Study on the potential allergen and mechanism of pseudo-allergic reactions induced by combined using of Reduning injection and penicillin G injection based on metabolomics and bioinformatics / 药学学报

Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Impairment of Autophagic Flux After Hypobaric Hypoxia Potentiates Oxidative Stress and Cognitive Function Disturbances in Mice / 神经科学通报·英文版

Acute hypobaric hypoxic brain damage is a potentially fatal high-altitude sickness. Autophagy plays a critical role in ischemic brain injury, but its role in hypobaric hypoxia (HH) remains unknown. Here we used an HH chamber to demonstrate that acute HH exposure impairs autophagic activity in both the early and late stages of the mouse brain, and is partially responsible for HH-induced oxidative stress, neuronal loss, and brain damage. The autophagic agonist rapamycin only promotes the initiation of autophagy. By proteome analysis, a screen showed that protein dynamin2 (DNM2) potentially regulates autophagic flux. Overexpression of DNM2 significantly increased the formation of autolysosomes, thus maintaining autophagic flux in combination with rapamycin. Furthermore, the enhancement of autophagic activity attenuated oxidative stress and neurological deficits after HH exposure. These results contribute to evidence supporting the conclusion that DNM2-mediated autophagic flux represents a new therapeutic target in HH-induced brain damage.

Formulation and technology of oxymatrine-astragaloside IV coloaded liposomes based on quality by design / 药学学报

To optimize the formulation and technology of oxymatrine-astragaloside IV coloaded liposomes (Om-As-Lip) based on quality by design (QbD) principles, and further to verify the feasibility of its amplification process, Om-As-Lip was prepared by ethanol injection combined with pH gradient method. The critical material attributions of Om-As-Lip were evaluated by dual-risk analysis tools and Plackett-Burman design (PBD). The formulation of Om-As-Lip was further optimized with the Box-Behnken design (BBD). The design space was also established based on the contour plots of BBD. In order to further investigate the amplification process of Om-As-Lip, the critical process parameters of high-pressure homogenization (HPH) were optimized by single-factor test, and the quality of the final product was also evaluated. The results of risk analysis and PBD confirmed that the astragaloside concentration, cholesterol concentration, and phospholipid ratio (HSPC∶SPC) were the ctitical material attributes. The model established by BBD had a good predictability, and the optimized mass ratio of As to phospholipids was 1∶40, cholesterol to phospholipids was 1∶10, HSPC to SPC was 51∶9. The design space of Om-As-Lip was as follows: the ratio of cholesterol to phospholipids was 1∶12-1∶5 and HSPC to SPC was 1∶7-17∶3. The optimized high-pressure homogenization pressure was 600 bar, temperature was 4 ℃, and cycle times was 6 times for HPH-Om-As-Lip. The quality of Om-As-Lip prepared based on the QbD concept can meet the expected CQAs, and the formulation and technology established can provide a reliable experimental basis for its future development and applications.

Study on brain mechanism of rehabilitation training of articulation disorder in cleft lip and palate patients based on functional magnetic resonance imaging / 生物医学工程学杂志

The cleft lip and palate (CLP) is one of the most common craniofacial malformations in humans. We collected functional magnetic resonance data of 23 CLP patients before rehabilitation training (Bclp) and 23 CLP patients after rehabilitation training (Aclp), who were performing Chinese character pronunciation tasks, and performed brain activation analysis to explore the changes of brain mechanism in CLP patients after articulation disorder rehabilitation training. The study found that Aclp group had significant activation in the motor cortex, Broca area, Wernicke area and cerebellum. While the Bclp group had weak activation in the motor cortex with a small activation range. By comparing the differences and co-activated brain regions between the two groups, we found that rehabilitation training increased the activity level of negatively activated brain areas (cerebellum, left motor area, Wernicke area, etc.) to a positive level. At the same time, the activity level of weakly activated brain areas (right motor area, Broca area, etc.) was also increased. Rehabilitation training promoted the activity level of articulation-related brain regions. So that the activation intensity of articulation-related brain regions can be used as a quantifiable objective evaluation index to evaluate the effect of rehabilitation training, which is of great significance for the formulation of rehabilitation training programs.

Preparation of two tanshinone Ⅱ_A-astragaloside Ⅳ co-loaded nano-delivery systems and in vitro antitumor activity comparison / 中国中药杂志

This study screened excellent carriers for co-loading tanshinone Ⅱ_A(TSA) and astragaloside Ⅳ(As) to construct antitumor nano-drug delivery systems for TSA and As. TSA-As microemulsions(TSA-As-MEs) were prepared by water titration. TSA-As metal-organic framework(MOF) nano-delivery system was prepared by loading TSA and As in MOF by the hydrothermal method. Dynamic light scattering(DLS), transmission electron microscopy(TEM), and scanning electron microscopy(SEM) were used to characterize the physicochemical properties of the two preparations. Drug loading was determined by HPLC and the effects of the two preparations on the proliferation of vascular endothelial cells, T lymphocytes, and hepatocellular carcinoma cells were detected by the CCK-8 method. The results showed that the particle size, Zeta potential, and drug loading of TSA-As-MEs were(47.69±0.71) nm,(-14.70±0.49) mV, and(0.22±0.01)%, while those of TSA-As-MOF were(258.3±25.2) nm,(-42.30 ± 1.27) mV, and 15.35%±0.01%. TSA-As-MOF was superior to TSA-As-MEs in drug loading, which could inhibit the proliferation of bEnd.3 cells at a lower concentration and improve the proliferation ability of CTLL-2 cells significantly. Therefore, MOF was preferred as an excellent carrier for TSA and As co-loading.

Analysis of the risk factors for extracorporeal membrane oxygenation use after surgical repair in patients with anomalous origin of the left coronary artery from the pulmonary artery combined with severe left ventricular dysfunction / 中国胸心血管外科临床杂志

@#Objective    To analyze the early outcomes of anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) patients with severe left ventricular dysfunction after surgical repair, and to explore the predictors for extracorporeal membrane oxygenation (ECMO) support for these patients. Methods    The clinical data of ALCAPA patients with severe left ventricular dysfunction (left ventricular ejection fraction<40%) who underwent coronary artery reimplantation in the pediatric center of our hospital from 2013 to 2020 were retrospectively analyzed. The patients were divided into an ECMO group and a non-ECMO group. Clinical data of the two groups were compared and analyzed. Results    A total of 64 ALCAPA patients were included. There were 7 patients in the ECMO group, including 4 males and 3 females aged 6.58±1.84 months. There were 57 pateints in the non-ECMO group, including 30 males and 27 females aged 4.34±2.56 months. The mortality of the patients was 6.25% (4/64), including 2 patients in the ECMO group, and 2 in the non-ECMO group. The postoperative complications rate was significantly higher in the ECMO group than that in the non-ECMO group (P=0.041). There were statistical differences in the cardiopulmonary bypass time [254 (153, 417) min vs. 106 (51, 192) min, P=0.013], aortic cross-clamping (ACC) time (89.57±13.66 min vs. 61.58± 19.57 min, P=0.039), and preoperative left ventricular end-diastolic diameter/body surface area (132.32±14.71 mm/m2 vs. 108.00±29.64 mm/m2, P=0.040) between the two groups. Multivariate logistic regression analysis showed that ACC time was an independent risk factor for postoperative ECMO support (P=0.005). Receiver operating characteristic (ROC) curve analysis showed that the area under the ROC curve was 0.757, the sensitivity was 85.70%, specificity was 66.70%, with the cut-off value of 66 min. Conclusion    ACC time is an independent risk factor for postoperative ECMO support. Patients with an ACC time>66 min have a significantly higher risk for ECMO support after the surgery.

Application of the Chinese Expert Consensus on Diabetes Classification in clinical practice / 中华内科杂志

Objective:To evaluate the diagnostic for classification of newly diagnosed diabetes patients and assess the application of the screening tests recommended by the 2022 Chinese Expert Consensus on Diabetes Classification.Methods:Retrospective case series study. The data from the electronic medical record system of patients with new-onset diabetes mellitus (within 1 year of disease onset) who attending the Diabetes Specialist Outpatient Clinic at the Second Xiangya Hospital of Central South University from January 1, 2018 to December 31, 2021 were collected for the analysis. Based on the consensus, patients were categorized according their age of onset, body mass index (BMI), and suspicion of type 1 diabetes mellitus (T1DM). The chi-square statistic was used to compare key classifier indicators, including C-peptide, islet autoantibodies, and genetic markers, in the subgroups. The diagnosis in suspected T1DM patients was also evaluated. The screening strategy recommended in the consensus was further assessed using a logistic regression model and the area under the receiver-operating curve (AUC).Results:A total of 3 384 patients with new-onset diabetes were included. The average age of disease onset was (46.3±13.9) years, and 61.0% (2 065/3 384) of the patients were male. The proportions of patients who completed C-peptide and glutamic acid decarboxylase antibody (GADA) tests were 36.6% (1 238/3 384) and 37.5% (1 269/3 384), respectively. There were no significant differences in C-peptide test results among the subgroups (all P>0.05). In contrast, the GADA detection rate was higher in patients with young age of onset (<30 years old), in those who were non-obese (BMI<24 kg/m 2), and in those clinically suspected of T1DM (all P<0.05). According to the diagnostic pathway proposed by the consensus, only 57.4% (1 941/3 384) of patients could be subtyped. For a definitive diagnosis, the remaining patients needed completion of C-peptide, islet autoantibody, genetic testing, or follow-up. Furthermore, among patients with clinical features of suspected T1DM, the antibody positivity rate was higher than in non-suspected T1DM patients [24.5% (154/628) vs. 7.1% (46/646), P<0.001]. When the clinical features of suspected T1DM defined in the consensus were taken as independent variables and antibody positivity was considered the outcome variable in the logistic regression model, young onset, non-obese onset, and ketosis onset could enter the model. Based on AUC analysis, the accuracy of the diagnostic model was 0.77 (95% CI 0.73-0.81), suggesting that the clinical features of suspected T1DM in the consensus have good clinical diagnostic value for this patient subgroup. Conclusions:There was a significant discrepancy between the clinical practice of diabetes classification and the process recommended by the consensus, which was specifically reflected in the low proportions of both subtyping indicator testing and definitively subtyped diabetes patients. Attention should be pay to the classification diagnosis process proposed in the consensus and the clinical detection rate of key diabetes subtyping indicators such as C-peptide and islet autoantibodies for diabetes classification should be improved. Noteworthy, the screening strategy for T1DM proposed by the consensus showed good clinical application value.

The impact of flash glucose monitoring on glycemic control, residual islet function, and patient-reported outcomes in children and adolescents with newly diagnosed type 1 diabetes / 中国医师杂志

Objective:To assess the effect of flash glucose monitoring (FGM) compared with self-monitoring of blood glucose (SMBG) on glycemic control, residual islet function, and patient-reported outcomes in children and adolescents with newly diagnosed type 1 diabetes within 1 year.Methods:133 children and adolescents with newly diagnosed T1DM in the T1D clinic of the Second Xiangya Hospital of Central South University from January 2016 to January 2020 were divided into two groups: FGM group ( n=82) and SMBG group ( n=51). The observation indexes included hemoglobin A1c (HbA 1c), fasting and postprandial blood glucose (FBG and 2 h BG), C-peptide (FCP and 2 h CP) during the one-year follow-up, Δ CP (2 h CP-FCP), patient-reported hypoglycemia and questionnaires regarding self-management of diabetes and quality of life. Results:At 6 months, HbA 1c in 2 groups was significantly decreased (all P<0.05); at 6 to 12 months, HbA 1c in FGM group tended to be stable ( P>0.05); at 12 months, HbA 1c in SMBG group was significantly increased compared with 6 months ( P=0.001). At 12 months, HbA 1c in SMBG group was higher than that in FGM group ( P=0.001). At 12 months, FBG in FGM group was equivalent to the baseline level ( P>0.05), while FBG in SMBG group was significantly higher than the baseline level ( P=0.006). 2 h BG only decreased at the 6th and 12th month in FGM group (all P<0.05). The FCP of SMBG group was significantly decreased at 12 months ( P<0.05), and the 2 h CP, Δ CP in the two groups decreased gradually (all P<0.05). FGM group had more hypoglycemic events at 6 and 12 months (all P<0.05). At 6 months, the score of Self-Management of T1D for Adolescents (SMOD-A) in FGM group was significantly improved ( P=0.001). During the follow-up period, the quality of life score of FGM group was stable ( P>0.05), while the quality of life score of SMBG group had a downward trend ( P=0.052). Conclusions:In newly diagnosed children and adolescents with T1DM, early application of FGM for blood glucose management will help to improve HbA 1c and reduce postprandial blood glucose. In addition, the self-management ability of children with FGM was improved after 6 months.

Clinical efficacy of etocoxib combined with low dose colchicine in the treatment of acute gouty arthritis in 37 patients / 中国基层医药

Objective:To investigate the clinical efficacy of etocoxib combined with low-dose colchicine in the treatment of acute gouty arthritis in 37 patients.Methods:A total of 74 patients with acute gouty arthritis who received treatment in The Second People's Hospital of Liaocheng from October 2019 to October 2021 were included in this study. They were randomly assigned to undergo treatment with etocoxib alone (control group, n = 37) or etocoxib combined with low-dose colchicine (observation group, n = 37). All patients were treated for 1 week. Clinical efficacy, Visual Analogue Scale score, laboratory indicators, incidence of adverse reactions, and Quality of Life Comprehensive Assessment Questionnaire-74 score were compared between the two groups. Results:The total response rate in the observation group was significantly higher than that in the control group [95% (35/37) vs. 65% (24/37)]. At 1, 3, and 6 days after treatment, the Visual Analogue Scale score in the observation group was significantly lower than that in the control group ( t = 19.77, 15.43, 29.01, all P < 0.001). After treatment, blood uric acid, C-reactive protein, and erythrocyte sedimentation rate in the observation group was (432.26 ± 31.26) μmol/L, (16.25 ± 1.62) mg/L, (31.26 ± 1.25) mm/h, respectively, which was significantly lower than (485.26 ± 39.62) μmol/L, (45.26 ± 3.88) mg/L, (46.52 ± 2.82) mm/h in the control group ( t = 6.39, 41.97, 30.09, all P < 0.001). Quality of Life Comprehensive Assessment Questionnaire-74 score in the observation group was significantly higher than that in the control group ( t = 13.41, 17.73, 16.09, 11.77, all P < 0.001). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Etocoxib combined with low-dose colchicine can effectively reduce pain and inflammatory reactions in patients with acute gouty arthritis and improve quality of life, with a low incidence of adverse reactions.

Epidemiological characteristics of varicella public health emergency events in Xinwu District Wuxi City in 2016-2020 / 公共卫生与预防医学

Objective To investigate the epidemiological characteristics of varicella public health emergency events (PHEEs) in Xinwu District from 2016 to 2020, and to provide a scientific basis for formulating prevention and control measures. Methods Data was retrieved from “Public Health Emergency Management Information System” in "Chinese Disease Control Information System" and “Jiangsu Provincial Vaccine Management Information System”. Descriptive epidemiological methods were employed to analyze the data. SPSS software was used for statistical analysis. Results A total of 35 varicella PHEEs were reported in Xinwu District from 2016 to 2020, accounting for 57.38% of all PHEEs of infectious diseases in the same period. A total of 1 033 cases were reported, with an attack rate of 1.91%. The events showed a bimodal distribution. A small peak occurred from April to June, and the number of events accounted for 17.14%. A large peak occurred from November to January of the following year, and the number of events accounted for 82.86%. All events occurred in schools. Kindergartens were the most dangerous places, and the number of events accounted for 45.71%. Preschoolers aged 3-6 years accounted for 48.83% of the total cases, and the male-to-female ratio of students was 1.40:1. Among 234 cases with a history of immunization with Varicella Attenuated Live Vaccine (VarV), the longer the time interval from the date of VarV inoculation to the data of onset, the higher the proportion of varicella cases. Varicella PHEEs reporting time was positively correlated with duration (rs=0.391 , P<0.05). Conclusion Early detection, early reporting and early isolation can effectively control the duration of the event. School varicella surveillance should be strengthened during the epidemic peak period. Preschoolers are vulnerable groups. It is suggested that VarV should be included in the inspection work for enrollment in kindergartens.

Changes and its influencing factors of procalcitonin in pediatric cardiac surgery under cardiopulmonary bypass / 中国胸心血管外科临床杂志

@#Objective    To explore the natural changes of procalcitonin (PCT) in the early period after pediatric cardiac surgery with cardiopulmonary bypass (CPB). Methods    A prospective and observational study was done on patients below 3 years of age, who underwent cardiac surgery involving CPB, with the risk adjustment of congenital heart surgery (RACHS) score of 2 to 5 and free from active preoperative infection or inflammatory disease. Blood samples for measurement of PCT, C-reactive protein (CRP) and white blood cell (WBC) were taken before surgery and daily for 7 days in postoperative period. Infections and complications within 7 days after operation were investigated. According to the presence or absence of infection and complications within 7 days after operation, the enrolled children were divided into an infection+complications group, a simple infection group, a simple complication group, and a normal group. Results     Finally, 429 children with PICU stay≥ 4 days were enrolled, including 268 males and 161 females, with a median age of 8.0 (0.7, 26.0) months. There were 145 children in the simple infection group, 38 children in the simple complication group, 230 children in the normal group and 16 children in the infection+complications group. The levels of PCT, CRP and WBC were significantly higher after CPB. CRP and WBC peaked on the second postoperative day (POD) and remained higher than normal until POD7. PCT peaked on POD1 and would generally decrease to normal on POD5 if without infection and complications. Age, body weight, RACHS scores, the duration of CPB and aortic cross-clamping time were correlated with PCT level. There was a statistical difference in PCT concentration between the simple infection group and the normal group on POD 3-7 (P<0.01) and a statistical difference between the simple complication group and the normal group on POD 1-7 (P<0.01). A statistical difference was found between the simple infection group and the simple complication group in PCT on POD 1-5 (P<0.05). Conclusion    WBC, CRP and PCT significantly increase after CPB in pediatric cardiac surgery patients. The factors influencing PCT concentration include age, weight, RACHS scores, CPB and aortic cross-clamping time, infection and complications.

Mechanism of electroacupuncture regulating the ligand pathway of tyrosine kinase receptor in improving vascular dementia / 解剖学报

Objective To observe the potential mechanism of electroacupuncture regulating the erythropoietin-producing hepatocellular receptor B2/erythropoietin-producing hepatocellular receptor-interacting B2/big mitogen-activated protein kinase 1(EphB2/EphrinB2/BMK1) signaling pathway to improve neural damage in vascular dementia rats. Methods Eighty SD male adult rats were randomly divided into a sham surgery group, a model group, a non acupoint electroacupuncture group, a nimodipine group, and an electroacupuncture three needle group. The vascular dementia rat model was made by the modified Pulsinelli four vessel occlusion method. After grouping, the rats in each group were subjected to water maze test, HE staining, Nissl staining, and transmission electron microscopy(TEM) to observe the pathological changes in the hippocampal CA1 area, and the expression of EphB2 and BMK1 in the hippocampal CA1 area was detected by immunohistochemistry; Detection of EphB2 and BMK1 protein expression in rat hippocampal CA1 region was detected by Western blotting. Results Compared with the model group, the escape latency of vascular dementia rats treated with electroacupuncture and nimodipine decreased (P0.05). Compared with the nimodipine group, the expression of EphB2 and BMK1 in the hippocampal CA1 region of rats in the electroacupuncture Zhisanzhen group significantly increased (P<0.05). Conclusion Electroacupuncture may improve the damage of hippocampal neurons in vascular dementia rats by increasing the expression of EphB2 and BMK1 in the CA1 region of the hippocampus, thereby improving the learning and memory of vascular dementia rats.

Mechanism of Bawei Chenxiang powder in treatment of ischemie heart disease through mitophagy based on network pharmacology / 中国药理学通报

Aim To explore the potential mechanism of Bawei Chenxiang powder against ischemie heart disease (IHD) through mitophagy based on network pharmacology, molecular docking and verification in vitro. Methods The targets of serum constituents of Bawei Chenxiang powder were mined by Swiss target predic-tion, and then the targets related to IHD and mitophagy were selected from Genecards, NCBI and OMIM data-bases to obtain the intersection targets of the three as the potential targets of Bawei Chenxiang powder for the treatment of IHD through mitophagy. Then the "ingre-dients-disease-potential target " network and " protein-protein interaction" (PPI) network were constructed to perform network analysis in order to screen the key ac-tive ingredients and core targets, using Autodock vina software for molecular docking operation. The targets CO function enrichment analysis and KEGG pathway enrichment analysis were analyzed by DAVID databas-es. The effeets of Bawei Chenxiang powder containing serum on celi viability, levels expressions mitophagy and key signaling pathway related protein in H9C2 cells were investigated by hypoxia-induced injury of H9c2 myocardial cells model in vitro. Results The 9 key active compounds and 8 core targets of Bawei Chenxiang powder were screened; molecular docking showed a good binding ability of key active ingredients and core targets. KEGG pathway enrichment analysis showed that the effect of Bawei Chenxiang powder on IHD through mitophagy was related to EGFR, PI3K-Akt, MAPK, FoxO signaling pathway, etc. Celi ex-periments showed that Bawei Chenxiang powder containing serum treatment could significantly improve the survival rate by hypoxia-induced injury in H9c2, the expression of LC3II and p62 were significantly down-regulated, and the expressions of p-PI3K/PI3K and p-AKT/AKT were significantly up-regulated. Conclu-sions Bawei Chenxiang powder plays an anti-IHD role by regulating mitophagy, which may be involved in AKT1, STAT3, MAPK3 and EGFR and other targets, through quercetin, Kaempferol, Naringenin and De-hydrodiisoeugenol as well as other components. Its mechanism may be related to improving PI3K-AKT pathway.

Report content and prenatal diagnosis of non-invasive prenatal testing for sex chromosome aneuploidy / 中华妇产科杂志

Objective: To analyze the report content, the methods and results of prenatal diagnosis of high risk of sex chromosome aneuploidy (SCA) in non-invasive prenatal testing (NIPT). Methods: A total of 227 single pregnancy pregnant women who received genetic counseling and invasive prenatal diagnosis at Drum Tower Hospital Affiliated to the Medical School of Nanjing University from January 2015 to April 2022 due to the high risk of SCA suggested by NIPT were collected. The methods and results of prenatal diagnosis were retrospectively analyzed, and the results of chromosome karyotype analysis and chromosome microarray analysis (CMA) were compared. The relationship between NIPT screening and invasive prenatal diagnosis was analyzed. Results: (1) Prenatal diagnosis methods for 277 SCA high risk pregnant women included 73 cases of karyotyping, 41 cases of CMA and 163 cases of karyotyping combined with CMA, of which one case conducted amniocentesis secondly for further fluorescence in situ hybridization (FISH) testing. Results of invasive prenatal diagnosis were normal in 166 cases (59.9%, 166/277), and the abnormal results including one case of 45,X (0.4%, 1/277), 18 cases of 47,XXX (6.5%, 18/277), 36 cases of 47,XXY (13.0%, 36/277), 20 cases of 47,XYY (7.2%, 20/277), 1 case of 48,XXXX (0.4%, 1/277), 20 cases of mosaic SCA (7.2%, 20/277), 5 cases of sex chromosome structural abnormality or large segment abnormality (1.8%, 5/277), and 10 cases of other abnormalities [3.6%, 10/277; including 9 cases of copy number variation (CNV) and 1 case of balanced translocation]. Positive predictive value (PPV) for SCA screening by NIPT was 34.7% (96/277). (2) Among the 163 cases tested by karyotyping combined with CMA, 11 cases (6.7%, 11/163) showed inconsistent results by both methods, including 5 cases of mosaic SCA, 1 case of additional balanced translocation detected by karyotyping and 5 cases of additional CNV detected by CMA. (3) NIPT screening reports included 149 cases of "sex chromosome aneuploidy"(53.8%, 149/277), 54 cases of "number of sex chromosome increased" (19.5%, 54/277), and 74 cases of "number of sex chromosome or X chromosome decreased" (26.7%, 74/277). The PPV of "number of sex chromosome increased" and "number of sex chromosome or X chromosome decreased" were 72.2% (39/54) and 18.9% (14/74), respectively, and the difference was statistically significant (χ2=34.56, P<0.01). Conclusions: NIPT could be served as an important prenatal screening technique of SCA, especially for trisomy and mosaicism, but the PPV is comparatively low. More information of NIPT such as the specific SCA or maternal SCA might help improving the confidence of genetic counseling and thus guide clinic management. Multi technology platforms including karyotyping, CMA and FISH could be considered in the diagnosis of high risk of SCA by NIPT.

Analysis of 59 cases of large vestibular aqueduct syndrome SLC26A4gene mutation frequency and new mutation sites / 临床耳鼻咽喉头颈外科杂志

Objective:To study the frequency of SLC26A4 gene mutation sites in children with enlarged vestibular aqueduct deafness in Yunnan, report the new mutation sites of SLC26A4 gene, further clarify the mutation spectrum of SLC26A4gene, and explore the association between biallelic and monoallelic mutations of SLC26A4 gene and CT phenotype of inner ear, so as to provide basis for clinical and genetic diagnosis of deafness. Methods:Review the results of temporal bone CT examination of 390 children after cochlear implantation in the Department of Otolaryngology, Kunming Children's Hospital from August 2016 to September 2021. Sanger sequencing of SLC26A4 gene was performed in 59 children with enlarged vestibular aqueduct. According to the genetic test results, the children who underwent temporal bone CT examination were divided into two groups: SLC26A4 biallelic mutation group（homozygous mutation and compound heterozygous mutation）, monoallelic mutation group, and the association with inner ear CT phenotype was analyzed, and the new sites were summarized and analyzed. Results:The c.919-2a>g mutation was the most common mutation in children with enlarged vestibular aqueduct with SLC26A4 gene mutation. Three new variants of SLC26A4 gene were found; CT examination combined with genetic testing found that a part of children with enlarged vestibular aqueduct was associated with SLC26A4 monoallelic mutation or no SLC26A4 gene mutation was detected. Further research is needed to investigate the involvement of other pathogenic factors in the pathogenesis of EVA.

ACSL5, a prognostic factor in acute myeloid leukemia, modulates the activity of Wnt/β-catenin signaling by palmitoylation modification / 医学前沿

Acyl-CoA synthetase long chain family member 5 (ACSL5), is a member of the acyl-CoA synthetases (ACSs) family that activates long chain fatty acids by catalyzing the synthesis of fatty acyl-CoAs. The dysregulation of ACSL5 has been reported in some cancers, such as glioma and colon cancers. However, little is known about the role of ACSL5 in acute myeloid leukemia (AML). We found that the expression of ACSL5 was higher in bone marrow cells from AML patients compared with that from healthy donors. ACSL5 level could serve as an independent prognostic predictor of the overall survival of AML patients. In AML cells, the ACSL5 knockdown inhibited cell growth both in vitro and in vivo. Mechanistically, the knockdown of ACSL5 suppressed the activation of the Wnt/β-catenin pathway by suppressing the palmitoylation modification of Wnt3a. Additionally, triacsin c, a pan-ACS family inhibitor, inhibited cell growth and robustly induced cell apoptosis when combined with ABT-199, the FDA approved BCL-2 inhibitor for AML therapy. Our results indicate that ACSL5 is a potential prognosis marker for AML and a promising pharmacological target for the treatment of molecularly stratified AML.

Prevalence of maturity-onset diabetes of the young in phenotypic type 2 diabetes in young adults: a nationwide, multi-center, cross-sectional survey in China / 中华医学杂志(英文版)

BACKGROUND@#Maturity-onset diabetes of the young (MODY) is the most common monogenic diabetes. The aim of this study was to assess the prevalence of MODY in phenotypic type 2 diabetes (T2DM) among Chinese young adults.@*METHODS@#From April 2015 to October 2017, this cross-sectional study involved 2429 consecutive patients from 46 hospitals in China, newly diagnosed between 15 years and 45 years, with T2DM phenotype and negative for standardized glutamic acid decarboxylase antibody at the core laboratory. Sequencing using a custom monogenic diabetes gene panel was performed, and variants of 14 MODY genes were interpreted as per current guidelines.@*RESULTS@#The survey determined 18 patients having genetic variants causing MODY (6 HNF1A , 5 GCK , 3 HNF4A , 2 INS , 1 PDX1 , and 1 PAX4 ). The prevalence of MODY was 0.74% (95% confidence interval [CI]: 0.40-1.08%). The clinical characteristics of MODY patients were not specific, 72.2% (13/18) of them were diagnosed after 35 years, 47.1% (8/17) had metabolic syndrome, and only 38.9% (7/18) had a family history of diabetes. No significant difference in manifestations except for hemoglobin A1c levels was found between MODY and non-MODY patients.@*CONCLUSION@#The prevalence of MODY in young adults with phenotypic T2DM was 0.74%, among which HNF1A -, GCK -, and HNF4A -MODY were the most common subtypes. Clinical features played a limited role in the recognition of MODY.

Effect of wheat-grain moxibustion on Wnt/β-catenin signaling pathway in bone marrow cell in mice with bone marrow inhibition / 中国针灸

OBJECTIVE@#To observe the effect of wheat-grain moxibustion at "Dazhui" (GV 14), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6) on Wnt/β-catenin signaling pathway in bone marrow cell in mice with bone marrow inhibition, and to explore the possible mechanism of wheat-grain moxibustion in treating bone marrow inhibition.@*METHODS@#Forty-five SPF male CD1(ICR) mice were randomly divided into a blank group, a model group and a wheat-grain moxibustion group, 15 mice in each group. The bone marrow inhibition model was established by intraperitoneal injection of 80 mg/kg of cyclophosphamide (CTX). The mice in the wheat-grain moxibustion group were treated with wheat-grain moxibustion at "Dazhui" (GV 14), "Zusanli" (ST 36) and "Sanyinjiao" (SP 6), 3 moxa cones per acupoint, 30 s per moxa cone, once a day, for 7 consecutive days. The white blood cell count (WBC) was measured before modeling, before intervention and 3, 5 d and 7 d into intervention. After intervention, the general situation of mice was observed; the number of nucleated cells in bone marrow was detected; the serum levels of interleukin-3 (IL-3), interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) were measured by ELISA; the protein and mRNA expression of β-catenin, cyclinD1 and C-Myc in bone marrow cells was measured by Western blot and real-time PCR method.@*RESULTS@#Compared with the blank group, the mice in the model group showed sluggish reaction, unstable gait, decreased body weight, and the WBC, number of nucleated cells in bone marrow as well as serum levels of IL-3, IL-6, GM-CSF were decreased (P<0.01), and the protein and mRNA expression of β-catenin, cyclinD1 and C-Myc was decreased (P<0.01). Compared with the model group, the mice in the wheat-grain moxibustion group showed better general condition, and WBC, the number of nucleated cells in bone marrow as well as serum levels of IL-3, IL-6, GM-CSF were increased (P<0.01, P<0.05), and the protein and mRNA expression of β-catenin, cyclinD1 and C-Myc was increased (P<0.05).@*CONCLUSION@#Wheat-grain moxibustion shows therapeutic effect on bone marrow inhibition, and its mechanism may be related to activating Wnt/β-catenin signaling pathway in bone marrow cells, improving bone medullary hematopoiesis microenvironment and promoting bone marrow cell proliferation.

Study of incubation period of infection with 2019-nCoV Omicron variant BA.5.1.3 / 中华流行病学杂志

Objective: To study the incubation period of the infection with 2019-nCoV Omicron variant BA.5.1.3. Methods: Based on the epidemiological survey data of 315 COVID-19 cases and the characteristics of interval censored data structure, log-normal distribution and Gamma distribution were used to estimate the incubation. Bayes estimation was performed for the parameters of each distribution function using discrete time Markov chain Monte Carlo algorithm. Results: The mean age of the 315 COVID-19 cases was (42.01±16.54) years, and men accounted for 30.16%. A total of 156 cases with mean age of (41.65±16.32) years reported the times when symptoms occurred. The log-normal distribution and Gamma distribution indicated that the M (Q1, Q3) of the incubation period from exposure to symptom onset was 2.53 (1.86, 3.44) days and 2.64 (1.91, 3.52) days, respectively, and the M (Q1, Q3) of the incubation period from exposure to the first positive nucleic acid detection was 2.45 (1.76, 3.40) days and 2.57 (1.81, 3.52) days, respectively. Conclusions: The incubation period by Bayes estimation based on log-normal distribution and Gamma distribution, respectively, was similar to each other, and the best distribution of incubation period was Gamma distribution, the difference between the incubation period from exposure to the first positive nucleic acid detection and the incubation period from exposure to symptom onset was small. The median of incubation period of infection caused by Omicron variant BA.5.1.3 was shorter than those of previous Omicron variants.

Analysis of enterovirus infection type among acute respiratory tract infection cases in Luohe City, Henan Province from 2017 to 2021 / 中华预防医学杂志

Objective: To understand the infection status of Enterovirus (EV) in cases of acute respiratory infections (ARIs) in Luohe City, Henan Province from 2017 to 2021, and analyze the prevalence and type composition of EV in ARIs. Methods: From October 2017 to May 2021, pharyngeal swab samples were collected from 1 828 patients with ARIs in Luohe Central Hospital and the clinical epidemiological data of these cases were also collected. EV-positive samples were identified by Quantitative Real-time Polymerase Chain Reaction (qPCR). The 5'-untranslated region (5'UTR) was amplified by Reverse Transcription-Polymerase Chain Reaction (RT-PCR). The results of 5'UTR region were initially typed by Enterovirus Genotyping Tool Version 1.0. Based on the typing results, the full-length of VP1 region was amplified by RT-PCR. The EV typing was identified again by VP1 region. Results: Among 1 828 cases of ARIs, 56.7% (1 036) were males. The median (Q1, Q3) age was about 3 (1, 5) years. Patients under 5 years old accounted for 71.6% (1 309 cases). Among all cases, a total of 71 EV-positive samples were identified by qPCR, with a detection rate of 3.88% (71/1 828). The EV detection rates for men and women were 3.28% (34/1 036) and 4.67% (37/792), without statistically significant differences (χ2=2.32, P=0.14). The EV detection rates for 2 to <6 years, 6 months to <2 years, 6 to <10 years, and <6 months were 6.29% (48/763), 3.00% (18/600), 2.52% (4/159), and 1.67% (1/60) (χ2=27.91, P<0.001). The EV detection rate was 0.92% (3/326) in autumn and winter of 2017. The EV detection rates were 1.18% (6/508), 2.47% (12/485) and 8.31% (34/409) in each year from 2018 to 2020, with an increasing trend year by year(χ2trend=29.76, P<0.001). The main prevalent seasons were summer and autumn. The detection rate in spring of 2021 was 4.00% (4/100). A total of 12 types were identified and classified as CVA2, CVA4, CVA5, CVA6, CVA10, CVB3, CVB5, E5, E11, E30, PV-1, and EV-D68. The types of CVA2, CVA10, CVA6, and CVB3 were the dominant phenotypes. In 59 sample of EV typing, the main clinical manifestation was upper respiratory tract infection (36/59, 61.01%). The dominant types detected in upper respiratory tract infections were CVA10 (10/36, 27.78%), CVA6 (9/36, 25.00%) and CVB3 (8/36, 22.22%). The dominant type detected in lower respiratory tract infections was CVA2 (7/19, 36.84%). Conclusion: In Luohe City, Henan Province from 2017 to 2021, EV infection in ARIs cases has clear seasonal and age-specific patterns, and the dominant types of upper and lower respiratory tract infections are different.