Meta-analysis on efficacy and safety of thalidomide combined with CAG regimen in the treatment of elderly patients with acute myeloid leukemia / 中国药房

OBJECTIVE To systematically evaluate the efficacy and safety of thalidomide combined with aclacinomycin， granulocyte colony-stimulating factor and cytarabine （CAG） regimen in the treatment of elderly patients with acute myeloid leukemia （AML）. METHODS CNKI， Wanfang data， VIP， Sino Med， PubMed， Embase， the Cochrane Library and Web of Science were searched comprehensively from the inception to Aug. 27th， 2023. Randomized controlled trials （RCTs） about thalidomide combined with CAG regimen （trial group） versus CAG regimen （control group） in the treatment of elderly AML patients were collected， and RevMan 5.3 software was used for meta-analysis of included studies. RESULTS Finally， 7 RCTs were included， with a total of 601 patients， including 307 patients in the trial group and 294 patients in the control group. Meta-analysis results showed that the trial group was superior to the control group in enhancing the overall response rate [Z＝4.75， P＜0.000 01， OR＝2.80， 95%CI （1.83，4.28）]， complete remission rate [Z＝2.82， P＝0.005， OR＝1.61， 95%CI （1.16， 2.25）]， and improving platelet count [Z＝2.70， P＝0.007， MD＝64.02， 95%CI （17.53， 110.51）]， vascular endothelial growth factor [Z＝13.63，P＜0.000 01， MD＝－65.17， 95%CI（－74.54， －55.80）]， vascular endothelial growth factor receptor [Z＝12.03， P＜ 0.000 01， MD＝－499.01， 95%CI （－580.31， －417.71）] and basic fibroblast growth factor [Z＝4.17， P＜0.000 1，MD＝－0.23， 95%CI（－0.35， －0.12）]. And there was no statistical difference between the trial group and the control group in the incidence of adverse drug reaction [Z＝0.99， P＝0.32， OR＝0.52， 95%CI（0.14，1.89）]， nausea and vomiting [Z＝ 1.06， P＝0.29， OR＝0.66， 95%CI （0.30，1.43）]， constipation or diarrhea [Z＝0.92， P＝0.36， OR＝0.65， 95%CI（0.26， 1.63）]， drowsiness [Z＝1.38， P＝0.17， OR＝0.57， 95%CI（0.26， 1.27）] or myelosuppression [Z＝0.88，P＝0.38，OR＝0.68，95%CI（0.28， 1.62）]. CONCLUSIONS The combination of thalidomide and CAG regimen in the treatment of elderly AML patients can significantly improve clinical efficacy and has high safety.

The correlation between EEG features and therapeutic effect in children with electrical status epilepticus during sleep / 实用医学杂志

Objective To explore EEG characteristics and the therapeutic effect in children with electrical status epilepticus during slow sleep(ESES).Methods The eligible ESES cases in our center from 2014 to 2020 were included.The age at diagnosis of ESES,the duration of ESES,spike wave index(SWI)during wakefulness and the distribution of spike wave during the period of ESES,age at seizure onset,the clinical syndromes and the outcomes after treatment were analyzed.The ESES cases were divided into 4 groups according to the distribution of spike wave:focal ESES,unilateral ESES,bilateral asymmetric ESES,multiple foci ESES.The SWI during the awake stage were divided into 3 groups based on the different rates:≤20%,21%～49%,≥50%.The therapeutic outcomes were classified into three groups:satisfactory response,seizure control and ineffective.Results 50 cases were included,with 32 males and 18 females.The average onset age of ESES was 6 years and 7 months,and the average duration of ESES was 28 months.A significant correlation between the distribution of ESES and the thera-peutic effects was found,bilateral asymmetric ESES had a good therapeutic effects,while multiple foci ESES showed a poor therapeutic effects.The duration of ESES was significantly correlated with therapeutic effects,and the efficacy was worse when the duration was longer than 1 year.A significant relationship between the SWI during wakefulness of ESES and the therapeutic effects was detected,the patient with SWI≤20%during wakefulness had a good therapeutic effect.There was a negative correlation between the onset age of ESES and the duration of ESES and SWI index during wakefulness.There was a positive correlation between the duration of ESES and SWI index during wakefulness.Conclusion Our results suggest that onset age,distribution,duration and SWI during wake-fulness of ESES were correlated with therapeutic outcomes,The patient with SWI≤20%during wakefulness had a good therapeutic effect and have unfavorable outcomes with ESES last more than 1 year.The earlier onset of ESES,the longer duration of ESES and higher SWI during wakefulness will be showed..

Earthworm Protein Protects Vascular Endothelial Function in Spontaneously Hypertensive Rats via PI3K/Akt/Nrf2 Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the effect of earthworm protein on the expression of phosphatidylinositol 3-kinase/protein kinase B/nuclear factor E2-related factor 2 （PI3K/Akt/Nrf2） pathway in the aorta of spontaneously hypertensive rats （SHR） and explore mechanism of earthworm protein in treating hypertensive vascular endothelial dysfunction （VED）. MethodTen 10-week-old Wistar Kyoto （WKY） rats and fifty SHR rats were selected for a week of adaptive feeding. WKY rats were selected as the normal group， and fifty SHR rats were randomized according to body weight into model， valsartan （8×10-3 g·kg-1·d-1）， and high-， medium-， and low-dose （0.2， 0.1， 0.05 g·kg-1·d-1， respectively） earthworm protein groups. The normal and model groups were administrated with equal volume of double distilled water by gavage. During the drug intervention period， the general situations of rats in each group were observed and their blood pressure was monitored at specific time points every other week before and after administration. After 8 weeks of drug intervention， enzyme-linked immunosorbent assay was employed to measure the levels of angiotensin-Ⅱ （Ang-Ⅱ） and endothelin-1 （ET-1） in the serum of rats in each group. The corresponding kits were used to determine the levels of nitric oxide （NO）， malondialdehyde （MDA）， glutathione peroxidase （GPX）， superoxide dismutase （SOD）， and ferrous ion （Fe2+）. Hematoxylin-eosin （HE） staining was employed to observe the changes in the intima of the aorta. Fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to measure the mRNA levels of PI3K， Akt， Nrf2， heme oxygenase-1 （HO-1）， and glutathione peroxidase 4 （GPX4） in the aortic tissue. Western blotting was used to determine the protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the thoracic aorta. ResultCompared with the normal group， the model group had decreased body mass， increased irritability， severe endothelial damage， elevated blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe2+ （P<0.01）， lowered NO level （P<0.01）， and down-regulated mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 in the aortic tissue （P<0.01）. Compared with the model group， drug intervention caused no significant change in the body mass， calmed the rats， alleviated the endothelial damage， lowered blood pressure and serum levels of Ang-Ⅱ， ET1， MDA， and Fe2+ （P<0.01）， elevated the NO level （P<0.05）， and up-regulated the mRNA and protein levels of p-PI3K （Tyr467/199）， PI3K， p-Akt （Ser473）， Akt， Nrf2， HO-1， and GPX4 （P<0.05）. ConclusionThe earthworm protein can exert antihypertensive effects by ameliorating VED in SHR. Specifically， it may regulate the PI3K/Akt/Nrf2 signaling pathway to inhibit oxidative stress and ferroptosis.

Role and mechanism of BRCA2 gene in immune killing of lung cancer cells / 中国免疫学杂志

Objective:To study the effect and molecular mechanism of BRCA2 gene on the killing of lung cancer by immune cells.Methods:siRNA was designed to reduce BRCA2 gene in lung cancer cells;BRCA2 expression was detected by qPCR and Western blot;cell growth was detected by MTT and CCK-8 methods;peripheral blood mononuclear cells were co-cultured with lung cancer cells,and GFP fluorescence was detected by enzyme labeling method.Killing efficiency of lung cancer cells was evaluated.Results:BRCA2 gene was expressed in moderate abundance in lung cancer cells A549 and H1299,and there was no significant differ-ence compared with lung epithelial cells BEAS-2B(P>0.05).When the BRCA2 gene in A549 and H1299 cells was successfully knocked down,the cell proliferation rate was significantly increased compared with control group;the killing efficiency of peripheral blood mononuclear cells to lung cancer cells A549 and H1299 were significantly higher than that of the control group;the expression of ATM,RAD51 and RAD50 were significantly reduced,while the expression of P53 protein was 7.2 times of the control group.Con-clusion:After knockdown of BRCA2 gene,peripheral blood monocytes are more effective in killing lung cancer cells.Intervention of BRCA2 and monocytes can synergistically inhibit lung cancer and regulate the expression of ATM signaling pathway molecules.

Protective effect of Xiebaisan on allergic asthma in rats based on non-targeted metabolomics and intestinal bacterial flora / 中国实验动物学报

Objective To explore the possible mechanism of Xiebaisan in protecting against allergic asthma in rats from the perspective of host intestinal flora metabolism.Methods SPF SD rats were divided into normal group(NC group),model group(M group),and Xiebaisan group.The allergic asthma rat model was established by ovalbumin.Changes in lung histopathology were observed by HE staining.Colon contents were harvested for 16S rDNA high-throughput sequencing to assess changes in the intestinal flora structure and function.Serum and lung tissue samples were collected for non-targeted metabolomics by Ultra-high performance liquid-time-of-flight mass spectrometer.Results HE staining showed some improvement of lung histomorphology in asthmatic rats in the Xiebaisan group compared with that in the M group.16S rDNA high-throughput sequencing showed that the diversity of intestinal flora was decreased in the M group and increased in the Xiebaisan group compared with the M group,the microecosystem of intestinal was improved.Non-targeted metabolomics of serum showed regulation of amino acid metabolism and the mTOR pathway in the Xiebaisan group,and partially reversed differential metabolite expression in the M group.Non-targeted metabonomics of lung tissue samples showed regulation of carbon metabolism,vascular smooth muscle and cAMP signaling pathways in the Xiebaisan group,and partially reversed differential metabolite expression in the M group.Conclusions The protective effects of Xiebaisan on allergic asthma in rats may be related to improvement of the morphological structure of lung tissue,the diversity of intestinal flora,and regulation of mTOR,vascular smooth muscle contraction,and cAMP pathways,which affect amino acid and carbon metabolism.

Contextual Fear Learning and Extinction in the Primary Visual Cortex of Mice / 神经科学通报·英文版

Fear memory contextualization is critical for selecting adaptive behavior to survive. Contextual fear conditioning (CFC) is a classical model for elucidating related underlying neuronal circuits. The primary visual cortex (V1) is the primary cortical region for contextual visual inputs, but its role in CFC is poorly understood. Here, our experiments demonstrated that bilateral inactivation of V1 in mice impaired CFC retrieval, and both CFC learning and extinction increased the turnover rate of axonal boutons in V1. The frequency of neuronal Ca2+ activity decreased after CFC learning, while CFC extinction reversed the decrease and raised it to the naïve level. Contrary to control mice, the frequency of neuronal Ca2+ activity increased after CFC learning in microglia-depleted mice and was maintained after CFC extinction, indicating that microglial depletion alters CFC learning and the frequency response pattern of extinction-induced Ca2+ activity. These findings reveal a critical role of microglia in neocortical information processing in V1, and suggest potential approaches for cellular-based manipulation of acquired fear memory.

Genetic analysis of a child with developmental disorder and epilepsy due to a homozygous variant of PIGW gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child featuring global developmental disorder with epilepsy.@*METHODS@#A child who had presented at Guangzhou Women and Children's Medical Center in July 2022 was selected as the study subject. Clinical data was collected. Potential variant was detected by whole exome sequencing (WES). Candidate variant was validated by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a three-year-old ethnic Zhuang Chinese girl, had presented with global developmental disorder and epilepsy, for which rehabilitation therapy was ineffective. Genetic testing revealed that she has harbored a homozygous c.821T>C (p.Leu274Pro) missense variant of the PIGW gene, for which both of her parents and sister were heterozygous carriers. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as variant of uncertain significance.@*CONCLUSION@#The homozygous c.821T>C (p.Leu274Pro) variant of the PIGW gene probably underlay the onset of disease in this child. Above finding has enriched the mutational spectrum of the PIGW gene.

Status quo of knowledge, attitudes and practice of general practitioners on potentially inappropriate medication in the elderly in Shanxi Province and relevant factors / 中华全科医师杂志

Objective:To investigate the levels of knowledge, attitudes and practice of general practitioners on potentially inappropriate medication(PIM)in the elders in Shanxi Province and to explore its relevant factors.Methods:A cross-sectional survey on knowledge, attitudes and practice of general practitioners on PIM in the elders was conducted from January to February 2021. A self-designed questionnaire was used for the survey, which included the basic information of general practitioners and the knowledge, attitudes and practice of elderly PIM. The convenient sampling method was used to select 16 primary, secondary and tertiary hospitals from the general practice alliance units in Shanxi Province, and 257 general practitioners in the selected hospital were recruited as the research objects. The related factors were investigated by univariate regression and multiple stepwise linear regression analyses.Results:A total of 257 questionnaires were distributed, and 248 valid questionnaires were recovered, with an effective rate of 96.5%. The scores of elderly PIM knowledge, attitudes and behavior of 248 general practitioners were (31.4±9.2), (32.9±4.6) and (34.9±8.3), respectively, with the scoring rates of 62.8% (31.4/50.0), 82.3% (32.9/40.0) and 69.8% (34.9/50.0). The total score was (99.2±16.3), and the total score rate was 70.9% (99.2/140.0). There was a statistically significant difference in the total score of elderly PIM knowledge, attitudes and practice among general practitioners with different educational background, work units, professional title, awareness level of PIM and needs for PIM training( F=6.14,4.39 and 5.38, t=2.97 and 2.62, all P<0.05). Multivariate analysis showed that general practitioners with undergraduate and graduate education and higher professional titles had better knowledge, attitudes and practice of PIM ( t=2.69, 2.98 and 2.36, all P<0.05), and general practitioners without knowledge of PIM and no needs for PIM training had worse knowledge, attitudes and practice of PIM ( t=-2.96 and -2.09, all P<0.05). Conclusions:The knowledge, attitudes and behavior intervention of general practitioners on elderly PIM needs to be improved. It is necessary to strengthen the elderly PIM knowledge and skill training for general practitioners with low educational background, lower professional titles without awareness and training of PIM.

Related factors of hypoparathyroidism after thyroid cancer surgery / 中华内分泌外科杂志

Objective:To analyze the risk factors of hypoparathyroidism after thyroid cancer surgery.Methods:The clinical data of 430 patients who underwent total thyroidectomy and central lymph node dissection due to thyroid cancer from Jan. 2021 to Dec. 2021 in the First Ward of Head and Neck Surgery of Sichuan Cancer Hospital were collected. They were divided into two groups according to their parathyroid hormone levels at day 1 and 6 months after surgery: temporary hypoparathyroidism group ( n = 174) and permanent hypoparathyroidism group ( n = 11). and patients with normal parathyroid function were selected as control group (256 cases on postoperative day 1 and 419 cases on postoperative month 6). Gender, age, body mass index, tumor diameter, invasion, central lymph node dissection, parathyroid transplantation, Hashimoto’s thyroiditis, and lymph node dissection in lateral neck region were monitored. The suspicious risk factors of hypoparathyroidism were evaluated by χ2 test and multivariate logistic regression analysis. Results:Univariate analysis showed that women (86.21% vs 77.34%, χ2 = 5.73, P = 0.022) and parathyroid autotransplantation (44.83% vs 28.91%, χ2 = 11.49, P = 0.001) were associated with postoperative transient hypoparathyroidism. The posterior capsule of tumor invasion (81.82% vs 45.11%, χ2 = 5.81, P = 0.016) was associated with postoperative hypoparathyroidism.Multivariate analysis showed that the independent risk factors of transient hypoparathyroidism were female ( P=0.028, OR=1.870), the largest diameter of tumor ( P=0.043, OR=1.595), extravasation of tumor ( P=0.018, OR=1.587), and parathyroid transplantation ( P=0.001, OR=1.966). The independent risk factor of permanent parathyroidism was the posterior capsule of tumor invasion ( P=0.046, OR=4.658) . Conclusions:Female, the largest tumor diameter, tumor invasion and parathyroid transplantation are independent risk factors for transient hypoparathyroidism after total thyroidectomy. The posterior capsule of tumor invasion is an independent risk factor for permanent hypoparathyroidism after total thyroidectomy.

Clinical and genetic analysis of a child with Mental retardation autosomal dominant 51 / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic basis of a child with Mental retardation autosomal dominant 51 (MRD51).@*METHODS@#A child with MRD51 who was hospitalized at Guangzhou Women and Children's Medical Center on March 4, 2022 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples of the child and her parents were collected and subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#The child, a 5-year-and-3-month-old girl, had manifested autism spectrum disorder (ASD), mental retardation (MR), recurrent febrile convulsions and facial dysmorphism. WES revealed that she has harbored a novel heterozygous variant of c.142G>T (p.Glu48Ter) in the KMT5B gene. Sanger sequencing confirmed that neither of her parents has carried the same variant. The variant has not been recorded in the ClinVar, OMIM and HGMD, ESP, ExAC and 1000 Genomes databases. Analysis with online software including Mutation Taster, GERP++ and CADD indicated it to be pathogenic. Prediction with SWISS-MODEL online software suggested that the variant may have a significant impact on the structure of KMT5B protein. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was predicted to be pathogenic.@*CONCLUSION@#The c.142G>T (p.Glu48Ter) variant of the KMT5B gene probably underlay the MRD51 in this child. Above finding has expanded the spectrum of KMT5B gene mutations and provided a reference for clinical diagnosis and genetic counseling for this family.

Mechanism of miR⁃148b⁃3p regulating proliferation of keloid derived fibroblasts / 安徽医科大学学报

Objective @#To analyze the effect of miR⁃148b⁃3p on the proliferation of keloid derived fibroblasts. @*Methods @#The expression levels of miR⁃148b⁃3p and SPARC in human keloid derived fibroblasts (HKF) and normal human fibroblasts (NFS) were analyzed by real time PCR. The expression level of SPARC protein was detected by Western blot. The effects of miR⁃148b⁃3p and SPARC on HKF proliferation were analyzed by CCK⁃8 method the luciferase reporter plasmid was constructed. The targeted binding site of miR⁃148b⁃3p and the target gene was analyzed by luciferase reporter gene method.@*Results @#miR⁃148b⁃3p was low expressed in HKF and SPARC was high expressed in HKF. Transfection of miR⁃148b⁃3p in HKF cells could down regulate the expression of SPARC and inhibit cell proliferation. Online analysis software predicted that miR⁃148b⁃3p could target the 3 ′⁃ UTR binding SPARC ; The results of dual luciferase reporter gene further confirmed that miR⁃148b⁃3p could target the 3 ′⁃ UTR of SPARC. Transfection of SPARC eukaryotic expression plasmid into HKF transfected with miR⁃148b⁃3p could counteract the effect of miR⁃148b⁃3p and restore cell proliferation. @*Conclusion @# miR⁃148b⁃3p can inhibit the proliferation of HKF by targeting the 3 ′⁃ UTR of SPARC and inhibiting its expression.

Mannose Attenuates Colitis-Associated Colorectal Tumorigenesis by Targeting Tumor-Associated Macrophages

Mannose has recently drawn extensive attention for its substantial anti-cancer activities, but the underlying mechanism remains largely unclear. The aim of this study was to investigate the effects of mannose on experimental colitis-associated colorectal tumorigenesis and underlying mechanisms. Data clearly showed that at plasma concentrations achieved after oral administration, mannose slightly affected malignancy of tumor cells or tumor promoter-induced transformation of pre-neoplastic cells, but substantially suppressed manifestation of the M2-like phenotype of tumor-associated macrophages (TAMs) in a cancer cell and macrophage co-culture model. Mechanistically, mannose might greatly impair the production of tumor cell-derived lactate which has a critical role in the functional polarization of TAMs. Importantly, oral administration of mannose protected mice against colitis-associated colorectal tumorigenesis by normalizing TAM polarization. Collectively, these findings highlight the importance of TAMs in colorectal tumorigenesis, and provide a rationale for introducing mannose supplementation to patients suffering from inflammatory bowel diseases.

Research progress on signaling pathway of Traditional Chinese Medicine inhibiting leukemia cell proliferation and inducing apoptosis / 国际中医中药杂志

Traditional Chinese Medicine (TCM) can inhibit the proliferation of leukemia cells and induce apoptosis. The signaling pathways involved mainly include PI3K/Akt pathway, MAPK signaling pathway, JAK-STAT pathway, Wnt pathway and mitochondrial pathway. Among them, the mitochondrial apoptotic pathway is affected by many key apoptotic pathways, which plays a terminal role in promoting apoptosis. At present, there is a great need for the systematic and comprehensive research on various signaling pathways and intermolecular interactions.

Factors influencing neurodevelopmental disorders in children with SCN8A-related early-onset epilepsy: a follow-up study of 21 cases / 中华实用儿科临床杂志

Objective:To explore the influence factors of neurodevelopmental disorders in children with SCN8A-related early-onset epilepsy through analyzing their clinical characteristics and following up their neurodeve-lopmental status. Methods:A retrospective analysis was carried out on 21 children (13 males and 8 females, the age ranged from 4 months to 8 years, average 31.6 months)with SCN8A-related early-onset epilepsy treated in Guangzhou Women and Children′s Medical Center and Kunming Children′s Hospital between January 2017 and February 2021.All patients underwent whole-exome sequencing and Sanger sequencing.The pathogenicity was estimated according to the American College of Medical Genetics and Genomics guidelines.The clinical data of all patients were also collected, including the age of onset of the disease, forms of seizures, seizure frequency, neurological development at onset, electroencephalogram (EEG) and brain magnetic resonance imaging (MRI). Besides, the patients were followed up to acquire the effect of sodium channel blockers after the onset of seizures, the process or improvement of neurodeve-lopment, EEG evaluation and neurodevelopmental outcomes.Patients were grouped based on data analysis results.The Fisher′s exact test was conducted to measure the effect of various factors on the neurodevelopmental process and outcome, and corresponding coe-fficients were calculated. Results:The average onset age of 21 patients was 0-9 months.The follow-up duration was 4 months-8 years.Three cases died.Sixteen cases (76.2%) had early infantile epileptic encephalopathy (EIEE), 5 cases (23.8%) had epilepsy without encephalopathy, and 1 case had benign infantile epilepsy.Fourteen cases (66.7%) belonged to drug resistant epilepsy.Only one child showed normal neurodevelopment.Eleven children showed delayed neurodevelopment, but improvement was observed.Nine children were retrogressed and stagnated in terms of neurodevelopment.Small age at onset ( Fisher=9.517, P=0.020, r=0.571), high seizure frequency ( Fisher=10.512, P=0.003, r=0.572), EEG background ( Fisher=10.512, P=0.003, r=0.572), epileptic discharges ( Fisher=8.288, P=0.008, r=0.542), and EEG changes before and after treatment ( Fisher=10.437, P=0.009, r=0.586) were important factors affecting the neurodevelopmental process.Neurodevelopmental outcome was normal in only 1 case, 1 child belonged to mild mental retardation (MR), 7 children belonged to moderate MR, 3 children belonged to severe MR, and 9 children belonged to profound MR.Statistical analysis indicated that the clinical phenotype ( Fisher=10.059, P=0.004, r=0.739) and drug resistance ( Fisher=13.706, P=0.001, r=0.640) were significantly correlated with neurodevelopmental outcomes.However, the forms of seizures, EEG findings at onset and mutation sites were not related to neurodevelopmental disorders. Conclusions:Most children with SCN8A-related early-onset epilepsy are accompanied with neurodevelopmental retardation of varying degrees.Epileptic encephalopathy and poor response to drug treatment will lead to severe neurodevelopmental disorders.

Research progress on antimalarial combination therapy based on artemisinin-based compounds / 中国药房

Malaria is a serio us and life-threatening infectious disease that has a profound impact on human life. Artemisinin is still the first-line drug for clinical antimalarial treatment recommended by the World Health Organization. The antimalarial activity of artemisinin is mainly reflected in the peroxide bridge structure. Artemisinin-based combination therapy （ACT）is the first-line treatment for malaria in many countries. ACT mainly include artemether-lumefantrine ，artesunate-amodiaquine and dihydroartemisinin- piperaquine，etc. Compared with artemisinin monotherapy ，ACT has the advantages of shortening the length of hospital stay ， speeding up parasite clearance ，and saving economic costs ，etc. However ，there are still problems such as drug resistance. This article reviews the application status ，advantages and disadvantages of ACT at home and abroad in recent years ，in order to provide ideas for the subsequent screening of long-acting adjuvant antimalarial drugs in ACT and to solve the problem of drug resistance.

Diagnosis of a child with mitochondrial myopathy and cerebellar atrophy with ataxia due to compound heterozygous variants of MSTO1 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a child with myopathy and cerebellar atrophy with ataxia.@*METHODS@#Clinical examinations and laboratory testing were carried out for the patient. The proband and the parents' genomic DNA was extracted from peripheral blood samples and subjected to trio whole-exome sequencing. Candidate variant was validated by Sanger sequencing.@*RESULTS@#The 1-year-and-8-month-old boy manifested motor developmental delay, ataxia, hypomyotonia, increased serum creatine kinase. Cranial MRI showed cerebellar atrophy with progressive aggravation. Genetic testing revealed that the patient has harbored compound heterozygous variants of the MSTO1 gene, namely c.13delG (p.Ala5ProfsTer68) and c.971C>T (p.Thr324Ile), which were respectively inherited from his mother and father. The former was unreported previously and was predicted to be likely pathogenic, whilst the latter has been reported previously and was predicted to be of uncertain significance.@*CONCLUSION@#The compound heterozygous c.13delG (p.Ala5ProfsTer68) and c.971C>T (p.Thr324Ile) variants probably underlay the disease in the proband. Above finding has enriched the spectrum of MSTO1 gene variants underlying mitochondrial myopathy and cerebellar atrophy with ataxia.

Study on absorbed components of Xiebai powder in rat blood / 中国药房

OBJECTIVE To study the absorbed components of Xiebai powder in blood. METHODS UPLC-Q-TOF-MS/MS method was adopted. SD rats were randomly divided into blank group and administration group ，with 10 rats in each group. Blank group was given water intragastrically ，and administration groups were given 2 g/mL（by the amount of crude drug ）Xiebai powder solution intragastrically. Administration volume was 11.3 mL/kg，twice a day for 3 days. One point five hours after last administration，blood was taken from the abdominal aorta of each rat ，the serum was processed to obtain the supernatant for analysis；the relevant data in positive and negative ion mode were collected ，and the absorbed components of Xiebai powder in blood were analyzed and identified by using self-built secondary mass spectrometry database and consulting the relevant literature. RESULTS Totally 17 components from Xiebai powder were identified ，among which 6 components came from sovereign Moru salba，7 from minister Cortex Lycii ，12 from assistant Glycyrrhiza uralensis ，i.e. kukoamine A ，chlorogenic acid ，tachiogroside B，astringin，neoglycyrrhizin，glycyrrhizin，azelaic acid ，isoglycyrrhizin，glycyroside，anthocyanin，sebacic acid ，parthenolide， anthocyanin，18β-glycyrrhetinic acid ，6-gingerol，palmitoamide，erucamide. These compounds were mainly flavonoids ，alkaloids and organic acids. CONCLUSIONS In this study ，17 absorbed components of Xiebai powder in blood are preliminarily determined，which are consistent with the effect of Xiebai powder. They may be the pharmacodynamic substances of Xiebai powder.

Glycogen storage syndrome type 0 caused by GYS2 gene variation and phenotypic differences between two siblings / 中华医学遗传学杂志

OBJECTIVE@#To provide a basis for genetic counseling and clinical precision therapy by exploring the genetic etiology of a child with recurrent hypoglycemia convulsion accompanied by language retardation.@*METHODS@#Peripheral blood samples were obtained from the proband, his sister and his parents. Whole genomic DNA was extracted and analyzed by the whole exon gene sequencing and confirmed by Sanger sequencing.@*RESULTS@#The proband and his sister were found to carry compound heterozygous variants c.731T>A (p.M244L) and c.928G>A (p.G244S) of the GYS2 gene, which had not been reported in the past, the c.731T>A (p.M244L) site was derived from the maternal heterozygous mutation, while c.928G>A (p.G244S) site from the father heterozygous mutation.@*CONCLUSION@#The compound heterozygous variants c.731T>A (p.M244L) and c.928G>A (p.G244S) of the GYS2 gene were the genetic cause of glycogen storage syndrome type 0 in children, providing basis for family genetic counseling. When the patient had Hypoglycemia often accompanied with convulsions, which was easy to be misdiagnosed as seizures, and the antiepileptic treatment was ineffective. After genetic diagnosis, the seizure can be controlled by improving diet to maintain blood glucose stability.

Clinical study on Jiedu-Huaban Decoction combined with montelukast sodium chewable tablets in the treatment of children with Henoch Schonlein purpura and blood heat syndrome / 国际中医中药杂志

Objective:To evaluate the efficacy of Jiedu-Huaban Decoction combined with montelukast sodium chewable tablets in the treatment of children with henoch schonlein purpura (HSP). Methods:A total of 80 children with HSP and blood heat syndrome who met the inclusion criteria, from January 2017 to December 2019, were randomly divided into two groups by random number table method, 40 in each group. The control group took montelukast sodium chewable tablets at night, and the study group took Jiedu-Huaban Decoction on the basis of the control group. Both groups were treated for 2 weeks. The disappearance time of gastrointestinal disease, skin purpura, kidney disease, joint swelling and pain were observed. The improvement score of skin purpura was evaluated before and after treatment. The serum levels of IL-6, IL-4, interferon-γ (IFN-γ) and TNF-α were detected by ELISA, and the levels of IgG, IgA and IgM. The T lymphocyte subsets (CD4 + and CD8 +) were measured by nephelometry, and the CD4 +/CD8 +values were calculated. The clinical efficacy was evaluated. Results:The total effective rate was 87.5% (35/40) in the study group and 67.5% (27/40) in the control group, with significant difference between the two groups ( χ2 =4.588, P=0.032). The disappearance time of gastrointestinal disease, skin purpura, kidney disease and joint swelling and pain in the study group were significantly earlier than those in the control group ( t=7.802, 12.167, 7.309, 9.365, all Ps<0.001). After treatment, the serum levels of IL-6, IL-4, IFN-γ and TNF-α in the study group were significantly lower than those in the control group ( t=9.319, 6.738, 8.221, 6.553, all Ps<0.001). The improvement score of skin purpura at 1 week after treatment (2.75 ± 0.69 vs. 3.92 ± 0.83, t=6.856) and 2 weeks after treatment (0.41 ± 0.15 vs. 1.55 ± 0.37, t=18.095) in the study group were significantly lower than those in the control group ( P<0.01). After treatment, the level of IgG, CD4 +, CD4 +/CD8 + in the study group were significantly higher than those in the control group ( t=5.160, 4.558, 3.442, all Ps<0.01), the level of IgA, IgM, CD8 + in the study group were significantly lower than those in the control group ( t=2.614, 6.712, 5.468, all Ps< 0.05). During the treatment, the incidence of adverse reactions in the control group was 17.5% (7/40), and that of the study group was 15.0% (6/40), wherer there was no statistical difference between the two groups ( χ2=0.092, P=0.762). Conclusion:Jiedu-Huaban Decoction combined with montelukast sodium chewable tablets can improve the clinical symptoms of children with HSP and blood heat syndrome, reduce the body inflammatory reaction, improve immunity, with good safety.

Analysis of a family with inherited generalized epilepsy with febrile seizures plus caused by the KCNT2 mutation and literature review / 中华实用儿科临床杂志

Objective:To explore the clinical characteristics and treatment of a family with inherited generalized epilepsy with febrile seizures plus (GEFS + ) caused by the KCNT2 gene mutation and review the literature. Methods:Clinical data of a child with GEFS + and his family members who visited Department of Pediatric Neurology, Guangzhou Women and Children′s Medical Center in May 2019 were collected.DNA samples were collected from the peripheral blood of the proband, his parents, his elder brother, and his maternal grandparents, and genetic analysis and verification were performed using the next-generation sequencing technique.Using " KCNT2" as the key word, literature was retrieved from PubMed, China National Knowledge Infrastructure and Wanfang databases (up to August 2019). Results:The proband was a 3-year-old boy who was admitted to Guangzhou Women and Children′s Medical Center because of frequent epileptic seizures in the past 5 months.He presented with a binocular gaze and experienced 3 to 8 times of extremities myoclonic-spastic epileptic attacks every day.He had a history of 3 times of febrile seizures at the age of 2 years old.His seizures were refractory to Sodium valproate, Topiramate, Nitrazepam and Levetiracetam.His elder brother and mother had a history of childhood febrile seizures.Other members in the family had no history of convulsion.Ictal electroencephalogram showed general 1 Hz high voltage spike-slow waves.A heterozygous nonsense mutation of KCNT2 gene c. 574C>T(p.Q192X) that was never reported previously was detected in the proband, his brother, mother and maternal grandmother.Furthermore, no other family members carried the mutation at the c. 574 locus of the KCNT2 gene.No article in Chinese was found, and 2 articles in a language other than Chinese provided the complete data of 3 sporadic cases.Together with 4 cases in the family studied in this article, there were 7 cases and 4 mutation sites in KCNT2 gene.Of these mutations, there were 3 missense mutations and 1 nonsense mutation.Three sporadic patients presented with early infantile epileptic encephalopathy.The family of this study was characterized with febrile seizures and febrile seizures plus. Conclusions:A de novo mutation and phenotype of the KCNT2 gene is found in a family with GEFS + .It would expand the gene mutation spectrum and provide basis for family genetic counseling. KCNT2 mutation induced GEFS + is refractory to antiepileptic drugs.