AIM:To analyze the clinical phenotypes and genotypes of children with incontinentia pigmenti(IP)and enhance clinicians' understanding of the condition.METHODS: A family with IP diagnosed in February 2020 at the ophthalmology department of People's Hospital of Ningxia Hui Autonomous Region was enrolled. The proband and family members underwent comprehensive systemic and ocular examinations. Peripheral venous blood was collected for DNA extraction, followed by whole-exome sequencing and MLPA assay to identify pathogenic variants. Corresponding treatments were administered based on the severity of fundus lesions, and ocular clinical features and therapeutic outcomes were monitored during follow-up.RESULTS: The child in this study was a female, aged 8 years, with typical skin changes and scarring alopecia and dental abnormalities at the time of initial consultation. The results of genetic testing suggested that the child carried a heterozygous deletion of exons 4-10 of the IKBKG gene chrX:153440010-153446570del. The child had asymmetric lesions in both eyes, with severe lesions in the left eye, atrophy of the eyeballs, and ocular B-ultrasound suggesting structural disturbances in the eye, and neovascularization was seen in the peripheral retina of the right eye, and the patient was given laser photocoagulation treatment for the right eye, and no progression of retinopathy was detected during follow-up.CONCLUSION:Children with IP have different ocular clinical phenotypes, and retinal vasculopathy is the main change. Early screening and timely and standardized treatment are crucial for children diagnosed with IP.

Objective To explore the effect of multi-sensory artificial intelligence feedback gait training on the recovery of walking function in stroke patients based on enriched environment theory. Methods From July,2021 to June,2023,a total of 80 stroke patients in Huashan Hospital Affiliated to Fudan University were randomly divided into control group(n=40)and experimental group(n=40).Both groups received rou-tine rehabilitation in the lying and seated positions,for 40 minutes.The control group received ground walking training,for 20 minutes,while the experimental group received multi-sensory feedback gait training in enriched environment,for 20 minutes.Before and after four weeks intervention,the digital motion monitoring treadmill was used to mearsure step speed,step length,hip and knee swing angle and weight symmetry.They were as-sessed with Berg Balance scale(BBS),Fugl-Meyer Assessment-Lower Extremities(FMA-LE)and Barthel Index(BI). Results After intervention,the hip swing angle,step length of both sides and step speed significantly improved in both groups(|t|＞3.162,P＜0.05),and they were better in the experimental group than in the control group(|t|＞2.568,P＜0.05);the average knee joint swing angle and bilateral weight-bearing symmetry significantly im-proved in the experimental group(|t|＞3.249,P＜0.01);the scores of BBS,FMA-LE and BI improved in both groups(|t|＞3.569,P＜0.01),and they were better in the experimental group than in the control group(|t|＞2.922,P＜0.05). Conclusion Multi-sensory feedback gait training based on enriched environment theory could effectively improve the walking and balance of stroke patients,and increase the ability of independence.

Purpose/Significance The relative positions of causality words are utilized to assist deep learning models to improve cau-sality prediction and mine medical text gain information.Method/Process The relative position information of causality words in medical texts is represented as a relational feature layer embedded in a pre-trained language model,and the baseline model is integrated for enti-ty recognition and relationship extraction.Result/Conclusion The F1 value of the model embedded in the relational feature layer is im-proved by 2.92 percentage points and 6.41 percentage points compared with the baseline models BERT-BiLSTM-CRF and CasRel,re-spectively,with better causal prediction capacity.

Objective To retrieve,analyse and integrate the best evidences in perioperative fluid management for elderly patients with hip fracture,therefore to provide references for patient care.Methods Following the 6S evidence model,databases and websites were searched to collect the evidences on perioperative fluid management of elderly patients with hip fracture.The searched databases including BMJ Best Practice,UpToDate,AAOS Clinical Practice Guidelines,ASBMR,ANZHFR,ESTES,NICE,SIGN,JBI,Cochrane Library,CINAHL,Embase,PubMed,Web of Science,CNKI,Wanfang Data,VIP database,CEBM Database,Medive,China Science and Technology Journal Database,SinoMed,and other websites about orthopaedics.The searched literatures included guidelines,clinical decision-making,best practices,expert consensus and systematic reviews.The time span for the published literatures was from the inception of the databases and websites to August 2022.Two researchers independently completed quality evaluations of the retrieved literatures,as well as extraction,assessment and integration of the abstracted evidences.Results A total of 15 articles were included,they were 2 guidelines,3 clinical decision-makings,1 best practice,7 expert consensus,and 2 systematic reviews.Thirty pieces of evidence were summarised from 7 aspects,covering multidisciplinary team collaboration,dynamic assessment and monitoring of fluid status,fluid resuscitation,fluid management before and after the surgery and health education.Conclusions This study summarised the best evidences in perioperative fluid management for elderly patients with hip fracture.The evidences provide an evidence-based solution which will enable the healthcare workers to fully combine the clinical scenarios,evaluate changes in fluid volume status dynamically,develope personalised fluid management strategies and improve patient outcomes.

Objective This study aims to investigate the application of symptom group management using a mo-bile health platform in managing heart failure patients during convalescence.Methods The research involved pa-tients with chronic heart failure who were treated at a tertiary A hospital in Qingdao from June 2022 to December 2022.The experimental group consisted of 235 patients who were discharged after treatment in ward A,while the control group consisted of 235 patients who were discharged during the same period in ward B.The experimental group received an mHealth-based symptom clusters management program following routine continuous nursing and the control group was given routine continuous nursing after discharge.6 months after the intervention,the heart function status,self-care level,and quality of life were compared between 2 groups.Results The experimental group ultimately included 232 cases,while the control group ultimately included 225 cases.Furthermore,the cardiac functional status,level of self-care,and quality of life of both the experimental group and the control group showed improvement compared to the pre-intervention period(P＜0.05).The experimental group exhibited significantly better cardiac function status compared to the control group,and the experimental group demonstrated higher levels of self-care confidence,and quality of life relative to the control group(P＜0.05).Conclusion The utilization of a mobile medical platform can enhance the management of heart failure patients'symptom groups,resulting in im-proved disease management efficiency.This platform provides patients with a comprehensive self-management plan,ultimately enhancing their self-management abilities and overall outcomes.

BACKGROUND: The molecular mechanisms driving tumorigenesis have continually been the focus of researchers. Cuproplasia is defined as copper-dependent cell growth and proliferation, including its primary and secondary roles in tumor formation and proliferation through signaling pathways. In this study, we analyzed the differences in the expression of cuproplasia-associated genes (CAGs) in pan-cancerous tissues and investigated their role in immune-regulation and tumor prognostication. METHODS: Raw data from 11,057 cancer samples were acquired from multiple databases. Pan-cancer analysis was conducted to analyze the CAG expression, single-nucleotide variants, copy number variants, methylation signatures, and genomic signatures of micro RNA (miRNA)-messenger RNA (mRNA) interactions. The Genomics of Drug Sensitivity in Cancer and the Cancer Therapeutics Response Portal databases were used to evaluate drug sensitivity and resistance against CAGs. Using single-sample Gene Set Enrichment Analysis (ssGSEA) and Immune Cell Abundance Identifier database, immune cell infiltration was analyzed with the ssGSEA score as the standard. RESULTS: Aberrantly expressed CAGs were found in multiple cancers. The frequency of single-nucleotide variations in CAGs ranged from 1% to 54% among different cancers. Furthermore, the correlation between CAG expression in the tumor microenvironment and immune cell infiltration varied among different cancers. ATP7A and ATP7B were negatively correlated with macrophages in 16 tumors including breast invasive carcinoma and esophageal carcinoma, while the converse was true for MT1A and MT2A . In addition, we established cuproplasia scores and demonstrated their strong correlation with patient prognosis, immunotherapy responsiveness, and disease progression ( P  <0.05). Finally, we identified potential candidate drugs by matching gene targets with existing drugs. CONCLUSIONS This study reports the genomic characterization and clinical features of CAGs in pan-cancers. It helps clarify the relationship between CAGs and tumorigenesis, and may be helpful in the development of biomarkers and new therapeutic agents.
Humans ; Female ; Genomics ; Carcinogenesis ; Carcinoma ; Breast Neoplasms ; Cell Transformation, Neoplastic ; Nucleotides ; Tumor Microenvironment

Epilepsy is a disorder of the brain charac-terized by abnormal neuron excitability.However,the underlying molecular mechanism of neuron excitability modulation remains elusive.With the help of bioinformatic methods,we have identified receptor-type tyrosine-pro-tein phosphatase-like N(PTPRN)as a critical gene dur-ing epileptogenesis.PTPRN recruits NEDD4L ubiquitin E3 ligase to NaV1.2 sodium channels,facilitating NEDD4L-mediated ubiquitination and endocytosis.Knockout of PTPRN endows hippocampal granule cells with augmented depolarization currents and higher intrinsic excitability,which is reflected by increased seizure susceptibility of transgenic mice.On the contrary,reduced neuron excit-ability and decreased seizure susceptibility are observed after PTPRN overexpression.Meanwhile,we find that a 133 aa fragment recaptures modulation effect of PTPRN full-length,and this fragment shows therapeutic potential towards epilepsy caused by NaV1.2 gain of function vari-ants.In brief,our results demonstrate PTPRN playsa criti-calroleinregulatingneuronexcitability,providing a poten-tial therapeutic approach for epilepsy.

Objective:To analyze the factors influencing breast milk volume in mothers of preterm infants during the period of maternal separation.Methods:This study retrospectively analyzed the data from lactation diaries of mothers of preterm infants ( n=371) in neonatal intensive care unit from the first Affiliated Hospital of Zhengzhou University from January 2017 to August 2021. According to whether the milk production reached 800 ml/d or not within two weeks after delivery, these women were divided into the reached group ( n=289) or unreached group ( n=82). Two independent sample t-test and Chi-square test were used for univariate analysis, and logistic regression was used to analyze the influencing factors. Results:Mothers who achieved the target milk volume accounted for 77.9% (289/371). There were no statistically significant differences in the ratio of milk production ≥50 ml between breasts or between two adjacent breastfeeding sessions (both P>0.05), while there were statistically significant differences in the maternal education background[high school education or below:16.3% (47/289) vs 41.5% (34/82); junior college or above:83.7% (242/289) vs 58.5% (48/82); χ2=23.77], type of breast pump [diaphragm breast pump:34.9% (101/289) vs 51.2% (42/82); piston pump: 65.1% (188/289) vs 48.8% (40/82); χ2=7.14], pre-pregnancy body mass index [<18.5 kg/m 2: 3.5% (10/289) vs 4.9% (4/82);≥18.5～<24.0 kg/m 2: 90.7% (262/289) vs 61.0% (50/82); ≥24.0 kg/m 2: 5.9% (17/289) vs 34.1% (28/82); χ2=40.89], and the initiation of lactation instruction [within 7 d after delivery: 77.2% (223/289) vs 45.1% (37/82);at 7-14 d after delivery: 22.8%(66/289) vs 54.9%(45/82); χ2=31.28] between the reached and unreached group (all P<0.05). Logistic regression analysis showed that high school education or below ( OR=4.279, 95% CI: 2.253-8.126, P<0.001), diaphragm breast pump ( OR=2.352, 95% CI: 1.309-4.226, P=0.004), pre-pregnancy body mass index ≥24.0 kg/m 2 ( OR=9.352, 95% CI: 4.389-19.928, P<0.001), and seeking lactation consultation at 7-14 d after delivery ( OR=3.654, 95% CI: 2.043-6.535, P<0.001) were risk factors for not achieving the target milk volume. Conclusions:Instruction on breastfeeding for less-educated mothers of preterm infants should be strengthened. Using piston breast pump, maintaining pre-pregnancy body mass index within the normal range, and receiving lactation instruction as early as possible will contribute to achieving the target milk volume.

Objective:To observe and analyze the gene mutation and clinical phenotype of patients with cone and rod dystrophy (CORD).Methods:A pedigree investigarion. Two CORD pedigrees including 2 patients and 6 family members were enrolled in Ningxia Eye Hospital of People' Hospital of Ningxia Hui Automous Region for this study. The patients were from 2 unrelated families, all of whom were probands. Take medical history with best-corrected visual acuity (BCVA), color vision, slit lamp microscopy, indirect ophthalmoscopy, fundus color photography, optical coherence tomography (OCT), autofluorescence (AF), fluorescein fundus angiography (FFA), electroretinogram (ERG). The peripheral venous blood of patients and their parents was collected, whole genome DNA was extracted, Trio whole genome exome sequencing was performed, Sanger verification and pedigree co-segregation were performed for suspected pathogenic mutation sites. According to the law of inheritance, family history was analyzed to establish its genetic type. Mutational loci pathogenicity was analyzed according to the American College of Medical Genetics (ACMG) guidelines and 4 online tools.Results:Two CORD families showed autosomal recessive inheritance. The proband of pedigree 1 was female, 49 years old. Binocular vision loss with photophobia lasted for 9 years and night blindness for 4 years. The BCVA of right eye and left eye were 0.03 and 0.06, respectively. The results of ERG showed that the amplitudes of dark adaptation 0.01 b-wave and dark adaptation 3.0 a-wave and b-wave in both eyes were slightly decreased, and the amplitudes of light adaptation 3.0 a-wave and b-wave were severely decreased. The proband of pedigree 2 was male, 30 years old. Vision loss in both eyes for 4 years. Denying a history of night blindness. The BCVA of right eye and left eye were 0.3 and 0.2, respectively. The results of ERG showed that the amplitudes of dark adaptation 0.01 b-wave and dark adaptation 3.0 a-wave and b-wave in both eyes were slightly decreased, and the amplitudes of light adaptation 3.0 a-wave and b-wave were severely decreased. The color of optic disc in both eyes was light red, the macular area was atrophic, the foveal reflection disappeared, and the peripheral retina was punctate pigmentation. The main fundus changes in 2 patients were macular atrophy. The proband of pedigree 1 carried compound heterozygous variations c.439-2A>G (M1) and c.676delT (p.F226fs) (M2) on CDHR1 gene. Her father and mother carried M2 and M1 heterozygous mutations, respectively. The proband of pedigree 2 carried compound heterozygous variations c.2665dupC (p.L889fs) (M3) and c.878T>C (p.L293P) (M4) on C2orf71 gene. His father and mother carried M4 and M3 heterozygous mutations, respectively. According to ACMG guidelines and on line tools, 4 variations were considered as pathogenic level. Conclusions:M1 and M2 of CDHR1 gene and M3 and M4 of C2orf71 gene are new pathogenic mutations of CORD. All patients presented with the clinical phenotype of decreased visual acuity and macular atrophy.

Objective:To investigate the application values of bone marrow morphology, bone marrow immunohistochemistry, flow cytometry, fluorescence in situ hybridization (FISH) and cytogenetic testing in newly diagnosed multiple myeloma.Methods:A total of 280 patients with multiple myeloma who were newly diagnosed in Tianjin KingMed Diagnosis Center from September 2018 to August 2019 were collected. The bone marrow biopsy was carried out according to the routine method, and bone marrow morphology, bone marrow immunohistochemistry, flow cytometry immunophenotyping, FISH and cytogenetic testing were performed. The detection results of each method were compared.Results:In 280 patients, the bone marrow immunohistochemistry results showed that the median ratio of plasma cells was higher than those of bone marrow morphology (20 cases, 0.675 vs. 0.300) and flow cytometry (47 cases, 0.650 vs. 0.147), and the differences were statistically significant ( Z = -3.883, P < 0.01; Z = -5.947, P < 0.01). Flow cytometry results showed that the positive rates of CD38, CD138, κ, λ, CD56 and CD19 were 100.0% (280/280), 100.0% (280/280), 57.5% (161/280), 42.5% (119/280), 62.1% (174/280) and 19.3% (54/280); bone marrow immunohistochemistry results showed that the positive rates of CD38, CD138, κ, λ and CD56 were 98.9% (277/280), 98.2% (275/280), 57.5% (161/280), 42.5% (119/280) and 62.1% (174/280); there was no statistical difference between the two detection methods in the detection coincidence rate of the same detection index (all P > 0.05). Among patients who underwent FISH detection, the detection rate of gene abnormalities was 69.9% (93/133); the detection rate of abnormalities by direct fluorescence in situ hybridization (D-FISH) was 42.9% (57/133); the detection rate of abnormalities by CD138 immunomagnetic sorting myeloma cells (MACS)-FISH was 82.7% (110/133). Among patients who underwent G-band karyotyping, the detection rate of abnormal karyotype was 38.5% (85/221). FSIH, especially MACS-FISH, had a higher detection rate of cytogenetic abnormalities than G-band karyotyping, and the difference was statistically significant ( χ2 = 65.697, P < 0.05). Conclusion:The comprehensive application of bone marrow morphology, bone marrow immunohistochemistry, flow cytometry, FISH (especially MACS-FISH), cytogenetic testing and other detection methods is more helpful for the diagnosis of multiple myeloma, and may be useful for prognostic judgment.