Progress of research on quantitative techniques for trace amount of crystals in solid state drugs / 中国药科大学学报

@#Abstract: It is well-known that crystal form of a drug is a key factor impacting the physicochemical properties of the drug, which in turn affects its in vivo efficacy, safety and stability. The study on crystal forms of solid-state drugs is crucial for drug quality control, selection of production process and evaluation of clinical efficacy. The combination of chemometric and analytical techniques exhibited its great ability to analyze a large amount of multidimensional data, providing the possibility for quantification of trace amount of crystals (< 1%). Meanwhile, using the process analytical technology (PAT) to monitor the crystal content real-time during prescription preparation process can further realize the control on formulation quality and serve as a core technology to support the patent protection of crystalline forms. In this review, the combined application of crystal analytical techniques and chemometric methods for the quantitative analysis of trace crystals were summarized, aiming to provide guidance for the manufacturing of pharmaceutical preparations and their quality control.

Efficacy of metoprolol versus ivabradine in treatment of POTS in elderly patients after COVID-19 infection / 中华老年心脑血管病杂志

Objective To explore the difference in efficacy of metoprolol versus ivabradine in the treatment of postural orthostatic tachycardia syndrome(POTS)in the elderly after COVID-19 infection.Methods A total of 110 patients diagnosed with POTS at our department from Decem-ber 1,2022 to January 31,2023 were included.According to their drug regimen,they were divided into metoprolol group(62 patients)and ivabradine group(48 patients).On the 28th day of out-patient follow-up,the resting heart rate,heart rate of 10 min of standing,symptom disappearance rate,hospitalization rate,and mortality rate were compared between the two groups.Results On the 28th day of treatment,the resting heart rate and postural heart rate for 10 min were decreased in both groups when compared with the levels at initial diagnosis(P＜0.01).And there were no significant differences in the two types of heart rate between the two groups on the 28th day(71.0±7.0 vs 72.1±7.0,P=0.401;76.5±7.2 vs 77.4±7.6,P=0.573).No obvious differences were observed between the two groups in symptom disappearance rate,hospitalization rate,or mortality rate(88.7％vs 89.6％,3.2％vs2.1％,0％vs 0％,P＞0.05).Conclusion Metoprolol and ivabradine can effectively treat POTS in the elderly patients after COVID-19 infection.

Practice and reflection on medical social work′s contribution to improving medical services in pediatric hospitals / 中华医院管理杂志

Medical social work, as a bridge between social welfare policies and healthcare services, is an important force in meeting the diverse and multi-level needs of the people in medical and health care. Due to the particularity of the pediatric population, pediatric medical social work is becoming one of the key areas in the development of medical social work. Beijing Children′s Hospital, Capital Medical University has established a service mode of " collaborative medical and social worker team". The medical social workers acted as supporters to assist healthcare professionals to meet the psychological and social service needs of patients and their families as much as possible, and empowered medical staff′s career development as supporters. At the same time, the medical social workers assisted in the construction of a " child friendly" medical environment, and built a social support network for patients and families. The appropriateness and future prospects of pediatric medical social work were explored, in order to provide reference for its development.

Comparison of clinical effects of different doses of meropenem in the treatment of septic shock / 中国药房

OBJECTIVE To compare the clinical effects of different doses of meropenem in the treatment of septic shock. METHODS One hundred and six patients with septic shock were randomly divided into standard-dose group and high-dose group， with 53 cases in each group. Patients in the standard-dose group were given standard dose of meropenem （initial intravenous injection of 1 g meropenem more than 30 minutes， followed by 1 g meropenem intravenously every 8 hours， each time for more than 3 hours）； patients in the high-dose group were given high dose of meropenem （initial intravenous injection of 2 g meropenem more than 30 minutes， followed by 2 g meropenem intravenously every 8 hours， each time for more than 3 hours）； other treatment measures were determined based on the specific conditions of the patients. The main observation indicators were the increments of sequential organ failure assessment （SOFA） scores and simplified acute physiology score Ⅱ （SAPS Ⅱ） after 3， 5 and 7 days of treatment in both groups. Secondary observation indicators included in-hospital mortality， 90-day all-cause mortality， 7-day microbial cure rate， 7-day clinical cure rate， serum procalcitonin （PCT） and C-reactive protein （CRP） levels after 3， 5 and 7 days of treatment， hospitalization days in the intensive care unit， ventilator treatment days， the highest dose of norepinephrine. The occurrence of adverse drug reaction in the two groups was observed. RESULTS The increments of SOFA scores and SAPS Ⅱ after 7 days of treatment， the levels of PCT and CRP after 5 and 7 days of treatment as well as the 90-day all-cause mortality in the high- dose group were significantly lower than the standard-dose group （P＜0.05）. There were no statistically significant differences in other indicators between the two groups （P＞0.05）. CONCLUSIONS High-dose meropenem treatment for septic shock has better clinical effects and is safer than standard-dose meropenem.

Expert opinions on operation rules of Morita therapy outpatient service / 中国心理卫生杂志

Morita therapy has been bom for more than 100 years.Inpatient Morita therapy is highly oper-able and easy to master.It can improve many refractory neuroses through four-stage treatment.But more neuroses are treated in outpatient clinics,and Morita therapy cannot be used in hospitalized patients.Therefore,the formula-tion of expert opinions on outpatient operations is particularly important.This paper is based on domestic and for-eign references,and after many discussions by domestic Morita therapy experts,and then drew up the first version of the expert opinions on operation of outpatient Morita therapy.Meanwhile the operation rule of Morita therapy in three stages of outpatient treatment was formulated:in the etiological analysis stage,under the theoretical guidance of Morita therapy,analyze the pathogenic factors,to improve treatment compliance and reduce resistance;during the operating stage,guide patients to engage in constructive and meaningful actions,realizing the achievement of letting nature take its course principle;in the cultivating character and enriching life stage,pay attention to positive infor-mation,expanding the scope and content of actions,improving the ability to adapt to complex life,and preventing recurrence caused by insufficient abilities.It will lay a foundation for the promotion of Morita therapy in domestic outpatient clinics,so that more patients with neurosis and other psychological diseases could receive characteristic Morita therapy treatment in outpatient clinics.

Development of Multifunctional and Multipoint Fixed Support Drainage Device for Digestive Tract / 中国医疗器械杂志

OBJECTIVE@#To discuss the development of a multifunctional and multipoint fixed support drainage device for the digestive tract, as well as the effect of its application on animal experimental models and patients.@*METHODS@#The digestive tract multifunctional and multipoint fixed support drainage device is designed according to the requirements of the various gastrointestinal surgery and interventional procedures. It has metal flaps and airbags to achieve multi point fixation. The cuffs and shears are used to achieve endoscopic removal. And through different tube diameters and lengths, surgeons can achieve different surgical purposes.@*RESULTS@#A multifunctional and multipoint fixed support drainage device for the digestive tract was successfully designed and developed. The application experiment of the winged pancreatico-intestinal supporting drainage tube on animal models and patients, showed lower drainage fluid amylase level, faster amylase recovery speed, and better perioperative safety.@*CONCLUSIONS@#The support drainage device has the characteristics of simple operation, firm fixation, and good controllability of removal. It is an ideal choice among support drainage tubes in gastrointestinal surgery and interventional operations.

Relationship between gene polymorphisms of methylenetetrahydrofolate reductase and plasminogen activator inhibitor-1 and lower limb deep venous thrombosis after colorectal cancer surgery / 中国医师进修杂志

Objective:To analyze the relationship between gene polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and plasminogen activator inhibitor-1 (PAI-1) and lower limb deep venous thrombosis (DVT) after colorectal cancer surgery.Methods:The clinical data of patients with colorectal cancer who underwent surgical treatment in Zhangjiakou First Hospital from February 2020 to February 2023 were analyzed retrospectively. According to the presence or absence of lower limb DVT after surgery, the patients were divided into DVT group (20 cases) and non-DVT group (80 cases). The polymorphism of MTHFR C677T and PAI-1 promoter 4G/5G were detected by polymerase chain reaction method. The relationship between the polymorphisms of MTHFR C677T and PAI-1 promoter 4G/5G and lower limb DVT after colorectal cancer surgery was discussed by logistic regression analysis.Results:TT genotype frequency and T allele frequency of MTHFR C677T in the DVT group were higher than those in the non-DVT group: 65.00% (13/20) vs. 25.00% (20/80), 80.00% (32/40) vs. 38.75% (62/160). CC genotype frequency and C allele frequency were lower than those in the non-DVT group: 5.00% (1/20) vs. 47.50% (38/80), 20.00% (8/40) vs. 61.25% (98/160), with statistically significant differences ( P<0.05). There was no significant difference in CT genotype frequency between the two groups ( P>0.05). 4G/4G gene frequency and 4G allele frequency of PAI-1 gene in the DVT group were higher than those in the non-DVT group: 50.00% (10/20) vs. 21.25% (17/80), 67.50% (27/40) vs. 38.75% (62/160). 5G/5G gene frequency and 5G allele frequency were lower than those in the non-DVT group: 15.00% (3/20) vs. 43.75% (35/80), 32.50% (13/40) vs. 61.25% (98/160), with statistically significant differences ( P<0.05). There was no significant difference in 4G/5G gene frequency between the two groups ( P>0.05). The distribution frequency of TT genotype of MTHFR C677T and 4G/4G genotype of PAI-1 promoter in DVT group was higher than that in non-DVT group: 55.00% (11/20) vs. 22.50% (18/80), with a statistically significant difference ( P<0.05). Multivariate Logistic regression analysis showed that MTHFR C677T TT genotype ( OR = 1.499, 95% CI 1.201 to 1.871), PAI-1 promoter 4G/4G genotype ( OR = 1.471, 95% CI 1.170 to 1.850) and MTHFR The C677T loci TT genotype combined with the 4G/4G genotype of the PAI-1 promoter ( OR = 1.592, 95% CI 1.258 to 2.014) were risk factors for lower limb DVT after colorectal cancer surgery ( P<0.05). Conclusions:The TT genotype of MTHFR C677T site and the 4G/4G genotype of PAI-1 promoter are closely related to the formation of lower limb DVT after colorectal cancer surgery, and the risk of lower limb DVT is higher in patients with both genotype TT and 4G/4G.

Research Progress on Establishing and Evaluation of Acne Animal Models / 实验动物与比较医学

According to understanding of the pathogenesis of acne, scholars have established animal models of acne inflammation, animal models of grafting human skin acne, and natural acne animal models. The acne inflammation model is mainly induced by bacterial infection, chemical drug application, and foreign matter injection. Natural acne animal models include animals that some are sensitivity to hormones and some have clinical symptoms of acne. It is necessary to select appropriate model animals and replicate model methods for the development of acne intervention products with different degrees and mechanisms. At present, there are only human evaluation standards of acne health functions in China, but no animal evaluation standards, which has affected the in-depth study of the pathogenesis of acne as well as the research and development progress of acne products. This article summarizes the conditions for the occurrence of acne, the characteristics of human skin, the bidirectional effect of Cutibacterium acnes on human skin, acne animal models, and commonly used observation and evaluation indicators, providing the reference for studying the pathogenesis of acne, promoting acne treatment and health care, and developing treatment products.

Research progress of bio-metal organic frameworks in drug delivery system / 中国药科大学学报

@#In recent years, bio-metal organic frameworks (Bio-MOFs) synthesized with biocompatible ligands have been widely investigated as a potential drug delivery carrier due to their large specific surface area and porosity, rich host-guest intermolecular interactions, and good biocompatibility.In this review, we summarized the design methods of Bio-MOFs including structural and toxic factors, as well as a variety of drug loading methods including click chemistry, with particular focus on recent research advances in Bio-MOFs for pulmonary drug delivery systems, improving pharmaceutical properties of drugs, sustained and controlled drug release, stimulation response and targeted drug delivery systems.Finally, we summarized the bottlenecks that constrain the development of Bio-MOFs in clinical studies of actual pharmaceutical formulations and their future directions for approved formulations, aiming to provide some theoretical reference for promoting the application of Bio-MOFs in drug delivery systems.

Crystallization transformation of amorphous extracts of traditional Chinese medicine and its effect on dissolution behavior — Taking total flavonoids from Pueraria lobata as an example / 中国药科大学学报

@#In order to guarantee the quality of traditional Chinese medicines (TCMs), the crystallization transformation of complex extracts of TCMs and the influence of solid form on their physicochemical properties were studied.The extract of total flavonoids from Pueraria lobata was taken as a model.Crystallization transformation happened when lofting under different conditions, and the intrinsic dissolution tests were carried out.It was found that humidity was the key factor to induce crystallization of total flavonoids from Pueraria lobata.The greater the wettability was, the more the crystallization was.The dissolution rate of total flavonoids from Pueraria lobata with the most crystallization amount significantly decreased by 96.51% compared to the sample without crystallization.After further simulating the preparation process of total flavonoids from Pueraria lobata, it was found that the wet granulation process with introduced water would also lead to crystallization and reduced dissolution rate.As for all crystallization samples, there was an inversely proportional relationship between the dissolution rates and the amount of crystallization.The risk of crystallization existed both in the storage and preparation process of TCM extracts.Crystallization would significantly affect the dissolution rate, and thus the quality of TCM products.In this study, the crystallization transformation of amorphous complex TCM extracts was discovered, and the effect of the crystallization transformation on its dissolution behavior was systematically studied, which provides a new research idea for assuring the quality of TCM products and promoting the improvement of TCM preparation level.

Effect of enhanced recovery after surgery on postoperative function and pain in total hip arthroplasty patients with high comorbidity / 中国修复重建外科杂志

OBJECTIVE@#To investigate the effects of enhanced recovery after surgery (ERAS) on postoperative function and pain in total hip arthroplasty (THA) patients with high comorbidity.@*METHODS@#Patients with THA who were admitted between January 2020 and January 2022 were selected as the study objects, and a total of 223 patients with high comorbidity met the selection criteria. Patients were randomly divided into two groups using the random envelope method. During perioperative period, 112 cases in the ERAS group were treated according to the ERAS protocol and 111 cases in the control group with the traditional protocol. There was no significant difference in gender, age, body mass index, Charlson comorbidity index, preoperative diagnosis, the type and number of the comorbidities, preoperative visual analogue scale (VAS) score between the two groups ( P>0.05). However, the Harris score of ERAS group was significantly lower than that of control group before operation ( P<0.05). Preoperative and postoperative hospital stays were recorded. The VAS score was used to evaluate the pain before operation, at 1 day after operation, at the leaving bed time, at the day after discharge, and at 2 weeks after operation. Harris score was used to evaluate hip function before operation and at 2 weeks, 1 month, 3 months, 6 months, and 12 months after operation. The incidence of complications, 30-day readmission rate, mortality rate, and patient's satisfaction were recorded.@*RESULTS@#The length of preoperative hospital stay in ERAS group was significantly shorter than that in control group ( P<0.05). But there was no significant difference in the length of postoperative hospital stay between groups ( P>0.05). All patients in the two groups were followed up 12 months. The VAS score in the two groups after operation was lower than that before operation, and showed a gradually trend with the extension of time, with significant differences between different time points ( P<0.05). VAS scores of ERAS group were significantly lower than those of control group at different time points after operation ( P<0.05). The postoperative Harris scores in both groups were higher than those before operation, and showed a gradually increasing trend with the extension of time, with significant differences between different time points ( P<0.05). Harris scores of ERAS group at 2 weeks, 1 month, and 3 months after operation were significantly higher than those of control group ( P<0.05). Complications occurred in 2 cases (1.79%) of the ERAS group and 6 cases (5.41%) of the control group, with no significant difference in incidence ( P>0.05). In the control group, 1 case was readmitted within 30 days after operation, and 1 case died of severe pneumonia within 1 year of follow-up. There was no readmission or death in ERAS group, and there was no significant difference in the above indexes between the two groups ( P>0.05). At last follow-up, the satisfaction rate of patients in ERAS group was slightly higher than that in control group, but the difference was not significant ( P>0.05).@*CONCLUSION@#For THA patients with high comorbidity, ERAS protocol can shorten preoperative waiting time, better reduce pain, and improve hip function.

Advances in rheological study of topical preparations for skin / 中国药科大学学报

@#Topical preparations for skin, including the commonly used dosage forms of ointments, creams, gels, patches and plasters, are convenient and can avoid the first-pass effect of drugs.Rheological study, which describes the flow characteristics and mechanical properties of products relevant to their Critical Quality Attributes, has become the main focus for topical preparations.Liquid and solid behaviors of products are usually investigated via steady rheology as well as dynamic rheology.This article reviews the research on topical preparations for skin and the data analysis models based on two rheological methods, aiming to provide some references for the rheological evaluation of topical preparations.

Mutation spectrum and clinical features of congenital long QT syndrome in 20 children: a single center study / 中华实用儿科临床杂志

Objective:To explore the pathogenic genes, clinical characteristics and treatment follow-up of children with congenital long QT syndrome (LQTS).Methods:Clinical data of 20 cases diagnosed with congenital LQTS and underwent gene testing from April 15, 2011 to April 15, 2021 in Department of Pediatric Cardiology, Shandong Provincial Hospital Affiliated to Shandong University were retrospectively collected and analyzed using independent sample t-test and Fisher′ s exact probability method. Results:LQTS-related gene mutations were detected in all the 20 cases, and pathogenic or suspected pathogenic mutations were identified in 18 cases (90.0%). Five LQTS mutation genes were discovered, including KCNQ1, KCNH2, SCN5A, CACNA1C and AKAP9.Eighteen cases (90.0%) had positive symptoms, and 13 cases (65.0%) had definite inducements.The inducement of symptoms in children with LQTS type 1(LQT1) was related to exercise, the causes of syncope in LQT1 and Jervell-Lange-Nielsen syndrome type 1 (JLNS1) with complex heterozygous mutations were exercise or emotional agitation; the causes of syncope in LQTS type 2 (LQT2) were unrelated to exercise; severe exercise in LQTS type 3 (LQT3) resulted in symptoms; and seizure in LQTS type 8 (LQT8) was non-induced.The corrected QT(QTc) interval of 20 cases was (553.1±66.6) ms, with a range of 460-707 ms, among which 17 cases showed QTc≥480 ms.The electrocardiogram(ECG) manifestations of children with various types of LQTS were different.There was no significant difference in QTc between different genders, or between children with syncope and those without syncope (all P>0.05). The follow-up time was (3.4±2.3) years, ranging from 0 to 8.3 years.Seventeen children received treatment[beta blockers and implantable cardiovertor-defibrillator(ICD)] and 3 cases did not.By the end of the follow-up, 1 child died, 19 cases survived, and 2 cases of the surviving children lost consciousness. Conclusions:There is a high consistency between genetic diagnosis and clinical diagnosis of congenital LQTS.The positive rate of gene detection is 90.0%.The clinical manifestations and ECG characteristics vary with genotypes.Beta blockers are protective.ICD therapy can prevent sudden cardiac death when oral medication does not respond.

Evaluation and Comparison of Predictive Value of Tumor Regression Grades according to Mandard and Becker in Locally Advanced Gastric Adenocarcinoma / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#Tumor regression grade (TRG) has been widely used in gastrointestinal carcinoma to assess pathological responses to neoadjuvant chemotherapy (NCT). There are various standards without a consensus, and it is still unclear which kind of system has better predictive value. This study aims to investigate and compare the predictive ability of the Mandard and Becker TRGs in patients with locally advanced gastric cancer. @*Materials and Methods@#A total of 290 patients with locally advanced gastric adenocarcinoma who underwent NCT and curative surgery were studied. Survival analysis for overall survival (OS) and disease-free survival (DFS) were based on the Kaplan-Meier method and Cox proportional hazards method. Predictive values of TRGs and models were assessed by time-dependent receiver operating characteristic (ROC) curve, the area under the ROC curve (AUC), nomogram, and calibration curve. @*Results@#In multivariable analysis, the Mandard TRG was associated with OS (hazard ratio [HR], 1.806; p=0.026) and DFS (HR, 1.792; p=0.017). The Becker TRG was also related to OS (HR, 1.880; p=0.014) and DFS (HR, 1.919; p=0.006). The Mandard and Becker TRG AUCs for 5-year survival were 0.72 and 0.71, respectively. The whole models showed an increased predictive value, with AUCs of 0.85 and 0.86, respectively. There was no significant difference between the two TRGs and two models. @*Conclusion@#TRG was an independent predictor for survival, and there was no significant difference between these two systems.

Preliminary study of neoadjuvant plus chemotherapy combined with concurrent chemoradiotherapy for locally advanced giant cervical cancer / 中华放射肿瘤学杂志

Objective:To preliminarily investigate the efficacy and safety of bevacizumab plus neoadjuvant chemotherapy combined with concurrent chemoradiotherapy in the treatment of locally advanced giant cervical cancer (LACC).Methods:Twenty-four patients with LACC who were treated with bevacizumab combined with neoadjuvant chemotherapy were assigned into the study group, and 30 patients receiving neoadjuvant chemotherapy in phase Ⅱ clinical trial (ChiCTR-TRC-11001832) were allocated in the control group. The survival rate was calculated by the Kaplan- Meier method, and the significance of differences between the variables was determined by the log-rank test. Results:The tumor volumes were (1.64±23.15) cm 3 and (12.83±15.08)( P=0.037), and the complete remission (CR) rates were calculated as 45.8% and 13.3%( P=0.004) in the study and control groups after neoadjuvant chemotherapy. The tumor volumes were (0±1.5) cm 3 and (1.00±10.63) cm 3( P=0.022) and the CR rates were 70% and 50%( P=0.009) in the study and control groups before afterloading treatment. The median follow-up was 24.6(9.3-101.7) months. The 1-and 2-year overall survival rates were 96%, 96% and 90%, 71%( P=0.110), the recurrence-free survival rates was 96%, 96% and 97%, 89%( P=0.512), and the distant metastasis-free survival rates were 96%, 88% and 83%, 80%( P=0.297) in the study and control groups, respectively. Adverse reactions were acceptable in both groups. Conclusion:Bevacizumab combined with neoadjuvant chemotherapy can significantly reduce the tumor volume, improve the tumor CR rate and yield tolerable adverse reactions.

Effect of GTPBP4 silencing on radiosensitivity of EC9706 cells / 中华放射肿瘤学杂志

Objective:To investigate the effect of GTPBP4 silencing by RNA interference on the radiosensitivity of esphageal cancer EC9706 cells line.Methods:The expression data of GTPBP4 in esophageal cancer tissues was obtained from public Gene Expression Omnibus (GEO) database. Recombinant plasmid-mediated RNA interference (RNAi) was employed to transfect the esophageal cancer EC9706 cell to evaluate the influence of GTPBP4 silencing on the proliferation, apoptosis and radiosensitivity of esphageal cancer EC9706 cells. The expression levels of GTPBP4 mRNA and protein and apoptosis-associated proteins of Bax, cleaved caspase-9, cleaved caspase-3 and Bcl-2 were determined by qRT-PCR and Western blot. The cell proliferation was determined by MTT assay. The changes in cell apoptosis were detected AnnexinⅤ-FITC/PI double staining flow cytometry. The variations in radiosensitivity after radiation exposure were assessed by clone formation assay.Results:The expression level of GTPBP4 in the esophageal cancer tissues was significantly higher than that in the normal adjacent esophageal tissues ( P<0.001). qRT-PCR and Western blot demonstrated that the expression levels of GTPBP4 mRNA and protein in the GTPBP4-siRNA group were significantly lower than those in the blank and negative control groups (both P<0.001), suggesting that the plasmid was successfully transfected into the EC9706 cells. MTT assay indicated that the EC9706 cell proliferation rate was significantly inhibited ( P<0.001). Flow cytometry found that the apoptosis rate was significantly increased in the GTPBP4-siRNA group ( P<0.001). After GTPBP4 gene interference combined with radiotherapy, the cell sensitivity enhancement ratio was 1.716. The apoptosis rate of EC9706 cells was significantly increased in the GTPBP4-siRNA group ( P<0.001). The expression levels of apoptosis-associated proteins including cleaved caspase-9, cleaved caspase-3 and Bax were significantly up-regulated, whereas that of Bcl-2 was significantly down-regulated in the EC9706 cells in the GTPBP4-siRNA group ( P<0.001, P=0.001, P=0.001 and P=0.005). Conclusions:GTPBP4 gene is highly expressed in human esophageal cancer tissues. RNAi technology can effectively inhibit the expression of GTPBP4 gene in the EC9706 cells, thereby suppressing cell proliferation, inducing cell apoptosis and enhancing the radiosensitivity of cells.

A pedigree analysis of a rare RhD 336-1G>A intron variant / 中华医学遗传学杂志

OBJECTIVE@#To explore the molecular mechanism of a case where RhD genotyping did not match serological results.@*METHODS@#The serological results of 8 members from two generations of this family were analyzed. And according to Mendelian law of inheritance, RhD genotyping, zygotic type determination and gene sequencing were performed for the family members.@*RESULTS@#The proband and one of her cousins have the same RhD alleles, both of them have a 336-1G>A intron variant RhD allele and a complete RhD deletion allele. The variant alleles are inherited from two of their parents with blood relationship, while the complete-deleted alleles come from the other. 336-1G>A means that the last base G of the second intron of the RhD gene is mutated to A, which leads to a negative RhD serology and a positive genotype in the proband.@*CONCLUSION@#There was a rare 336-1G> A intron variant gene (RhD * 01N.25) in this family, which was a recessive gene relative to the RhD gene and resulted in RhD phenotype negative.

Kinematics analysis and scale optimization of four degree of freedom generalized spherical parallel mechanism for ankle joint rehabilitation / 生物医学工程学杂志

By analyzing the physiological structure and motion characteristics of human ankle joint, a four degree of freedom generalized spherical parallel mechanism is proposed to meet the needs of ankle rehabilitation. Using the spiral theory to analyze the motion characteristics of the mechanism and based on the method of describing the position with spherical coordinates and the posture with Euler Angle, the inverse solution of the closed vector equation of mechanism position is established. The workspace of mechanism is analyzed according to the constraint conditions of inverse solution. The workspace of the moving spherical center of the mechanism is used to match the movement space of the tibiotalar joint, and the workspace of the dynamic platform is used to match the movement space of subtalar joint. Genetic algorithm is used to optimize the key scale parameters of the mechanism. The results show that the workspace of the generalized spherical parallel mechanism can satisfy the actual movement space of human ankle joint rehabilitation. The results of this paper can provide theoretical basis and experimental reference for the design of ankle joint rehabilitation robot with high matching degree.

Prenatal diagnosis of Rasopathies in Ras/MAPK signaling pathway / 中华医学遗传学杂志

RASopathies are a group of disorders caused by germline variants of genes involved in RAS/MAPK pathway with overlapping features which may complicate their diagnosis. Since almost all RASopathies are autosomal dominant inherited disorders, the affected families may give birth to multiple children with the disease. Owning to the advance in sequencing technology, the genotype-phenotype correlation of RASopathies has become clearer in recent years, and genetic testing is now available in many places, which make prenatal diagnosis for couples with increased risk possible. For de novo variants of RASopathies, prenatal diagnosis is still difficult as the findings in routine ultrasonography are not specific enough. Nevertheless, certain findings may still be used as clues for prenatal diagnosis. This article overviews the common disorders of RASopathies, with an emphasis on the features that can be used as clues for the prenatal diagnosis of RASopathies.

AMG-102 inhibits proliferation and induces apoptosis of laryngeal squamous cell carcinoma cells by regulating c-Met/PI3K/Akt pathway / 中华肿瘤杂志

Objective@#To investigate the effects of c-Met inhibitor AMG-102 on the proliferation and apoptosis of laryngeal squamous carcinoma Hep-2 cells and the underlying mechanism.@*Methods@#Laryngeal squamous carcinoma cell line Hep-2 cells were treated with 2.5, 5 and 10 μmol/L AMG-102, respectively. The proliferation activities of Hep-2 cells were detected by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT). The apoptotic rate of Hep-2 cells was detected by flow cytometry analysis and Hoechst staining. The mRNA expression levels of apoptosis-related genes were detected by real-time quantitative polymerase Chain reaction (RT-qPCR), and the protein expressions of c-Met/PI3K/AKT pathway were detected by western blot.@*Results@#Compared with the control group, the proliferation rates of Hep-2 cells treated with 2.5, 5 and 10 μmol/L AMG-102 for 24 hours were (89.8±1.1)%, (79.8±1.0)% and (69.1±1.2)%, respectively; for 48 hours were (76.8±2.0)%, (60.2±1.1)% and (49.8±1.2)%, respectively; for 72 hours were (50.1±2.0)%, (41.5±1.1)% and (33.6±1.0), respectively, with significant differences (all P<0.05). The apoptotic rates of Hep-2 cells treated with 2.5, 5 and 10 μmol/L AMG-102 for 48 hours were (16.09±1.53)%, (27.51±2.02)% and (36.57±1.42)%, respectively, which were significantly higher than (3.62±0.10) % in the control group (all P<0.05). After treated with 2.5, 5 and 10 μmol/L AMG-102 for 48 hours, the relative expression levels of Bcl-2 mRNA in Hep-2 cells were 0.58±0.13, 0.38±0.12 and 0.20±0.13, respectively; the relative protein expression of p-Met were 80.0±3.8, 50.6±4.2 and 28.5±1.3, respectively; the relative protein expression of p-PI3K were 87.1±0.9, 54.2±1.2 and 21.0±1.2, respectively; the relative protein expression of p-AKT were 98.7±5.6, 56.9±3.2 and 32.2±4.3, respectively; which were significantly lower than those in the control group (all P<0.05). The relative expression levels of Bax mRNA were 1.78±0.13, 2.37±0.14 and 3.05±0.13, respectively, and the relative expression levels of caspase-3 mRNA were 1.98±0.14, 2.47±0.14 and 3.15±0.13, respectively, which were significantly higher than those in the control group (all P<0.05).@*Conclusion@#c-Met inhibitor AMG-102 could inhibit the proliferation and induce apoptosis of laryngeal squamous carcinoma Hep-2 cells by regulating the c-Met/PI3K/Akt pathway.