient and accurate way, which can improve the effectiveness of the present pelvic floor examination. FSPFU software can be an useful tool in the diagnosis of pelvic floor dysfunctional diseases.

Thyroid hormone levels in healthy adults with non-occupational exposure to cadmium， lead and perfluoroalkyl substances / 上海预防医学

ObjectiveTo assess the effects of non-occupational mixed exposure to cadmium， lead and perfluoroalkyl substances （PFASs） on thyroid hormones （TH） in healthy adult residents in Shanghai. MethodsIn November 2018， adults in Shanghai Suburban Adult Cohort and Biobank study， who visited a community health service center for examination with no history of occupational exposure， thyroid diseases or chronic diseases， were recruited. A social-demographic information questionnaire survey was conducted and urine and blood samples were collected. Inductively coupled plasma mass spectrometry （ICP-MS） was used to measure their urinary cadmium （UCd）， blood cadmium （BCd） and blood lead （BPb） concentrations. Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （UPLC-Q/TOF MS） was used to measure 11 kinds of PFASs. Total and free triiodothyronine （TT3， FT3）， total and free thyroxine （TT4， FT4） and thyroid simulating hormones were measured by chemiluminescence enzyme-linked immunoassay. 436 participants were finally included and LASSO regression， multivariate regression and weighted quantile sum regression were used to evaluate the associations of these environmental pollutants with thyroid hormones. ResultsAmong the participants， 185 were male （42.5%） and the median age was 60 （P25‒P75： 50‒66）. The detection rates of urinary cadmium， blood cadmium and blood lead were all more than 95% and the detection rates of 7 PFASs （PFOS， PFOA， PFHxS， PFUnDA， PFNA， PFD， and PFBS） were more than 90%. The median exposure level of PFOA was the highest （49.6 µg‧L-1） among PFASs， followed by PFHxS （22.8 µg‧L-1） and PFOS （15.4 µg‧L-1）， and the median exposure levels of urinary cadmium， blood cadmium and blood lead were 0.7 μg‧g-1（Corrected for creatinine of urine）， 0.8 µg‧L-1， and 15.4 µg‧L-1， respectively. The results showed that UCd was negatively associated with TSH and BCd was positively associated with TT3， while PFASs mainly affected FT4， TT4， and TT3， with gender differences. In males， 7 PFASs had a significant negative mixture effect on TT3 and TT4， while the direction of effect of PFASs in females differed， with PFOS and PFUnDA having a significant positive correlation with FT4 and TT4 while PFDA having a significant negative correlation with FT4 and TT4. ConclusionIn a healthy population with no occupational exposure， co-exposure to cadmium， lead and PFASs affects different thyroid hormone indicators， and such effect could be gender-related， indicating that the effect of mixed exposure to metal and emerging compounds on thyroid functions warrants further attention.

A recurrent homozygous missense mutation in CCDC103 causes asthenoteratozoospermia due to disorganized dynein arms / 亚洲男科学杂志(英文版)

Asthenoteratozoospermia is one of the most severe types of qualitative sperm defects. Most cases are due to mutations in genes encoding the components of sperm flagella, which have an ultrastructure similar to that of motile cilia. Coiled-coil domain containing 103 (CCDC103) is an outer dynein arm assembly factor, and pathogenic variants of CCDC103 cause primary ciliary dyskinesia (PCD). However, whether CCDC103 pathogenic variants cause severe asthenoteratozoospermia has yet to be determined. Whole-exome sequencing (WES) was performed for two individuals with nonsyndromic asthenoteratozoospermia in a consanguineous family. A homozygous CCDC103 variant segregating recessively with an infertility phenotype was identified (ENST00000035776.2, c.461A>C, p.His154Pro). CCDC103 p.His154Pro was previously reported as a high prevalence mutation causing PCD, though the reproductive phenotype of these PCD individuals is unknown. Transmission electron microscopy (TEM) of affected individuals' spermatozoa showed that the mid-piece was severely damaged with disorganized dynein arms, similar to the abnormal ultrastructure of respiratory ciliary of PCD individuals with the same mutation. Thus, our findings expand the phenotype spectrum of CCDC103 p.His154Pro as a novel pathogenic gene for nonsyndromic asthenospermia.

Effects of NLRP3-mediated pyroptosis on olfaction dysfunction in allergic rhinitis / 中华耳鼻咽喉头颈外科杂志

Objective: To explore the relationship between NLRP3-mediated pyroptosis and olfactory dysfunction (OD) in allergic rhinitis (AR), and to evaluate the therapeutic potential of CY-09, a selective NLRP3 inhibitor for OD. Methods: An AR mouse model was established with ovalbumin, and the olfactory function of AR mice was detected by the buried food pellet test. Mice with OD were intraperitoneally injected with CY-09 or saline. The activation of microglia and astrocytes in olfactory bulb was detected by immunohistochemistry. The expression level of pyroptosis associated protein was detected by Western blot. The level of pyroptosis associated proinflammatory factor mRNA was determined by real-time PCR. SPSS 24.0 software was used for statistical analysis. Results: After the test, ovalbumin successfully established AR mice model, in which 52.5% (21/40) of them showed OD. The number of activated microglia and astroglia in olfactory bulb tissue in OD group were more than those in non-OD group (all P<0.05). Compared with the control group, the expression of NLRP3, caspase-1 and gasdermin D (GSDMD) was significantly increased in the olfactory bulb of the OD group (all P<0.05). CY-09 could significantly reduce the level of NLRP3, caspase-1, GSDMD, IL-1β and IL-18 expression, and inhibite the activation of microglia and astrocytes in the olfactory bulb tissues (all P<0.05). Conclusion: NLRP3-mediated pyroptosis is closely related to the OD associated with AR. CY-09 could improve the olfactory function in AR mice, which may be related to blocking the NLRP3-mediated pyroptosis.

The National Life Science Competition for College Students assists fostering life science talents in colleges and universities / 生物工程学报

The National Life Science Competition for College Students has been held for five times, which has become the largest and most influential life science competition in China. The competition is designed to follow principles of "interest-driven, scientific exploration, process evaluation and ability improvement". The holding of the competition has effectively improved the training quality of life science talents in colleges and universities. This paper summarized the development, organization and management of the competition as well as the organizational characteristics of the competition. It may serve as a guidance for colleges and universities to organize students to participate in the competition, and improve the fostering of talents in the field of life sciences in colleges and universities nationwide.

Recent progress on dissolution and absorption of amorphous solid dispersions / 药学学报

The amorphous solid dispersion is one of the most effective formulation approaches to enhance the oral bioavailability of poorly water-soluble drugs. However, the amorphous drugs tend to crystallize during storage or dissolution due to inadequate formulations, preparation techniques, storage and dissolution conditions, thus negating their advantages. Meanwhile, it is often difficult to establish in vitro-in vivo correlation for amorphous solid dispersions owing to the difference between dissolution media and physiological environments and between the apparent concentration and membrane transport flux, the dynamic process of the in vivo absorption, which put great challenges to the development of amorphous solid dispersion products. This review covers the recent progress on the mechanistic study of the in vitro dissolution and in vivo absorption of amorphous solid dispersions, aiming to provide guidance for the formulation development of poorly soluble drugs.

JAG1 promotes migration, invasion, and adhesion of triple-negative breast cancer cells by promoting angiogenesis / 南方医科大学学报

OBJECTIVE@#To investigate the effect of JAG1 on the malignant phenotype of triple-negative breast cancer (TNBC) and its role in angiogenesis in breast cancer microenvironment.@*METHODS@#The expressions of Notch molecules were detected in human TNBC 231 and 231B cells using RT-qPCR. Five female nude mice were inoculated with 231 cells and another 5 with 231B cells into the mammary fat pads, and 4-6 weeks later, the tumors were collected for immunohistochemical and immunofluorescence tests. 231 cells and 231B cells were treated with recombinant JAG (rJAG) protein and DAPT, respectively, and changes in their malignant phenotypes were assessed using CCK-8 assay, Hoechst 33258 staining, wound healing assay, Transwell chamber assay and endothelial cell adhesion assay. Western blotting was used to detect the changes in the expressions of proteins related with the malignant phenotypes of 231 and 231B cells. The effects of conditioned medium (CM) derived from untreated 231 and 231 B cells, rJAG1-treated 231 cells and DAPT-treated 231B cells on proliferation and tube formation ability of cultured human umbilical vein endothelial cells (HUVECs) were evaluated using CCK-8 assay and tube-forming assay.@*RESULTS@#The expression of JAG1 was higher in 231B cells than in 231 cells (P < 0.05). Tumor 231B showed higher expression of VEGFA and CD31. Compared with 231-Blank group, the migration, invasion and adhesion of 231 cells in 231-rJAG1 were significantly enhanced (P < 0.05). Protein levels of Twist1 and Snail increased (P < 0.01), anti-apoptotic protein Bcl-2 increased (P < 0.05), while DAPT inhibited the related phenomena and indicators of 231B. The 231-rJAG1-CM increased the cell number and tubule number of HUVEC (P < 0.05).@*CONCLUSION@#JAG1 may affect the malignant phenotype of TNBC and promote angiogenesis in the tumor microenvironment.

The success rate of His-Purkinje system pacing in patients with various sites of atrioventricular block / 中华心血管病杂志

Objective: To evaluate the success rate of His-Purkinje system pacing (HPSP) in patients with various sites of atrioventricular block (AVB) and provide clinical evidence for the selection of HPSP in patients with AVB. Methods: This is a retrospective case analysis. 637 patients with AVB who underwent permanent cardiac pacemaker implantation and requiring high proportion of ventricular pacing from March 2016 to September 2021 in the Department of Cardiology, General Hospital of Northern Theater Command were enrolled. The site of AVB was determined by electrophysiological examination. His bundle pacing (HBP) was performed in the first 130 patients (20.4%) who were classified as the HBP group and HPSP included HBP and/or left bundle branch pacing (LBBP) was performed in later 507 patients (79.6%) and these patients were classified as the HPSP group. The basic clinical information such as age and sex of the two groups was compared, and the success rates of HBP or HPSP in patients with different sites of AVB and QRS intervals were analyzed. Results: The age of HBP group was (66.4±15.9) years with 75 males (57.7%). The age of HPSP group was (66.8±13.6) years with 288 (56.8%) males. Among 637 patients, 63.0% (401/637) had atrioventricular node block; 22.9% (146/637) had intra-His block; 14.1% (90/637) had distal or inferior His bundle block. Totally, the success rate of HPSP was higher than that of HBP [93.9% (476/507) vs. 86.9% (113/130), P<0.05]. In each group of patients with various AVB sites, the success rate of HPSP was higher than that of HBP respectively and both success rates of HBP and HPSP showed a declining trend with the distant AVB site. The success rate of HBP in patients with atrioventricular node block and intra-His block was higher than that in patients with distal or inferior His bundle block [95.2% (79/83) vs. 47.1% (8/17), P<0.001; 86.7% (26/30) vs. 47.1% (8/17), P=0.010]. The success rate of HPSP was higher than that of HBP in patients with distal or inferior His bundle block [87.7% (64/73) vs 47.1% (8/17), P=0.001]. In patients with QRS<120 ms, 94.9% (520/548) of AVB sites were in atrioventricular node or intra-His, and HBP had a similar high success rate with HPSP [95.6% (109/114) vs. 96.3% (418/434), P=0.943] in these patients. In patients with QRS ≥ 120 ms, 69.7% (62/89) of AVB sites were at distal or inferior His bundle, and the success rate of HBP was only 25.0% (4/16), while the success rate of HPSP was as high as 79.5% (58/73), P<0.001. Conclusions: In patients with QRS<120 ms and atrioventricular node block or intra-His block, success rates of HBP and HPSP are similarly high and HBP might be considered as the first choice. In patients with QRS ≥ 120 ms and AVB site at distal or inferior His bundle, the success rate of HPSP is higher than that of HBP, suggesting LBBP should be considered as the first-line treatment option.

Logistic regression analyses for preoperative assessment of liver functional reserve based on virtual touch tissues quantification and fibrosis-4 / 中华肝胆外科杂志

Objective:To investigate the effect of logistic regression model based on virtual touch tissues quantification (VTQ) and fibrosis index based on four factors (FIB-4) in assessing impaired liver reserve function (LFR) in hepatic surgery patients before surgical resection.Methods:From January 2016 to October 2018, 173 patients including 135 males and 38 females with the mean age of 58.6 years old, scheduled for potential hepatectomy in Nanjing Drum Tower Hospital, the Affiliated Hospital of Nanjing University Medical School, were enrolled in our retrospective study. According to indocyanine green retention test at 15 minutes (ICG R15), the patients were divided into two groups, LFR-impaired group ( n=11, ICG R15≥20%) and control group ( n=162, ICG R15 < 20%). VTQ, FIB-4, platelet count and other parameters were compared between two groups. The multivariate logistic regression model was used to establish a risk model to access the impaired LFR. Receiver operating characteristic (ROC) curve was used to analyze the efficacy of each parameter in LFR-impaired. Results:The platelet count in LFR-impaired group was lower than that in control group, VTQ and FIB-4 were higher than that in control group (all P<0.05). Logistic regression showed that VTQ ( OR=4.382, 95% CI: 1.380-13.918)) and FIB-4 ( OR=2.112, 95% CI: 1.342-3.325) were risk factors for LFR-impaired. The final prediction model of LFR-impaired group was Logit (P)=-6.185+ 0.748×FIB-4+ 1.477×VTQ. The cut-off point (sensitivity, specificity, accuracy) of logistic model, FIB-4 and VTQ were 0.098 (72.8%, 90.1%, 89.0%), 0.990 (90.9%, 79.0%, 79.8%) and 1.8 m/s (81.8%, 77.8%, 78.0%), respectively. The specificity, accuracy of logistic model was higher than FIB-4 or VTQ. Conclusions:Logistic regression model based on VTQ and FIB-4 may improve the specificity and accuracy in the diagnosis of significant LFR impairment. VTQ can further assist clinicians in preoperative evaluation of LFR.

Effects of polygonatum polysaccharide on p38 MAPK/N-cadherin in zebrafish with Alzheimer disease / 中国药理学与毒理学杂志

OBJECTIVE To study the effect of polygonatum polysaccharide on zebrafish with Alzheimer disease. METHODS Zebrafish were trained in T maze for 7 d. The 40 zebrafish successfully trained were divided into 4 groups:blank group, model group, positive group and polygonatum polysaccharide group. Model group, positive group and polygonatum polysaccharide group were put in AlCl3100μg·L-1 for 6 d. The positive group was exposed to Huperzine A solution 4μg·L-1, and the polygonatum polysaccharide group was exposed to polygonatum polysaccharide solution 6 g·L-1 for 6 d. The model group was not treated, and the blank group was not treated. Each stage of zebrafish was recorded by video, and the time of each group in the EC region was analyzed. After administration, the brain tissue was taken out and the expression of N-cadherin, P38 and p-P38 protein factors was determined by Western blotting. RESULTS In behavior, the analysis of the time spent in the EC area, the blank group, the positive group and the polygonatum polysac?charide group were compared with the model group, respectively, there were statistically significant differences (P<0.05). At the protein level, compared with the model group, the P38 and p-P38 proteins in the positive group and the polygonatum polysaccharide group were down-regulated, while the N-cadherin protein was up-regulated, with statistical difference (P<0.05). CONCLUSION Polygonatum polysaccharide can improve the learning and memory ability of zebrafish with Alzheimer disease by up regulating the protein level of N-cadherin and hindering P38 phosphorylation.

Regulatory Effect of Modified Erzhu Erchentang on Patients with Polycystic Ovary Syndrome and Spleen Deficiency and Phlegm Dampness / 中国实验方剂学杂志

Objective:To observe the regulatory effect of modified Erzhu Erchentang on metabolization of polycystic ovary syndrome （PCOS） with spleen deficiency and phlegm dampness syndrome. Method:Patients 140 cases were divided into control group and observation group. Both groups were given metformin hydrochloride tablets， 500 mg/time， 3 times/day. Control group was given Yuejun Erchen pills， 0.5 g/time， 3 times/day， while observation group was given modified Erzhu Erchentang， 1 dose/day. The course of treatment lasted for 24 weeks. Before and after treatment， levels of fasting blood glucose （FBG）， fasting insulin （FINS）， glycosylated hemoglobin Alc （HbA1c）， 2-hour postprandial blood glucose （2 h PG）， blood lipid， waist circumference （WC）， body mass index （BMI）， waist hip ratio （WHR）， luteinizing hormone （LH）， follicle stimulating hormone （FSH）， serum testosterone （T）， estradiol （E₂）， dehydroepiandrosterone sulfate （DHEAS）， sex hormone binding globulin （SHBG）， leptin （LP）， adiponectin （APN）， resistin， visfatin and tumor necrosis factor-<italic>α</italic> （TNF-<italic>α</italic>） were detected. Homeostasis model assessment insulin resistance （HOMA-IR） was calculated， modified Erzhu Erchentang was scored， and recovery of menstruation and ovulation and ovarian volume were recorded. Result:Levels of FBG， 2 h PG， HbA1c， FINS， HOMA-IR， triglyceride （TG）， total cholesterol （TC）， low-density lipoprotein cholesterol （LDL-C）， LH， FSH， T， E₂， DHEAS， LP， resistin， visfatin and TNF-<italic>α</italic> in observation group were lower than those in control group （<italic>P</italic><0.01）， and levels of BMI， WC and WHR were lower than those of control group （<italic>P</italic><0.05）. And levels of high-density lipoprotein cholesterol （HDL-C）， SHBG and APN were higher than those in control group （<italic>P</italic><0.01）. Score of modified Erzhu Erchentang was lower than that in control group （<italic>P</italic><0.01）， and ovarian volume was smaller than that in control group （<italic>P</italic><0.01）. The normal rate of BMI was 49.23% （32/65）， which was higher than 30.30% （20/66） in control group （<italic>χ</italic>²=5.151， <italic>P</italic><0.05）. The normal rate of blood lipid was 93.85% （61/65）， which was higher than 81.82 % （54/66） in control group （<italic>χ</italic>²=4.418， <italic>P</italic><0.05）. The normal rate of blood glucose was 96.92% （63/65）， which was higher than 86.36% （57/66） in control group （<italic>χ</italic>²=4.474， <italic>P</italic><0.05）. Conclusion:In addition to adipocytokines， modified Erzhu Erchentang could regulate adipokines of patients of PCOS with spleen deficiency and phlegm dampness， improve glucose， lipid metabolism and overweight， adjust endocrine hormone， reduce clinical symptoms and improve ovarian structure， so as to create conditions for conception.