Comparative study of different large language models and medical professionals of different levels responding to ophthalmology questions / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To evaluate the performance of three distinct large language models(LLM), including GPT-3.5, GPT-4, and PaLM2, in responding to queries within the field of ophthalmology, and to compare their performance with three different levels of medical professionals: medical undergraduates, master of medicine, and attending physicians.METHODS: A total of 100 ophthalmic multiple-choice tests, which covered ophthalmic basic knowledge, clinical knowledge, ophthalmic examination and diagnostic methods, and treatment for ocular disease, were conducted on three different kinds of LLM and three different levels of medical professionals(9 undergraduates, 6 postgraduates and 3 attending physicians), respectively. The performance of LLM was comprehensively evaluated from the aspects of mean scores, consistency and confidence of response, and it was compared with human.RESULTS: Notably, each LLM surpassed the average performance of undergraduate medical students(GPT-4:56, GPT-3.5:42, PaLM2:47, undergraduate students:40). Specifically, performance of GPT-3.5 and PaLM2 was slightly lower than those of master's students(51), while GPT-4 exhibited a performance comparable to attending physicians(62). Furthermore, GPT-4 showed significantly higher response consistency and self-confidence compared with GPT-3.5 and PaLM2.CONCLUSION: LLM represented by GPT-4 performs well in the field of ophthalmology, and the LLM model can provide clinical decision-making and teaching aids for clinicians and medical education.

Optimal design and application of information management system of biobank in hospitals / 中华医学科研管理杂志

Objective:To establish a standardized information management system (IMS) for preserving, managing, querying, and performing statistics on biospecimens and their clinical data, which is conducive to improving the utilization of biobank.Methods:Under the premise of ensuring operating environment and data security, a database-based data logic relationship model is created and applied to the IMS to manage and analyze biospecimens and their supporting clinical information of patients enrolled in the biobank of our center.Results:To ensure the establishment of the follow-up cohort, biospecimens and clinical information of inpatients and outpatients were continuously collected in the biobank of our center. Since December 2014, more than 270 000 biospecimens from inpatient, outpatient, and scientific research have been preserved. The IMS optimized by this model efficiently completes the basic work of the biobank. At the same time, the data can be queried jointly and in batches, and then converted into a report format for statistical analysis.Conclusions:The IMS of our center is suitable for application and popularization as a construction and management model for the hospital-level biobank, which meets the daily work of the biobank and diverse research needs, and provides a convenient platform and rich resources for the development of precision medicine.

Application and efficacy of patient-based real-time quality control in intralaboratory comparison of various hematology analyzers / 中华检验医学杂志

Objective:To evaluate the application value of patient-based real-time quality control (PBRTQC) algorithms in intralaboratory comparison between various hematology analyzers.Method:From April 1 st 2020 to March 31 th 2021, data of white blood cell (WBC) counts and daily comparison results of fresh venous blood, measured by five hematology analyzers, were collected at the Department of Laboratory Medicine in Hebei Children′s Hospital. First, the professional intelligent PBRTQC software system was applied to conduct the parameter setting, program establishment, and performance verification. Three concentration ranges of WBC were selected, low concentration (2.5-4.5)×10 9/L, medium concentration (6.0-8.0)×10 9/L and high concentration (12.0-14.0)×10 9/L for the comparison. Next, WBC counts were calculated with both of the EWMA and median methods, the results were then analyzed by PBRTQC using the module of"intralaboratory comparison of hematology analyzers". Finally, bias of intralaboratory comparison among various hematology analyzers analyzed by means of EWMA and daily comparison results of fresh venous blood were compared. Based on the standard of WS/T 406-2012,allowable error ±7.50% in WBC counts was set as the relative bias standard among different instruments. Results:(1) A total of 38 313 sample results were included, there were 70 warning results out of these samples based on the EWMA quality control method established on the data of patients with white blood cell count in our laboratory, with an early warning rate of 0.183‰, a probability of error detection of 100%, and a probability of false loss of control of 0. EWMA quality control efficiency met the quality objectives. (2) In the comparison monitoring of the results of 5 blood cell analyzers at high concentrations, the coincidence rate between EWMA and median method were both 100% (46/46) in weekly and monthly comparison, and EWMA could maintain a relatively stable monitoring efficiency in daily comparison. (3) In the selected natural month, the consistency rate between EWMA method and fresh blood comparison method was 95.24% (20/21).Conclusion:PBRTQC can be used as a valuable supplementary tool of IQC to continuously and effectively monitor the consistency of data derived from intralaboratory hematology analyzers with different bands and types, which can not only reduce the risk of quality and operating costs, but also improve the efficiency of laboratory management.

Isolation and identification of Balneatrix alpica from patient′s blood and hot spring water / 中华微生物学和免疫学杂志

Objective:To identify and characterize two Balneatrix alpica strains isolated from a patient′s blood sample (strain X117) and the natural hot spring water in the patient′s residential district (strain GN-1), and to provide experimental evidence for the pathogenic diagnosis of clinical infection caused by this rare pathogen. Methods:Biochemical phenotypic identification, matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS), 16S rRNA gene sequencing, phylogenetic analysis, single-nucleotide polymorphism (SNP) analysis, and genome-wide analysis were performed to accurately determine the taxonomic status of the isolates X117 and GN-1 by using Balneatrix alpica DSM 16621 T as a reference. Microdilution broth method was used to test their antimicrobial susceptibility. The virulence genes carried by them were annotated and analyzed using the virulence factor database (VFDB). Results:Strains X117 and GN-1 formed light yellow or tan colonies with mottled surfaces on Columbia blood agar and chocolate agar plates after 4 d of culture. They were Gram-negative rods and positive for oxidase and indole tests, which were consistent with the characteristics of Balneatrix alpica DSM 16621 T. The phylogenetic analysis based on the 16S rRNA gene showed that the isolates X117 and GN-1 were both Balneatrix alpaca. The average nucleotide identity (ANI) values between the two isolates and Balneatrix alpica DSM 16621 T were 98.44% and 98.41%, respectively, and the digital DNA-DNA hybridization (dDDH) values were both 87.1%. The SNP distance between the two strains was 13, indicating that X117 and GN-1 might belong to the same clone. The antibiotic susceptibility testing showed that all of the three Balneatrix alpica strains were sensitive to the commonly used antibiotics against Gram-negative rods. The virulence genes carried by the three Balneatrix alpica strains were mainly involved in adhesion, invasion, flagella and biofilm formation. Conclusions:This study identified a case of bloodstream infection caused by Balneatrix alpica which was closely related to natural hot spring water. Natural hot spring water migh be an important source of clinical infections caused by this species.

Research progress on neoadjuvant immunotherapy for esophageal cancer / 中华放射肿瘤学杂志

Neoadjuvant therapy, especially neoadjuvant chemoradiotherapy, has become the standard preoperative treatment for locally advanced resectable esophageal cancer, whereas the recurrence and distant metastasis rates after surgery remain high. In recent years, programmed cell death protein 1 (PD-1) / programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors have been widely adopted in immunotherapy for cancer. Whether PD-1/PD-L1 immune checkpoint inhibitors combined with neoadjuvant chemotherapy / neoadjuvant chemoradiotherapy could further improve clinical efficacy, increase the complete surgical resection rate and safety are current research hotspots. In this article, neoadjuvant immunotherapy combined with chemotherapy / radiochemotherapy for esophageal cancer was reviewed.

CT anatomical features of the sustentaculum fragment and their clinical significance / 中华创伤骨科杂志

Objective:To determine the anatomical parameters concerning the length, width and height of the sustentaculum fragment of the calcaneus using CT imaging data and their clinical significance.Methods:A retrospective study was conducted to analyze the CT imaging data of normal calcaneus in 96 patients (100 feet) which had been collected by Department of Orthopedics, Shanghai Tongji Hospital from January 2019 to September 2020. There were 45 males (48 feet) and 51 females (52 feet) with an age of (42.1±13.6) years, and 56 left feet and 44 right feet. After 3D models were reconstructed with the CT data using software Mimics 22.0, the calcaneus was viewed layer by layer at each level of the scan. After the first continuous bone trabecula on the medial side of the calcaneal central triangle was taken as the boundary, the model of the sustentaculum fragment was segmented. The length, width, and height of the sustentaculum fragment were measured. The outer contour of the sustentaculum fragment was projected onto the lateral wall of the calcaneus to draw the contour line using software Materialise 3-Matic 22.0. By overlaying projection line diagrams, a summary of projection line diagrams of 100 sustentaculum fragments was obtained. Seven screw insertion points were selected in the summary region of the projection line diagrams of the lateral wall of the calcaneus, and the distance from each point to the medial side of the calcaneus were measureed. The length, width, and height of the sustentaculum fragment, as well as the distance from the 7 insertion points to the medial side of the calcaneus, were compared between different feet and genders.Results:The length, width, and height of the sustentaculum fragment were (45.19±4.60) mm, (38.57±4.59) mm and (40.76±5.48) mm, respectively. There were no significant differences in the length, width or height of the sustentaculum fragment between different feet or in the height of the sustentaculum fragment between different genders ( P>0.05), but the length and width of the sustentaculum fragment in females were significantly smaller than those in the males ( P<0.05). The projection of the sustentaculum fragment was approximately ellipse on the summary region of the projection line diagrams on the lateral wall of the calcaneus, with the long axis approximately parallel to the midpoint tangent of the lateral edge of the calcaneal posterior articular surface, ranging from 2 to 20 mm from the posterior articular surface. The distances from the 7 insertion points to the medial surface of the calcaneus were (39.91±3.77) mm at point A, (40.89±3.55) mm at point B, (36.42±5.98) mm at point C, (39.12±5.52) mm at point D, (40.04±4.84) mm at point E, (33.00±3.96) mm at point F, and (33.04±3.82) mm at point H. There was no significant difference in the distances from the 7 insertion points to the medial surface of the calcaneus between different feet ( P>0.05), but the distances from the 7 insertion points to the medial surface of the calcaneus in the females were significantly smaller than those in the males ( P<0.05). Conclusions:Anatomical measurements of the sustentaculum fragment can provide a theoretical basis for the range of fixation of the sustentaculum screws. A summary of projection line diagrams of the sustentaculum fragment on the lateral surface of the calcaneus can serve as a reference for placement of sustentaculum screws. Measurement of the distances from 7 insertion points to the medial surface of the calcaneus can facilitate determination of the lengths of sustentaculum screws.

Virtual simulation teaching exploration of clinical laboratory instrumentation based on "Internet +" / 中华医学教育探索杂志

Clinical laboratory instrumentation is a practical course. In order to change the limitations of the experimental site and the lack of large automatic testing instruments in the current teaching, this paper puts forward the idea of virtual simulation teaching of clinical laboratory instrument. Based on the training objective of medical laboratory application-oriented talents, the design and management of virtual simulation teaching of single instrument and comprehensive project training are formed. The teaching effect evaluation and quality control method are constructed, which significantly improves the students' autonomous learning ability and the comprehensive practical ability. It further promotes the connotation construction of medical laboratory experiment teaching with the help of Internet sharing advantages.

Effect of decision aid tools for advance care planning in patients with cancer: a Meta-analysis / 中国实用护理杂志

Objective:To systematically evaluate the effect of decision aid tools for advance care planning (ACP) in patients with cancer.Methods:Randomized controlled trials about the effect of decision aid tools for ACP in patients with cancer were retrieved from Embase, PubMed, CINAHL, the Cochrane Library, PsycINFO, Chinese Biomedical Literature Database, VIP, China National Knowledge Internet and Wanfang Data. The retrieval time was from inception to February 23, 2022. Literature screening, quality evaluation and data consolidation were carried out independently by two researchers. Then, RevMan 5.3 software was used for Meta analysis.Results:A total of 13 researches were included, involving 2 151 cancer patients. Meta-analysis showed that the signing of advance directives ( OR=1.81, 95% CI 1.22-2.69, Z=2.95, P<0.01) and knowledge scores related to ACP( MD=0.58, 95% CI 0.35-0.81, Z=4.90, P<0.01) in experimental group was higher than that in control group, but receiving cardiopulmonary resuscitation treatment before death ( MD=0.33, 95% CI 0.21-0.53, Z=4.64, P<0.01) and the level of decision confliction ( MD=-3.69, 95% CI-6.43--0.95, Z=2.64, P<0.01) in experimental group was lower than those in control group, and the differences were statistically significant. Conclusions:Existing evidence shows that decision aid tools can improve cancer patients′ awareness of ACP, help patients to join in ACP discussions and sign advanced directives, reduce patients' preference for cardiopulmonary resuscitation treatment before death and reduce decision-making conflicts.

The neuroprotective effect of salidroside prophylactic administration on MCAO model rats / 中国药理学通报

Aim To investigate the neuroprotective effect of prophylactic administration of salidroside (Sal) on MCAO rats. Methods A total of 52 SD adult male rats were randomly divided into sham operation group (Sham), model group (MCAO) and salidroside pre-administration group (MCAO + Sal). The dose of Sal was 50 mg·kg

Diffuse lung involvement in rheumatoid arthritis: a respiratory physician's perspective / 中华医学杂志(英文版)

The lungs are one of the most common extra-articular organs involved in rheumatoid arthritis (RA), which is reported to occur in up to 60% to 80% of RA patients. Respiratory complications are the second leading cause of death due to RA. Although there is a wide spectrum of RA-associated respiratory diseases, interstitial lung disease is the most common manifestation and it impacts the prognosis of RA. There has been progress in understanding the management and progression of rheumatoid arthritis-associated interstitial lung disease (RA-ILD) and RA-associated respiratory diseases recently, for example, opportunistic pulmonary infectious diseases and toxicity from RA therapies. From a chest physicians' perspective, we will update the diagnosis and treatment of RA-associated ILD, methotrexate-associated lung disease, and the complication of Pneumocystis jiroveci pneumonia in RA in this review.

Quantifying carotid stiffness in a pre-hypertensive population with ultrafast ultrasound imaging

Purpose@#The aim of this study was to assess carotid stiffening in a pre-hypertensive (PHT) population using ultrafast pulse wave velocity (ufPWV). @*Methods@#This study retrospectively enrolled 626 individuals who underwent clinical interviews, serum tests, and assessments of the systolic blood pressure (SBP), diastolic blood pressure (DBP), carotid intima-media thickness (cIMT), pulse wave velocity-beginning of systole (PWV-BS), and pulse wave velocity-end of systole (PWV-ES) between January 2017 and December 2021. The patients were divided into three groups according to their blood pressure (BP)—normal BP (NBP): SBP 0.05). However, the NBP group had a notably lower PWV-ES than the PHT (P0.05). @*Conclusion@#Carotid morphological and biomechanical properties in the PHT group differed from those in the NBP group. ufPWV could be used for an early evaluation of carotid stiffening linked to pre-hypertension.

Progress of potential therapeutic targets and small molecule ligands of anti-colorectal cancer pathogenic Fusobacterium nucleatum / 药学学报

The composition of intestinal microflora is closely related to the occurrence and development of colorectal cancer (CRC). Among them, Fusobacterium nucleatum (Fn) has been proved directly related to the recurrence, metastasis and chemotherapy resistance of CRC. Therefore, it is of great significance for the prevention and treatment of colorectal cancer by the exploration potential anti-Fn drug targets and discovery small molecule drugs. However, no selective anti-Fn small molecule inhibitors have been reported so far as well as their anti-Fn thereby "anti-Fn further anticancer" mechanisms are unclear. Herein, this article reviews the potential therapeutic targets and small molecule ligands of Fn in order to provide a reference for the development of anti-Fn and anti-CRC small molecule drugs.

Investigation on the mechanism of anti-drug-induced liver injury and related effector substances of traditional Chinese medicine from the perspective of metabolism / 药学学报

Drug-induced liver injury (DILI) is one of the common clinical adverse drug reactions and remains a major cause of drug restriction, development termination and withdrawal from the pharmaceutical market today. In recent years, a variety of chemical components and metabolites of traditional Chinese medicine (TCM), as well as the endogenous effector substances influenced by metabolism of both, have attracted much attention for their significant hepatoprotective activities. However, the mechanism of TCM against DILI is complex, the related effector substances are still unclear, and its metabolism-related studies are still relatively weak. Therefore, this review summarized the mechanisms of DILI and its treatment by TCM from the perspective of metabolism, and for the first time, innovatively classified the Chinese medicine effector substances into two categories: exogenous (active components and metabolites of TCM) and endogenous (intestinal probiotics and endogenous metabolites), in order to reduce the occurrence of DILI, explore and develop effective anti-drug-induced liver injury effector substances of TCM, and further develop clinical drugs with hepatoprotective effects.

Sporadic Creutzfeldt-Jakob Disease With Slow Progression:Report of One Case / 中国医学科学院学报

Sporadic Creutzfeldt-Jakob disease(sCJD)is a prion-caused degenerative disease of the central nervous system,with the typical clinical manifestation of rapidly progressive dementia.The course of disease is less than 1 year in most patients and more than 2 years in only 2% to 3% patients.We reported a case of sCJD with expressive language disorder and slow progression in this paper.By summarizing the clinical manifestations and the electroencephalograhpy,MRI,and pathological features,we aimed to enrich the knowledge about the sCJD with slow progression.

Application of precision-cut lung slice technology to study the role of DDR2 in pulmonary fibrosis / 生理学报

Pulmonary fibrosis is a severe lung interstitial disease characterized by the destruction of lung tissue structure, excessive activation and proliferation of fibroblasts, secretion and accumulation of a large amount of extracellular matrix (ECM), and impaired lung function. Due to the complexity of the disease, a suitable animal model to mimic human pulmonary fibrosis has not yet been established. Precision-cut lung slice (PCLS) has been a widely used in vitro method to study lung physiology and pathogenesis in recent years. This method is an in vitro culture technology at the level between organs and cells, because it can preserve the lung tissue structure and various types of airway cells in the lung tissue, simulate the in vivo lung environment, and conduct the observation of various interactions between cells and ECM. Therefore, PCLS can compensate for the limitations of other models such as cell culture. In order to explore the role of discoidin domain receptor 2 (DDR2) in pulmonary fibrosis, Ddr2flox/flox mice were successfully constructed. The Cre-LoxP system and PCLS technology were used to verify the deletion or knockdown of DDR2 in mouse PCLS. Transforming growth factor β1 (TGF-β1) can induce fibrosis of mouse PCLS in vitro, which can simulate the in vivo environment of pulmonary fibrosis. In the DDR2 knock down-PCLS in vitro model, the expression of various fibrosis-related factors induced by TGF-β1 was significantly reduced, suggesting that knocking down DDR2 can inhibit the formation of pulmonary fibrosis. The results provide a new perspective for the clinical study of DDR2 as a therapeutic target in pulmonary fibrosis.

Hunyuan moxibustion for diarrhea-predominant irritable bowel syndrome of spleen and kidney yang deficiency: a randomized controlled trial / 中国针灸

OBJECTIVE@#To compare the therapeutic effect between Hunyuan moxibustion and oral western medication on diarrhea-predominant irritable bowel syndrome（IBS-D）of spleen and kidney yang deficiency.@*METHODS@#Sixty patients with IBS-D of spleen and kidney yang deficiency were randomly divided into a Hunyuan moxibustion group and a western medication group, 30 cases each group. The Hunyuan moxibustion group was treated with Hunyuan moxibustion at Guanyuan（CV 4），40 min each time, once a day; in the western medication group，loperamide hydrochloride capsules (2 mg each time, 3 times a day) and bacillus licheniformis live capsules (0.5 g each time, 3 times a day) were given orally.Both groups were treated for 20 days. The scores of irritable bowel syndrome（IBS）symptom severity scale（IBS-SSS）, IBS quality of life scale (IBS-QOL) and TCM symptom grading quantitative were observed before and after treatment, and the clinical efficacy and safety were evaluated in the two groups.@*RESULTS@#After treatment，each item scores and total scores of IBS-SSS in the two groups were lower than those before treatment（P<0.05）, and the total scores of IBS-QOL were higher than those before treatment (P<0.05)；each item score and total score of IBS-SSS in the Hunyuan moxibustion group were lower than those in the western medication group (P<0.05), and the total score of IBS-QOL in the Hunyuan moxibustion group was higher than that in the western medication group (P<0.05).After treatment, each item score and total score of TCM symptom grading quantitative in the Hunyuan moxibustion group were lower than those before treatment (P<0.05), the abdominal pain, diarrhea, lack of appetite scores and total score in the western medication group were lower than those before treatment (P<0.05)；and the abdominal pain, soreness and weakness of waist and knees, fear to cold and cold limbs scores and total score in the Hunyuan moxibustion group were lower than those in the western medication group (P<0.05).The total effective rate was 90.0%（27/30）in the Hunyuan moxibustion group, which was higher than 73.3%（22/30）in the western medication group (P<0.05). No adverse reactions occurred in both groups during treatment.@*CONCLUSION@#Hunyuan moxibustion can effectively improve the symptom severity and quality of life in patients with IBS-D of spleen and kidney yang deficiency, especially in improving the symptoms of abdominal pain, soreness and weakness of waist and knees, fear to cold and cold limbs.Its therapeutic effect is superior to western medication.

HBsAg non-reactive but HBV DNA reactive blood donors in Wuhu area: infection status and tracing results / 中国输血杂志

【Objective】 To detect and analyze the infection status of HBsAg non-reactive /HBV DNA reactive blood donors by individual donor-NAT (ID-NAT) and chemiluminescence technology, and to explore the feasibility and potential risks of reentry. 【Methods】 The blood screening results of blood donors in Wuhu from January 2018 to October 2021 were queried by blood station information management software. The blood donation information of all HBsAg non-reactive /HBV DNA reactive blood donors was collected and then recalled by telephone. After informed consent, samples were taken for HBV DNA nucleic acid single test, enzyme-linked immunoassay for HBsAg, chemiluminescence assay for HBV seromarkers(including HBsAg, anti-HBs, HBeAg, anti-HBe and anti-HBc), and alanine aminotransferase (ALT) test. All the results were statistically analyzed. 【Results】 From January 2018 to October 2021, there were 142 051 donations, and the positive rate of sole HBV DNA was 0.06% (91/142 051), and 33 people (37 person-times) were successfully followed up. The yield rates of HBsAg, anti-HBs and anti-HBc were 6.06% (2/33), 39.39% (13/33) and 96.97% (32/33), respectively; None HBeAg was yielded. After two times of ID-NAT, 8 patients remained non-reactive to both systems, with a negative conversion rate of 24.24% (8/33). Meanwhile, 25 patients were at least once reactive to ID-NAT, and 23 of them were occult HBV infection with serologically reactivity. There were 2(6.25%) patients with HBsAg positive conversion and HBV DNA persistent reactivity, which were window period infection. One person was confirmed as false reactivity (no HBV infection) as he remained unreactive to both repeated ID-NAT and serological tests. 【Conclusion】 Chemiluminescence assay is more sensitive than ELISA in detecting HBV serum markers, which is beneficial to early detection of HBV samples in window period. The yielding rate of anti-HBc among HBsAg non-reactive/HBV DNA reactive blood donors detected by blood screening in this region is very high, and most of them are occulting infection, so the ID-NAT should be no less than 2 times in the reentry strategy.

Analysis of risk factors in blood donors with confirmed positive syphilis / 中国输血杂志

【Objective】 To study the risk factors of blood donors confirmed to be positive for syphilis, so as to avoid highrisk groups, guide the recruitment of blood donors and improve blood safety. 【Methods】 From September 2021 to August 2022, 44 514 blood samples were screened using two enzyme-linked immunosorbent reagents for syphilis, and the reactive samples were confirmed by TPPA. Blood collection time, blood collection location, blood donation numbers, gender, age, marital status and educational level of blood donors were taken as the prediction risk factors, and factors with statistically significant differences by univariate Logistic regression analysis were further analyzed using multivariate factor Logistic regression analysis to determine the final independent risk factors. 【Results】 A total of 121 syphilis antibody reactive samples were detected by enzyme-linked immunosorbent assay, and 64 were confirmed positive by TPPA. Excluding those with incomplete information, a total of 44 505 blood donors were included in the analysis. Logistic regression analysis showed that there were statistically significant differences in blood collection location, blood donation numbers, age and education level. 【Conclusion】 Based on the analysis results of risk factors of syphilis positive blood donors in Wuhu, it is necessary to strengthen the consultation of blood donors in blood donation sites. The high-risk groups are first-time blood donors over 50 years old, with education level of junior high school or below.

Analysis of genotypes on 850 newborns with SLC26A4 single-allele mutation and the phenotypes of those with second variant / 中华耳鼻咽喉头颈外科杂志

Objective: To clarify the phenotypes of the newborns with SLC26A4 single-allele mutation in deafness genetic screening and second variant; to analyze the SLC26A4 genotype and hearing phenotype. Methods: 850 newborns born in Beijing from April 2015 to December 2019 were included and there were 468 males and 382 females. They received genetic deafness screening for 9 or 15 variants, with the result of SLC26A4 single-allele mutation. Firstly, three step deafness gene sequencing was adopted in this work, i.e., the first step was "SLC26A4 gene whole exons and splice sites" sequencing; the second step was "SLC26A4 gene promoter, FOXI1 gene and KCNJ10 gene whole exons" sequencing; and the third step was detection for "SLC26A4 gene copy number variation". Secondly, we collected the results of newborn hearing screening for all patients with the second mutation found in the three step test, and conducted audiological examinations, such as acoustic immittance, auditory brainstem response and auditory steady state response. Thirdly, for novel/VUS mutations, we searched the international deafness gene database or software, such as DVD, ClinVar and Mutation Taster, to predict the pathogenicity of mutations according to the ACMG guideline. Lastly, we analyzed the relationship between genotype and phenotype of newborns with SLC26A4 single allele mutation. Results: Among 850 cases, the median age of diagnosis was 4 months. In the first step, 850 cases were sequenced. A total of 32 cases (3.76%, 32/850) of a second variants were detected, including 18 cases (2.12%, 18/850) with identified pathogenic variants; 832 cases were sequenced and 8 cases of KCNJ10 gene missense variants were detected among the second step. No missense mutations in the FOXI1 gene and abnormal SLC26A4 gene promoter were detected; the third step sequencing results were all negative. Genotypes and hearing phenotypes included 18 cases combined with the second clear pathogenic variant, 16 cases (16/18) referred newborn hearing screening and 2 cases (2/18) passed in both ears; degree of hearing loss consisted of 18 profound ears (18/36), 13 severe ears (13/36) and 5 moderate ears (5/36); audiogram patterns comprised 17 high frequency drop ears (17/36), 14 flat ears (14/36), 3 undistinguished ears (3/36), and 2 U shaped ears (2/36); 11 cases underwent imaging examination, all of which were bilateral enlarged vestibular aqueduct. As for 22 cases of other genotypes, all passed neonatal hearing screening and the hearing diagnosis was normal, including 9 cases with VUS or possibly novel benign variants, 8 cases with KCNJ10 double gene heterozygous variants, and 5 cases with double heterozygous variants. Conclusions: The probability of individuals with SLC26A4 single-allele variant who merge with a second pathogenic variant is 2.12%, all of which are SNV, which can provide scientific basis for the genetic diagnosis and genetic counseling of SLC26A4 variants. Those who have merged with second pathogenic variant are all diagnosed with sensorineural hearing loss. Patients with KCNJ10 gene mutations do not manifest hearing loss during the infancy, suggesting the need for further follow-up.

Clinical phenotype and genetic analysis of twelve children with ring chromosomes / 中华医学遗传学杂志

OBJECTIVE@#To explore the prevalence and clinical manifestations of ring chromosomes among children featuring abnormal development.@*METHODS@#From January 2015 to August 2021, 7574 children referred for abnormal development were selected, and their peripheral blood samples were subjected to G-banded chromosomal karyotyping analysis.@*RESULTS@#Twelve cases of ring chromosomes were detected, which have yielded a prevalence of 0.16% and included 1 r(6), 2 r(9), 1 r(13), 1 r(14), 2 r(15), 1 r(21) and 3 r(X). The children had various clinical manifestations including growth and mental retardation, limb malformation, and congenital heart disease. For two children with r(9) and two with r(15) with similar breakpoints, one child with r(9) and one with r(15) only had growth retardation, whilst another with r(9) and another with r(15) also had peculiar facies and complex congenital heart disease. The r(X) has featured some manifestations of Turner syndrome.@*CONCLUSION@#Ring chromosomes are among the common causes for severe growth and mental retardation in children with diverse clinical phenotypes. Clinicians should pay attention to those with developmental anomalies and use chromosomal analysis to elucidate their genetic etiology.