miR-429-3p mediates memory decline by targeting MKP-1 to reduce surface GluA1-containing AMPA receptors in a mouse model of Alzheimer's disease

Alzheimer's disease (AD) is a leading cause of dementia in the elderly. Mitogen-activated protein kinase phosphatase 1 (MKP-1) plays a neuroprotective role in AD. However, the molecular mechanisms underlying the effects of MKP-1 on AD have not been extensively studied. MicroRNAs (miRNAs) regulate gene expression at the post-transcriptional level, thereby repressing mRNA translation. Here, we reported that the microRNA-429-3p (miR-429-3p) was significantly increased in the brain of APP23/PS45 AD model mice and N2AAPP AD model cells. We further found that miR-429-3p could downregulate MKP-1 expression by directly binding to its 3'-untranslated region (3' UTR). Inhibition of miR-429-3p by its antagomir (A-miR-429) restored the expression of MKP-1 to a control level and consequently reduced the amyloidogenic processing of APP and Aβ accumulation. More importantly, intranasal administration of A-miR-429 successfully ameliorated the deficits of hippocampal CA1 long-term potentiation and spatial learning and memory in AD model mice by suppressing extracellular signal-regulated kinase (ERK1/2)-mediated GluA1 hyperphosphorylation at Ser831 site, thereby increasing the surface expression of GluA1-containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs). Together, these results demonstrate that inhibiting miR-429-3p to upregulate MKP-1 effectively improves cognitive and synaptic functions in AD model mice, suggesting that miR-429/MKP-1 pathway may be a novel therapeutic target for AD treatment.

Clinical and genetic analysis of two children with Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language due to de novo variants of MEF2C gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic etiology for two children with Neurodevelopmental disorder with hypotonia, stereotypic hand movements, and impaired language (MEDHSIL).@*METHODS@#Two children who had visited the Ningbo Women and Children's Hospital on October 15, 2021 were selected as the study subjects. Whole exome sequencing (WES) was carried out for both patients. Candidate variants were verified by Sanger sequencing of their family members.@*RESULTS@#The two children were respectively found to harbor a heterozygous c.138delC (p.Ile47Serfs*42) variant and a c.833del (p.L278*) variant of the MEF2C gene. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be pathogenic (PVS1+PS2+PM2_Supporting).@*CONCLUSION@#The c.138delC and c.833del variants of the MEF2C gene probably underlay the pathogenesis of MEDHSIL in the two children. Above findings have enriched the mutational spectrum of the MEF2C gene and enabled genetic counseling for their families.

Analysis of clinical characteristics and genetic variants in two children with Limb-girdle muscular dystrophy autosomal recessive 9 FKRP-related / 中华医学遗传学杂志

OBJECTIVE@#To explore the correlation between clinical manifestations of Limb-girdle muscular dystrophy autosomal recessive 9 FKRP-related (R9 FKRP-related) and variants of the FKRP gene.@*METHODS@#Two children who had presented at the Children's Hospital of Nanjing Medical University respectively due to increased serum myocardial zymogram and hepatic dysfunction on September 30, 2018 and August 3, 2018 were selected as the study subjects. Clinical data of the children were collected. Both children were suspected for Duchenne or Becker muscular dystrophy for asymptomatic high creatine kinase (CK) levels. Peripheral blood samples of the children and their parents were collected for whole exome sequencing, and candidate variants were validated by Sanger sequencing.@*RESULTS@#Genetic testing revealed that both children have carried compound heterozygous variants of the FKRP gene. The c.545A>G and c.941C>T variants in child 1 have been reported previously, among which the c.545A>G is a hot spot mutation in the Chinese population. Child 2 has carried c.602T>C and c.961G>A variants, both of which were unreported previously.@*CONCLUSION@#Both children have met the diagnostic criteria for LGMD R9 FKRP-related. Carriers of the c.545A>G variant may present milder symptoms. Compared with patients carrying null variants, carriers of compound heterozygous missense variants may present with a milder phenotype, manifesting as asymptomatic high CK level.

Effect of amantadine dimer adjuvant on humoral immune response induced by SARS-CoV-2 protein vaccine in mice / 中国生物制品学杂志

Effect of amantadine dimer adjuvant on humoral immune response induced by SARS-CoV-2 protein vaccine in mice@#Objective To investigate the effect of amantadine dimer adjuvant on humoral immune response induced by SARS-CoV-2 crown protein vaccine in mice.Methods The amantadine dimer was synthesized by substitution reaction ligation,hydrolytic acidification reaction ligation and amide condensation reaction ligation,with which as adjuvant,female BALB/c mice were immunized with the receptor-binding domain(RBD).The mice were randomly divided into five groups,six for each as follows:R6A+RBD group[21 μg(0.033 μmol)amantadine dimer+10 μg RBD],Ada+RBD group[10 μg(0.066 μmol)amantadine+10 μg RBD],Alu+RBD group(35 μg aluminum adjuvant+10 μg RBD),RBD group(10 μg RBD)and Blank group(0.9% normal saline),which were immunized i.m.on day 0,14 and 28 respectively.Serum samples were collected from tail vein of mice 7 d after the second dose and 14 d after the last dose and determined for specific IgG antibody levels by ELISA.Results The amantadine dimer was purified by thin layer chromatography(TLC)and identified by electrospray ionization-MS(ESI-MS)positive/negative ion mode.After two times of immunization,the antibody levels in sera at various dilutions of mice in R6A+RBD group were all higher than those of Ada+RBD group,while lower than those of Alu+RBD group.However,after three times of immunization,the antibody levels in sera at various dilutions of mice in R6A+RBD group were all significantly higher than those of Ada+RBD and Alu+RBD groups(each F > 30,each P < 0.000 1 and each P < 0.01).Conclusion Amantadine dimer adjuvant enhanced humoral immune response induced by SARS-CoV-2 protein vaccine in mice with good adjuvant effect,which may be used as an alternative adjuvant.This strategy based on existing drug transformation provided a new idea for the development of novel adjuvants.

The role of mother-child relationship in the association between maternal parenting stress and emotional and behavioral problems in preschool children / 中国当代儿科杂志

OBJECTIVES@#To study the moderating effect of mother-child relationship in the association between maternal parenting stress and emotional and behavioral problems in preschool children, and to provide reference for the prevention and control of emotional and behavioral problems in preschool children.@*METHODS@#Using a stratified cluster sampling method, 2 049 preschool children were surveyed from November to December 2021, who sampled from 12 kindergartens in Wuhu City, Anhui Province. The emotional and behavioral problems of preschool children were assessed with the Strength and Difficulties Questionnaire. Pearson correlation analysis was used to evaluate the relationship of maternal parenting stress and mother-child relationship with children's emotional and behavioral problems. The PROCESS Macro was used to analyze the moderating effect of conflicted and dependent mother-child relationships in the association between maternal parenting stress and emotional and behavioral problems in these preschool children.@*RESULTS@#Among these preschool children, maternal parenting stress was positively correlated with the scores of emotional symptoms, conduct problems, hyperactivity, and peer problems subscales and total difficulty scores (P<0.001); intimate mother-child relationships were negatively correlated with the scores of conduct problems, hyperactivity, and peer problems subscales and total difficulty scores (P<0.001); conflicted and dependent mother-child relationships were positively correlated with the scores of emotional symptoms, conduct problems, hyperactivity, and peer problems subscales and total difficulty scores (P<0.001). After controlling for relevant confounding factors, conflicted mother-child relationship (β=0.05, P=0.001) and dependent mother-child relationship (β=0.04, P=0.012) were found to have a moderating effect on the association between maternal parenting stress and total difficulty scores in these preschool children.@*CONCLUSIONS@#Negative mother-child relationships play a moderating role in the association between maternal parenting stress and emotional and behavioral problems in preschool children. Prevention of emotional and behavioral problems in preschool children should focus on reducing maternal parenting stress and improving negative mother-child relationships.

Dose-response association between fluid overload and hospital mortality in patients with sepsis / 中华内科杂志

Objective: To investigate dose-response associations between fluid overload (FO) and hospital mortality in patients with sepsis. Methods: The current cohort study was prospective and multicenter. Data were derived from the China Critical Care Sepsis Trial, which was conducted from January 2013 to August 2014. Patients aged≥18 years who were admitted to intensive care units (ICUs) for at least 3 days were included. Fluid input/output, fluid balance, fluid overload (FO), and maximum FO (MFO) were calculated during the first 3 days of ICU admission. The patients were divided into three groups based on MFO values: MFO<5%L/kg, MFO 5%-10%L/kg, and MFO≥10% L/kg. Kaplan-Meier analysis was used to predict time to death in hospital in the three groups. Associations between MFO and in-hospital mortality were evaluated via multivariable Cox regression models with restricted cubic splines. Results: A total of 2 070 patients were included in the study, of which 1 339 were male and 731 were female, and the mean age was (62.6±17.9) years. Of 696 (33.6%) who died in hospital, 968 (46.8%) were in the MFO<5%L/kg group, 530 (25.6%) were in the MFO 5%-10%L/kg group, and 572 (27.6%) were in the MFO≥10%L/kg group. Deceased patients had significantly higher fluid input than surviving patients during the first 3 days [7 642.0 (2 874.3, 13 639.5) ml vs. 5 738.0 (1 489.0, 7 153.5)ml], and lower fluid output [4 086.0 (1 367.0, 6 354.5) ml vs. 6 130.0 (2 046.0, 11 762.0) ml]. The cumulative survival rates in the three groups gradually decreased with length of ICU stay, and they were 74.9% (725/968) in the MFO<5% L/kg group, 67.7% (359/530) in the MFO 5%-10%L/kg group, and 51.6% (295/572) in the MFO≥10%L/kg group. Compared with the MFO<5%L/kg group, the MFO≥10%L/kg group had a 49% increased risk of inhospital mortality (HR=1.49, 95%CI 1.28-1.73). For each 1% L/kg increase in MFO, the risk of in-hospital mortality increased by 7% (HR=1.07, 95% CI 1.05-1.09). There was a"J-shaped"non-linear association between MFO and in-hospital mortality with a nadir of 4.1% L/kg. Conclusion: Higher and lower optimum fluid balance levels were associated with an increased risk of in-hospital mortality, as reflected by the observed J-shaped non-linear association between fluid overload and inhospital mortality.

Analysis of the clinical characteristics and therapeutic effect of refractory juvenile dermatomyositis to tofacitinib / 中华儿科杂志

Objective: To elucidate the clinical features of patients with refractory juvenile dermatomyositis (JDM), and to explore the efficacy and safety of tofacitinib in the treatment of refractory JDM. Methods: A total of 75 JDM patients admitted to the Department of Rheumatology and Immunology in Shenzhen Children's Hospital from January 2012 to January 2021 were retrospectively analyzed, and to analyze the clinical manifestations, efficacy and safety of tofacitinib in the treatment of refractory JDM. Patients were divided into refractory group with using of glucocorticoids in combination with two or more anti-rheumatic drugs for treatment, and the presence of disease activity or steroid dependence after a one-year follow-up. The non-refractory group is defined as clinical symptoms disappeared, laboratory indicators were normal, and clinical remission was achieved after initial treatment, and the clinical manifestations and laboratory indexes of the two groups were compared. The Mann-Whitney U test, Fisher's precision probability test was used for intergroup comparison. Binary Logistic multivariate regression analysis was used to identify risk factors for refractory JDM. Results: Among the 75 children with JDM, 41 were males and 34 were females with a age of onset of 5.3 (2.3, 7.8) years. The refractory group consisted of 27 cases with a age of onset of 4.4 (1.5, 6.8) years, while the non-refractory group consisted of 48 cases with a age of onset of 5.9 (2.5, 8.0) years. Compared with 48 cases in the non-refractory group, the proportion of interstitial lesions and calcinosis in the refractory group was higher than that in the non-refractory group (6 cases (22%) vs. 2 cases (4%), 8 cases (30%) vs. 4 cases (8%), both P<0.05). Binary Logistic regression analysis showed that observation group were more likely to be associated with to interstitial lung disease (OR=6.57, 95%CI 1.22-35.31, P=0.028) and calcinosis (OR=4.63, 95%CI 1.24-17.25, P=0.022). Among the 27 patients in the refractory group, 22 cases were treated with tofacitinib, after treatment with tofacitinib, 15 of 19 cases (86%) children with rashes showed improvement, and 6 cases (27%) with myositis evaluation table score less than 48 score both were improved, 3 of 6 cases (27%) had calcinosis were relieved, and 2 cases (9%) had glucocorticoid-dependence children were successfully weaned off. During the tofacitinib treatment, there was no increase in recurrent infection, blood lipids, liver enzymes, and creatinine were all normal in the 22 cases. Conclusions: Children with JDM with calcinosis and interstitial lung disease are more likely to develop refractory JDM. Tofacitinib is safe and effective for refractory JDM.

BCS1Neonatal growth retardation and lactic acidosis initiated by novel mutation sites in L gene / 中华预防医学杂志

This study aims to analyze the clinical characteristics and genetic variations of two cases with developmental delay and lactic acidosis in a family, and to explore the relationship between genetic variations and clinical features. A retrospective analysis was conducted on the clinical characteristics of two siblings with developmental delay and lactic acidosis who were treated at the Neonatal Department of Children's Hospital of Chongqing Medical University in May 2019 and December 2021, respectively. Whole-exome sequencing was used to detect genetic variations in the affected children. Homology modeling of the BCS1L protein was performed to analyze the structural and functional changes of the protein. The correlation between genetic variations and clinical phenotypes was analyzed. The results showed that the main clinical features of the two affected children in this family were manifestations of mitochondrial respiratory chain complex Ⅲ deficiency, including prematurity, developmental delay, respiratory failure, lactic acidosis, cholestasis, liver dysfunction, renal tubular lesions, coagulation dysfunction, anemia, hypoglycemia, hypotonia, and early death. Whole-exome sequencing revealed a novel deletion mutation c.486_488delGGA (p.E163del) and a novel missense mutation c.992C>T (p.T331I) in the BCS1L gene. Structural analysis of the homology modeling showed that the compound heterozygous mutation had a significant impact on protein function. In conclusion, the novel mutation site c.992C>T (p.T331I) in the BCS1L gene is a "likely pathogenic" mutation, and the compound heterozygous mutation is closely related to the phenotype of mitochondrial respiratory chain complex Ⅲ deficiency.

Network controllability analysis of awake and asleep conditions in the brain / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

The difference between sleep and wakefulness is critical for human health. Sleep takes up one third of our lives and remains one of the most mysterious conditions; it plays an important role in memory consolidation and health restoration. Distinct neural behaviors take place under awake and asleep conditions, according to neuroimaging studies. While disordered transitions between wakefulness and sleep accompany brain disease, further investigation of their specific characteristics is required. In this study, the difference is objectively quantified by means of network controllability. We propose a new pipeline using a public intracranial stereo-electroencephalography (stereo-EEG) dataset to unravel differences in the two conditions in terms of system neuroscience. Because intracranial stereo-EEG records neural oscillations covering large-scale cerebral areas, it offers the highest temporal resolution for recording neural behaviors. After EEG preprocessing, the EEG signals are band-passed into sub-slow (0.1‍-‍1 Hz), delta (1‍-‍4 Hz), theta (4‍-‍8 Hz), alpha (8‍-‍13 Hz), beta (13‍-‍30 Hz), and gamma (30‍-‍45 Hz) band oscillations. Then, dynamic functional connectivity is extracted from time-windowed EEG neural oscillations through phase-locking value (PLV) and non-overlapping sliding time windows. Next, average and modal network controllability are implemented on these time-varying brain networks. Based on this preliminary study, it appears that significant differences exist in the dorsolateral frontal-parietal network (FPN), salience network (SN), and default-mode network (DMN). The combination of network controllability and dynamic functional networks offers new insight for characterizing distinctions between awake and asleep stages in the brain. In other words, network controllability captures the underlying brain dynamics under both awake and asleep conditions.

Considerations on investigation on quality standard of Chinese patent medicine / 药学学报

Chinese patent medicine (CPM) is an important part of traditional and Chinese medicine (TCM). Its quality has direct impact on the safety and effectiveness of clinical use. The quality standard is the pivotal approach to guarantee the quality of CPM. Due to the complex material basis, multitudinous quality influencing factors and unveiled active ingredients, dose-effect relationship and action mechanism, the investigation on quality standard faces many difficulties. This paper surveys the current quality status of CPM and the general situation of CPM standards. At present, the dosing problem has the crucial impact on the quality of CPM. The current quality standard system of CPM is confirmed and the limitations are indicated. Based on the above analysis, the principles and considerations on investigation of quality standard are proposed as follows: ① Adhere to safety as the bottom line, strengthen the risk-control ability of the standard of CPM; ② Adhere to theory of TCM and comprehensive quality, improve the integrative control level of the CPM standard; ③ Emphasize technological development and innovation, promote the quality control competence of CPM standard; ④ Facilitate planning and coordination, optimize the management of the CPM standard system; ⑤ Reinforce investigation on evaluation method, develop grade evaluation standard, accelerate high-quality development of CPM. Finally, the future perspective on investigation of CPM quality standard is prospected.

Relationship between depressive mood and non-suicidal self-injury in middle school students： the mediating role of impulsivity / 四川精神卫生

BackgroundNon-suicidal self-injury （NSSI） behavior poses a significant risk to the psychosomatic health of middle school students. However， the intrinsic mechanisms underlying the risk factors associated with NSSI behavior remain unclear. ObjectiveTo explore the relationship and underlying mechanism between depressive mood， impulsivity， and NSSI behavior in middle school students， and provide valuable insights for the prevention and intervention of NSSI behavior in this population. MethodsIn March 2021， 1 161 middle school students were recruited by cluster random sampling. They were assessed using Adolescent Non-Suicidal Self-Injury Assessment Questionnaire （ANSAQ）， Center for Epidemiologic Studies Depression Scale （CES-D）， and Barratt Impulsivity Scale （BIS-II）. Spearman's correlation analysis was used to examine the correlation between depressive mood， impulsivity and NSSI behavior in middle school students. Moreover， the Process mediation effect analysis was adopted to test the mediating role of impulsivity between depressive mood and NSSI behavior. ResultsTotal of 122 people（10.51%） with NSSI behavior were detected. CES-D score was positively correlated with the total score of BIS-II and scores of all dimensions （r=0.340~0.556， P<0.01）， and also were positively correlated with the total score of ANSAQ and scores of all dimensions （r=0.437~0.540， P<0.01）. Additionally， the total score and dimension scores of BIS-II were positively correlated with the total score and dimension scores of ANSAQ （r=0.157~0.437， P<0.01）. Impulsivity played a partial mediating role between depressive mood and NSSI behavior ［indirect effect=0.035 （95% CI： 0.004~0.067， P<0.01）， indirect effect accounted for 5.81% of the total effect］. ConclusionDepressive mood in middle school students has both a direct and indirect influence on NSSI behavior， partially mediated by impulsivity. Consequently， impulsivity plays a partial mediating role between depressive mood and NSSI behavior.［Funded by Humanities and Social Sciences Research Science Institute of Chongqing Municipal Education Commission （number， 23KSZ017）］

Lateral septum adenosine A2A receptors control stress-induced depressive-like behaviors via signal-ing to hypothalamus and habenula / 中国药理学与毒理学杂志

Depressive disorder ranks as a major bur-den of disease worldwide,yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects.The lateral septum(LS)is thought to control of depression,however,the cellular and circuit substrates are largely unknown.Here,we identified a subpopulation of LS GABAergic adenosine A2A receptors(A2AR)-positive neurons mediating depres-sive symptoms via direct projects to the lateral habenula(LHb)and the dorsomedial hypothalamus(DMH).Activa-tion of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipula-tion of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive pheno-types.Thus,the optogenetic modulation(stimulation or inhibition)of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH,phenocopied depressive behaviors.Moreover,A2AR are upregulated in the LS in two male mouse mod-els of repeated stress-induced depression.This identifica-tion that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant poten-tial of A2AR antagonists,prompting their clinical transla-tion.

Effect of emergency nursing process in hospital for acute massive hemoptysis based on business reengineering theory / 中国实用护理杂志

Objective:Based on the business reengineering theory, to construct the emergency nursing process of acute massive hemoptysis in hospital and explore the effect of it.Methods:According to the order of hospitalization, 200 patients with acute massive hemoptysis admitted to the emergency department in Shanghai Pulmonary Hospital Affilated to Tongji University from January to June in 2020 were selected as the control group, and the original treatment process was adopted. Two hundred patients admitted to the emergency department of this hospital from July to December in 2020 were selected as the experimental group, and the reconstructed in-hospital emergency nursing process for acute massive hemoptysis was applied. In both groups, the researchers recorded the time spent in each sub-process by using the in-hospital treatment time record of acute massive hemoptysis and collected the clinical outcomes of patients through electronic cases. The time-consuming, treatment efficiency and patient outcome of each link of the treatment process in the backyard of the two groups were compared.Results:Finally, 192 patients were enrolled in the control group and the experimental group. The median time from admission to intravenous use of hemostatic drugs and from admission to endovascular treatment in the experimental group were 21.50(20.00, 22.50) and 82.50(79.50, 84.50) min, which were lower than those in the control group which spent 40.87(37.06, 44.43) and 135.50(123.50, 147.00) min, and the differences between the two groups were statistically significant ( Z=-16.84, 16.63, both P<0.01). The incidence of asphyxia caused by acute massive hemoptysis in the experimental group was 4.2%(8/192), which was lower than that in the control group, which was 13.0%(25/192) . There was a statistically significant difference in the incidence of asphyxia between the two groups( χ2=9.58, P<0.01). Conclusions:The emergency nursing process of acute massive hemoptysis effectively shortens the time of in-hospital treatment of acute massive hemoptysis, further promotes the seamless connection of multiple links of in-hospital treatment of acute massive hemoptysis, and improves the overall efficiency of in-hospital treatment of patients with acute massive hemoptysis.

Analysis of Safe Storage Moisture Content of Mume Flos Decoction Pieces Based on Theory of Water Activity and Water Molecular Mobility / 中国实验方剂学杂志

ObjectiveThe hygroscopic properties of Mume Flos decoction pieces were studied from the perspectives of macroscopic［water activity（Aw）］ and microscopic（water molecular mobility）， which provided a theoretical basis for the determination of the safe storage moisture content. MethodAdsorption isotherm of Mume Flos decoction pieces was obtained by static weighing method， and seven common hygroscopic models were fitted and estimated. The best model was selected according to the principle that determination coefficient（R2） was closer to 1， residual sum of squares（RSS） was closer to 0 and Akaike information criterion（AIC） was smaller. According to the optimal model， the absolute and relative safe moisture contents of Mume Flos decoction pieces at 25， 35， 45 ℃ was calculated. Low-field nuclear magnetic resonance（LF-NMR） was used to measure the water molecular mobility in the hygroscopic process of Mume Flos decoction pieces. ResultThe best model to describe the adsorption isotherm of Mume Flos decoction pieces was the Peleg model. According to the model expression， the absolute safe moisture contents of Mume Flos decoction pieces at 25， 35， 45 ℃ were 9.59%， 7.96% and 7.68%， and the relative safe moisture contents were 13.05%， 11.99%， 11.77%， respectively. Mume Flos decoction pieces all contained two water states during the process of hygroscopic absorption at different temperatures， namely bound water T21 and free water T22. During the process of hygroscopic absorption， bound water had the largest increase in peak area. The sum of peak areas of the bound water and free water had a good linear relationship with the moisture contents， and the R2 were 0.959 9， 0.911 8 and 0.974 7 at 25， 35， 45 ℃， respectively. When Aw<0.57， T21 did not change， and the water molecular mobility remained unchanged. When Aw>0.57， T21 showed an increasing trend， and the water molecular mobility increased. The moisture contents of Mume Flos decoction pieces were 8.44%， 6.81% and 6.25% when the water molecular mobility increased at 25， 35， 45 ℃， respectively. ConclusionCombined with the theory of water activity and water molecular mobility， 6.25% is recommended as the safe storage moisture content of Mume Flos decoction pieces， this study can provide reference for determining the safe storage moisture content of other decoction pieces.

Effects of Ganbao capsules on intestinal mucosal barrier and gut microbiota in rats with non-alcoholic fatty liver disease / 中国药房

OBJECTIVE To study the effects of Ganbao capsules on intestinal mucosal barrier and gut microbiota in rats with non-alcoholic fatty liver disease （NAFLD）， and to explore its mechanism of prevention and treatment of NAFLD. METHODS Eight of 26 SD rats were randomly selected as blank group and fed with ordinary diet， and the remaining 18 rats were fed with high diet to establish NAFLD model （2 for modeling inspection）； after successful modeling， they were divided into model group and Ganbao group， with 8 rats in each group. Ganbao group were given Ganbao capsules solution （1 440 mg/kg） intragastrically， and the blank group and model group were given the constant volume of distilled water intragastrically， once a day， for consecutive 5 weeks. The contents of alanine aminotransferase （ALT）， aspartate aminotransferase （AST） and triglyceride （TG） in serum of rats were detected by automatic analyzer； the contents of lipopolysaccharide， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β in serum of rats were detected by enzyme-linked immunosorbent assay. The pathological morphology of liver and ileum tissues were observed by HE staining， the expressions of Occludin and zonula occludens-1 （ZO-1） were detected by immunohistochemistry method， and the intestinal flora were detected by 16S ribosomal RNA gene sequencing technology. RESULTS Compared with the model group， the serum contents of ALT， AST， TG， lipopolysaccharide， TNF-α， IL-6 and IL-1β in Ganbao group were decreased significantly （P＜0.01）， the pathological changes of liver and ileum tissues were improved 262 significantly， and the expressions of Occludin and ZO-1 were increased significantly （P＜0.01）. Intestinal microbiotaanalysis revealed that compared with the model group， Ganbao capsules could recover the abundance and diversity of the gut E-mail：hdf8833@126.com microbiota in rats. At the phylum level， Ganbao capsules could significantly increase the relative abundance of Bacteroidetes， and significantly reduce the relative abundance of Firmicutes and the ratio of Firmicutes to Bacteroidetes （P＜0.01）. At the genus level， Ganbao capsules could significantly increase the relative abundance of Lactobacillus， Blautia， Bacteroides and Akkermansia， and significantly reduce the relative abundance of Prevotella， Turicibacter， Weissella， SMB53 and Desulfovibrio （P＜0.05 or P＜0.01）. There were different species among the gut microbiota of rats in each group. CONCLUSIONS Ganbao capsules may improve NAFLD by protecting intestinal mucosal barrier function and regulating gut probiotics/harmful bacteria structure.

Clinical research of multisystem inflammatory syndrome in children / 中华儿科杂志

Objective: To analyze the clinical characteristics of children with multisystem inflammatory syndrome (MIS-C) associated with SARS-CoV-2 in China, and to improve the understanding of MIS-C among pediatricians. Methods: Case series study.Collect the clinical characteristics, auxiliary examinations, treatment decisions, and prognosis of 64 patients with MIS-C from 9 hospitals in China from December 2022 to June 2023. Results: Among the 64 MIS-C patients, 36 were boys and 28 were girls, with an onset age being 2.8 (0.3, 14.0) years. All patients suffered from fever, elevated inflammatory indicators, and multiple system involvement. Forty-three patients (67%) were involved in more than 3 systems simultaneously, including skin mucosa 60 cases (94%), blood system 52 cases (89%), circulatory system 54 cases (84%), digestive system 48 cases (75%), and nervous system 24 cases (37%). Common mucocutaneous lesions included rash 54 cases (84%) and conjunctival congestion and (or) lip flushing 45 cases (70%). Hematological abnormalities consisted of coagulation dysfunction 48 cases (75%), thrombocytopenia 9 cases (14%), and lymphopenia 8 cases (13%). Cardiovascular lesions mainly affected cardiac function, of which 11 patients (17%) were accompanied by hypotension or shock, and 7 patients (12%) had coronary artery dilatation.Thirty-six patients (56%) had gastrointestinal symptoms, 23 patients (36%) had neurological symptoms. Forty-five patients (70%) received the initial treatment of intravenous immunoglobulin in combination with glucocorticoids, 5 patients (8%) received the methylprednisolone pulse therapy and 2 patients (3%) treated with biological agents, 7 patients with coronary artery dilation all returned to normal within 6 months. Conclusions: MIS-C patients are mainly characterized by fever, high inflammatory response, and multiple organ damage. The preferred initial treatment is intravenous immunoglobulin combined with glucocorticoids. All patients have a good prognosis.

KCTD4 interacts with CLIC1 to disrupt calcium homeostasis and promote metastasis in esophageal cancer

Increasing evidences suggest the important role of calcium homeostasis in hallmarks of cancer, but its function and regulatory network in metastasis remain unclear. A comprehensive investigation of key regulators in cancer metastasis is urgently needed. Transcriptome sequencing (RNA-seq) of primary esophageal squamous cell carcinoma (ESCC) and matched metastatic tissues and a series of gain/loss-of-function experiments identified potassium channel tetramerization domain containing 4 (KCTD4) as a driver of cancer metastasis. KCTD4 expression was found upregulated in metastatic ESCC. High KCTD4 expression is associated with poor prognosis in patients with ESCC and contributes to cancer metastasis in vitro and in vivo. Mechanistically, KCTD4 binds to CLIC1 and disrupts its dimerization, thus increasing intracellular Ca2+ level to enhance NFATc1-dependent fibronectin transcription. KCTD4-induced fibronectin secretion activates fibroblasts in a paracrine manner, which in turn promotes cancer cell invasion via MMP24 signaling as positive feedback. Furthermore, a lead compound K279-0738 significantly suppresses cancer metastasis by targeting the KCTD4‒CLIC1 interaction, providing a potential therapeutic strategy. Taken together, our study not only uncovers KCTD4 as a regulator of calcium homeostasis, but also reveals KCTD4/CLIC1-Ca2+-NFATc1-fibronectin signaling as a novel mechanism of cancer metastasis. These findings validate KCTD4 as a potential prognostic biomarker and therapeutic target for ESCC.

Awareness of sexual knowledge among primary and middle schoolstudents in Butuo County / 预防医学

Objective@#To investigate the awareness and identify the influencing factors of sexual knowledge among primary and middle school students in Butuo County, Sichuan Province, so as to provide insights into sex education.@*Methods@#Six primary and middle schools were randomly sampled from 40 primary and middle schools in Butuo County using the cluster sampling method on March and April, 2021, and a class was randomly sampled from each of grades 4 to 6 of primary schools and grades 1 to 3 of junior high schools, with all students from the class as study subjects. Students' demographic features and awareness of sexual knowledge were investigated using self-designed questionnaires, and the factors affecting the awareness of sexual knowledge were identified among primary and middle school students using multivariable linear regression analysis.@*Results@#A total of 980 questionnaires were allocated, and 957 valid questionnaires were recovered, with an effective recovery rate of 97.65%. The respondents included 458 boys ( 47.86% ) and 499 girls ( 52.14% ), and included 908 students with Yi Ethnicity. The respondents included 802 primary school students ( 83.80% ) and 155 junior high school students ( 16.20% ). The awareness of sexual knowledge was 21.94% among the primary and middle school students, and their sexual knowledge was predominantly derived from parents ( 338 students, 35.32% ) and teachers ( 335 students, 35.01% ). The awareness of sexual knowledge was significantly lower in boys than in girls ( 17.69% vs. 25.86%; χ2=8.344, P=0.004 ), and the awareness of sexual knowledge appeared a tendency towards a rise with age ( χ2trend = 63.908, P<0.001 ). Low awareness of sexual knowledge was seen in students with fathers going out for labor ( 19.54% ), mothers going out for labor (11.24%) and living in the countryside ( 14.32% ) ( χ2=7.790, 9.224 and 34.144, all P<0.01 ). Multivariable linear regression analysis showed that students living in the countryside, students’ mothers going out for labor, ages of 12 to 14 years and ages of over 14 years were factors affecting the score of sexual knowledge ( β'=-0.072, 0.341, 0.645 and 0.843, all P<0.05 ).@*Conclusions@#The awareness of sexual knowledge is low among primary and middle school students in Butuo County. Health education of sexual knowledge should be emphasized on male students, those living in the countryside and students with mothers going out for labor.

Targeting PFKL with penfluridol inhibits glycolysis and suppresses esophageal cancer tumorigenesis in an AMPK/FOXO3a/BIM-dependent manner

As one of the hallmarks of cancer, metabolic reprogramming leads to cancer progression, and targeting glycolytic enzymes could be useful strategies for cancer therapy. By screening a small molecule library consisting of 1320 FDA-approved drugs, we found that penfluridol, an antipsychotic drug used to treat schizophrenia, could inhibit glycolysis and induce apoptosis in esophageal squamous cell carcinoma (ESCC). Gene profiling and Ingenuity Pathway Analysis suggested the important role of AMPK in action mechanism of penfluridol. By using drug affinity responsive target stability (DARTS) technology and proteomics, we identified phosphofructokinase, liver type (PFKL), a key enzyme in glycolysis, as a direct target of penfluridol. Penfluridol could not exhibit its anticancer property in PFKL-deficient cancer cells, illustrating that PFKL is essential for the bioactivity of penfluridol. High PFKL expression is correlated with advanced stages and poor survival of ESCC patients, and silencing of PFKL significantly suppressed tumor growth. Mechanistically, direct binding of penfluridol and PFKL inhibits glucose consumption, lactate and ATP production, leads to nuclear translocation of FOXO3a and subsequent transcriptional activation of BIM in an AMPK-dependent manner. Taken together, PFKL is a potential prognostic biomarker and therapeutic target in ESCC, and penfluridol may be a new therapeutic option for management of this lethal disease.

Effects of increasing efficacy and decreasing toxicity of ginkgo flavone aglycone on doxorubicin in the treatment of liver cancer / 中国药房

OBJECTIVE To study the effects of increasing efficacy and decreasing toxicity of ginkgo flavone aglycone （GA） on doxorubicin （DOX）in the treatment of liver cancer. METHODS A tumor bearing model was established by inoculating liver cancer cell H 22 into the right axillary skin of ICR mice. The successfully modeled mice were randomly divided into model control group，DOX group （2.5 mg/kg，once every other day ，via tail vein ），GA group （30 mg/kg，once a day ，gavage）and GA+DOX group（the usage was the same as single drug groups ），with 6 mice in each group. The administration cycle was 15 days. The general growth of mice in each group were observed ，body weight and tumor weight were measured ，and the inhibition rate of tumor was calculated. Jin’s formula was used to evaluate the effect of combined medication （Q）. The serum level of alpha-fetal protein（AFP），the pathological changes of tumor tissue ，cell apoptosis and the expression of platelet-endothelial cell adhesion molecule-1（CD31）were detected in each group. The cardiac index，serum levels of B-type natriuretic peptide （BNP）and N-terminal pro-brain natriuretic peptide （NT-pro BNP ），pathological changes of heart and myocardial fibrosis degree were also detected. RESULTS The percentage of body weight change （except for GA group ） and tumor weights of DOX group，GA group and GA + DOX group were all decreased significantly，compared with model control group （P＜0.05 or P＜0.01），while tumor weight of GA+DOX gro up was significantly lower than DOX group （P＜0.01）. Inhibitory rates of tumor in 3 administration groups were 54.29％，42.50％ and 89.29％ respectively，and Q of two-drug combination was 1.21. The tumor tissues of mice in each administration group were necrotic to varying degrees ；the serum level of AFP and the expression of CD31 in tumor tissue were decreased significantly ，compared with model control group （P＜0.05 or P＜0.01）；the percentage of necrosis area of tumor tissue and the positive rate of apoptosis （except for single drug groups ）were significantly increased （P＜0.05 or P＜0.01），while positive rate of apoptosis in GA+DOX group was significantly higher than DOX group （P＜0.05）. Cardiac index of mice in DOX group was significantly lower than model control group （P＜0.01）；serum levels of BNP and NT-pro BNP in DOX group and GA+ DOX group were significantly higher than model control group （P＜0.05 or P＜0.01）；pathological changes of heart and the degree of myocardial fibrosis in GA+DOX group were lower than DOX group. CONCLUSIONS GA combined with DOX show synergistic antitumor effect. GA can strengthen the apoptosis promoting effect of DOX ，and can help to reduce the cardiotoxicity of DOX.