Heliangin acts as a covalent ligand of RPS2 that disrupts pre-rRNA metabolic processes in NPM1-mutated acute myeloid leukemia

Although NPM1 mutations are frequently found in acute myeloid leukemia patients, therapeutic strategies are scarce and unsuitable for those who cannot tolerate intensive chemotherapy. Here we demonstrated that heliangin, a natural sesquiterpene lactone, exerts favorable therapeutic responses in NPM1 mutant acute myeloid leukemia cells, with no apparent toxicity to normal hematogenous cells, by inhibiting their proliferation, inducing apoptosis, causing cell cycle arrest, and promoting differentiation. In-depth studies on its mode of action using quantitative thiol reactivity platform screening and subsequent molecular biology validation showed that the ribosomal protein S2 (RPS2) is the main target of heliangin in treating NPM1 mutant AML. Upon covalent binding to the C222 site of RPS2, the electrophilic moieties of heliangin disrupt pre-rRNA metabolic processes, leading to nucleolar stress, which in turn regulates the ribosomal proteins-MDM2-p53 pathway and stabilizes p53. Clinical data shows that the pre-rRNA metabolic pathway is dysregulated in acute myeloid leukemia patients with the NPM1 mutation, leading to a poor prognosis. We found that RPS2 plays a critical role in regulating this pathway and may be a novel treatment target. Our findings suggest a novel treatment strategy and lead compound for acute myeloid leukemia patients, especially those with NPM1 mutations.

Clinical and genetic analysis of three children with KBG syndrome due to novel variants of ANKRD11 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic characteristics of three children with KBG syndrome.@*METHODS@#Clinical data of the three children from two families who have presented at the First Affiliated Hospital of Zhengzhou University between October 2019 and September 2020 and their family members were collected. Trio-whole exome sequencing (trio-WES) and Sanger sequencing were carried out.@*RESULTS@#All children had feeding difficulties, congenital heart defects and facial dysmorphism. The sib- pair from family 1 was found to harbor a novel de novo heterozygous c.6270delT (p.Q2091Rfs*84) variant of the ANKRD11 gene, whilst the child from family 2 was found to harbor a novel heterozygous c.6858delC (p.D2286Efs*51) variant of the ANKRD11 gene, which was inherited from his mother who had a mild clinical phenotype.@*CONCLUSION@#The heterozygous frameshift variants of the ANKRD11 gene probably underlay the disease in the three children. Above findings have enriched the spectrum of the ANKRD11 gene variants.

Guideline for clinical comprehensive evaluation of Chinese patent medicine (2022 version) / 中国中药杂志

Currently,the research or publications related to the clinical comprehensive evaluation of Chinese patent medicine are increasing,which attracts the broad attention of all circles. According to the completed clinical evaluation report on Chinese patent medicine,there are still practical problems and technical difficulties such as unclear responsibility of the evaluation organization,unclear evaluation subject,miscellaneous evaluation objects,and incomplete and nonstandard evaluation process. In terms of evaluation standards and specifications,there are different types of specifications or guidelines with different emphases issued by different academic groups or relevant institutions. The professional guideline is required to guide the standardized and efficient clinical comprehensive evaluation of Chinese patent medicine and further improve the authority and quality of evaluation. In combination with the characteristics of Chinese patent medicine and the latest research achievement at home and abroad,the detailed specifications were formulated from six aspects including design,theme selection,content and index,outcome,application and appraisal,and quality control. The guideline was developed based on the guideline development requirements of China Assoication of Chinese medicine. After several rounds of expert consensus and public consultation,the current version of the guideline has been developed.

Clinical Significance of Thrombospondin Type 1 Domain-Containing 7A and Neural Epidermal Growth Factor-Like 1 Protein in M-Type Phospholipase A2 Receptor-Negative Membranous Nephropathy / 中国医学科学院学报

Objective To investigate the clinical significance of thrombospondin type 1 domain-containing 7A (THSD7A) and neural epidermal growth factor-like 1 protein (NELL1) in phospholipase A2 receptor (PLA2R)-negative membranous nephropathy (MN). Methods A total of 116 PLA2R-negative MN patients treated in Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University from 2014 to 2021 were enrolled in this study.Immunohistochemistry was employed to detect THSD7A and NELL1 in the renal tissue.The pathological characteristics,treatment,and prognosis were compared between positive and negative groups. Results The 116 PLA2R-negative MN patients included 23 THSD7A-positive patients and 9 NELL1-positive patients.One patient was tested positive for both proteins.The THSD7A-positive group showed higher positive rate of IgG4 (P=0.010),more obvious glomerular basement membrane (GBM) thickening (P=0.034),and higher proportion of stage Ⅱ MN and lower proportion of stage I MN (P=0.002) than the THSD7A-negative group.The NELL1-positive group had lower positive rates of C1q and IgG2 (P=0.029,P=0.001),less obvious GBM thickening (P<0.001),more extensive inflammatory cell infiltration (P=0.033),lower proportion of deposits on multi-locations (P=0.001),and lower proportion of atypical MN (P=0.010) than the NELL1-negative group.One patient with THSD7A-positive MN was diagnosed with colon cancer,while none of the NELL1-positive patients had malignancy.Survival analysis suggested that THSD7A-positive MN had worse composite remission (either complete remission or partial remission) of nephrotic syndrome than the negative group (P=0.016),whereas NELL1-positive MN exhibited better composite remission of nephrotic syndrome than the negative group (P=0.015).The MN patients only positive for NELL1 showed better composite remission of nephrotic syndrome than the MN patients only positive for THSD7A (P<0.001). Conclusions THSD7A- and NELL1-positive MN is more likely to be primary MN,and there is no significant malignancy indication.However,it might have a predictive value for the prognosis of MN.

Variant analysis of SEC23B gene in 4 families with congenital dyserythropoietic anemia / 中华医学遗传学杂志

OBJECTIVE@#To identify the pathogenic variants of 4 patients with hemolytic anemia of unknown cause.@*METHODS@#Peripheral blood samples of the patients and their family members were collected to extract DNA. The coding region and splice region in all exons of gene of erythrocyte related diseases were analyzed by using target sequence capture and high-throughput sequencing technology. Suspected pathogenic variants were verified by PCR combined Sanger sequencing technology.@*RESULTS@#Each of the probands was detected two compound heterozygous variants, and CDA II was diagnosed. Six variants were detected in the 4 probands, four variants were reported and the other two were first reported.@*CONCLUSION@#By high-throughput sequencing, gene variant of CDA II be analyzed fast and accurately. It is an effective supplement to convenional diagnostic methods. Furthermore, the novel variant sites have enriched the variant database of the SEC23B gene.

Analysis of gene inversion in Hemophilia A by Nanopore sequencing / 中华医学遗传学杂志

OBJECTIVE@#To detect gene inversion in two pedigrees affected with Hemophilia A by using Nanopore sequencing technology.@*METHODS@#Peripheral blood samples were taken from members of the two pedigrees. Following extraction of genome DNA, genetic variants of the carriers were detected by Nanopore sequencing and subjected to bioinformatic analysis.@*RESULTS@#Nanopore sequencing has identified the niece of the proband of the pedigree 1 as carrier of Hemophilia A Inv22, and the mother of the proband of the pedigree 2 as carrier of Hemophilia A Inv1, which was consistent with clinical findings. Breakpoint sites in both pedigrees were accurately mapped. Statistical analysis of the sequencing results revealed a large number of variations in the carriers' genomes including deletions, duplications, insertions, inversions and translocations.@*CONCLUSION@#Nanopore sequencing can be used to analyze gene inversions associated with Hemophilia A, which also provided a powerful tool for the diagnosis of diseases caused by gene inversions.

Clinical observation of acupuncture plus repetitive transcranial magnetic stimulation in thetreatment of post-stroke insomnia / 针灸推拿医学（英文版）

Objective: To evaluate the clinical efficacy of the Governor Vessel-unblocking and mind-regulating acupuncture method plus repetitive transcranial magnetic stimulation (rTMS) in the treatment of post-stroke insomnia. Methods: A total of 72 patients with post-stroke insomnia were randomly divided into 2 groups, with 36 cases in each group. The control group received rTMS treatment with a frequency of 1 Hz and a motion threshold value of 90％. The observation group received acupuncture with Governor Vessel-unblocking and mind-regulating method based on the rTMS treatment of the control group. The points were Baihui (GV 20), Shenting (GV 24), Yintang (GV 29), Fengfu (GV 16), Sishencong (EX-HN 1), Shenmen (HT 7), Sanyinjiao (SP 6), Shenmai (BL 62) and Zhaohai (KI 6). The treatment was performed once a day for 5 d a week followed by 2 d of rest for 4 weeks. The improvements of Pittsburgh sleep quality index (PSQI), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) scores were observed after treatment, and the clinical efficacy was compared between the two groups. Results: After 4 weeks of treatment, the PSQI, SAS, and SDS scores of the two groups were all reduced, and the intra-group differences were statistically significant (all P<0.001). After treatment, the three scores in the observation group were all lower than those in the control group, and the differences between the two groups were statistically significant (P<0.05, P<0.05, P<0.001). There was a statistically significant difference between the observation group and the control group comparing the clinical efficacy (P<0.05). Conclusion: The therapeutic effect of the Governor Vessel-unblocking and mind-regulating acupuncture method plus rTMS in treating post-stroke insomnia is better than rTMS alone, and it can better improve the anxiety and depression of patients.

Crebanine N-oxide, a natural aporphine alkaloid isolated from Stephania hainanensis, induces apoptosis and autophagy in human gastric cancer SGC-7901 cells

Objective: To investigate the cytotoxic effects and the potential mechanisms of crebanine N-oxide in SGC-7901 gastric adenocarcinoma cells. Methods: The cytotoxicity of crebanine N-oxide was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and cellular morphology was observed under a microscope. Cell apoptosis was determined by flow cytometry using propidium iodide staining. The expression levels of apoptotic-related proteins, cleaved caspase-3, cytochrome C, p53 and Bax, and autophagyrelated proteins p62, beclin1 and LC3 were detected by Western blotting assays. Results: Crebanine N-oxide treatment significantly inhibited the proliferation of SGC-7901 cells in a dose-dependent and timedependent manner via induction of G2-phase cell cycle arrest, apoptosis, and autophagy in SGC-7901 cells. Conclusions: Crebanine N-oxide could inhibit the growth of gastric cancer cells by promoting apoptosis and autophagy and could be used as a potential agent for treating gastric cancer.

Distribution Characteristics of Traditional Chinese Medicine Syndromes in Patients with Critical Lesions of Coronary Heart Disease / 中国实验方剂学杂志

Objective::To explore the distribution characteristics of traditional Chinese medicine (TCM) syndromes of critical lesions of coronary heart disease, and determine the classification and diagnostic criteria of syndromes, so as to provide reference for the differentiation and treatment of this disease. Method::Totally 1 000 patients with critical lesions of coronary heart disease treated in the Department of Cardiology, Yunnan Provinceal Hospital of TCM from January 2016 to December 2018 were selected as the subjects by clinical epidemiological research methods. Basic information, diagnosis and treatment of the patients, as well as the information obtained through observation, hearing, inquiry and pulse-taking of TCM were collected. Symptoms, signs, tongue signs, pulse signs and other four diagnostic information, as well as relevant clinical data were collected for mathematical statistics analysis by cluster analysis and factor analysis research methods, and expert group opinions were also included in discussion. Result::First, the results of cluster analysis showed six types of basic TCM syndromes in accordance with the clinically actual critical lesions of coronary heart disease: blood stasis syndrome, phlegm turbidity syndrome, cold congealing heart pulse syndrome, Qi deficiency syndrome, heart-kidney Yin deficiency syndrome, Heart-Yang deficiency syndrome. Second, a factor analysis was carried out on the basis of cluster analysis, and the main syndromes of each basic syndromes were preliminarily determined. Third, because of the duplicate content or the unified combination of different syndromes, the TCM syndromes of the critical lesions of coronary heart disease can be summarized in five categories, namely phlegm turbidity and blood stasis syndrome (368 cases, 36.80%), cold congestion heart pulse syndrome (156 cases, 15.60%), Qi deficiency and blood stasis syndrome (315 cases, 31.50%), Yin deficiency of heart and kidney (91 cases, 9.10%) and Heart-Yang depression (70 cases, 7.00%). The main and secondary syndromes refer to factor analysis results of six basic syndromes. Conclusion::Cluster analysis and factor analysis can be made on TCM syndromes of critical lesions of coronary heart disease to pave the way for the classification of TCM syndromes and the establishment of diagnostic criteria of TCM syndromes of coronary heart disease, with an important clinical significance.

A study of preschoolers tooth-brushing behavior in Shaanxi province / 中国实用护理杂志

Objective:Understand the status of brushing teeth behavior of preschoolers in Shaanxi Province, to provide basis for oral health of preschoolers.Methods:By adopting the methods of multi-stage, stratified, geometric and cluster sampling, 1 370 kindergarten students at the age of 3-5 in Shaanxi Province were sampled as respondents to implement oral health questionnaire.Results:49.2%(674/1 370) children brushed their teeth every day, including only 14.8%(203/1 370) children brushing their teeth twice or above. Therefore, the difference of the brushing frequency (≥ 1 time/day) between urban and rural areas had obvious statistical significance ( χ2 value was 47.588, P<0.01). 98.7%(741/750) children used toothpaste, including only 6.9% (51/741) using toothpaste with fluoride. Therefore, the use of toothpaste between urban and rural areas has no statistical significance. Only 0.5% (4/751) children started to brush their teeth when their first deciduous tooth erupted. Therefore, the age for children starting to brush their teeth between urban and rural areas had obvious statistical significance ( χ2 value was 24.217, P<0.01). 65.2% (490/751)parents never helped their children to brush teeth, parents in rural areas even reached to 72.8% (227/312). Therefore, the brushing frequency for parents helping their children to brush teeth between urban and rural areas had statistical difference ( χ2 value was 16.192, P<0.01). Conclusions:The status of brushing teeth behavior of preschoolers in Shaanxi Province is lower than the national level, and the level in rural areas is obviously lower that in urban areas. The education and cultivation on brushing teeth behavior should be further strengthened in the future propaganda and education, especially, the power of propaganda on children and parents in rural areas should be strengthened.

Genetic testing and prenatal diagnosis in seven pedigrees affected with ornithine transcarbamylase deficiency / 中华医学遗传学杂志

OBJECTIVE@#To detect genetic variants among 7 pedigrees affected with ornithine transcarbamylase deficiency (OTCD) and provide prenatal diagnosis for them.@*METHODS@#The pedigrees were subjected to targeted next-generation sequencing (NGS) with a gene panel for inherited metabolic diseases. Suspected pathological variants were confirmed by Sanger sequencing of the probands and their family members. Prenatal diagnosis was provided for 4 of the pedigrees.@*RESULTS@#Seven variants of the OTC gene, including c.583G>A (p.Gly195Arg), c.626C>T (p.Ala209Val), c.674C>T(p.Pro225Leu), c.482A>G (p.Asn161Ser), IVS1-2A>G, c.116G>T(p.Gly39Val), c.898delT(p.300Phefs*22), were detected, among which IVS1-2A>G, c.116G>A (p.Gly39Val) and c.898delT (p.300Phefs*22) were unreported previously. Three male fetuses were found to carry hemizygotic variants upon prenatal diagnosis. One female fetus were found to be heterozygous for a variant, and appeared to be normal at birth as well as by newborn screening.@*CONCLUSION@#OTC gene variant is the etiology of OTCD in the 7 pedigrees. Genetic testing of OTC could assist physicians in OTCD diagnosis and provide genetic counseling and prenatal diagnosis for the pedigrees.

Crebanine N-oxide, a natural aporphine alkaloid isolated from Stephania hainanensis, induces apoptosis and autophagy in human gastric cancer SGC-7901 cells

Objective: To investigate the cytotoxic effects and the potential mechanisms of crebanine N-oxide in SGC-7901 gastric adenocarcinoma cells. Methods: The cytotoxicity of crebanine N-oxide was evaluated by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay and cellular morphology was observed under a microscope. Cell apoptosis was determined by flow cytometry using propidium iodide staining. The expression levels of apoptotic-related proteins, cleaved caspase-3, cytochrome C, p53 and Bax, and autophagy-related proteins p62, beclin1 and LC3 were detected by Western blotting assays. Results: Crebanine N-oxide treatment significantly inhibited the proliferation of SGC-7901 cells in a dose-dependent and time-dependent manner via induction of G

Effect of estradiol valerate on expression of adrenergic rceptors in the preoptic area of hypothalamus of ovariectomized rats / 医学研究生学报

Objective The occurrence of perimenopausal hot flashes involves many theories, among which the study of neurotransmitter mechanism has attracted much attention. This study aims to investigate the changes of α1 and α2 adrenoreceptors in the preoptic area of the hypothalamus(POAH) in ovariectomized rats after 4 weeks treatment with estradiol valerate, and explore the potential neurotransmitter mechanism of perimenopausal hot flashes. Methods 30 female Sprague-Dawley rats, weighing 230±10 g and aged 6-8WK, were divided into three groups: ovariectomy (OVX)group , sham group, and ovariectomy plus estradiol valerate (OVX+E2) group, each 10. Rats in sham-operated group opened pelvic cavity to find ovaries, but did not remove them. The other rats underwent bilateral ovariectomy under sterile conditions. Rats in OVX group and (OVX+E2) group received bilateral ovariectomy, rats in OVX group received isotonic saline gavage (10 mg/kg), and rats in (OVX+E2) group received estradiol valerate gavage (0.8 mg /kg). Anesthesia, cardiac perfusion and paraffin section were made after taking the brain. The expression of α1 and α2 adrenoreceptors in POAH of the rats was detected by immunohistochemistry. Results After 4 weeks’ treatment, the number of α1[(54.0±3.9)/100μm2] and α2[(89.0±2.4)/100μm2] adrenoreceptor positive cells in POAH of OVX group significantly decreased compared with that in sham group[(66.3±4.0)、(71.0±2.2)/100μm2](P<0.01),while the number of α1 and α2 [(63.7±4.5)、(73.1±3.5)/100μm2)] adrenoreceptor positive cells in POAH of（OVX+E2 ）group significantly increased compared with that in OVX group(P<0.01). The difference was statistically significant. Conclusion The expression of two adrenergic receptors in the POAH of ovariectomized rats changed. The central noradrenergic system may be involved in the mechanism of perimenopausal hot flashes,which need further studying.

Study on commodity specification and grade standard and quality evaluation of Galla Chinensis / 中国中药杂志

This paper is aimed to study the commodity specification and grade standard of Galla Chinensis,for standardizing market order and guide the market circulation,and provide a basis for standardization of Galla Chinensis. With 33 samples of Galla Chinensis from market as the object of the research,the herbal textual research and market research were carried out. Then the grading indicator were selected by the descriptive statistics,principal component analysis and cluster analysis,combining with production practice,the commodity specification and grade standard of Galla Chinensis were set out. The data of moisture,ash,gallic acid as the internal index were used to analyze the relationship between the quality difference between grades and the appearance characters and the intrinsic composition. Herbal textual research and market research found that the high quality of Galla Chinensis characterized with large,complete,wall thick,grayish brown characteristics,and Galla Chinensis could be divided into gallnuts and horned gall. Through principal component analysis and cluster analysis,combining actual production and herbal record,screening,the length,diameter,single weight,the number of 500 g were determined as 4 grading indicators,the commodity specification was divided into two: gallnuts and horned gall,the grades was divided into two: selected goods and mixed goods. The result of correlation analysis showed there was no significant correlation between the internal index and the appearance characters of Galla Chinensis. The result of multiple comparison showed that the ash content of the selected goods was smaller than that of the mixed goods,but it did not reach significant. The content of gallic acid of the selected goods and the mixed goods of gallnuts were higher than selected goods of horned gall,and higher than mixed goods of horned galls. Using the length,diameter,single weight,the number of 500 g as the appearance characters index. Combining with the herbal textual research and market research,we have divided two specifications and two grades for the commodity specification and grade standard of Galla Chinensis,which can provide a basis for industry standards and national standards.

Study on commodity specification and grade standard and quality evaluation of Dipsaci Radix / 中国中药杂志

Through the records of herbal and market investigations,the samples collected from different market and origin were analyzed,and the appearance character indexes were determined in order to revise the commodity specification and grade standard of Dipsaci Radix combined with production practice. This is also to analyze association of the appearance with quality different of intrinsic components. The investigation results indicated the root's long and thick was better,and atrovirens of fracture surface,there are most of the market is dominated by the ungraded goods. Through principal component analysis,variance analysis and cluster analysis,combining with the feasibility of actual operation and herbal record,the length,middle diameter and phloem color were filtrated and the specification was divided into 2 ranks: the selection and ungraded goods,and the grade was divided into 2 ranks for the selection goods: big,small selected goods. Moreover,there were no significant correlation between the appearance and the intrinsic quality index of Dipsaci Radix,the content of extractum were significantly positive correlation with the moisture,but had extremely negative correlation with the total ash. Multiple comparisons indicated that the content of the moisture,extractum and asperosaponin VI of the selected goods were higher than the ungraded goods,while the total ash content were lower,and they hasn't significant difference. The commodity specification and grade standard of Dipsaci Radix as a basis provide commodity specification and grade standard of communities and standardizing market trade order.

False negative non-invasive prenatal screening result for trisomy 18: a case report / 中华围产医学杂志

We hereby reported a case of false negative non-invasive prenatal screening (NIPS) for trisomy 18. The fetus with increased nuchal translucency (3.2 mm) detected by ultrasound scan at 13+4 gestational weeks received NIPS and the result was negative in chromosomes 21, 18 and 13. A routine ultrasound examination at 22 weeks of gestation revealed multiple anomalies and a second NIPS was offered, which showed a negative result again. The pregnancy was terminated at 22+3 weeks. Multiple fetal and placental biopsies were collected for chromosome analysis using copy number variation sequencing based on high-throughput sequencing and fluorescence in situ hybridization. The fetal karyotype was shown to be 47,XY,+18 in fetal tissues (skin and liver) and umbilical cord, while no chromosomal abnormalities was detected at or near the center of the fetal and maternal surface of the placenta. Results of the chromosomal analysis along the edges of the fetal and maternal surfaces of the placenta were Chr18:47,XY,+18[60]/46,XY[40] and Chr18:47,XY,+18[35]/46,XY[65], respectively. We inferred that placental mosaicism was the cause of the false negative NIPS result. Therefore, genetic counseling before and after NIPS is necessary. Follow-up ultrasound is important for NIPS-negative patients. Invasive prenatal diagnosis is recommended when abnormal ultrasound markers with possible genetic etiology were recognized.

Clinical and genetic analysis of mucolipidosis in 3 pedigrees and literature review / 中华儿科杂志

Objective@#To investigate the clinical and genetic characteristics of 3 patients with mucolipidosis and to perform literature review.@*Methods@#A retrospective analysis was made on the clinical data and genetic test results of 3 pedigrees with mucolipidosis. The patients were followed up at the Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from February 2016 to August 2018. A neonatal inherited metabolic diseases gene panel including GNPTAB, GNPTG, MCOLN1, etc. was used for next-generation sequencing (NGS) based testing. Sanger sequencing was subsequently used to confirm the suspected pathological variants in the patients and their family members. Original papers on mucolipidosis published up to December 2018 were retrieved from PubMed, CNKI and WanFang databases by using the key words "mucolipidosis" AND "Chinese" .@*Results@#The onset ages ranged from (9-90) days. The common clinical characteristics of the 3 patients are developmental delay and skeletal abnormalities. Targeted NGS revealed 5 different variations all in GNPTAB including p.Arg364Ter, p.Ser385Leu, p.Try404Ter, p. Arg587Ter, c.1284+1G>T. Two variants p.Ser385Leu and c.1284+1G>T were novel. Twenty-six cases of mucolipidosis have been reported in Chinese from 8 papers, which included 11 type ML Ⅱα/β, 11 type ML Ⅲ α/β and 4 type ML Ⅲ γ. c.2715+1G>A and p.Arg364Ter variants are likely the hot variants in Chinese ML patients.@*Conclusions@#Mucolipidosis is a rare autosomal recessive disorder characterized by developmental delay and skeletal abnormalities. NGS plus Sanger sequencing detection is effective and accurate for making genetic diagnosis. p.Ser385Leu and c.1284+1G>T of GNPTAB gene are identified as novel pathogenic variants. GNPTAB gene is the main disease causing gene among Chinese ML patients, and c.2715+1G>A and p.Arg364Ter are the most common variants.

Tricho-rhino-phalangeal syndrome due to a novel frameshift variation of the TRPS1 gene / 中华医学遗传学杂志

Objective@#To explore the genetic etiology of a pedigree affected with tricho-rhino-phalangeal syndrome.@*Methods@#Next-generation sequencing (NGS) using a gene panel for hereditary osteopathies was carried out for the proband. Suspected mutation was validated in the proband and her parents by Sanger sequencing.@*Results@#A heterozygous frameshift variation c. 1995dupA (p.Gly666Argfs*20) of the TRPS1 gene was detected in the proband but not in her parents.@*Conclusions@#The novel c. 1995dupA (p.Gly666Argfs*20) mutation of the TRPS1 gene probably underlies the disease in the proband.

Tricho-rhino-phalangeal syndrome due to a novel frameshift variation of the TRPS1 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of a pedigree affected with tricho-rhino-phalangeal syndrome.@*METHODS@#Next-generation sequencing (NGS) using a gene panel for hereditary osteopathies was carried out for the proband. Suspected mutation was validated in the proband and her parents by Sanger sequencing.@*RESULTS@#A heterozygous frameshift variation c.1995dupA (p.Gly666Argfs*20) of the TRPS1 gene was detected in the proband but not in her parents.@*CONCLUSION@#The novel c.1995dupA (p.Gly666Argfs*20) mutation of the TRPS1 gene probably underlies the disease in the proband.

The Design and Practice in"four in two"Basis of Life Integrated Curriculum / 昆明医科大学学报

Objective To explore the thinking and methods of integration curriculum. Methods The content of theory and experiment of the biochemistry,molecular biology, cell biology, medical genetics are optimized, streamlined and integrated to form theory course and experiment experimental course of " basis fo life", namely"four in two". Forming a teaching team across departments, multi-disciplinary teaching is carried out. The theory takes " cell-moleculeinheritance-disorders" as the main line, interspersed with " flipped class model" . The experimental course deletes repeated confirmatory experiments and adds some comprehensive experiments. The course assessment and performance evaluation are carried out with the combination of formative assessment and summative evaluation. Results The teaching mode of integration curriculum has been carried out in the experimental class of undergraduate students for two years. Compared with the theoretical examination scores, the results of the experimental class were significantly higher than that of the control class, and the difference was statistically significant (P＜0.05) . 24 students took part in research in experimental class, but only 10 students did in control class.Conclusion The implementation of integrated curriculum can promote student’s independent learning, improve student’s ability to analyze and solve problems, and mobilize student’s interest in scientific research practice. It provides useful reference and experience for the integration of basic course in the life science field of higher medical colleges.