Advancements in research on the pathogenesis and treatment of radiation-induced intestinal injury based on gut microbiota / 中华放射医学与防护杂志

The intestinal dysbacteriosis is closely associated with the occurrence and progress of radiation-induced intestinal injury. However, the specific mechanism remains unclear. Symbiotic bacteria in the human body play a significant role in maintaining the homeostasis of the intestinal microenvironment while participating in various physiological and pathological processes such as metabolism, immunoregulation, inflammation, and tumorigenesis. Ionizing radiation can destroy the intestinal epithelial barrier, creating an oxidative stress microenvironment. Consequently, the composition and structure of microbiota change, leading to dysbacteriosis through downstream inflammatory factors. Dysbacteriosis can further exacerbate radiation-induced intestinal injury by weakening the resistance of the intestinal epithelial barrier, activating inflammatory signaling pathways, and upregulating radiation-induced apoptosis response. The probiotic supplementation and fecal bacteria transplantation can reduce radiation-induced intestinal injury by regulating the balance of intestinal microbiota. This study reviews the advances in research on the pathogenesis and clinical protection of radiation enteritis based on gut microbiota, in order to provide a theoretical basis and reference for the prevention and treatment of radiation enteritis.

Analysis of Moral Emotion from the Perspective of Moral Injury Research / 中国医学伦理学

Moral emotion is a kind of psychological activity that generated when dealing with realistic moral relationship or analyzing human behaviors, expressed as emotional emotions of love and hatred. From the perspective of moral injury research, on the one hand, moral emotion expresses as emotional collapse, which reflects the huge gap between reality and moral cognition, and deviates from values; on the other hand, it shows the typical symptoms of moral injury, such as shame, guilt, anger, apathy and so on. Based on this, the therapy of moral injury should start from solving the ethical conflict of moral injury, and carry out the healing process of "ethical and moral cognitive education, enlightening the thinking of core value issues, encouraging and guiding independent moral practice" in stages according to the different levels of individual moral emotion. As a result, moral emotion can be rational enough to promote healing moral injury.

Effect of Tongluo Juanbi Granules on Inflammatory Injury and Apoptosis of Osteoarthritis Based on TLR4/MyD88/NF-κB Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo investigate the effects of Tongluo Juanbi granules on chondrocyte apoptosis and Toll-like receptor 4 （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor-κB （NF-κB） signaling pathway of rabbits with knee osteoarthritis （KOA） and study the mechanism of Tongluo Juanbi granules in the prevention and treatment of KOA. MethodThirty New Zealand rabbits were randomly assigned to the following five groups （n=6）： sham group， model group， low-dose and high-dose groups of Tongluo Juanbi granules （4.1 and 8.2 g·kg-1·d-1）， and celecoxib group （10.9 mg·kg-1·d-1）. The KOA model was established by destabilization of the medial meniscus （DMM） for six weeks. Six weeks after the modeling， the drug was given once a day for eight weeks. The pathological changes of cartilago articularis were observed by hematoxylin-eosin （HE） staining and Safranin O-Fast Green staining. Terminal deoxynucleotidyl transferase dUTP nick end labeling （TUNEL） staining was performed to detect chondrocyte apoptosis. Enzyme-linked immunosorbent assay （ELISA） was used to detect the contents of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in synovial fluid. The mRNA and protein expression levels of genes related to the TLR4/MyD88/NF-κB signaling pathway were detected by real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot， respectively. ResultCompared with the sham group， the cartilago articularis of the model group significantly degenerated. Mankin's score was increased （P<0.01）， and the contents of IL-1β and TNF-α in synovial fluid were increased （P<0.01）. The number of apoptosis of chondrocytes was increased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were up-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were down-regulated （P<0.01）. Compared with the model group， chondrocyte degeneration in both low-dose and high-dose groups of Tongluo Juanbi granules was improved， and Mankin's score was decreased （P<0.01）. The contents of IL-1β and TNF-α were decreased （P<0.01）， and the number of apoptosis of chondrocytes was decreased （P<0.01）. The mRNA and protein expressions of TLR4， MyD88， and NF-κB p65 in cartilage tissue were down-regulated （P<0.01）， while the mRNA and protein expressions of Bcl-2 were up-regulated （P<0.01）. In addition， in the above observation indicators， the high-dose group of Tongluo Juanbi granules was significantly superior to the low-dose group of Tongluo Juanbi granules. ConclusionTongluo Juanbi granules could inhibit chondrocyte apoptosis in rabbits with KOA and improve cartilage degeneration， which may be related to inhibiting inflammatory responses mediated by TLR4/MyD88/NF-κB signaling pathway.

Lipid-lowering Effect of Active Components in Common Chinese Medicine： A Review / 中国实验方剂学杂志

Dyslipidemia is a common metabolic disease caused by abnormal lipoprotein metabolism in human body. According to pathogenesis， it is divided into primary dyslipidemia and secondary dyslipidemia. The former is caused by genetic defects， and the latter is caused by diseases， drugs， unhealthy diets， and lifestyle. The clinical manifestations are xanthoma， arteriosclerosis， and other symptoms of coronary heart disease and peripheral vascular disease. Dyslipidemia can cause a variety of diseases， such as cardiovascular disease， diabetes， and cancer， seriously threatening people's quality of life and life safety， so the research on drugs against dyslipidemia is more urgent. In spite of manifest efficacy， chemical antilipemic agents such as lovastatin are accompanied by some adverse reactions， and there is recurrence after drug withdrawal. Compared with chemical drugs， Chinese medicine has the advantages of multi-pathway， multi-target， multi-level regulation of dyslipidemia， with few side effects. Modern medical research has shown that Chinese medicine can affect lipid synthesis， decomposition， and absorption and improve liver lipid and bile acid metabolism by regulating the peroxisome proliferator-activated receptor （PPAR） signaling pathway， AMP-activated protein kinase （AMPK） signaling pathway， cyclic adenosine monophosphate （cAMP） signaling pathway， adipocytokine signaling pathway， farnesoid X receptor （FXR）/small heterodimer partner （SHP） signaling pathway， phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway， etc.， thereby exerting a role in lowering lipid. Therefore， this paper summarized the mechanism of effective components in Chinese medicine in lowering blood lipid to provide new ideas and a theoretical basis for the prevention and treatment of lipid metabolic diseases by Chinese medicine in clinical practice.

Analysis of findings of ear, nose, and throat exam of some freshmen in military college entrance examination in Shandong Province / 中国学校卫生

Objective@#To analyze the ear, nose, and throat exam of some freshmen in the military college entrance examination in Shandong Province in 2020 and to facilitate adolescent targeted health promotion.@*Methods@#The 1 411 freshmen participating in the military college entrance examination in Jinan, Zibo and Weifang of Shandong Province were included. The ear, nose, and throat exam were performed by professionals using electric otoscope, 5 meter whispering test, and front rhinoscope.@*Results@#Nasal septal deviation and hypertrophy of inferior turbinate accounted for the highest proportion. Among 489 cases of nasal septum deviation, the detection rate of Jinan (15.97%) was significantly lower than that of Weifang (43.60%) and Zibo (46.53%) ( χ 2=63.32， P <0.05). For deviation of nasal septum, the detection rate in students with urban residence (31.53%) was significantly lower than that of rural students (39.03%) ( χ 2=4.11， P <0.05). Seventy two cases of inferior turbinate hyperplasia were detected, and the detection rate in Jinan (2.99%) was significantly lower than that in Weifang (6.51%) and Zibo (6.04%) ( χ 2=6.63， P <0.05). The detection rate of tonsil hypertrophy was significantly lower in boys (4.63%), students from urban area (3.94%), compared with that of girls(9.56%) and rural students (6.70%) ( χ 2=5.35，4.86， P <0.05). In pharyngeal examination, tonsil hyperplasia was the most common condition of enlarged tonsils ( n =214), which was significantly higher in Jinan(22.36%) than that of Weifang (11.71 %) and Zibo (10.74%) ( χ 2=22.39， P <0.05), and was significantly lower in boys (14.38%) and rural students (12.40%) than that in girls (22.79%) and urban students (17.24%) ( χ 2=4.70，4.65， P <0.05).@*Conclusion@#Nasal septum deviation and tonsil hypertrophy are the most prevalent upper airway diseases among freshmen participating in the military college entrance examination. Prevention and treatment of nasopharynx diseases should be emphasized.

Effect of ACC oxidase gene AhACOs on salt tolerance of peanut / 生物工程学报

ACC oxidase (ACO) is one of the key enzymes that catalyze the synthesis of ethylene. Ethylene is involved in salt stress response in plants, and salt stress seriously affects the yield of peanut. In this study, AhACO genes were cloned and their functions were investigated with the aim to explore the biological function of AhACOs in salt stress response, and to provide genetic resources for the breeding of salt-tolerant varieties of peanut. AhACO1 and AhACO2 were amplified from the cDNA of salt-tolerant peanut mutant M29, respectively, and cloned into the plant expression vector pCAMBIA super1300. The recombinant plasmid was transformed into Huayu22 by pollen tube injection mediated by Agrobacterium tumefaciens. After harvest, the small slice cotyledon was separated from the kernel, and the positive seeds were screened by PCR. The expression of AhACO genes was analyzed by qRT-PCR, and the ethylene release was detected by capillary column gas chromatography. Transgenic seeds were sowed and then irrigated with NaCl solution, and the phenotypic changes of 21-day-seedings were recorded. The results showed that the growth of transgenic plants were better than that of the control group Huayu 22 upon salt stress, and the relative content of chlorophyll SPAD value and net photosynthetic rate (Pn) of transgenic peanuts were higher than those of the control group. In addition, the ethylene production of AhACO1 and AhACO2 transgenic plants were 2.79 and 1.87 times higher than that of control peanut, respectively. These results showed that AhACO1 and AhACO2 could significantly improve the salt stress tolerance of transgenic peanut.

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

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

Analysis of a child with autosomal dominant mental retardation type 40 due to variant of CHAMP1 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical and genetic features of a child with autosomal dominant mental retardation type 40 (MRD40) due to variant of the CHAMP1 gene.@*METHODS@#Clinical characteristics of the child were analyzed. Genetic testing was carried out by low-depth high-throughput and whole genome copy number variant sequencing (CNV-seq) and whole exome sequencing (WES). A literature review was also carried out for the clinical phenotype and genetic characteristics of patients with MRD40 due to CHAMP1 gene variants.@*RESULTS@#The child, a 11-month-old girl, has presented with intellectual and motor developmental delay. CNV-seq revealed no definite pathogenic variants. WES has detected the presence of a heterozygous c.1908C>G (p.Y636*) variant in the CHAMP1 gene, which was carried by neither parent and predicted to be pathogenic. Literature review has identified 33 additional children from 12 previous reports. All children had presented with developmental delay and mental retardation, and most had dystonia (94.1%), delayed speech and/or walking (85.2%, 82.4%) and ocular abnormalities (79.4%). In total 26 variants of the CHAMP1 gene were detected, with all nonsense variants being of loss-of-function type, located in exon 3, and de novo in origin.@*CONCLUSION@#The heterozygous c.1908C>G (p.Y636*) variant of the CHAMP1 gene probably underlay the WRD40 in this child. Genetic testing should be considered for children featuring global developmental delay, mental retardation, hypertonia and facial dysmorphism.

Clinical features and genetic analysis of a patient with type 2 neurofibromatosis manifested as oculomotor nerve palsy / 中华医学遗传学杂志

OBJECTIVE@#To report on a rare case of Neurofibromatosis type 2 (NF2) manifesting as oculomotor nerve palsy and explore its genetic basis.@*METHODS@#A patient with NF2 who had presented at Beijing Ditan Hospital Affiliated to Capital Medical University on July 10, 2021 was selected as the study subject. Cranial and spinal cord magnetic resonance imaging (MRI) was carried out on the patient and his parents. Peripheral blood samples were collected and subjected to whole exome sequencing. Candidate variant was verified by Sanger sequencing.@*RESULTS@#MRI revealed bilateral vestibular Schwannomas, bilateral cavernous sinus meningiomas, popliteal neurogenic tumors, and multiple subcutaneous nodules in the patient. DNA sequencing revealed that he has harbored a de novo nonsense variant of the NF2 gene, namely c.757A>T, which has replaced a codon (AAG) encoding lysine (K) at position 253 with a stop codon (TAG). This has resulted in removal of the Merlin protein encoded by the NF2 gene from position 253 onwards. The variant was not found in public databases. Bioinformatic analysis suggested that the corresponding amino acid is highly conserved. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was rated as pathogenic (PVS1+PS2+PM2_Supporting+PP3+PP4).@*CONCLUSION@#The heterozygous nonsense variant c.757A>T (p.K253*) of the NF2 gene probably underlay the disease in this patient with an early onset, atypical but severe phenotype.

Genetic testing and prenatal diagnosis for a Chinese pedigree affected with Waardenburg syndrome type 4C due to heterozygous deletion of SOX10 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree featuring congenital profound syndromic deafness and chronic constipation, and provide prenatal diagnosis for a high-risk fetus.@*METHODS@#Whole-exome sequencing was carried out to analyze the sequences of genes associated with hereditary deafness, and multiplex ligation-dependent probe amplification (MLPA) was used to verify the candidate variant in the proband's parents and the fetus.@*RESULTS@#The proband was found to have harbored a heterozygous deletion of SOX10, a pathogenic gene associated with Waardenburg syndrome type 4C (WS4C). The same deletion was found in her mother (with profound syndromic deafness and chronic constipation) and the fetus, but not in her father with normal hearing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG) and Association for Molecular Pathology (AMP), the SOX10 gene deletion was predicted to be a pathogenic variant (PVS1+PM2_Supporting+PP1+PP4).@*CONCLUSION@#The pedigree was diagnosed with WS4C, which has conformed to an autosomal dominant inheritance. Deletion of the entire SOX10 gene, as a loss-of-function variant, probably underlay its pathogenesis. Above finding has facilitated genetic counseling and prenatal diagnosis for this family.

Effect of endovascular therapy on the requirement for decompressive craniectomy and functional outcomes in patients with large anterior circulation ischemic stroke / 国际脑血管病杂志

Objective:To investgate the effect of endovascular therapy (EVT) on the requirement for decompressive craniectomy (DC) and functional outcomes in patients with large anterior circulation ischemic stroke.Methods:Patients with large anterior circulation ischemic stroke within 24 hours of onset admitted to the Department of Neurology, West China Hospital, Sichuan University between September 2017 and December 2019 were included. Outcome indicators included DC demand and poor outcome at 3 months. The latter was defined as a modified Rankin Scale score >2. Multivariate logistic regression analysis was used to determine independent factors of DC requirement and functional outcomes at 3 months. Results:A total of 381 patients with large anterior circulation ischemic stroke were enrolled, including 203 males (53.3%), and the mean age was 70.7±14.3 years. The median time from onset to admission was 4.5 hours. The median baseline National Institutes of Health Stroke Scale score was 17 and median baseline Alberta Stroke Program Early Computed Tomography Score (ASPECTS) was 7. Totally 139 patients (36.5%) received EVT, and 64 (16.8%) required DC; 376 patients (98.7%) completed a 3-month follow-up (5 who did not complete follow-up did not require DC, of which 2 received EVT), 312 (83.0%) had poor outcome at 3 months, and 146 (38.8%) died. Multivariate logistic regression analysis showed that EVT was an independent predictor for the requiremet of DC (odds ratio [ OR] 4.42, 95% confidence interval [ CI] 1.81-10.81; P=0.001), higher baseline ASPECTS ( OR 0.80, 95% CI 0.71-0.89; P<0.001) and successful recanalization ( OR 0.37, 95% CI 0.15-0.90; P=0.028) were independent protective factors of reducing the requirement of DC. Successful recanalization ( OR 0.09, 95% CI 0.01-0.72; P=0.023) and antiplatelet therapy ( OR 0.29, 95% CI 0.11-0.76; P=0.012) were independent predictors for reduced risk of poor outcome. In 139 patients who received EVT, 27 (19.4%) received intravenous thrombolysis, 96 (69.1%) achieved successful recanalization, 88 (63.3%) had hemorrhagic transformation, 61 (43.9%) had symptomatic hemorrhagic transformation, and 34 (24.5%) required DC; 137 (98.6%) completed a 3-month follow-up, 116 (84.7%) had poor outcome at 3 months, and 67 (48.9%) died. For patients receiving EVT, a higher baseline ASPECTS ( OR 0.72, 95% CI 0.60-0.88; P=0.001) and successful recanalization ( OR 0.35, 95% CI 0.14-0.90; P=0.029) were independent predictors of reducing the requirement of DC, while successful recanalization ( OR 0.09, 95% CI 0.01-0.71; P=0.022) was an independent predictor for reduced risk of poor outcome. Among 64 patients who required DC, 22 (34.4%) received DC. Receiving DC significantly reduced the mortality within 3 months ( OR 0.25, 95% CI 0.07-0.86; P=0.028), but had no significant effect on functional outcome at 3 months ( OR 0.35, 95% CI 0.03-4.38; P=0.412). There was no significant interaction of either EVT or successful recanalization in the effect of DC on 3-month death ( P for interaction > 0.05). Conclusions:Successful recanalization after EVT reduces requirement for DC in patients with large anterior circulation ischemic stroke and improves functional outcome at 3 months. DC can reduce the mortality in patients required DC, and have no interactive effect with EVT or successful recanalization.

Effect of radiofrequency combined with magnetic stimulation on mild and moderate pelvic organ prolapse / 中南大学学报(医学版)

Objective:The efficacy of using a single electrical or magnetic stimulation for treating pelvic floor dysfunction is limited.This study aims to investigate the efficacy of radiofrequency combined with magnetic stimulation treatment for mild to moderate pelvic organ prolapse. Methods:Patients who completed the treatment in the Third Xiangya Hospital,Central South University were screened,and were divided into 2 groups based on different treatment plans.There were 28 patients who completed magnetic stimulation therapy(the magnetic stimulation therapy group)and 21 patients who completed radiofrequency combined with magnetic stimulation therapy(the combined treatment group).The pelvic organ prolapse quantitation(POP-Q),pelvic floor muscle strength,and pelvic floor ultrasound results were analyzed to assess the efficacy before and after the treatment in both groups,and the POP-Q results of 3 months after the treatment were used to evaluate the maintenance effect of the treatment mode. Results:The POP-Q evaluation results of Aa,Ap,and C points after the treatment in both groups were better than those before the treatment,with statistical significance(all P＜0.05).The Aa point POP-Q result of the combined treatment group was better than that of the magnetic stimulation therapy group,with statistical significance(P＜0.05).Pelvic floor ultrasound evaluation showed that the bladder neck position during the valsalva maneuver in the combined treatment group was higher than that in the magnetic stimulation treatment group,with statistical significance(P＜0.05).The persistence effect of the combined treatment group was long better than that of the magnetic stimulation treatment group,with significant statistical significance(P＜0.01). Conclusion:The combined treatment is more effective and has a longer lasting effect than single magnetic stimulation treatment.

Research Status of Biosynthesis and Pharmacological Effects of Podophyllotoxin Drugss / 世界科学技术-中医药现代化

Objective This paper summarizes the research progress of biosynthesis and pharmacological effects of podophyllotoxin drugs,in order to provide reference for the wide application of these drugs.Methods The plant source,chemical structure,action mechanism and synthesis pathway of podophyllotoxin drugs were summarized.The pharmacological and toxicological characteristics and mechanisms of these drugs were discussed,and the research progress of new dosage forms of podophyllotoxin drugs was reviewed.Results Podophyllotoxin and its derivatives are important chemical constituents in the plants of the podophyllum,such as Dysosma versipellis,Diphylleia sinensis,Sinopodophyllum hexandrum.This kind of drug has few natural sources and can be artificially produced through chemical and biosynthetic pathways.Podophyllotoxin drugs have pharmacological effects such as anti-inflammatory,anti-tumor and anti-virus,but their toxic effects need to be paid attention to.Drugs can be transported by carriers to reduce toxicity and increase effect.Conclusion Podophyllotoxin drugs have broad clinical application prospects,and will be further studied and applied in the fields of anti-inflammatory,anti-tumor and anti-virus in the future.

Clinical study on patient-derived organoids as a predictive model for assessing treatment response in pancreatic cancer / 中华普通外科杂志

Objective:To construct a biospecimen bank of patient derived organoids (PDOs) from pancreatic cancer tissues and to explore the feasibility of PDOs drug sensitivity assay technology to guide chemotherapy drug selection for pancreatic cancer.Methods:Pancreatic cancer tissue specimens obtained after surgical resection and puncture biopsy from Mar 2020 to Dec 2022 at Drum Tower Hospital, Nanjing University School of Medicine were collected. Pancreatic cancer PDOs were cultured in vitro and histologically identified; PDOs were treated with gemcitabine, Nab-paclitaxel, fluorouracil, Oxaliplatin, and Irinotecan and cell viability was measured to analyze the correlation between PDOs drug sensitivity and the actual clinical treatment response.Results:The PDOs can reproduce the pathological features of corresponding tumor tissues; the sensitivity of different PDOs to the same chemotherapeutic drug is significantly different; The sensitivity of PDOs was highly consistent with the actual treatment effect of the corresponding patients 75.76% (25/33); organoid organ-based susceptibility testing had predictive value for the treatment response of patients (AUC=0.733, 95% CI: 0.546-0.919, P<0.05). Conclusion:A biobank of pancreatic cancer PDOs was successfully constructed, and the drug susceptibility test results were significantly correlated with the actual medication response of patients, suggesting that the drug susceptibility test technology based on PDOs has the potential to guide individualized chemotherapy for pancreatic cancer.

Genetic testing and prenatal diagnosis of 64 pedigrees with autosomal dominant polycystic kidney disease / 中华肾脏病杂志

Objective:To detect and analyze the gene variation types of 64 unrelated pedigrees affected with autosomal dominant polycystic kidney disease (ADPKD), and explore the detection efficiency of multiple gene analysis techniques and variation characteristics.Methods:It was a cross-sectional study. The clinical data of 64 pedigrees with ADPKD from Nephrology Department or Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from December 2017 to August 2020 were retrospectively analyzed. The blood samples of probands and other family members were collected. Genetic analysis was carried out by next generation sequencing, and suspected mutations were verified by multiplex ligation-dependent probe amplification, or long-range PCR combined with Sanger sequencing. Prenatal diagnosis for high-risk fetuses was performed by fetal villi or amniotic fluid cells after genotyping without maternal genomic DNA contamination.Results:Among detected 64 pedigrees, 57 pedigrees (89.06%) had genetic variants in PKD1/PKD2. A total of 49 pathogenic/likely pathogenic variants in PKD1/PKD2 were identified in 51 pedigrees (79.69%), including 14 nonsense variants (28.57%), 14 frameshift variants (28.57%), 11 missense variants (22.45%), 5 splicing variants (10.20%) and 5 deletion variants (10.20%). Of these variants, 87.76% (43/49) were in PKD1 and 12.24% (6/49) were in PKD2. Totally, 14 novel variants in PKD1/ PKD2 were identified, including 7 frameshift variants, 3 splicing variants, 2 nonsense variants, 1 deletion variant and 1 missense variant, of which 11 variants were in PKD1 and 3 variants were in PKD2. Twenty high-risk fetuses from 17 pedigrees received prenatal diagnosis, in whom 6 fetuses had PKD1 variation, and other 14 fetuses had no PKD1/ PKD2-genetic variation. Conclusions:The combination of next-generation sequencing, multiplex ligation-dependent probe amplification, and long-range PCR combined with Sanger sequencing can be helpful for rapid, efficient and accurate genetic diagnosis of ADPKD pedigrees. Point mutations are the most common types in PKD1/PKD2. Fourteen novel variants in PKD1/PKD2 extend its pathogenic variant spectrum and can provide basis for genetic counseling and prenatal diagnosis of ADPKD pedigrees.

Exploration of management system for hospital localized high-throughput sequencing / 中华医院管理杂志

High-throughput sequencing has the characteristics of complex experimental procedures, multiple quality control nodes, and a high proportion of bioinformatics technology. It is difficult to uniformly management and reuse the related detection samples and data. In May 2023, a tertiary hospital launched the construction of a localized high-throughput sequencing management system. Based on the design principles of security, friendliness, compatibility, and scalability, the management system had established three core modules: standardized data collection integration, clinical high-throughput sequencing full process management, and scientific research services, as well as a large clinical high-throughput sequencing database of hospital. By connecting with big data storage devices, local and third-party high-throughput sequencing detection platforms, sample libraries, and user terminals, this system broke down the data barriers of high-throughput sequencing related systems and devices, and met the different application scenarios of physician users, technician users, management users, and scientific research users in the hospital. As of October 2023, the system had been integrated with two high-throughput sequencing manufacturer devices in a public network environment and hospital information systems in an internal network environment, improving data retrieval efficiency and achieving closed-loop management of high-throughput sequencing detection projects preliminary, which can provided references for promoting the standardized management of high-throughput sequencing projects in hospitals in China.

Design and application of heating device and temperature control system for dialysis fluid bag in continuous renal replacement therapy / 中华危重病急救医学

In the process of continuous renal replacement therapy (CRRT), various factors such as the temperature of replacement fluid, the flow of fluid and the circulation of blood in cardiopulmonary bypass, lead to the temperature of the blood injected back into the body is often lower than normal. It leads to the decrease of body temperature and the occurrence of hypothermia, which can be life-threatening in severe cases. In clinical practice, medical staff mostly reduces the occurrence of hypothermia in patients with CRRT by means of the heating device of the machine, the heating of the liquid temperature box for cardiopulmonary bypass, and the application of heating blankets, but the effect is not ideal. Therefore, medical staff of the department of critical care medicine of the Second Affiliated Hospital of Anhui Medical University designed a heating device and temperature control system for CRRT dialysis fluid bag, and obtained the National Invention Patent of China (ZL 2021 1 0334906.7). The device includes a heating and thermal insulation device and a temperature control system, wherein the heating and thermal insulation device is composed of the body of the heating dialysis fluid bag and the temperature control structure, which solves the problems of safe and efficient liquid heating and thermal insulation during the CRRT process. The temperature control system can display the dynamic state of the patient's body temperature, adjust the temperature of the dialysis fluid bag in time, and monitor the temperature of the blood transfusion in real time through the cooperation of the five modules of data collection, data handle, data analysis, regulation and display. This design is applied to CRRT, which can achieve precise control of body temperature of critically ill patients, and has certain clinical significance.

Clinical characteristics of family clustering pediatric and adult cases with severe acute respiratory syndrome coronavirus 2 Omicron variant infection / 中华传染病杂志

Objective:To investigate the clinical characteristics of family clustering pediatric and adult cases with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant infection in Shanghai City.Methods:A field investigation among the pediatric cases with Omicron variant infection and their household contacts from April 4 to April 30, 2022 in Children′s Hospital of Fudan University was conducted. The informations on case finding, clinical manifestations and SARS-CoV-2 vaccination status were collected. The epidemiological and clinical characteristics were compared between pediatric cases and adult cases. The independent sample t test or chi-square test was used for statistical analysis, and the relative risk ( RR) and 95% confidence interval (95% CI) were used to evaluate the protective effect of vaccination on the infection of Omicron variant. Results:There were 1 274 family members in 297 families including 370 children and 904 adults of whom 1 110(87.13%) were infected with Omicron variant, with 989(89.10%) symptomatic and 121(10.90%) asymptomatic. There were 355 children infected with Omicron variant, of whom 337(94.93%) were symptomatic, and the main manifestations were fever (96.74%(326/337)) and cough (40.36%(136/337)). Only one pediatric case with Rett syndrome developed critically severe pneumonia. A total of 194 pediatric cases had imaging examination, 64(32.99%) showed pulmonary inflammatory lesions. There were 755 adult cases infected with Omicron variant, of whom 652(86.26%) reported symptoms, and the main manifestations were fever (73.16%(477/652)) and cough (49.85%(325/652)). Among symptomatic cases, fever was more common in pediatric cases than in adult cases, while cough was more common in adult cases than in pediatric cases, and the differences were both statistically significant ( χ2=80.87 and 8.04, respectively, both P<0.01). The fever spike was higher in pediatric cases than in adult cases ((39.3±0.7) ℃ vs (38.6±0.6) ℃), and the difference was statistically significant ( t=9.85, P<0.001). The interval from the onset of symptoms to cycle threshold (Ct) value of the nucleic acid of Omicron variant≥35 was longer in pediatric cases than in adult cases ((13.0±3.1) d vs (10.9±3.6) d), and the difference had statistically significance ( t=2.97, P=0.004). Among 160 children aged 3 to 18 years, 54 (33.75%) received two-dose vaccination. Among the 904 adults, 388 (42.92%) received two-dose vaccination and 293 (32.41%) received a booster dose. In the adult cases, the risk of symptomatic infection was reduced by only 8% ( RR=0.92, 95% CI 0.86 to 0.98, P=0.014) following two-dose vaccination, and the risks of fever and cough following booster vaccination were reduced by 42%( RR=0.58, 95% CI 0.49 to 0.67, P=0.001) and 50% ( RR=0.50, 95% CI 0.34 to 0.78, P=0.001), respectively. Conclusions:Secondary attack rate and symptomatic rate of household infection are high in the context of the Omicron variant outbreak in Shanghai. Symptomatic infection is common in children and adults in household setting. Fever is the most common symptom and fever duration is short. Booster vaccination may provide certain protection against common symptoms caused by Omicron variant infection.

Bioequivalence study of cinacalcet hydrochloride tablets in healthy Chinese volunteers / 中国临床药理学与治疗学

AIM: To evaluate the bioequivalence of cinacalcet hydrochloride tablets in healthy Chinese volunteers. METHODS: A randomized, open, double-period and crossover trial was conducted, 48 healthy volunteers were administered a single dose of cinacalcet test tablets or reference tablets orally under each fasting and fed condition. The concentration of cinacalcet was determined by validated LC-MS/MS method. Pharmacokinetic parameters were calculated by Phoenix WinNonlin 8.0 to study its bioequivalence. RESULTS: The main pharmacokinetic parameters of test tablets and reference tablets under fasting condition were as follows: C

Genetic diagnosis of Branchio-Oto syndrome pedigree due to a de novo heterozygous deletion of EYA1 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a Chinese pedigree affected with Branchio-Oto syndrome (BOS).@*METHODS@#A pedigree with BOS which had presented at the Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University in May 2021 was selected as the study subject. Clinical data of the pedigree was collected. Peripheral blood samples of the proband and her parents were collected. Whole exome sequencing (WES) was carried out for the proband. Multiplex ligation-dependent probe amplification (MLPA) was used to verify the result of WES, short tandem repeat (STR) analysis was used to verify the relationship between the proband and her parents, and the pathogenicity of the candidate variant was analyzed.@*RESULTS@#The proband, a 6-year-old girl, had manifested severe congenital deafness, along with inner ear malformation and bilateral branchial fistulae. WES revealed that she has harbored a heterozygous deletion of 2 466 kb at chromosome 8q13.3, which encompassed the EYA1 gene. MLPA confirmed that all of the 18 exons of the EYA1 gene were lost, and neither of her parents has carried the same deletion variant. STR analysis supported that both of her parents are biological parents. Based on the guidelines from the American College of Medical Genetics and Genomics, the deletion was classified as pathogenic (PVS1+PS2+PM2_Supporting+PP4).@*CONCLUSION@#The heterozygous deletion of EYA1 gene probably underlay the pathogenicity of BOS in the proband, which has provided a basis for the clinical diagnosis.