ABSTRACT
@#<b>Objective</b> To investigate the current status of application of resources on medical exposure in Dongying, China, and to provide fundamental data for setting up the health information management system of occupational radiation diseases and implementing health supervision and management strategies. <b>Methods</b> According to the requirements of monitoring program on radiation health of Dongying in 2021, a general survey was carried out in all medical institutions (other than dental clinics) providing radiodiagnosis and radiotherapy services by the field investigation method using the unified questionnaires and survey content, and a descriptive analysis was conducted on the results. <b>Results</b> There were 92 institutions of radiodiagnosis and radiotherapy in Dongying, 1112 radiation workers who accounted for 5.9% of all workers on duty, including 679 (61.1%) males and 433 (38.9%) females, and 364 pieces of radiation equipment, including 339 for X-ray diagnosis, 8 for radiotherapy, 2 for nuclear medicine, and 15 for interventional radiology. The allocation of personal protective equipment for interventional radiology staff in tertiary hospitals was higher than that in secondary hospitals, in which there were 0.36 and 0.23 pieces of lead-rubber aprons, 0.43 and 0.30 pieces of lead-rubber hats, 0.50 and 0.35 pieces of lead-rubber collars, 0.05 and 0 pairs of lead-rubber gloves, and 0.31 and 0.17 pairs of lead protection glasses per capita, respectively. The allocation rates of lead-rubber collars and lead protection glasses in the nuclear medicine staff were higher than those in the interventional radiology staff, with 0.63 collars and 0.88 pairs per capita, respectively. The annual frequency of medical exposure was calculated to be 864.3 person-times per 1000 population for radiodiagnosis and 5.2 patients per 1000 population for radiotherapy. <b>Conclusion</b> The allocation and application of resources on medical exposure in Dongying is unbalanced, so it is demanded to set up a health information management system of occupational radiation diseases for continuously mastering the application of medical exposure and adopting differentiated regulatory measures such as rating classification in Dongying.
ABSTRACT
@#In this paper, micellar electrokinetic chromatography (MEKC) with glucose-β-cyclodextrin (Glu-β-CD) as chiral selector and ionic liquid surfactant N-butyl-N-methyl pyrrolidine lauryl sulfate ([C4MP] [C12SO4]) micelles formed at low pH as a pseudo stationary phase was applied for the chiral separation of four acidic drugs naproxen,warfarin, ketoprofen and ibuprofen.Under the same conditions,significantly improved separation of tested drug enantiomers was achieved with the MEKC system based on [C4MP][C12SO4] compared with the system based on the conventional surfactant sodium dodecyl sulfate (SDS).Several primary parameters affecting enantioseparation such as type and proportion of organic modifier, concentration and pH of the running buffer, concentration of chiral selector,concentration of ionic liquid surfactant and applied voltage were systematically investigated.
ABSTRACT
Psychogenic non-epilepsy seizures (PNES) are defined as paroxysms with clinical symptoms similar to epilepsy without epileptiform discharges. It is often misdiagnosed as epilepsy. Misdiagnosis not only delays the time for patients with PNES to get correct diagnoses and treatments, but also may increase the risk of adverse effects from improper use of antiseizure medications. The diagnostic method of PNES is video electroencephalogram monitoring, but there is no consensus on the optimal duration of monitoring. At the same time, the use of diverse physiological signals, brain imaging, laboratory examination, and the application of machine learning provide new perceptions for the precise identification of PNES and epilepsy. This article reviewed the progress of precise differential diagnosis between PNES and epilepsy.
ABSTRACT
Objective@#To investigate the epidemiological features of notifiable infectious diseases in Zhejiang Province in 2021, so as to provide the evidence for formulating infectious disease control measures.@*Methods@#The data pertaining to notifiable infectious diseases reported in Zhejiang Province in 2021 were retrieved from the Infectious Disease Surveillance System of China Information System for Disease Control and Prevention. The incidence and mortality of notifiable infectious diseases in Zhejiang Province in 2021 were descriptively analyzed.@*Results@#Totally 29 types of notifiable infectious diseases with 396 623 cases and 391 deaths were reported in Zhejiang Province in 2021, with a reported incidence of 614.28/105 and a reported mortality of 0.605 6/105, respectively. There were 93 204 cases with class B notifiable infectious diseases, with a reported incidence rate of 144.35/105 and 303 419 cases with class C notifiable infectious diseases, with a reported incidence rate of 469.92/105; while no cases with class A notifiable infectious diseases were reported. Syphilis (39.45/105), tuberculosis (37.12/105), viral hepatitis (31.90/105) and gonorrhea (26.34/105) were the four most common class B notifiable infectious diseases, and AIDS (0.477 0/105) and pulmonary tuberculosis (0.116 2/105) were the two most deadly class B notifiable infectious diseases, while hand, foot and mouth disease (192.00/105), other infectious diarrhea (184.24/105) and influenza (86.45/105) were the three most common class C notifiable infectious diseases. According to the transmission route, intestinal and respiratory infectious diseases were the two most common infectious diseases, with reported incidence rates of 384.10/105 and 133.73/105, respectively; and according to the reported region, the highest incidence of class B notifiable infectious diseases was reported in Zhoushan and Ningbo cities, and the highest incidence of class C notifiable infectious diseases was reported in Ningbo City. Totally 1 101 COVID-19 cases were reported in Zhejiang Province in 2021, including 712 confirmed cases and 389 asymptomatic cases, and no deaths occurred.@*Conclusions@#The reported incidence of notifiable infectious diseases declined in Zhejiang Province in 2021 as compared to that prior to COVID-19 epidemics, with remarkable reductions in the incidence of respiratory and intestinal infectious diseases. The management of pulmonary tuberculosis, viral hepatitis and AIDS requires to be reinforced during the containment of COVID-19, to prevent the seasonable epidemic of influenza, hand, foot and mouth disease and other infectious diarrhea in Zhejiang Province.
ABSTRACT
Objective:To explore the genetic etiology of fetuses with high suspicion of congenital skeletal malformation detected by prenatal ultrasound.Methods:This retrospective study collected 21 pregnant women with highly suspected fetal skeletal malformation indicated by ultrasound (the couples had no skeletal malformation) at Institute of Medical Genetics, Henan Provincial People's Hospital from January 2019 to August 2020. Amniotic fluid/umbilical cord blood of the fetus and peripheral blood of the couples were obtained for karyotype analysis, chromosomal microarray analysis, and whole-exome sequencing. Sanger sequencing was performed for the "pathogenic" "suspected pathogenic" "variants of uncertain significance" variants detected by whole exome sequencing. Genetic etiology of the 21 fetuses was described.Results:A total of five chromosomal abnormalities were detected, including four cases of trisomy 21 and one trisomy 18. Chromosome microarray analysis detected one case of abnormal copy number variation, 16 p11.2 microdeletion syndrome. Ten cases of monogenic diseases were found by whole exome sequencing and eight genes were involved ( SGMS2, FGFR3, DYNC2H1, WDR35, TBX5, COL2A1, FGFR2, and ALPL). Totally, 14 variations were detected, among which seven were novel variations (c.8129T>A, c.7126G>A, c.10307_10320del, and c.2641G>T in DYNC2H1 gene; c.3085G>A and c.491G>A in WDR35 gene; c.1070G>T in COL2A1 gene). Conclusions:For fetus, whose parents have no skeletal malformation, highly suspected of congenital malformation of skeletal system by prenatal ultrasound, genetic factor is the primary reason, including chromosomal abnormalities, copy number variations, and monogenic mutations.
ABSTRACT
Objective:To provide experimental evidence for genetic counseling and prenatal diagnosis by analyzing the clinical characteristics, screening and identification of the function of suspicious variants in a X-1inked spondyloepiphyseal dysplasia tarda (SEDT) family.Methods:The family members' medical history, general physical examination, femur, spine X-ray examination were collected. Peripheral blood samples of the family members were collected and DNA was extracted from these samples. Sequencing clinical whole exons of proband DNA by targeted gene high-throughput sequencing method, then analysis sequencing data. The suspicious mutation was confirmed in pedigree members by PCR and Sanger sequencing. Reverse transcription polymerase chain reaction (RT-PCR) experiments of total RNA from blood lymphocytes were performed. The amplification of exons 3 and 4 of the pathogenic gene were amplified and identified by agarose gel. The expression of the pathogenic gene was also detected.Results:Three affected males of the family were diagnosed with SEDT according to their clinical and radiological features. A nonsense mutation in the transport protein particle complex subunit 2 ( TRAPPC2) gene NM_001011658: c.91A>T (p.K31*) was found in the proband using whole exome sequencing. This variation was also detected in his cousin, but not in non-phenotypic members of the family. The RT-PCR result for amplification of exon 3 and 4 of peripheral blood lymphocytes was the same as those of normal controls, indicating that the mutation did not affect the splicing of transcripts. qPCR results showed that the transcriptional expression of TRAPPC2 in patients was significantly lower than that in family normal controls and normal people controls. Conclusion:Identification of the novel nonsense mutation (c.91A>T) in the SEDT family enables early patients screening, carrier detection, genetic counseling, prenatal diagnosis, and clinical prevention and treatment. The detailed genotype/phenotype descriptions contribute to the SEDT mutation spectrum. The study of the function of TRAPPC2 mutation will help to further elucidate the role of sedlin in cartilage.
ABSTRACT
Objective@#To establish a prediction model of herpangina epidemic trend based on Baidu index and hand, foot and mouth disease, so as to provide insights into analyses of communicable disease epidemics with limited or missing surveillance data.@*Methods@#The incidence of hand, foot and mouth disease in Zhejiang Province during the period from the first week of 2015 through the 39th week of 2021 was retrieved from the China Information System for Disease Control and Prevention, and the Baidu index of hand, foot and mouth disease and herpangina was collected via the Baidu search engine during the same period. The correlation between the Baidu index and time series of hand, foot and mouth disease was examined using wavelet analysis. In addition, a random forest training model was created based on the Baidu index and incidence of hand, foot and mouth disease, and the fitting effectiveness was evaluated using the mean percentage error, while the Baidu index of herpangina was included in the model to predict the epidemic trend of herpangina during the study period.@*Results@#The Baidu index of herpangina and hand, foot and mouth disease, and the Baidu index and incidence of hand, foot and mouth disease all appeared two peaks at the 26th and 52th week. The phase difference was less than 0.1 week between the Baidu index and time series of hand, foot and mouth disease, and the mean percentage error of the training model was 13.07%, with high concordance between the predicted number and actual report number of cases with hand, foot and mouth disease. The numbers of herpangina cases were predicted to be 28 822, 27 341, 28 422, 51 782, 52 457 and 5 691 from 2015 to 2020, and there were totally 48 702 herpangina cases reported until the 39th week of 2021. Like hand, foot and mouth disease, the incidence of herpangina peaked between May and July.@*Conclusion@#The random forest training model based on the Baidu index and incidence of hand, foot and mouth disease is feasible to predict the epidemic trend of herpangina.
ABSTRACT
OBJECTIVE@#To investigate the effect of suppressing high-mobility group box 1 (HMGB1) on neuronal autophagy and apoptosis in rats after intracerebral hemorrhage (ICH) in rats.@*METHODS@#Rat models of ICH induced by intracerebral striatum injection of 0.2 U/mL collagenase Ⅳ were treated with 1 mg/kg anti-HMGB1 mAb or a control anti-IgG mAb injected via the tail immediately and at 6 h after the operation (n=5). The rats in the sham-operated group (with intracranial injection of 2 μL normal saline) and ICH model group (n=5) were treated with PBS in the same manner after the operation. The neurological deficits of the rats were evaluated using modified neurological severity score (mNSS). TUNEL staining was used to detect apoptosis of the striatal neurons, and the expressions of HMGB1, autophagy-related proteins (Beclin-1, LC3-Ⅱ and LC3-Ⅰ) and apoptosis-related proteins (Bcl-2, Bax and cleaved caspase-3) in the brain tissues surrounding the hematoma were detected using Western blotting. The expression of HMGB1 in the striatum was detected by immunohistochemistry, and serum level of HMGB1 was detected with ELISA.@*RESULTS@#The rat models of ICH showed significantly increased mNSS (P < 0.05), which was markedly lowered after treatment with anti- HMGB1 mAb (P < 0.05). ICH caused a significant increase of apoptosis of the striatal neurons (P < 0.05), enhanced the expressions of beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), lowered the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and increased the content of HMGB1 (P < 0.05). Treatment with anti-HMGB1 mAb obviously lowered the apoptosis rate of the striatal neurons (P < 0.05), decreased the expressions of Beclin-1, LC3-Ⅱ, Bax and cleaved caspase-3 (P < 0.05), increased the expressions of LC3-Ⅰ and Bcl-2 (P < 0.05), and reduced the content of HMGB1 in ICH rats (P < 0.05).@*CONCLUSION@#Down- regulation of HMGB1 by anti-HMGB1 improves neurological functions of rats after ICH possibly by inhibiting autophagy and apoptosis of the neurons.
Subject(s)
Animals , Rats , Apoptosis , Apoptosis Regulatory Proteins/metabolism , Autophagy , Beclin-1 , Caspase 3/metabolism , Cerebral Hemorrhage/therapy , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats, Sprague-Dawley , bcl-2-Associated X Protein/metabolismABSTRACT
Objective@#To investigate the characteristics of public health emergencies and related information in schools of Zhejiang Province from 2012 to 2021, so as to provide insights into the management of public health risks in schools.@*Methods@#The public health emergencies and related information in schools of Zhejiang Province during the period from 2012 to 2021 were retrieved from the Public Health Emergency Management Information System of Chinese Disease Prevention and Control Information System. The type, temporal distribution and regional distribution of the events and the type of schools were analyzed, and the trends in disease attack rates were evaluated.@*Results@#A total of 1 284 public health emergencies and related information were reported in schools of Zhejiang Province from 2012 to 2021, accounting for 72.34% of all public health emergencies and related information, and a total of 40 562 cases were reported, accounting for 87.72% of all cases; no death was recorded. There were 1 276 infectious disease events reported, accounting for 99.38%, and norovirus enteritis (649 cases), varicella (281 cases), influenza (181 cases), hand, foot and mouth disease (94 cases) and mumps (22 cases) were predominant infectious diseases, accounting for 95.56% of all public health emergencies and related information in schools. The number of public health emergencies and related information in schools peaked during the period between March and June (361 events, 28.12% of all events) and the period between November and December each year from 2012 to 2021 (629 events, 48.99% of all events), and the events occurred across 11 cities of Zhejiang Province, with the largest number of events reported in Hangzhou City (507 events). In addition, there were 627, 328 and 242 events reported in primary schools, kindergartens, and middle schools, accounting for 93.22%, and the events predominantly occurred in city schools. Nevertheless, there were no significant changes in the trends for attack rates of norovirus enteritis, varicella, influenza and hand, foot and mouth disease and mumps in schools of Zhejiang Province from 2012 to 2021.@*Conclusions@#Norovirus enteritis, varicella, influenza, hand, foot and mouth disease and mumps were the predominant types of public health emergencies and related information in schools of Zhejiang Province from 2012 to 2021, and the largest number of events were reported in primary schools.
ABSTRACT
Cachexia is a common complication in patients with lung cancer. It aggravates the toxic and side effects of chemotherapy, hinders the treatment plan, weakens the responsiveness of chemotherapy, reduces the quality of life, increases complications and mortality, and seriously endangers the physical and mental health of patients with lung cancer. The causes and pathogenesis of tumor cachexia are extremely complex, which makes its treatment difficult and complex. Controlling cachexia in lung cancer patients requires many means such as anti-tumor therapy, inhibition of inflammatory response, nutritional support, physical exercise, and relief of symptoms to exert the synergistic effect of multimodal therapy against multiple mechanisms of tumor cachexia. To date, there has been a consensus within the discipline that no single therapy can control the development of cachexia. Some therapies have made some progress, but they need to be implemented in combination with multimodal therapy after fully assessing the individual characteristics of lung cancer patients. This article reviews the application of drug therapy and nutritional support in lung cancer patients, and looks forward to the research direction of cachexia control in lung cancer patients. .
Subject(s)
Humans , Cachexia/therapy , Combined Modality Therapy , Lung Neoplasms/drug therapy , Neoplasms/complications , Nutritional Support/adverse effects , Quality of LifeABSTRACT
OBJECTIVE@#To analyze the clinical features and genetic variant in a patient with Usher syndrome.@*METHODS@#Whole exome sequencing was carried out for the patient. Suspected variants were validated by Sanger sequencing of her parents and fetus.@*RESULTS@#The proband was found to harbor compound heterozygous variants c.17_18insA (p.Tyr6Ter*) and c.4095_4096insA (p.Arg1366Lys fs*38) of the PCDH15 gene (NM_033056), which were respectively inherited from her father and mother. The same variants were not detected in 100 healthy controls. Based on the guidelines of the American Society of Medical Genetics and Genomics, both variants were predicted to be pathogenic (PVS1+PM2+PP4). By prenatal diagnosis, her fetus was found to carry the c.4095_4096insA variant. After birth, the child has passed neonatal hearing screening test, and no abnormal auditory and visual function was found after the first year.@*CONCLUSION@#The compound heterozygous variants c.17_18insA (p.Tyr6Ter*) and c.4095_4096insA (p.Arg1366Lys fs*38) of the PCDH15 gene probably underlay the Usher syndrome is this proband.
Subject(s)
Child , Female , Humans , Infant, Newborn , Pregnancy , Cadherin Related Proteins , Cadherins/genetics , China , Genetic Testing , Pedigree , Prenatal Diagnosis , Usher Syndromes/geneticsABSTRACT
OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with dyschromatosis symmetrica hereditaria (DSH).@*METHODS@#PCR and Sanger sequencing were carried out for the proband, and suspected variant was validated by Sanger sequencing in the pedigree.@*RESULTS@#The proband was found to harbor a novel variant of c.1352delA (p.N451Mfs*13) of the ADAR (NM_001111) gene. The same variant was found in her affected mother and sister, but not in her unaffected father, uncle, and 100 healthy individual.@*CONCLUSION@#The novel variant of the ADAR gene probably underlay the pathogenesis of DSH in this pedigree.
Subject(s)
Female , Humans , Adenosine Deaminase/genetics , China , Mutation , Pedigree , Pigmentation Disorders/congenital , RNA-Binding Proteins/geneticsABSTRACT
Cell migration is defined as the directional movement of cells toward a specific chemical concentration gradient, which plays a crucial role in embryo development, wound healing and tumor metastasis. However, current research methods showed low flux and are only suitable for single-factor assessment, and it was difficult to comprehensively consider the effects of other parameters such as different concentration gradients on cell migration behavior. In this paper, a four-channel microfluidic chip was designed. Its characteristics were as follows: it relied on laminar flow and diffusion mechanisms to establish and maintain a concentration gradient; it was suitable for observation of cell migration in different concentration gradient environment under a single microscope field; four cell isolation zones (20 μm width) were integrated into the microfluidic device to calibrate the initial cell position, which ensured the accuracy of the experimental results. In particular, we used COMSOL Multiphysics software to simulate the structure of the chip, which demonstrated the necessity of designing S-shaped microchannel and horizontal pressure balance channel to maintain concentration gradient. Finally, neutrophils were incubated with advanced glycation end products (AGEs, 0, 0.2, 0.5, 1.0 μmol·L -1), which were closely related to diabetes mellitus and its complications. The migration behavior of incubated neutrophils was studied in the 100 nmol·L -1 of chemokine (N-formylmethionyl-leucyl-phenyl-alanine) concentration gradient. The results prove the reliability and practicability of the microfluidic chip.
Subject(s)
Cell Movement , Chemotaxis , Equipment Design , Lab-On-A-Chip Devices , Microfluidic Analytical Techniques , Microfluidics , Neutrophils , Reproducibility of ResultsABSTRACT
OBJECTIVE@#To explore the clinical feature and gene variant for two cases of primary male infertility caused by severe asthenospermia and to analyze the etiology of the disease.@*METHODS@#Genomic DNA of peripheral blood samples of patients and their parents was extracted and gene variant analysis of the patients was conducted by using whole exome sequencing. Suspected pathogenic variant was verified by Sanger sequencing and pathogenic analysis.@*RESULTS@#Whole exome sequencing showed that the DNAH1 gene of patient 1 had two heterozygous variants of c.2016T>G(p.Y672X) and c.6017T>G (p.V2006G). The DNAH1 gene of patient 2 had a homozygous variant of c.2610G>A(p.W870X), which were inherited from his father and mother, respectively. According to American College of Medical Genetics and Genomics standards and guidelines, the c.2016T>G (p.Y672X) and c.2610G>A (p.W870X) varaints of DNAH1 gene were predicted to be pathogenic (PVS1+PM2+PM3+PP3).@*CONCLUSION@#The two patients of multiple morphological abnormalities of the sperm flagella may be caused by DNAH1 gene variant, which has resulted in primary male infertility.
Subject(s)
Humans , Male , Dyneins/genetics , Genomics , Infertility, Male/genetics , Mutation , Sperm Tail/pathology , Exome SequencingABSTRACT
Objective:To investigate the early predictive factors of periprocedural thrombus migration and the relationship between periprocedural thrombus migration and prognosis after mechanical thrombectomy (MT) in stroke patients.Methods:The patients with anterior circulation acute large vessel occlusion stroke (ALVOS) who underwent MT in the Stroke Center of Yijishan Hospital of Wannan Medical College from May 2015 to December 2019 were retrospectively analyzed. The baseline characteristics, procedural and clinical outcomes were collected. Univariate and multivariate regression analysis was used to explore the risk factors of thrombus migration and the relationship between thrombus migration and prognosis of patients.Results:There were 302 ALVOS patients [(68.8±11.0) years old and 166 males (55.0%)] included, of whom thrombus migration was identified in 80 patients (26.5%), including 60 cases (75.0%) of proximal migration. Cardiogenic stroke ( OR=2.722, 95% CI 1.367-5.418, P=0.004) and clot burden score (CBS; OR=0.849, 95% CI 0.745-0.968, P=0.015) were independent risk factors of thrombus migration. Proximal migration ( OR=2.822, 95% CI 1.220-6.528, P=0.015) was an independent risk factor of 90-day clinical outcome, while the effect of distal migration on 90-day clinical outcome was not statistically significant. Conclusions:Cardiogenic stroke and lower CBS score are independent predictors of periprocedural thrombus migration in ALVOS patients who underwent MT. Proximal migration is an independent risk factor for the prognosis of patients, which has important clinical intervention significance.
ABSTRACT
Objective:To systematically compare the prognosis in non-compressible torso hemorrhage（NCTH）treated by resuscitative endovascular balloon occlusion of the aorta（REBOA）and resuscitation thoracotomy（RT）.Methods:Data were searched form MEDLINE, EMBASE, PubMed, WanFang, CNKI and VIP databases to collect studies on the prognosis of patients with NCTH undergone REBOA and RT from inception to December 2020. Two reviewers independently screened studies according to the inclusion and exclusion criteria, extracted data and evaluated the quality of the included studies. The Meta-analysis was performed using Revman 5.3. The patients were divided into REBOA group and RT group according to the different surgical treatment methods on admission, and the prognosis of each group was evaluated. The difference of mortality rate, reoperation rate of laparotomy after operation, reoperation rate of embolization after operation and mortality rate in different operating room area were compared between the two groups. Publication bias was assessed using the Egger test.Results:A total of 2 prospective studies and 4 retrospective studies involving 2, 588 subjects were included. There were 1, 591 patients in REBOA group and 997 patients in RT group. Significant differences were observed in the mortality rate（ I2=68%, OR=0.33, 95% CI 0.26-0.42, P<0.01）, reoperation rate of laparotomy after operation（ I2=76%, OR=1.41, 95% CI 1.11-1.77, P<0.01）and reoperation rate of embolization after operation（ I2=84%, OR=0.76, 95% CI 0.59-0.99, P<0.05）between REBOA group and RT group. Subgroup analysis showed that the mortality rate in the ICU were not statistically different between the two groups（ I2=83%, OR=0.69, 95% CI 0.45-1.05, P>0.05）, but the mortality rate in the emergency room was lower in REBOA group than that in RT group（ I2=94%, OR=0.52, 95% CI 0.38-0.70, P<0.01）. Egger test showed that publication bias had little effect on the results. Conclusions:For patients with NCTH, REBOA can reduce the mortality rate and reoperation rate of embolization after operation, but increase the reoperation rate of laparotomy after operation when compared with RT. In addition, the emergency room may be a more suitable operationg room area for REBOA.
ABSTRACT
Aplastic anemia(AA) is characterized by severe pancytopenia. The clinical features of bone marrow failure syndrome are closely related to viral infection, environment toxin, genetic and acquired gene mutation. Aplastic anemia is a historic disease that often occurred in young people, which was fatal to patients. However, here are many methods can treat and cure this fatal disease. Pathological and physiological studies have important guiding significance for the treatment of aplastic anemia. The diagnosis and treatment of current situation and prospect of aplastic anemia are reviewed in this article.
ABSTRACT
Objective:To analyze the pathogenic genes and clinical phenotypes of a Chinese Han family with autosomal dominant retinitis pigmentosa (ADRP).Methods:A pedigree investigation study was conducted, and a Chinese Han RP family that underwent genetic counseling in the Henan Provincial People's Hospital in November 2019 was collected.Twenty members of this family from 4 generations, including 9 patients and 11 phenotypically normal individuals, were enrolled.Visual acuity, peripheral visual field test and fundus examination were performed on some family members.Peripheral blood samples were collected from the family members, and DNA was extracted.Exon-targeted sequencing containing 43 genes associated with RP was performed on the proband using the Ion Torrent PGM sequencing platform.The mutations were verified by polymerase chain reaction and Sanger sequencing.Online software was applied to predict the protein function of the variant.The amino acid sequences of the variant loci were compared using the ClustalW2 multiplex alignment program.The pathogenicity of the variant was analyzed according to American College of Medical Genetics and Genomics (ACMG) criteria and guidelines for classification of genetic variant.This study adhered to the Declaration of Helsinki.The study protocol was approved by an Ethics Committee of Henan Provincial People's Hospital (No.HNEECKY-2019[15]).Results:The family was consistent with autosomal dominant inheritance.The proband, a 26-year-old male, had bilateral night blindness since childhood, with visual acuity of 0.25 in the right eye and 0.5 in the left eye.There was osteoblast-like pigmentation in his both retinas, thinned retinal vessels and pale optic disc.Full-field electroretinogram examination showed reduced scotopic a- and b-wave peaks and severely reduced photopic a- and b-wave peaks.The rest of the family began to develop night blindness when 7 to 10 years old, having complete loss of peripheral vision around 50 years of age, and typical RP changes were found in ophthalmic examination.Genetic testing revealed a heterozygous missense variant c. 982delC (p.L328fs) in exon 5 of the family's rhodopsin ( RHO) gene (NM_000539.3). This variant resulted in the change of 21 amino acids after amino acid 328 in the encoded RHO protein, increasing amino acids in the coding region from 348 to 358 and altering the structure of the RHO protein.The analysis of protein homology sequence alignment between several different species showed that the locus was highly conserved.According to the guidelines of the ACMG criteria and guidelines for classification of genetic variants, the variant was a pathogenic mutation because there were six evidences including one very strong evidence of pathogenicity PVS1, two moderate evidences of pathogenicity PM2 and three supporting evidences of pathogenicity, PP1, PP3 and PP4. Conclusions:The c. 982delC variant in the RHO gene is a pathogenic mutation in this pedigree, and this variant is reported for the first time in a Chinese Han family.
ABSTRACT
Objective:To explore the potential targets and pathways of steroid alkaloids<italic> </italic>from<italic> Solanum</italic> <italic>nigrum</italic> （SASN） in the treatment of non-small cell lung cancer （NSCLC） and analyze the possible mechanism. Method:The active SASN against NSCLC were searched from literature. Then potential targets of SASN were screened through SwissTargetPrediction and PharmMapper， and those of NSCLC through GeneCards. Venny was employed to yield the common targets of the two， and Cytoscape to construct the 'medicinal-component-disease-target' network. Metascape was applied to enrich the Gene Ontology （GO） terms and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathways of the common targets， and STRING was used to generate the protein-protein interaction （PPI） network， followed by screening of key targets by Cytoscape. Finally， Western blot was used to verify the effects of the medicinal on key targets. Result:A total of 6 active SASN were screened out： solasonine， solamargine， solasodine， solanocapsine， solanidine， and <italic>N</italic>-methylsolasodine， which had 96 potential anti-NSCLC targets. These targets mainly involved the pathways in cancer， proteoglycans in cancer， and Forkhead box protein O （FoxO） pathway. PPI network analysis demonstrated 15 key anti-NSCLC targets of SASN， such as mitogen-activated protein kinase （MAPK）1， MAPK8， MAPK14， protein kinase B （Akt1）， signal transducer and activator of transcription 3 （STAT3）， and proto-oncogene tyrosine protein kinase （SRC）. Meanwhile， Western blot results showed that SASN could significantly down-regulate the expression of the key proteins Akt1， SRC， and STAT3. Conclusion:We predicted the potential targets and pathways of SASN against NSCLC and obtained 15 key targets， from which we selected three key proteins for validation. The validation results were consistent with the prediction results. This paper is expected to lay a scientific basis for the subsequent in-depth study of the mechanisms of SASN against NSCLC.
ABSTRACT
Objective:To summarize the diagnosis features of the prenatal genetic diagnosis of fetal renal cystic disease and to explore the clinical feasibility and significance of prenatal genetic diagnosis of congenital cystic nephrosis.Methods:A total of 25 fetuses with congenital renal cystic disease were examined via invasive prenatal diagnosis in Henan Provincial People's Hospital from June 2017 to September 2019. Amniotic fluid samples were extracted by amniocentesis. Chromosomal microarray analysis (CMA) were performed in 17 cases. In addition to CMA, the other 8 cases were analyzed by G-band karyotype. Whole exome sequencing (WES) was performed in 6 cases which got normal results by CMA and karyotype, and highly suspected as hereditary disease.Results:Of the 25 fetuses assessed, 4 cases (16.0%) pathogenic copy number variation (pCNV) were found, including 2 cases of 17q12 deletion, 1 case of 10p15.1p14 deletion and 1 case of 4q21.28q22.1 deletion(including PKD2 gene). There were 8 cases without chromosome abnormality by karyotype analysis. Six clinical WES analysis found NPHS1 gene c.1440+1 G>A and c.925G > T mutations were related to Finnish type congenital nephrotic syndrome in 1 case, PKD1 gene c.6878C>T mutation was related to autosomal dominant polycystic kidney disease (ADPKD) in 1 case, and there was no definitive mutation in 4 cases. Conclusions:CMA and next generation sequencing are powerful tools for accurate diagnosis, treatment and genetic counseling of fetal congenital renal cystic diseases. For congenital cystic nephropathy, genetic detection is helpful to clarify the etiology, and provide more exactly informations for prognosis evaluation, treatment and family genetic counseling.