One case of developmental epileptic encephalopathy caused by NR4A2 gene variation and literature review / 中华神经科杂志

Objective:To analyze the clinical characteristics of a child with developmental epileptic encephalopathy caused by NR4A2 gene mutation, and to summarize the clinical phenotypes and genotypes to improve the clinician′s understanding of this disease. Methods:The clinical data of a child with developmental epileptic encephalopathy admitted to Linyi People′s Hospital in August 2022 were collected, video electroencephalogram, craniocerebral magnetic resonance imaging and family whole exon sequencing were improved, and the suspected mutation sites were verified by Sanger sequencing. Relevant literature was consulted to summarize the clinical phenotypes and genetic characteristics of nervous system diseases caused by NR4A2 gene. Results:It was found that there was a heterozygous missense mutation at the locus c.866G>A (p.A289H) of NR4A2 gene in the child, which was a de novo mutation, and both parents were wild type. According to the American Society of Medical Genetics and Genomics variation classification, it was assessed as a suspected pathogenic variation. Through literature review, there were 16 related cases reported internationally, with clinical phenotypes including mental retardation/mental retardation, language disorders, seizures, muscle tone changes and different psychological and behavioral problems. Conclusions:The NR4A2 gene is not only associated with dopa responsive disorders, but also with neurological development, intellectual impairment, language development delay, and epilepsy. The mutation of NR42A gene c.866G>A (p.A289H) is the genetic cause of the patient, and the detection of this locus expands the NR4A2 gene spectrum. NR4A2 gene is one of the pathogenic genes of developmental epileptic encephalopathy.

Clinical analysis of a family with autosomal recessive spastic paraplegia caused by IBA57 gene mutations / 中华神经科杂志

Objective:To investigate the clinical, imaging and gene variation characteristics of hereditary spastic paraplegia type 74 caused by mutations in IBA57 gene. Methods:A retrospective analysis was performed on 2 cases of autosomal recessive spastic paraplegia caused by mutations in IBA57 gene who visited the Department of Neurology, the Affiliated Wuxi Children′s Hospital of Nanjing Medical University in 2010 and 2021, and the patients′ clinical data were collected. Results:The 2 patients were siblings with onset age of 4 years and 7 months, 1 year and 3 months, respectively. The same compound heterozygous mutations in IBA57 gene were found in the sibling patients [c.473G>C (p.R158P) and c.697C>T (p.R233X)]. Both patients were diagnosed as spastic paraplegia type 74. They had mild to moderate gait abnormalities, optic atrophy, decreased vision, and leukodystrophy with periventricular white matter abnormality, but no obvious growth and mental retardation in developmental assessment. Conclusions:Cases of spastic paraplegia type 74 caused by compound heterozygous mutations in IBA57 gene mainly manifested as childhood onset and slowly progressive inferior spasmodic weakness. The patients did not display significant cognitive impairment, and imaging examinations showed obvious leukodystrophy.

Helicobacter pylori promotes gastric cancer metastasis via up-regulating the expression of Bmi-1 / 细胞与分子免疫学杂志

Objective To clarify whether Helicobacter pylori (H. pylori) can promote metastasis of gastric cancer cells via the high-expression of induced B cell specific Moloney murine leukemia virus integration site 1 (Bmi-1). Methods The gastric cancer tissue specimens from 82 patients were collected for this study. The protein and gene expression level of Bmi-1 in gastric adenocarcinoma tissue were detected by immunohistochemistry and real time quantitative PCR, respectively. And meanwhile the correlation between Bmi-1 levels and pathological features, and prognosis of gastric cancer were analyzed retrospectively. Then, the GES-1 cells were transfected with pLPCX-Bmi-1 plasmid and infected with H. pylori respectively. After the Bmi-1 overexpression in GES-1 cells, the invasion ability of the GES-1 cells was detected by Transwell assay, and the cell cycle and apoptosis were detected by flow cytometry. Results The mRNA and protein of Bmi-1 expression in gastric cancer tissues were higher than tumor-adjacent tissue, and the high expression of Bmi-1 was positively correlated with tumor invasion, TNM stage, tumor differentiation, lymph node metastasis and H. pylori infection. When expression of Bmi-1 was up-regulated as a result of H.pylori infection or pLPCX-Bmi-1 transfection, the GES-1 cells had higher invasiveness and lower apoptosis rate with the above treatment respectively. Conclusion H. pylori infection can inhibit the apoptosis of gastric cancer cells and promote their invasion via up-regulating expression of Bmi-1.

Risk factors of elbow stiffness after open reduction and internal fixation of intercondylar fracture of humerus / 中国骨伤

OBJECTIVE@#To investigate the risk factors of elbow stiffness after open reduction and internal fixation of intercondylar fracture of humerus.@*METHODS@#From March 2015 to February 2019, 120 patients with humeral intercondylar fractures were treated with open fixation including 59 males and 61 females, aged from 25 to 77 years with an average of(53.5±3.2) years. According to the occurrence of elbow stiffness after operation, 120 patients were divided into stiffness group(37 cases) and control group(83 cases). The related factors of elbow stiffness were analyzed by single factor analysis, and the risk of elbow stiffness after internal fixation of humeral intercondylar fracture was analyzed by logistic regression factor.@*RESULTS@#There were 37 cases of elbow stiffness(stiff group), and 83 cases had no elbow stiffness(control group). The incidence of joint stiffness was 30.83%. There were significant differences between the stiffness group and the control group in age, injury energy, fracture to operation time, AO classification of fracture, open injury and postoperative premature or hyperactivity. Multivariate logistic regression analysis showed that age>50 years old, high energy injury, AO classification of fracture, open fracture and postoperative premature or hyperactivity were risk factors for elbow stiffness after internal fixation of humeral intercondylar fracture. The postoperative mobility and Mayo elbow performance score(MEPS) scores of the postoperative stiffness group were lower than those of the non-stiffness group with statistical significance(P<0.05). There were no significant differences in postoperative mobility and MEPS scores between flexion stiffness and rotation stiffness after humeral intercondylar fracture(P>0.05).@*CONCLUSION@#In view of the risk factors of elbow stiffness after internal fixation of humeral intercondylar fracture, reasonable operation plan and rehabilitation strategy should be formulated before operation to minimize the incidence of elbow stiffness.

CiteSpace knowledge map of research hotspots and frontiers of traditional Chinese medicine intervention in psoriasis in recent ten years / 中国中药杂志

This study aimed to investigate the development status of traditional Chinese medicine(TCM) intervention in psoriasis in recent ten years, analyze the research hotspots, and summarize the development trends to provide reference materials for scholars in this field. Taking the available literature related to the field of TCM intervention in psoriasis as the research object, the trends, contents, and source publications were statistically analyzed based on bibliometrics. The research cooperation and co-occurrence of keywords in this field were studied by the knowledge map analysis method based on CiteSpace. The total number of Chinese papers was 2 993 and English papers 285. In terms of publication trend, the annual publication of English papers was low but showed an obvious upward trend, while the increase in Chinese papers fluctuated and tended to be flat. In terms of the content of Chinese papers published, TCM ranked first according to the discipline(2 415). In English papers, the number of publications in pharmacology and pharmaceutical science was the highest(87). Literature source analysis showed that the Chinese and English journals with the most publications were China Journal of Traditional Chinese Medicine and Pharmacy and Evidence Based Complementary and Alternative Medicine, respectively. Beijing University of Chinese Medicine published the most dissertations in China(99). The authors with the most publications in Chinese and English were LI Bin(Yueyang Hospital of Integrated Traditional Chinese and Western Medicine Affiliated to Shanghai University of Traditional Chinese Medicine) and LU Chuan-jian(Guangdong Hospital of Traditional Chinese Medicine). As revealed by the CiteSpace analysis of the research cooperation network, there were four mature and stable core teams in this field, but the cooperation intensity between different teams was weak. According to the keywords co-occurrence knowledge graph constructed by CiteSpace, the current hot keywords in this field are as follows: psoriasis, blood-heat syndrome, blood-stasis syndrome, fire needle, blood-dryness type, imiquimod, TCM bath, etiology and pathogenesis, cytokines, cupping therapy, etc. In summary, Chinese scholars have conducted active exploration and research in the field of TCM intervention in psoriasis in recent ten years. The overall development trend is good, and the breadth and depth of the research are constantly extending. It is suggested that relevant research should be free from discipline restrictions and strive for interdisciplinary integration.

Research Progress on the Role of Tumor-Associated Macrophages in Multiple Myeloma --Review / 中国实验血液学杂志

Bone marrow microenvironment is a highly complex environment surrounding tumor, which plays an important role in the survival, proliferation, drug resistance and migration of multiple myeloma (MM) cells. As an important cellular component in tumor microenvironment, tumor-associated macrophages(TAM) has attracted attention due to its key role in tumor progression and drug resistance. Targeting TAM has shown potential therapeutic value in cancer treatment. In order to clarify the role of macrophages in MM progression, it is necessary to understand the differentiation of TAM and its characteristics of promoting MM. This paper reviews the research progress on how TAM is programmed in MM and the mechanism of TAM promoting tumor development and drug resistance.

Deepening the Action on Salt Reduction in China-suggestions on strategy and implementation plan / 中华预防医学杂志

Excessive sodium/salt intake is the leading dietary risk factor for the loss of healthy life in the Chinese population. The "Healthy China 2030" Action Plan set the goal of reducing salt intake by 20% by 2030. However, salt intake in China is still at a very high level in the world, with adults reaching 11 g/d, more than twice the recommended limit of 5 g/d. The current policies and action plans of China have targeted catering workers, children, adolescents, and home chefs in salt, oil, and sugar reduction actions. However, there are still obvious deficiencies in the coordinated promotion and implementation. This study, therefore, proposed a set of comprehensive strategies (named CHRPS that is composed of communication and education, salt reduction in home cooking, salt reduction in restaurants, reducing salt content in pre-packaged food, and surveillance and evaluation) and key implementation points for further deepening the salt reduction action in China. These strategies were developed based on the main sources of dietary sodium for Chinese residents, the status of "knowledge, attitude and practice" in salt reduction, evidence of effective intervention measures, existing policies and requirements, and the salt reduction strategies of the World Health Organization and experience from some other countries. As a scientific reference, the CHRPS strategies will help the government and relevant organizations quickly implement salt reduction work and facilitate the earlier realization of China's salt reduction goal.

Analysis of CSF3R Gene Mutations and Clinical Characteristics in Patients with t(8;21) Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the occurrence of CSF3R mutation in patients with t(8;21) acute myeloid leukemia (AML) and its correlation with some clinical parameters.@*METHODS@#The clinical and laboratory data of 167 newly diagnosed AML patients with t(8;21) translocation were analyzed retrospectively. High-throughput DNA sequencing technology combined with Sanger sequencing method was used to detect 112 gene mutations. The occurrence of CSF3R gene mutation and its influence on the remission rate after chemotherapy were analyzed.@*RESULTS@#Among 167 patients with t(8;21) AML, 15 patients (9.0%) carried CSF3R mutations, including 6 cases of membrane proximal region mutations and 9 cases of truncation mutations in the cytoplasmic tail. The most common coexisting mutations of CSF3R were KIT (40.0%), TET2 (33.3%), DNMT3A (26.7%), FLT3 (20.0%), CBL (20.0%), IDH1 (13.3%), etc. Compared with the wild type, the CSF3R mutant group had a higher mutation rate of DNA methylation-related genes（P <0.001）. The median peripheral white blood cell (WBC) count of patients with CSF3R gene mutation was 5.80 (3.20-8.56)×109/L at initial diagnosis, which was significantly lower than 8.80 (5.26-19.92)×109/L of the CSF3R wild-type patients (P =0.017). There was no significant difference between the two groups in sex, median age, FAB classification, hemoglobin level, platelet count, etc. (P >0.05). The CR rate of the CSF3R gene mutation group (100%) was significantly higher than that of the wild-type group (86.8%), but the difference was not statistically significant (P >0.05). The CSF3R gene mutation group had a significantly higher CD19 positive rate and a higher -X rate than the wild group (86.7% vs 47.4%, P =0.004; 33.3% vs 13.2%, P =0.037).@*CONCLUSION@#There is a high incidence of CSF3R mutation in t (8;21) AML patients. The clinical characteristics and coexisting mutation genes of CSF3R mutation-positive patients are different from those of wild-type patients.

Genetic analysis and prenatal diagnosis of a child with Multiple congenital malformations-hypotonia-epilepsy syndrome type 3 due to variants of PIGT gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical features and genetic etiology of a child with Multiple congenital malformations-hypotonia-epilepsy syndrome type 3 (MCAHS3) and provide prenatal diagnosis for her parents.@*METHODS@#A female child who had presented at Linyi People's Hospital on 27 July 2022 for recurrent convulsions for over 4 years was selected as the study subject. Clinical data of the child were collected. Peripheral blood samples were taken from the child and her parents and subjected for whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing. Prenatal diagnosis was carried out on amniotic fluid sample at 18 weeks' gestation. Bioinformatic software was used to analyze the pathogenicity of the protein model for the variant loci.@*RESULTS@#The child was a 4-year-old female with frequent seizures, peculiar facial appearance, hypotonia and severe developmental delay. Genetic analysis revealed that she has harbored compound heterozygous variants of the PIGT gene, namely c.1126del (p.H376Tfs*56) and c.1285G>C (p.E429Q), which were respectively inherited from her mother and father. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.1126del (p.H376Tfs*56) variant was predicted to be pathogenic (PVS1+PM2_Supporting+PM4), and c.1285G>C (p.E429Q) variant was predicted to be likely pathogenic (PM2_Supporting+PM3+PM4). Prenatal diagnosis suggested that the fetus also harbored the same compound heterozygous variants, and the pregnancy was terminated with induced labor.@*CONCLUSION@#The c.1126del (p.H376Tfs*56) and c.1285G>C (p.E429Q) compound heterozygous variants of the PIGT gene probably underlay the MCAHS3 in this patient, and prenatal diagnosis has prevented birth of further affected child in this family.

Relationship between parental reproductive age and the risk of overweight and obesity in offspring / 中华预防医学杂志

Objective: To explore the role of parental reproductive age on the risk of overweight and obesity in offspring. Methods: The participants were derived from physical examination data of students aged 6-18 years in seven provinces in China, and questionnaire survey was used to collect demographic characteristics and lifestyle information of the students and their parents. A total of 41 567 children with complete data were included. According to the restricted cubic spline curve, maternal reproductive age was divided into three categories, 14-23, 24-28, and 29-38 years, and paternal reproductive age was divided into 14-23, 24-30, and 31-42 years. Multivariate logistic regression model was used to analyze the association between parental reproductive age and parental nutritional status and the risk of overweight and obesity in offspring. Results: The mean age of 41 567 children was (10.6±3.2) years, and the mean paternal and maternal age were (27.9±4.4) years and (25.8±4.0) years, respectively. The detection rate of overweight and obesity was 23.4%. After adjusting factors of children diet and behaviors, the OR(95%CI)of offspring overweight and obesity in groups of fathers aged 24-30 years and mothers aged 24-28 years was 1.11 (1.04-1.18) and 1.16 (1.08-1.24), respectively. When none parents were overweight and obese, the difference of obesity risk was not statistically significant. When both parents were overweight and obese, the OR(95%CI)of offspring overweight and obesity in groups of fathers aged 24-30 years and mothers aged 14-28 years old was 1.27 (1.00-1.62) and 1.33 (1.07-1.65) respectively. Conclusion: Parental reproductive age and parental overweight and obesity status may both increase the risk of overweight and obesity in offspring, with a significant interaction effect.

Changes in the morphology and function of the meibomian glands in patients with type 2 diabetes mellitus and their effects on the function of tear film / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the changes of morphology and function of meibomian glands in patients with type 2 diabetes mellitus and its influence on the tear film. METHODS: A total of 52 patients(104 eyes)with type 2 diabetes mellitus who came to our hospital from January 2018 to January 2020 were selected. Then they were divided into non-diabetic retinopathy group(NDR group, 31 cases with 62 eyes)and diabetic retinopathy group(DR group, 21 cases with 42 eyes)according to the fundus changes. While 38 cases(76 eyes)of diabetic-free cataract patients who treated at the same time were selected as the control group. The differences of three groups were compared with the morphology and the scores of the function of lid edge and meibomian glands, the scores of fluorescence staining of cornea, break-up time(BUT)of tear film, lipid layer thickness(LLT), blink times(BT)and partial blink rate(PBR).RESULTS: The morphology and the scores of function of lid edge and meibomian glands, the scores of fluorescence staining of cornea were significantly higher than the control group, and the DR group was significantly higher than the NDR group(all P<0.05). The BUT in the DR group and NDR group was significantly lower than that in the control group, and the DR group was significantly lower than that in the NDR group(all P<0.05). There were differences in LLT, BT and PBR among the three groups(P<0.05). The LLT and BT in the DR group and NDR group were significantly lower than those in the control group, and PBR was significantly higher than that in control group(all P<0.05), but there was no significant difference between the DR group and the NDR group(all P>0.05). Type 2 diabetes mellitus patients with morphology abnormalities of meibomian gland have a higher incidence of abnormal tear film function.CONCLUSION: Patients with type 2 diabetes mellitus are prone to shortening and loss of meibomian glands, which is easy to cause the dysfunction of the meibomian gland and decrease the stability of the tear film. While the patients with DR, the morphology abnormalities and dysfunction of the meibomian glands are more pronounced, and the stability of the tear film is worse.

The management of total anomalous pulmonary venous connection and risk factors for postoperative pulmonary venous obstruction / 中华实用儿科临床杂志

Objective:To discuss the treatment strategies and experiences of total anomalous pulmonary venous connection (TAPVC) and study the risk factors for postoperative pulmonary venous obstruction (PVO).Methods:Clinical data of 125 children with TAPVC in the Children Heart Center of Fuwai Central China Cardiovascular Hospital from January 2018 to December 2020 were included in this study and analyzed retrospectively.Of the 125 cases, 116 were treated surgically.They were divided into 2 groups according to whether PVO appeared after repair of TAPVC.The t-test or chi- square test was used to compare the clinical data of the 2 groups, and Logistic regression analysis was adopted to analyze the risk factors for postoperative PVO. Results:Among the 116 patients undergoing surgery, including 73 males (62.9%) and 43 females (37.1%), and according to Darling′s classification, there were 58 cases (50.0%) of supracardiac, 35 cases(30.2%)of intracardiac, 15 cases(12.9%) of infracardiac and 8 cases (6.9%) of mixed.The median age and body weight during surgery were 3.0 (1.2, 7.0) months and 5.0 (4.0, 6.8) kg.There were 13 deaths (11.2%), and recurrent PVO was observed in 18 patients (15.9%). Statistically significant diffe-rences were observed in terms of Darling′s classification (supracardiac 27.8% vs.56.6%, intracardiac 27.8% vs.31.6%, infracardiac 27.8% vs.10.5%, mixed 16.6% vs.5.3%, χ2=8.571, P=0.036) of PVO group and non-PVO group after operation preoperative PVO (83.3% vs.21.1%, χ2=25.293, P<0.01), with confluence (55.6% vs.81.1%, χ2=6.049, P=0.014), preoperative critical state (83.3% vs.31.6%, χ2=12.938, P<0.01), cardiopulmonary bypass time[ (128.800±47.254) min vs.(106.700±37.288) min, t=-2.094, P=0.039 ], delayed thoracic closure(27.8% vs.5.3%, χ2=6.227, P=0.013), and anastomotic velocity at 1 day after operation[1.0(0.9, 1.4) m/s vs.0.9(0.8, 1.1) m/s, Z=-2.004, P=0.045], anastomotic velocity at 1 week after operation[1.4 (1.3, 1.8) m/s vs.0.9 (0.7, 1.1) m/s, Z=-4.446, P<0.001], and mechanical ventilation time[121.0 (76.8, 246.9) h vs.91.5 (60.4, 135.9) h, Z=-1.989, P=0.047]. All of these data were included in the Logistic regression analysis.The results showed that preoperative PVO ( OR=797.179, 95% CI: 8.074-78 712.270, P=0.004) and increased anastomotic flow velocity at 1 week after operation ( OR=11 848.376, 95% CI: 23.746-5 912 017.803, P=0.003) were associated with postoperative PVO. Conclusions:Surgical correction in patients with TAPVC with a biventricular anatomy in this center is satisfactory.Preoperative PVO and early anastomotic flow velocity increase after operation are the high risk factors for postoperative PVO.

Clinical efficacy and safety of Treprostinil in the treatment of children with early decompensation after the Fontan procedure / 中华实用儿科临床杂志

Objective:To investigate the efficacy and safety of Treprostinil in the treatment of children with early decompensation after the Fontan procedure.Methods:A retrospectively analysis was performed on the clinical data of 16 children with early decompensation after the Fontan procedure treated with Treprostinil injection from December 2017 to June 2020 at Fuwai Central China Cardiovascular Hospital.A total of 16 patients were included, including 5 boys (31.2%) and 11 girls (68.8%). The age was (4.6 ±1.2) years, the weight was (16.0±2.1) kg.The changes of central venous pressure (CVP), heart rate (HR), systolic blood pressure (SBP), central venous oxygen saturation (ScvO 2), lactic acid (Lac), oxygenation index and B-type natriuretic peptide (BNP) were recorded at the infusion of Treprostinil and 3 hours, 24 hours, 48 hours and 72 hours after the infusion.The short-term efficacy of Treprostinil was observed[mortality, mechanical ventilation time, and length of intensive care unit (ICU) stay]; paired t-test was used to analyze the above indexes at different time points.The adverse reactions during the administration were also recorded. Results:Of the 16 children, the median mechanical ventilation time was 9 (5, 22) h, and the median ICU stay time was 2 (1, 12)days.After 72 hours of drug administration, CVP, Lac, BNP and HR decreased: CVP decreased from(16±5) mmHg (1 mmHg=0.133 kPa) to (11±2) mmHg ( P<0.001), Lac decreased from(6.8±3.2) mmol/L to (3.2±1.2) mmol/L ( P=0.002), BNP decreased from(980±223) ng/L to (250±120) ng/L( P<0.001), HR decreased from(150±20) times/min to (125±16) times/min( P=0.002); SBP, ScvO 2 and oxygenation index increased: SBP increased from(83±10) mmHg to (98±12) mmHg( P<0.001), ScvO 2 increased from 0.53±0.13 to 0.65±0.11 ( P=0.003), oxygenation index increased from (200±72) mmHg to (298±13) mmHg ( P<0.001), and the differences were statistically significant(all P< 0.05). One case died (6.3%), 2 cases (12.5%) had transient blood pressure drop and 1 case (6.3%) had nausea and vomiting.Besides, no other treatment-related complications were observed. Conclusions:As for children with early decompensation after the Fontan procedure, the intravenous application of Treprostinil can reduce pulmonary artery pressure rapidly, effectively improve circulatory status and oxygenation and ultimately improve the prognosis.

Analysis of Coexisting Gene with NRAS in Acute Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the coexisting mutations and clinical significance of Homo sapiens neuroblastoma RAS viral oncogene homolog (NRAS) gene in acute myeloid leukemia (AML) patients.@*METHODS@#High-throughput DNA sequencing and Sanger sequencing were used to detect 51 gene mutations. The occurrence, clinical characteristics and treatment efficacy of coexisting genes with NRAS were investigated.@*RESULTS@#A total of 57 NRAS mutations (17.5%) were detected in 326 patients with AML. Compared with the patients in NRAS non-mutation group, patients in the mutant group were younger (P=0.018) and showed lower platelet count (P=0.033), but there was no significant difference in peripheral leukocyte count, hemoglobin, and sex. For FAB classification, NRAS mutation and M2 subtype showed mutually exclusive (P=0.038). Among 57 patients carried with NRAS mutation, 51 (89.5%) patients carried with other gene mutations, 25 (43.9%) carried with double gene mutations, 10 (17.5%) carried with 3 gene mutations, and 16 (28.1%) corried with ≥ 4 gene mutations. The most common coexisting gene mutation was KRAS (24.6%, 14/57), followed by FLT3-ITD (14.0%, 8/57), RUNX1 (12.3%, 7/57), NPM1 (10.5%, 6/57), PTPN11 (10.5%, 6/57), DNMT3A (10.5%, 6/57) and so on. The age (P=0.013, P=0.005) and peripheral platelet count (P=0.007, P=0.021) of patients with NPM1 or DNMT3A mutations were higher than those of the patients with wild type, but there was no significant difference in peripheral leukocyte count and hemoglobin. Also, there was no significant difference in age, peripheral leukocyte count, hemoglobin, and peripheral platelet count between the patients in KRAS, FLT3-ITD, RUNX1 or PTPN11 mutant group and the wild group. Patients with FLT3-ITD mutations showed a lower complete remission (CR) rate (P=0.044). However, there was no significant difference in CR rate between the patients with KRAS, NPM1, RUNX1, PTPN11 or DNMT3A mutations and the wild group. The CR rate of the patents with single gene mutation, double gene mutations, 3 gene mutations, and≥ 4 gene mutations were decreased gradually, and there was no significant difference in CR rate between pairwise comparisons.@*CONCLUSION@#The mutation rate of NRAS mutation is 17.5%, 89.5% of AML patients with NRAS mutation coexist with additional gene mutations. The type of coexisting mutations has a certain impact on clinical characteristics and CR rate of patients with AML.

Caprylic Acid Improves Lipid Metabolism, Suppresses the Inflammatory Response and Activates the ABCA1/p-JAK2/p-STAT3 Signaling Pathway in C57BL/6J Mice and RAW264.7 Cells / 生物医学与环境科学（英文）

OBJECTIVE@#This study aimed to investigate the effects of caprylic acid (C8:0) on lipid metabolism and inflammation, and examine the mechanisms underlying these effects in mice and cells.@*METHODS@#Fifty-six 6-week-old male C57BL/6J mice were randomly allocated to four groups fed a high-fat diet (HFD) without or with 2% C8:0, palmitic acid (C16:0) or eicosapentaenoic acid (EPA). RAW246.7 cells were randomly divided into five groups: normal, lipopolysaccharide (LPS), LPS+C8:0, LPS+EPA and LPS+cAMP. The serum lipid profiles, inflammatory biomolecules, and ABCA1 and JAK2/STAT3 mRNA and protein expression were measured.@*RESULTS@#C8:0 decreased TC and LDL-C, and increased the HDL-C/LDL-C ratio after injection of LPS. Without LPS, it decreased TC in mice ( P < 0.05). Moreover, C8:0 decreased the inflammatory response after LPS treatment in both mice and cells ( P < 0.05). Mechanistic investigations in C57BL/6J mouse aortas after injection of LPS indicated that C8:0 resulted in higher ABCA1 and JAK2/STAT3 expression than that with HFD, C16:0 and EPA, and resulted in lower TNF-α, NF-κB mRNA expression than that with HFD ( P < 0.05). In RAW 264.7 cells, C8:0 resulted in lower expression of pNF-κBP65 than that in the LPS group, and higher protein expression of ABCA1, p-JAK2 and p-STAT3 than that in the LPS and LPS+cAMP groups ( P < 0.05).@*CONCLUSION@#Our studies demonstrated that C8:0 may play an important role in lipid metabolism and the inflammatory response, and the mechanism may be associated with ABCA1 and the p-JAK2/p-STAT3 signaling pathway.

Effect of Zhenzhu Tiaozhi Capsule on HbA1c in Patient with Type 2 Diabetes Mellitus： A Real-world Study / 中国实验方剂学杂志

Objective:To explore the long-term effect of Zhenzhu Tiaozhi capsule（FTZ） on hemoglobin A1c（HbA1c）in patients with type 2 diabetes mellitus （T2DM） based on real-world data. Method:T2DM patients who were provided with FTZ （FTZ group） and those receiving conventional hypoglycemic drugs （control group） were extracted from the hospital information system （HIS） of the First Affiliated Hospital of Guangdong Pharmaceutical University， followed by propensity score matching （PSM） for balancing the confounding factors between groups. With HbA1c as the efficacy evaluation index， the difference in efficacy between the two groups was compared using <italic>t</italic>-test and <italic>χ</italic>² test. For repeated measurement data of the same patient， the difference in efficacy and the stability of FTZ against HbA1c were analyzed by generalized estimating equation （GEE）. The factors that might affect the efficacy of FTZ against HbA1c were subjected to multivariate linear regression analysis （MLRA）， and the subgroup analyses were then conducted after the stratification of relevant factors. Result:There were 46 patients included in the FTZ group and 1 208 patients in the control group. PSM yielded 42 pairs of samples with balanced covariates between groups. As revealed by one-year observation， ① HbA1c in the FTZ group after treatment was 6.51%±1.09%. No significant difference was observed either in pre- and post-treatment comparison in the FTZ group or in its comparison with the control group. At the same time， the HbA1c compliance rate in the FTZ group was 73.8% after treatment. No significant difference was observed either in pre- and post-treatment comparison in the FTZ group or in its comparison with the control group. ② The GEE results showed that the post-treatment HbA1c levels in the two groups were not significantly different from each other. Moreover， the HbA1c level remained stable over treatment time. ③ MLRA and subgroup analyses results demonstrated that FTZ was more effective in patients with high baseline HbA1c ［<italic>β</italic>=-0.530，95% confidence interval（CI） -0.850～-0.209，<italic>P</italic><0.01］ or those who were complicated with hypertension （<italic>β</italic>=-0.918，95%CI -1.614～-0.222，<italic>P</italic><0.05）. Conclusion:In the real world， FTZ is able to control the blood sugar， and its effect is similar to those of conventional hypoglycemic drugs. Besides， it is capable of stabilizing the blood sugar for a long time.

In vitro functional similarity assessment of a proposed biosimilar BAT1706 to bevacizumab / 药学学报

Biosimilars are biological medicinal products that are highly similar to an already licensed reference product in terms of quality, safety, and efficacy. BAT1706 is being developed by Bio-Thera Solutions, Ltd. as a proposed biosimilar candidate to bevacizumab reference product (Avastin®). Bevacizumab acts by specifically binding to vascular endothelial growth factor A (VEGF-A), and preventing the interaction of VEGF-A with its receptors on the surface of endothelial cells, then blocking the downstream signaling pathway mediated by ligand-receptor, and inhibiting endothelial angiogenesis, thus inhibiting tumor growth. Comprehensive analytical characterization studies incorporating orthogonal analytical techniques were performed to compare the in vitro functional activities of BAT1706 and Avastin®. BAT1706 and Avastin® showed highly similar binding activity to multiple VEGF-A isoforms and equivalent VEGF-A neutralizing activity, as well as inhibitory activity of VEGF receptor (VEGFR)-2 tyrosine kinase autophosphorylation. Both products exhibited similar binding of the Fcγ receptors and a lack of Fc-related effector functions such as antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC). Overall, the results demonstrate that BAT1706 and Avastin® are highly similar in terms of in vitro functional activities.

Spectrum analysis of gene mutations in retinitis pigmentosa and cone-rod dystrophy / 国际眼科杂志(Guoji Yanke Zazhi)

@#AIM: To analyze the gene mutation spectrum of autosomal recessive retinitis pigmentosa(ARRP)pedigrees and cone-rod dystrophy(CORD)pedigrees in Ningxia region of China. <p>METHODS:Totally 35 ARRP pedigrees and 18 CORD pedigrees were included in Ningxia Eye Hospital from September 2016 to February 2020. Peripheral venous blood samples of the proband were collected for targeted capture enrichment and high-throughput sequencing using a genetic retinal disease capture chip that contain 232 pathogenic genes. Online analysis software was used to predict the pathogenicity of suspicious gene variation, and Sanger sequencing was used to analyze the co-segregation of the family members. <p>RESULTS: Totally 16 pathogenic genes were confirmed in 35 ARRP pedigrees, the mutations rate of RP1 gene was the highest, accounting for 14%(5/35), following were ABCA4, CRB1 and EYS gene, accounted for 11%(4/35); 18 CORD pedigrees carried 10 pathogenic genes. The mutation rate of ABCA4 gene was the highest, accounting for 28%(5/18), followed by ALMS1, PROM1, RPE65, USH2A gene, accounting for 11%(2/18). There were 5 co-exist disease-causing genes in ARRP and CORD pedigrees, which were ABCA4, CLN3, CRB1, PROM1, NRL, accounting for 42%(22/53).<p>CONCLUSION: There are similarities and crossover in the phenotype of ARRP and CORD. The pathogenic genes were overlaped. The most common overlaping gene between the two diseases is ABCA4.

Analysis of clinical phenotype and SCN1A gene variant in a pedigree affected with genetic epilepsy with febrile seizures / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with genetic epilepsy with febrile seizures plus (GEFS+).@*METHODS@#Clinical data of the proband and his family members were collected. Following extraction of genomic DNA, the proband was subjected to high-throughput sequencing. Candidate variant was verified by Sanger sequencing of the proband and other family members.@*RESULTS@#The pedigree, including 6 patients with febrile seizures from 3 generations, was diagnosed with typical GEFS+. Among them, 2 had febrile seizures (FS), 1 had febrile seizures plus (FS+), and 3 had febrile seizures with focal seizures. High-throughput sequencing revealed that the proband has carried a heterozygous missense variant of c.4522T>A (p.Tyr1508Asn) of the SCN1A gene. Sanger sequencing confirmed that other five patients and one normal member from the pedigree have also carried the same variant, which yielded a penetrance of 85.7%.@*CONCLUSION@#The c.4522T>A (p.Tyr1508Asn) of the SCN1A gene probably underlay the disease in this pedigree. The pattern of inheritance was consistent with autosomal dominant inheritance with incomplete penetrance. Above finding has enriched the variant spectrum of the SCN1A gene.

Rescue of male infertility through correcting a genetic mutation causing meiotic arrest in spermatogonial stem cells / 亚洲男科学杂志(英文版)

Azoospermia patients who carry a monogenetic mutation that causes meiotic arrest may have their biological child through genetic correction in spermatogonial stem cells (SSCs). However, such therapy for infertility has not been experimentally investigated yet. In this study, a mouse model with an X-linked testis-expressed 11 (TEX11) mutation (Tex11