Application and prospect of artificial intelligence in antimicrobial peptides screening / 中国药科大学学报

@#Antimicrobial peptides (AMPs) are a class of small molecule peptides with broad-spectrum antimicrobial activity.Their unique antimicrobial mechanism can effectively treat infectious diseases, with rare drug resistance.However, though AMPs with antimicrobial activity can be screened by traditional methods, the whole process is complicated.The artificial intelligence (AI) screening method is faster and more convenient, with great potential in exploring new natural antimicrobial peptides.In this paper, strategies related to AMPs screening by AI were summarized and compared, including data sources applied to model training, artificial intelligence machine model and omics data applied to model screening of novel antimicrobial peptides.The application prospects and advantages were reviewed, in hope of providing new ideas for identification, research and development of antimicrobial peptides.

A case of combined oxidative phosphorylation deficiency 32 caused by MRPS34 gene variation and literature review / 中华儿科杂志

Objective: To investigate the clinical features and genetic features of combined oxidative phosphorylation deficiency 32 (COXPD32) caused by MRPS34 gene variation. Methods: The clinical data and genetic test of a child with COXPD32 hospitalized in the Department of Neurology, Children's Hospital, Capital Institute of Pediatrics in March 2021 were extracted and analyzed. A literature search was implemented using Wanfang, China biology medicine disc, China national knowledge infrastructure, ClinVar, human gene mutation database (HGMD) and Pubmed databases with the key words "MRPS34" "MRPS34 gene" and "combined oxidative phosphorylation deficiency 32" (up to February 2023). Clinical and genetic features of COXPD32 were summarized. Results: A boy aged 1 year and 9 months was admitted due to developmental delay. He showed mental and motor retardation, and was below the 3rd percentile for height, weight, and head circumference of children of the same age and gender. He had poor eye contact, esotropia, flat nasal bridge, limbs hypotonia, holding instability and tremors. In addition, Grade Ⅲ/6 systolic murmur were heard at left sternal border. Arterial blood gases suggested that severe metabolic acidosis with lactic acidosis. Brain magnetic resonance imaging (MRI) showed multiple symmetrical abnormal signals in the bilateral thalamus, midbrain, pons and medulla oblongata. Echocardiography showed atrial septal defect. Genetic testing identified the patient as a compound heterozygous variation of MRPS34 gene, c.580C>T (p.Gln194Ter) and c.94C>T (p.Gln32Ter), with c.580C>T being the first report and a diagnosis of COXPD32. His parents carried a heterozygous variant, respectively. The child improved after treatment with energy support, acidosis correction, and "cocktail" therapy (vitaminB1, vitaminB2, vitaminB6, vitaminC and coenzyme Q10). A total of 8 cases with COXPD32 were collected through 2 English literature reviews and this study. Among the 8 patients, 7 cases had onset during infancy and 1 was unknown, all had developmental delay or regression, 7 cases had feeding difficulty or dysphagia, followed by dystonia, lactic acidosis, ocular symptoms, microcephaly, constipation and dysmorphic facies(mild coarsening of facial features, small forehead, anterior hairline extending onto forehead,high and narrow palate, thick gums, short columella, and synophrys), 2 cases died of respiratory and circulatory failure, and 6 were still alive at the time of reporting, with an age range of 2 to 34 years. Blood and (or) cerebrospinal fluid lactate were elevated in all 8 patients. MRI in 7 cases manifested symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia. Urine organic acid test were all normal but 1 patient had alanine elevation. Five patients underwent respiratory chain enzyme activity testing, and all had varying degrees of enzyme activity reduction. Six variants were identified, 6 patients were homozygous variants, with c.322-10G>A was present in 4 patients from 2 families and 2 compound heterozygous variants. Conclusions: The clinical phenotype of COXPD32 is highly heterogenous and the severity of the disease varies from development delay, feeding difficulty, dystonia, high lactic acid, ocular symptoms and reduced mitochondrial respiratory chain enzyme activity in mild cases, which may survive into adulthood, to rapid death due to respiratory and circulatory failure in severe cases. COXPD32 needs to be considered in cases of unexplained acidosis, hyperlactatemia, feeding difficulties, development delay or regression, ocular symptoms, respiratory and circulatory failure, and symmetrical abnormal signals in the brainstem, thalamus, and (or) basal ganglia, and genetic testing can clarify the diagnosis.

Comparison of bacterial and human drug metabolizing enzymes in database and prospect of influence of intestinal bacteria on drug metabolism / 中国药科大学学报

@#This study focused on various databases and literatures related to drug metabolism, collated and analyzed the information related to bacterial and human drug metabolic enzymes, and compared the similarities and differences between the information included in the database of bacterial and human drug metabolic enzymes. Results found more bacterial drug metabolic enzymes than human drug metabolic enzymes (9 703 vs 964), but much less than the total number of bacterial enzymes in BRENDA database (9 703 vs 20 835 235), indicating that the influence of bacteria on drug metabolism could have been greatly underestimated, and that further systematic research is needed.We summarized the progress and shortcomings of the current research on the influence of intestinal flora on drug metabolism, and proposed a research idea, that is, to predict through artificial intelligence whether intestinal bacterial proteins have the ability to metabolize drugs, to verify their biological functions by in vitro/in vivo experiments and gene editing, and to establish a database of drug metabolic enzymes from intestinal bacteria with complete annotation functions, in an attempt to provide a solid theoretical basis for further exploration of the effects of intestinal flora on drug metabolism.

Analysis of the chloroplast genome of Incarvillea younghusbandii Sprague / 生物工程学报

Incarvillea younghusbandii Sprague is a traditional tonic herb. The roots are used as herbal medicine for nourishing and strengthening, as well as treating postpartum milk deficiency and weakness. In this study, the chloroplast genome of I. younghusbandii was sequenced and assembled by the high-throughput sequencing technology. The sequence characteristics, sequence repeats, codon usage bias, phylogenetic relationships and estimated divergence time of I. younghusbandii were analyzed. The 159 323 bp sequence contained a large single copy (80 197 bp), a small single copy (9 030 bp) and two inverted repeat sequences (35 048 bp). It contained 120 genes, including 77 protein coding genes, 8 ribosomal RNA genes and 35 transfer RNA genes. AAA was the most frequent codon in the chloroplast coding sequence of I. younghusbandii. A total of 42 simple sequence repeats were identified in the chloroplast genome. Phylogenetic analysis revealed I. younghusbandii was mostly like its taxonomically close relative Incarvillea compacta. The divergence between I. younghusbandii and I. compacta was dated to 4.66 million years ago. This study was significant for the scientific conservation and development of resources related to I. compacta. It also provides a basic genetic resource for the subsequent species identification of the genus Incarvillea, and the population genetic diversity study of Bignoniaceae.

Clinical features of children with febrile seizures caused by Omicron variant infection / 中国当代儿科杂志

OBJECTIVES@#To study the clinical features of children with febrile seizures after Omicron variant infection.@*METHODS@#A retrospective analysis was performed on the clinical data of children with febrile seizures after Omicron variant infection who were admitted to the Department of Neurology, Children's Hospital Affiliated to the Capital Institute of Pediatrics, from December 1 to 31, 2022 (during the epidemic of Omicron variant; Omicron group), and the children with febrile seizures (without Omicron variant infection) who were admitted from December 1 to 31, in 2021 were included as the non-Omicron group. Clinical features were compared between the two groups.@*RESULTS@#There were 381 children in the Omicron group (250 boys and 131 girls), with a mean age of (3.2±2.4) years. There were 112 children in the non-Omicron group (72 boys and 40 girls), with a mean age of (3.5±1.8) years. The number of children in the Omicron group was 3.4 times that in the non-Omicron group. The proportion of children in two age groups, aged 1 to <2 years and 6-10.83 years, in the Omicron group was higher than that in the non-Omicron group, while the proportion of children in two age groups, aged 4 to <5 years and 5 to <6 years, was lower in the Omicron group than that in the non-Omicron group (P<0.05).The Omicron group had a significantly higher proportion of children with cluster seizures and status convulsion than the non-Omicron group (P<0.05). Among the children with recurrence of febrile seizures, the proportion of children aged 6-10.83 years in the Omicron group was higher than that in the non-Omicron group, while the proportion of children aged 3 years, 4 years, and 5 years in the Omicron group was lower than that in the non-Omicron group (P<0.05).@*CONCLUSIONS@#Children with febrile seizures after Omicron variant infection tend to have a wider age range, with an increase in the proportion of children with cluster seizures and status convulsion during the course of fever.

Design and biomechanical analysis of a self-force source power-assisted knee orthotics actuated by liquid spring / 生物医学工程学杂志

A micro silicone oil liquid spring was designed and manufactured in this article. The performance of the liquid spring was studied by simulation analysis and mechanical test. A self-force source power-assisted knee orthosis was designed based on the liquid spring. This power-assisted knee orthosis can convert the kinetic energy of knee flexion into the elastic potential energy of liquid spring for storage, and release elastic potential energy to generate assisted torque which drives the knee joint for extension. The results showed that the average maximum reset force of the liquid spring was 1 240 N, and the average maximum assisted torque for the knee joint was 29.8 N·m. A musculoskeletal multibody dynamic model was used to analyze the biomechanical effect of the knee orthosis on the joint during knee bending (90°knee flexion). The results showed that the power-assisted knee orthosis could effectively reduce the biomechanical load of the knee joint for the user with a body weight of 80 kg. The maximum forces of the femoral-tibial joint force, patellar-femoral joint force, and quadriceps-ligament force were reduced by 24.5%, 23.8%, and 21.2%, respectively. The power-assisted knee orthosis designed in this article provides sufficient assisted torque for the knee joint. It lays a foundation for the subsequent commercial application due to its small size and lightweight.

Prediction of lipid nanoparticles for mRNA vaccines by the machine learning algorithm

Lipid nanoparticle (LNP) is commonly used to deliver mRNA vaccines. Currently, LNP optimization primarily relies on screening ionizable lipids by traditional experiments which consumes intensive cost and time. Current study attempts to apply computational methods to accelerate the LNP development for mRNA vaccines. Firstly, 325 data samples of mRNA vaccine LNP formulations with IgG titer were collected. The machine learning algorithm, lightGBM, was used to build a prediction model with good performance (R 2 > 0.87). More importantly, the critical substructures of ionizable lipids in LNPs were identified by the algorithm, which well agreed with published results. The animal experimental results showed that LNP using DLin-MC3-DMA (MC3) as ionizable lipid with an N/P ratio at 6:1 induced higher efficiency in mice than LNP with SM-102, which was consistent with the model prediction. Molecular dynamic modeling further investigated the molecular mechanism of LNPs used in the experiment. The result showed that the lipid molecules aggregated to form LNPs, and mRNA molecules twined around the LNPs. In summary, the machine learning predictive model for LNP-based mRNA vaccines was first developed, validated by experiments, and further integrated with molecular modeling. The prediction model can be used for virtual screening of LNP formulations in the future.

Exploration and reflection on evaluation methodology of human use experience for new Chinese drug development / 中国中药杂志

The "triple combination" review system provides an opportunity for the transformation of human use experience into new Chinese drugs. However, there are some methodological and technical limitations in the assessment of human experience. Hence, the efficacy and safety evaluation methods should be established in accordance with the characteristics of Chinese herbs. This study summarized some evidence-based methodology to promote the transformation of human use experience to new Chinese drugs, mainly including the individualized pragmatic randomized controlled trial(RCT), cluster RCT, single-case RCT, single arm RCT with objective performance criteria, and partially nested RCT. As the real world data can be used to support the transformation of human experience, attention should be paid to convenient and efficient collection of data, prudent selection of design types, and adoption of appropriate ana-lysis methods to deal with confounding bias, including multi-factor regression model and propensity score. The newly proposed mixed research method can also be utilized to assess the human use experience, which is suitable for mining the theory of traditional Chinese medicine(TCM) and expert experience from different aspects. Meanwhile, considering the study design requirements and TCM cha-racteristics, this study put forward the common problems and solutions in the development of new Chinese drugs based on human use experience, including how to select the feasible outcome indicators, how to collect prescription data in the case of herb and dosage adjustment, and how to evaluate the comprehensive effectiveness of TCM from the perspective of "combination of disease and syndrome".

Placebo control and its methodological issues on clinical trials of acupuncture therapy / 中国针灸

The paper introduces the placebo acupuncture simulation devices commonly used in clinical trial of acupuncture therapy. These devices are composed of Streitberger, Park, Takakura, Foam and Phantom acupuncture. Because acupuncture therapy is a kind of complex intervention, there are the controversies in methodology for the acupuncture placebo control of clinical trial. Placebo acupuncture may be an effective control, with a certain of specific therapeutic effect. The blinding effect of placebo acupuncture is highly questioned, specially, the sensation of deqi is hardly imitated during acupuncture. On these grounds, in this research, the suggestions has been proposed on the selection and the setting of placebo control in clinical trial of acupuncture therapy.

Follow-up and recurrence markers analysis of anti-myelin oligodendrocyte glycoprotein IgG associated disorders in children / 中华神经科杂志

Objective:To summarize clinical features, outcome and prognosis of anti-myelin oligodendrocyte glycoprotein IgG associated disorders (MOGAD) in children, and to explore the markers of recurrent MOGAD.Methods:The clinical features, imaging, serum and cerebrospinal fluid immune markers, treatments and outcomes were analyzed and compared between children with monophasic and recurrent MOGAD, who were hospitalized in the Department of Neurology, Children′s Hospital Affiliated to the Capital Institute of Pediatrics from January 2019 to February 2020.Results:A total of 22 children were included, of whom 8 patients (36.4%) had a recurrent course and 14 patients (63.6%) had a monophasic course. There was no statistically significant difference in sex, age of onset, clinical symptoms, modified Rankin Scale score, location of lesions and serum anti-myelin oligodendrocyte glycoprotein-IgG (MOG-IgG) titer, overall duration of total immunotherapy, positive antinuclear antibody and history of precursory infection between the two groups ( P>0.05). The serum MOG-IgG titer in the recurrent course group was more likely to remain unchanged or increased, and even increased after treatment, while there was no increase in the serum MOG-IgG titer in the monophasic course group, and the proportion of the patients with serum MOG-IgG titer decreased was higher in the monophasic course group (the monophasic course group: 6/8, the recurrent course group: 2/8), and there was statistically significant difference between the two groups ( P=0.030). The positive rate of MOG-IgG in cerebrospinal fluid in the recurrent course group was significantly higher than that in the monophasic course group at the first attack, the difference being statistically significant (the monophasic course group: 1/10, the recurrent course group: 4/6, P=0.036). The both groups were effecive to first-line immunotherapy, and the clinical symptoms and imaging were completely or partially recovered compared to the acute phase. Seven of 8 patients with recurrent MOGAD were treated with mycophenolate mofetil, and the recurrence rate decreased significantly [annual recurrence rate before treated with mycophenolate mofetil: 2.06 (1.36, 2.34) times/year, annual recurrence rate after treated with mycophenolate mofetil: 0 (0, 0) time/year, Z=-3.26, P=0.001]. The humoral immune status of children treated with mycophenolate mofetil was monitored regularly, and no obvious adverse reactions were found during the follow-up. Conclusions:At least one third of children with MOGAD were recurrent, and the serum MOG-IgG titer of children with recurrent MOGAD continued to be high, and even increased after treatment. Positive MOG-IgG in cerebrospinal fluid at the first attack was found to be a high risk factor for recurrence. The maintenance treatment of mycophenolate mofetil in patients with recurrent MOGAD can significantly reduce the annual recurrence rate and was well tolerated.

Total flavonoids from Saussurea involucrata attenuate inflammation in lipopolysaccharide-stimulated RAW264.7 macrophages via modulating p65, c-Jun, and IRF3 signaling pathways

Objective: To investigate the anti-inflammatory effects of the total flavonoids from Saussurea involucrata on lipopolysaccharides (LPS)-stimulated murine RAW264.7 macrophages and explore its underlying mechanism of action. Methods: Total flavonoids from Saussurea involucrata were extracted using chromatographic column method. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The production of nitric oxide was detected by Griess assay and the release of cytokines (IL-10 and TNF-α) and chemokines (MCP-1, MIP-1a, and CCL5/RANTES) was determined by ELISA to evaluate the anti-inflammatory activity of total flavonoids from Saussurea involucrata. Moreover, nuclear translocation of p65, c-Jun, and IRF3 was detected by immunofluorescence microscopy and Western blotting analysis was performed to determine the expression of related proteins. Results: Total flavonoids extracted from Saussurea involucrata were 751.5 mg/g and the content of rutin was 506.5 mg/g. The production of inflammatory mediators including nitric oxide, cytokines, and chemokines was effectively inhibited by total flavonoids from Saussurea involucrata. Meanwhile, total flavonoids also suppressed the nuclear translocation of p65, c-Jun, and IRF3 in LPS-stimulated RAW264.7 cells. The LPS-induced expression of iNOS and COX-2 was remarkably reduced by treatment with total flavonoids from Saussurea involucrata. Moreover, total flavonoids decreased the expression levels of p-IKKa/β, p-TBK1, p-p38, p-ERK, p-JNK, p-p65, p-c-Jun, and p-IRF3 in LPS-exposed RAW264.7 macrophages. Conclusions: Total flavonoids from Saussurea involucrata potentially inhibit the secretion of pro-inflammatory mediators, which may be related to inhibition of p65, c-Jun, and IRF3 signaling pathways in LPS-stimulated RAW264.7 cells.

Total flavonoids from Saussurea involucrata attenuate inflammation in lipopolysaccharide-stimulated RAW264.7 macrophages via modulating p65, c-Jun, and IRF3 signaling pathways

Objective: To investigate the anti-inflammatory effects of the total flavonoids from Saussurea involucrata on lipopolysaccharides (LPS)-stimulated murine RAW264.7 macrophages and explore its underlying mechanism of action. Methods: Total flavonoids from Saussurea involucrata were extracted using chromatographic column method. Cell viability was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay. The production of nitric oxide was detected by Griess assay and the release of cytokines (IL-10 and TNF-α) and chemokines (MCP-1, MIP-1a, and CCL5/RANTES) was determined by ELISA to evaluate the anti-inflammatory activity of total flavonoids from Saussurea involucrata. Moreover, nuclear translocation of p65, c-Jun, and IRF3 was detected by immunofluorescence microscopy and Western blotting analysis was performed to determine the expression of related proteins. Results: Total flavonoids extracted from Saussurea involucrata were 751.5 mg/g and the content of rutin was 506.5 mg/g. The production of inflammatory mediators including nitric oxide, cytokines, and chemokines was effectively inhibited by total flavonoids from Saussurea involucrata. Meanwhile, total flavonoids also suppressed the nuclear translocation of p65, c-Jun, and IRF3 in LPS-stimulated RAW264.7 cells. The LPS-induced expression of iNOS and COX-2 was remarkably reduced by treatment with total flavonoids from Saussurea involucrata. Moreover, total flavonoids decreased the expression levels of p-IKKa/β, p-TBK1, p-p38, p-ERK, p-JNK, p-p65, p-c-Jun, and p-IRF3 in LPS-exposed RAW264.7 macrophages. Conclusions: Total flavonoids from Saussurea involucrata potentially inhibit the secretion of pro-inflammatory mediators, which may be related to inhibition of p65, c-Jun, and IRF3 signaling pathways in LPS-stimulated RAW264.7 cells.

Moxibustion on plaque psoriasis of blood stasis: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the short-term and long-term effects of moxibustion on plaque psoriasis of blood stasis, and to compare the curative effect between moxibustion and calcipotriol ointment.@*METHODS@#A total of 80 patients with plaque psoriasis of blood stasis were randomly divided into an observation group (40 cases, 2 cases dropped off) and a control group (40 cases, 4 cases dropped off). Both groups were given routine medical vaseline topical emollient basic treatment. In the observation group, moxibustion was applied to @*RESULTS@#After treatment, the PASI scores in the both groups were lower than before treatment (@*CONCLUSION@#Both moxibustion and calcipotriol ointment have good short-term effects on plaque psoriasis of blood stasis. Moxibustion has more advantages in reducing the recurrence rate of psoriasis, improving the main clinical symptoms of TCM and quality of life.

Fetal survival rate and residual anastomoses after selective fetoscopic laser occlusion of chorioangiopagous vessels versus Solomon surgery for treatment of twin-to-twin transfusion syndrome / 中华围产医学杂志

Objective:To explore the influence of selective fetoscopic laser occlusion of chorioangiopagous vessels (FLOC) versus Solomon surgery in the management of twin-to-twin transfusion syndrome (TTTS) on procedure-related complications, fetal survival rate, and residual anastomoses.Methods:A total of 59 pregnant women with TTTS who underwent FLOC in the Third Affiliated Hospital of Zhengzhou University from May 2018 to March 2020 were retrospectively enrolled and divided into Solomon ( n=33) and selective FLOC groups ( n=26) based on the FLOC operation method. Placentae of 25 pregnant women (15 in the Solomon group, 10 in the selective FLOC group) with both survival twins were perfused to observe the type and diameter of the residual anastomoses. Fetal survival rate, procedure-related complications, and the type and diameter of residual anastomoses were analyzed and compared between the two groups using two independent samples t-test, Mann-Whitney U test, χ2 test and Fisher's exact test. Results:(1) The operating time of Solomon was shorter than that of selective FLOC [74 min (60-90 min) vs 95 min (81-123 min), Z=2.906, P=0.004]. But no statistically significant differences in the gestational week at operation, time of pregnancy end, and the interval between operation and pregnancy end was observed between the two groups (all P>0.05). (2) There was no statistically significant difference in the survival rate of both twins, one fetus, at least one fetus, and the incidence of postoperative twin anemia-polycythemia sequence (TAPS) and recurrent TTTS in the Solomon group and selective FLOC group [64%(21/33) vs 50%(13/26), χ2=1.107; 15%(5/33) vs 35%(9/26), χ2=3.044; 79%(26/33) vs 85%(22/26), χ2=0.326; 3%(1/33) vs 12%(3/26), χ2=1.368; 0% (0/33) vs 4%(1/26), χ2=1.118; all P>0.05]. (3) There was no statistically significant difference in the number of placentae with residual anastomoses or the number of artery-to-vein, vein-to-artery, artery-to-artery, and vein-to-vein anastomoses between the two groups (7/15 vs 6/10, 2/8 vs 4/15, 3/8 vs 4/15, 2/8 vs 5/15, 1/8 vs 2/15; Fisher's exact test, all P>0.05), but the diameter of the residual anastomoses in the Solomon group was smaller than that in the selective FLOC group [(0.8±0.3) and (2.2±0.7) mm, t=0.764, P=0.034]. (4) Among the four pregnant women developed TAPS after operation, one patient had two residual artery-to-vein anastomoses in the placenta with diameter of 0.54 mm and 0.43 mm, respectively; one patient had one artery-to-vein anastomosis with a diameter of 0.64 mm; one had one artery-to-artery and one vein-to-vein anastomosis with diameter of 1.56 mm and 1.89 mm, respectively. Conclusions:Compared with selective FLOC, Solomon surgery can reduce the vessel diameter of residual anastomoses in women with TTTS, but does not reduce postoperative complications, nor improve the pregnancy outcomes.

Caspase recruitment domain-containing protein 9 gene deficiency associated invasive candidiasis: a case report and literature review / 中华神经科杂志

Objective:To summarize the clinical characteristics, diagnosis and treatment of caspase recruitment domain-containing protein 9 (CARD9) gene deficiency associated invasive candidiasis, and report a novel mutation in CARD9 gene.Methods:The clinical characteristics, laboratory tests, treatment and the outcome of follow-up in a boy with invasive candidiasis were described. The boy′s main clinical manifestations were central nervous system infection and retroperitoneal mass. Whole-exome sequencing was performed and Sanger sequencing was verified to identify the CARD9 gene mutations in the patient and his parents. A literature search for “CARD9”and “invasive candidiasis”was conducted in PubMed, Wanfang and CNKI databases from their establishment to May 2020.Results:A 10-year-old boy suffered onset symptom of chronic diarrhea, which lasted for two months. The symptom was followed by progressive neurological symptoms such as headache, vomiting, seizures and disorder of consciousness. His unusual medical history was absent. Candida albicans were cultured several times in cerebrospinal fluid and blood, and yeast-like fungi were found in the stool high power field of vision. Cerebral magnetic resonance imaging indicated obstructive hydrocephalus and abdominal CT scan showed retroperitoneal mass and thickening of the intestinal wall. The whole-exome sequencing analyses of blood samples from the boy and his parents were performed. The results showed that there was a homozygous mutation of c.952-12_956delinsAG in the CARD9 gene, which was an unreported pathogenic mutation. This was confirmed by Sanger sequencing. There was no significant relief from intravenous combined antifungal medications. After lateral ventricular drainage surgery and injection of amphotericin B into the lateral ventricle, improvement of clinical symptoms and cerebral spinal fluid abnormalities was observed after nine weeks, and the retroperitoneal mass shrank. At follow-up after four-month oral combined antifungal medications, the child had no complaint except fatigue. However, cerebral spinal fluid analysis showed increased protein level and decreased glucose. Persistent hydrocephalus and periventricular white matter abnormal signals were revealed on the brain magnetic resonance imaging and the smaller retroperitoneal mass than before on the abdominal CT scan. In addition to this case, totally 21 cases with CARD9 gene deficiency associated invasive candidiasis have been reported worldwide, most of which featured central nervous system infections.Conclusions:CARD9 gene deficiency is an autosomal recessive primary immunodeficiency that confers human susceptibility to fungal disease. The associated invasive candidiasis often affects the central nervous system and makes the patient severely ill. Adequate systemic antifungal therapies should be given, and patients with hydrocephalus need surgical treatment. A novel mutation is reported that expands the variant diversity of CARD9 gene. For patients with unexplained invasive candidiasis, including those without a history of previous recurrent infection, genetic testing is recommended for primary immunodeficiency including CARD9 gene deficiency.

Sample size estimation in acupuncture and moxibustion clinical trials / 中国针灸

The appropriate sample size estimation is very important in the design of clinical trials. However, insufficient or inappropriate sample size estimation is still a prominent problem in the currently published acupuncture and moxibustion clinical trials. At present, the superiority test, non-inferiority test and equivalence test have been widely used in acupuncture and moxibustion clinical trials. This article focuses on the application, calculation methods and PASS11 software using of these three hypothesis test types. In view of the problems in the estimation of sample size in acupuncture and moxibustion clinical trials, the particularity of sample size estimation in acupuncture and moxibustion is summarized from the aspects of parameter setting, ratio of intervention group and control group, and multi-group comparison, in order to guide acupuncture clinical researchers to correctly estimate sample size when conducting clinical trials.

Clinical features and gene variant of a pedigree affected with X-linked recessive mental retardation Claes-Jensen type / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a pedigree affected with X-linked recessive mental retardation Claes-Jensen type.@*METHODS@#Genomic DNA was extracted from peripheral blood samples of the patient, his parents (phenotypically normal) and two elder brothers with similar clinical manifestations. Whole exome sequencing was carried out for the proband, and the result was verified by Sanger sequencing.@*RESULTS@#The proband was found to harbor a hemizygous c.1565C>T missense variant in exon 11 of the KDM5C gene. The transition has resulted in replacement of serine by phenylalanine at position 522 (p.Ser522Phe). Sanger sequencing showed that the patient's two elder brothers and mother carried the same variant, which was predicted to be probably damaging by SIFT, PolyPhen2 and Mutation_Taster. The three affected brothers presented with similar clinical phenotypes characterized by mental retardation, speech delay, behavioral problem, self-limited epilepsy responsible to medication, short stature and microcephaly. The mother only had mild cognitive impairment and learning disability. The same variant was not found in their father and was unreported previously.@*CONCLUSION@#The c.1565C>T (p.Ser522Phe) of the KDM5C gene probably underlay the X-linked recessive mental retardation Claes-Jensen type in this pedigree.

Clinical characteristics and molecular genetic analysis of patients with mitochondrial disease caused by acute central respiratory failure due to mtDNA8344A>G gene mutation / 中华神经科杂志

Objective:To summarize the phenotype of mtDNA8344A>G and to explore the new phenotype.Methods:A family with mtDNA 8344A>G was retrospectively analyzed in the Children′s Hospital Affiliated to the Capital Institute of Pediatrics in April 2019. The clinical data of the proband and his mother were collected and summarized.Results:A four-year-old boy presented with rapidly progressing central respiratory failure and continuous mechanical ventilation, whose serum lactate levels fluctuated between 4.5 to 8.3 mmol/L. Linear abnormality signals from dorsal medulla to the first and second cervical spine were displayed on cranial magnetic resonance imaging. Ragged red fiber and ragged broken blue fibers, cytochrome C oxidase negative muscle fibers and enhanced vascular succinate dehydrogenase reaction were seen in muscle biopsy, accorded with the pathological characteristics of mitochondrial myopathy. The activity detection of respiratory chain enzyme complex in muscle tissues showed decreased activity of mitochondrial respiratory chain enzyme complex Ⅰ and complex Ⅳ. mtDNA 8344A>G mutation was detected in his peripheral blood lymphocyte and urine exfoliated epithelial cells. The proportion of mutations in his blood lymphocytes was 77.29%, and the proportion of mutations in his urothelial epithelial cells was 90.13%. His mother was 30 years old, thin in stature without obvious clinical symptoms and signs. The mutant mtDNA 8344A>G was also detected in her peripheral blood and urine. The mutant rate in her blood and urine was 77.29% and 90.13% respectively.Conclusions:A case of rapidly progressive central respiratory failure in children and his family are reported. Genetic testing showed mtDNA8344A>G mutation, and both muscle biopsy pathology and muscle tissue respiratory chain enzyme complex activity test results supported mitochondrial disease. By this case, the phenotype spectrum of the gene was expanded.

Biomechanical study of the initial stability of acetabular cup with different acetabular rim defects for developmental dysplasia of hip / 中华骨科杂志

Objective@#To investigate the effects of acetabular coverage on the initial stability of the cup during total hip arthroplasty in developmental dysplasia of hip.@*Methods@#There were 50 fourth-generation synthetic hemi-pelvises. The different cup coverage rate (100% group, 70% group, 60% group, 50% group, 40% group) was created in pelvis with 10 specimens per group. The synthetic hemi-pelvis was fixed rigidly to a customized fixture which was placed on the testing table of the material testing machine. Pull-out and torque test were conducted by computer-control in torsion testing machine.@*Results@#In the acetabular cup pull-out test, the average pull-out force for mode of failure in 100%, 70%, 60%, 50%, and 40% group was 1 560.4±438.7, 1 467.2±349.8, 1 137.8±427.4, 737.4±134.8, 506.6±119.0 N, respectively. The pull-out force was reduced gradually. The pull-out force in 100% group was significantly higher than that in 50% (P=0.004) and 40% (P=0.001) group. The pull-out force in 70% group was significantly higher than that in 50% group (P=0.002) and 40% group (P=0.000). The force in 40% group was significantly lower than that in 60% group (P=0.013) and 50% group (P=0.021). In the acetabular cup torque test, the average torque for mode of failure in 100%, 70%, 60%, 50%, and 40% group was 28.0±3.7, 17.0±2.2, 9.4±1.1, 7.6±1.1, 6.4±1.1 N·m, respectively. The torque was reduced gradually. The torque in 100% group was significantly higher than that in other groups (P<0.05). There was no significant difference between 50% and 40% group (P>0.05). The torque in other groups were similar (P>0.05).@*Conclusion@#The present biomechanical study showed that different acetabular cup coverage rate affected the initial stability of the cup. The highest initial stability was observed in the cup with a 100% of cup coverage rate. The cup could not obtain 100% coverage when with acetabular rim defect. We should try our best to make the cup coverage reach to 70%. The 70% coverage rate has sufficient initial stability to meet daily activities without increasing the cup loosening rate.

Efficacy and safety of huperzine A in treating patients with mild cognitive impairment: a systematic review and Meta-analysis / 中国中药杂志

To evaluate the efficacy and safety of huperzine in treating patients with mild cognitive impairment. The randomized controlled trials(RCT) were retrieved from EMbase, Cochrane Library, PubMed, CNKI, Wanfang and VIP. The methodology quality of the included studies was evaluated, and a Meta-analysis was performed using RevMan 5.3 software. A total of nine RCTs were included. The Meta-analysis results showed that compared with placebo, Huperzine significantly increased the scores of memory quotient(MQ) and mini-mental state examination(MMSE). However, there was no statistical difference between oral tablet and capsule. Compared with placebo, huperzine A was superior in the scores of MQ and MMSE. Huperzine is safe with mild side effects. Due to the low quality of original studies, more high-quality studies are needed to verify its efficacy.