Trastuzumab Biosimilar (HLX02), Pertuzumab Plus Chemotherapy in Patients with HER2-Positive Metastatic Breast Cancer after Progression of Trastuzumab: A Prospective, Phase II Study / Journal of the Korean Cancer Association, 대한암학회지

Purpose@#This study aims to evaluate the efficacy and safety of trastuzumab biosimilar (HLX02) in combination with pertuzumab and chemotherapy in patients with human epidermal growth factor receptor 2 (HER2)–positive metastatic breast cancer (MBC) after progression of trastuzumab. @*Materials and Methods@#In this prospective, single-arm, phase II study, patients with HER2-positive MBC after progression of trastuzumab received pertuzuamb, HLX02, and chemotherapy in Beijing Cancer Hospital from March 2020 to December 2022. The primary endpoint was progression-free survival (PFS), and secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. The study was registered with ClinicalTrials.gov (NCT05188495). @*Results@#A total of 45 patients were included in this study. Twelve patients (26.7%) were treated in second-line and 33 patients (73.3%) were in third-line and later setting. Eighty percent and 15.5% patients had previously received pyrotinib/lapatinib and T-DM1, respectively. With a median follow-up of 24.4 months (range, 1.2 to 43.9 months), the median PFS was 7.6 months (95% confidence interval, 4.3 to 10.9), OS was not reached, the ORR was 31.1%, and DCR was 91.1%. The treatment was well tolerated. @*Conclusion@#The combination of trastuzumab biosimilar HLX02, pertuzumab, and chemotherapy exhibited promising efficacy and a favorable safety profile as second- and beyond-line treatment in HER2-positive MBC.

Genetic diagnosis,observation of sperm ultrastructure and outcome analysis for assisted reproduction in Hui and Uyghur pa-tients with globozoospermia / 临床检验杂志

Objective To investigate the clinical phenotype,sperm characteristics,genetic etiology and the outcomes of assisted repro-ductive technology of 2 minority patients(P1 Hui and P2 Uyghur)with globozoospermia.Methods The clinical data and various pa-rameters of semen examination in the 2 minority patients with globozoospermia were analyzed.The ultrastructure of their sperms was ob-served,and the genetic etiology of the patients was analyzed by whole exome sequencing(WES)and qPCR.Intracytoplasmic sperm in-jection(ICSI)combined with artificial oocyte activation(AOA)were applied for assisted reproduction thyrapy.The outcomes of assis-ted reproduction in the two couples were observed.Results Homozygous 109681 bp deletion in DPY19L2 gene was found in both the patients.The homozygous deletion of DPY19L2 gene in P2 patient came from his inbred parents.Low sperm motility and high sperm DNA fragmentation rate were observed in the P1 patient,the and the rate of round-headed sperm was 100％in morphology.The ab-sence of sperm acrosome and ultrastructural defects of plasma membrane,mitochondria and microtubules were found under the electron microscope.In the P2 patient,sperm motility and sperm DNA fragmentation rate patient were normal,and the sperm morphology was 100％round-headed sperm.Under the electron microscope,the main defects of sperm were small and round head with acrosomal ab-sence,structural damage,but the ultrastructural defects of organelles were rare,such as plasma membrane,mitochondria and microtu-bules.Both couples of the two patients received ICSI+AOA for assisted pregnancy,and the ICSI fertilization rate was 62.5％for P1 pa-tient and 75％for P2 patient.Both the patients successfully obtained clinical pregnancy.Conclusion The abnormal DPY19L2 gene is the main genetic cause in the globozoospermia patients with different ethnic backgrounds.Both structural damage and ultrastructural de-fects of organelles such as plasma membrane,mitochondrial and microtubule damage could be found in globozoospermia.ICSI combined with AOA should be an effective assisted reproductive thyrapy strategy for the patients with globozoospermia.

Mechanisms of exercise-regulated telomere length and health promotion / 中国组织工程研究

BACKGROUND:As we age,the function of various systems in the human body gradually decreases and the telomeres,located at the ends of chromosomes,consequently shorten,leading to the development and progression of various chronic age-related diseases.As a cost-effective intervention,scientific exercise has been shown to reduce the rate of telomere wear,maintain telomere length,delay the aging process and reduce the probability of disease.At the same time,better health level is important for healthy aging. OBJECTIVE:To sort out the role of telomeres in health promotion by analyzing telomere and physical fitness,the common adverse factors of telomere length shortening and chronic disease occurrence,and the influence of telomere length on the regulation of the occurrence and development of common chronic diseases such as cardiovascular disease,cancer,diabetes,obesity and mental disease,as well as to summarize the possible regulatory mechanism of exercise regulating telomere length,and to explore the role of telomere in the regulation of exercise on the above-mentioned chronic diseases for the purpose of health promotion. METHODS:The search terms of"exercise,telomere,aerobic capacity,muscle strength,aging"in Chinese and English were used to search the relevant literatures in CNKI and PubMed,respectively.A total of 108 articles were included for final review. RESULTS AND CONCLUSION:In terms of physical fitness and health promotion,there is a strong correlation between the maximum aerobic exercise capacity and muscle strength of the human body and telomere length.Long-term physical exercise can enhance the level of physical fitness to maintain telomere length and promote the heath of the human body.In terms of chronic diseases and health promotion,abnormal telomere length can promote the occurrence of some chronic diseases such as cardiovascular diseases,cancer,diabetes,obesity,and mental diseases,and the factors that accelerate the shortening of telomere length,such as oxidative stress,inflammation,and telomerase activity,also have adverse effects on the development of these diseases.The regulation of telomere length by exercise can reduce the levels of oxidative stress and inflammation,improve the activity of telomerase and enhance the stability of telomere protein complex.Through these regulatory mechanisms,exercise slows the rate of telomere wear and maintains consistent telomere length,thereby reducing the risk of chronic diseases associated with abnormal telomere length,such as cardiovascular disease,cancer,diabetes,obesity,and mental diseases.Therefore,telomeres play a positive role when exercise is used to regulate related diseases and promote human health.

Effect of stress perception on depression in medical staff: the mediating role of resilience / 中华行为医学与脑科学杂志

Objective:To explore the impact of stress perception on depression and the potential mediating role of resilience in medical staff.Methods:A total of 606 medical staff were recruited and investigated by self-designed questionnaire, the perceived stress scale (PSS-10), the 10-item Connor-Davidson resilience scale (CD-RISC-10), and the patient health questionnaire-9 (PHQ-9) from February to March, 2020.SPSS 26.0 software was used to execute Pearson or Spearman correlation analysis, common method biases test, and multicollinearity test.Model 4 in PROCESS 3.2 macro program and Bootstrap method were used for mediating effects analysis.Results:There was a positive correlation between stress perception score(16.93±6.65) and depression score (5.00(2.00, 9.00))( r=0.551, P<0.01), and a negative correlation between stress perception score and resilience score (27.08±8.68) ( r=-0.285, P<0.01) among 606 medical staff.There was a negative correlation between resilience score and depression score ( r=-0.474, P<0.01). Mesometric effect examination showed that resilience played a partial mediating role in the relationship between stress perception and depression, and the mediating effect accounted for 10.87% of the total effect. Conclusion:Stress perception can directly or indirectly influence depression scores, and resilience partially mediates the relationship between stress perception and depression.Depression can be reduced clinically by reducing stress perception or enhancing the resilience of medical personnel.

Genetic analysis of a Chinese pedigree affected with branchiootic syndrome due to a nonsense variant of EYA1 gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotype and genetic basis for a Chinese pedigree suspected for branchiootic syndrome (BOS).@*METHODS@#The proband was subjected to target-capture high-throughput sequencing to detect potential variant of deafness-associated genes. Candidate variants were verified by Sanger sequencing of the family members.@*RESULTS@#The proband was found to harbor a c.1627C>T (p.Gln543Ter) nonsense variant of the EYA1 gene. Sanger sequencing confirmed that all of the 4 patients with the BOS phenotype from the pedigree have harbored the same heterozygous variant. Based on the guidelines of the American College of Medical Genetics and Genomics, the variant was predicted to be pathogenic (PVS1+PS+PP3+PP4).@*CONCLUSION@#The c.1627C>T (p.Gln543Ter) variant of the EYA1 gene probably underlay the BOS phenotype in this pedigree. Above finding has provided a basis for its clinical diagnosis.

Clinical Characteristics of Coronavirus Disease 2019 in Hainan, China

BackgroundSince January 2020, coronavirus disease 2019 (Covid-19) has spread rapidly and developing the pandemic model around the world. Data have been needed on the clinical characteristics of the affected patients in an imported cases as model in island outside Wuhan. MethodsWe conducted a retrospective study included all 168 confirmed cases of Covid-19 in Hainan province from 22 January 2020 to 13 March 2020. Cases were confirmed by real-time RT-PCR and were analysed for demographic, clinical, radiological and laboratory data. ResultsOf 168 patients, 160 have been discharged, 6 have died and 2 remain hospitalized. The median age was 51.0 years and 51.8% were females. 129 (76.8%) patients were imported cases, and 118 (70.2%), 51 (30.4%) and 52 (31%) of patients lived in Wuhan or traveled to Wuhan, had contact with Covid-19 patients, or had contact with Wuhan residents, respectively. The most common symptoms at onset of illness were fever (65.5%), dry cough (48.8%) and expectoration (32.1%). On admission, ground-glass opacity was the most common radiologic finding on chest computed tomography (60.2%). The elderly people with diabetes, hypertension and CVD are more likely to develop severe cases. Follow-up of 160 discharged patients found that 20 patients (12.5%) had a positive RT-PCR test results of pharyngeal swabs or anal swabs or fecal. ConclusionsIn light of the rapid spread of Covid-19 around the world, early diagnosis and quarantine is important to curb the spread of Covid-19 and intensive treatments in early stage is to prevent patients away from critical condition.

Analysis of TGM1 gene mutation in a collodion baby / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To explore the genetic cause for a Uyghur Chinese child with collodion skin.</p><p><b>METHODS</b>G-banded chromosomal karyotyping was carried out for the child and his parents. High-throughput sequencing for 25 genes related to ichthyosis and ichthyosiform dermatosis was also performed for the child.</p><p><b>RESULTS</b>No karyotypic abnormality was found in the child and his parents. High-throughput sequencing has detected in the patient a previously described pathogenic mutation c.919C>T (p.Arg307Trp) and a novel c.856C>T (p.Arg286Trp) mutation in the TGM1 gene. By Sanger sequencing, the child was verified to have carried both mutations. His father was found to be a heterozygous carrier of the c.856C>T (p.Arg286Trp) mutation, while neither mutation was found in the mother.</p><p><b>CONCLUSION</b>Congenital ichthyosis associated with the TGM1 gene may show an autosomal recessive inheritance. The collodion condition of the child is probably due to the compound heterozygous mutations of the TGM1 gene.</p>

Gene mutation and clinical phenotype analysis of patients with Noonan syndrome and hypertrophic cardiomyopathy / 中华儿科杂志

Objective@#To analyze the gene mutations and clinical features of patients with Noonan syndrome and hypertrophic cardiomyopathy.@*Method@#Determined the mutation domain in five cases diagnosed with Noonan syndrome and hypertrophic cardiomyopathy and identified the relationship between the mutant domain and hypertrophic cardiomyopathy by searching relevant articles in pubmed database.@*Result@#Three mutant genes (PTPN11 gene in chromosome 12, RIT1 gene in chromosome 1 and RAF1 gene in chromosome 3) in five cases all had been reported to be related to hypertrophic cardiomyopathy. The reported hypertrophic cardiomyopathy relevant genes MYPN, MYH6 and MYBP3 had also been found in case 1 and 2. Patients with same gene mutation had different clinical manifestations. Both case 4 and 5 had RAF1 mutation (c.770C>T). However, case 4 had special face, low IQ, mild pulmonary artery stenosis, and only mild ventricular hypertrophy.@*Conclusion@#Noonan syndrome is a genetic heterogeneity disease. Our study identified specific gene mutations that could result in Noonan syndrome with hypertrophic cardiomyopathy through molecular biology methods. The results emphasize the importance of gene detection in the management of Noonan syndrome.

Effect of tubulin in skeletal muscle on mitochondrial Rho-GTPase1 protein (Miro1) after high-intensity exercise and the underlying mechanism / 中国组织工程研究

BACKGROUND: High-intensity exercise can induce the depolymerization and/or degradation of tubulin in the skeletal muscle. According to the close relation with the mitochondria, tubulin may influence mitochondrial movement track and molecular motor, thereby varying the movement and distribution of mitochondria. OBJECTIVE: To observe the effect of high-intensity exercise on α-tubulin, MAP4, Miro1 and mitochondrial ultrastructures, analyze their sequential changes and further explore whether tubular depolymerization regulates the movement and distribution of mitochondria via Miro1. METHODS: Fifty-six Sprague-Dawley rats were divided into control (n=8) and exercise (n=48) groups. The rats in the exercise group ran on the treadmill ( -16°, 20 m/minute) for 90 minutes, and the soleus samples were removed immediately, 6, 12, 24, 48 and 72 hours after exercise (n=8 each time point). The expression levels of α-tubulin, MAP4 and Miro1 were detected by western blot assay, and the ultrastructural changes of mitochondria were observed under transmission electron microscope. RESULTS AND CONCLUSION: The expression level of α-tubulin was decreased significantly at 6 and 12 hours after exercise. The expression level of MAP4 was increased significantly at 6, 12, 48 and 72 hours after exercise. The expression level of Miro1 was increased firstly at 6 and 12 hours after exercise, and decreased at 72 hours after exercise. In the control group, the paired mitochondria were arranged on the both sides of Z line, and few appeared in the myolemma. Mitochondria began to accumulate in the myolemma immediately and 6 hours after exercise; the number achieved the peak at 12 hours, reduced at 24 and 48 hours, and returned to normal at 72 hours. These results suggest that high-intensity exercise can induce the depolymerization of microtubules in the skeletal muscle, thus regulating the movement and distribution of mitochondria via Miro1.

Effects of heavy load exercise and acupuncture treatment on tubulin in rat skeletal muscle / 中国组织工程研究

BACKGROUND:Heavy load exercises can induce the ultrastructural changes in the skeletal muscle by the depolymerization and/or degradation of tubulin in the skeletal muscle, thereby lessening contraction activities of the skeletal muscle. OBJECTIVE:To observe the effects of heavy load exercise and acupuncture on tubulin levels, and to analyze their roles and mechanisms in skeletal muscle injury and repair. METHODS:138 male Sprague-Dawley rats aged 8 weeks were randomly divided into acute exercise group (n=114) and long-term exercise group (n=24). The acute exercise group included four subgroups:sedentary group (n=6), exercise group (n=36), acupunctured group (n=36) and exercise plus acupuncture group (n=36). In the acute exercise experiment, rats were acupunctured after a medium-large intensity downhil running. Rat’s soleus samples were taken immediately, 6, 12, 24, 48 and 72 hours after exercise and/or acupuncture. In the long-term exercise experiment, rats underwent exercise and acupuncture for 3 weeks, and rat’s soleus samples were col ected at 24 hours after the last training. Expressions ofα-tubulin and microtubule-associated protein 4 (MAP4) in the soleus were detected by western blot assay. RESULTS AND CONCLUSION:After acute exercise, expression ofα-tubulin and MAP4 was up-or down-regulated transiently. After acute exercise combined with acupuncture, the protein expressions ofα-tubulin and MAP4 changed slightly. However, the long-term exercise induced an increase inα-tubulin protein expression, while a significant decrease in MAP4 protein expression. It was worth noting that acupuncture treatment reduced long-term exercise-induced variations of MAP4 expression. These results suggest that the heavy load exercise can induce the depolymerization of tubulins in the skeletal muscle, and acupuncture may relieve this effect.

Effect ofβ2-adrenergic receptor expression on migration of early-EPCs in COPD patients / 中国病理生理杂志

AIM:To investigate whether early endothelial progenitor cells (early-EPCs) expressβ2-adrenergic receptor (β2 AR) in the chronic obstructive pulmonary disease ( COPD) patients and the effect of β2 AR expression on the migration of early-EPCs.METHODS:Venous blood samples (20 mL) were obtained from antecubital vein of COPD pa-tients or healthy controls .Peripheral blood mononuclear cells were isolated by standard Ficoll gradient centrifugation , and purified by CD34 positive selection cocktail .The mRNA expression of β2 AR in the early-EPCs was detected by RT-PCR. The protein levels of β2 AR were assessed by Western blotting and flow cytometry .Chemotaxis was studied by Transwell as-say.Cultured early-EPCs were treated with ICI118551, norpinephrine (NE) or monoclonal antibody of β2AR (mAb-β2 AR) for 24 h.The number of migratory cells was counted under a light microscope .RESULTS:The level of β2 AR ex-pression in the COPD patients was higher than that in the controls .The number of migratory early-EPCs to stromal cell-de-rived factor 1αwas significantly improved by ICI 118551 compared with other COPD groups .When early-EPCs from the COPD patients or the controls were treated with different concentrations of mAb-β2 AR for 24 h, the number of migratory early-EPCs from the COPD patients and the controls treated with NE at concentration of 100 nmol/L was significantly re-duced.However, a marked decrease in the number of migratory early-EPCs from the COPD patients treated with NE was observed compared with control group .Before treated with ICI118551 or NE for 24 h, the early-EPCs were co-incubated with mAb-β2 AR for 40 min, and the number of migratory early-EPCs was not significantly different between COPD group and control group .Genetic down-regulation of β2 AR promoted the migration of early-EPCs in COPD group .CONCLU-SION:The level of β2 AR expression in the COPD patients is increased compared with the controls .The down-regulation ofβ2 AR improves the migration of early-EPCs.

Effect of midkine, a newly heparin - binding cytokine, on cardiovascular functions / 中国病理生理杂志

Midkine (MK) , a newly discovered heparin - binding growth factor, promotes growth, survival, and migration in various cells. Meanwhile, MK stimulates statistically significant forms in new arterioles and capillaries, causes vascular remodeling, prevents ischemia myocardial cells from injury via inhibiting apoptosis. MK also regulates the level of blood - fat.In general, MK plays key roles in cardiovascular diseases.

Effect of midkine,a newly heparin-binding cytokine,on cardiovascular functions / 中国病理生理杂志

Midkine (MK),a newly discovered heparin-binding growth factor,promotes growth,survival,and migration in various cells. Meanwhile,MK stimulates statistically significant forms in new arterioles and capillaries,causes vascular remodeling,prevents ischemia myocardial cells from injury via inhibiting apoptosis. MK also regulates the level of blood-fat. In general,MK plays key roles in cardiovascular diseases.