OBJECTIVE To analyze the clinical characteristics of aplastic anemia （AA）/pure red cell aplasia （PRCA） induced by pembrolizumab， and provide reference for clinical safe drug use. METHODS Using search terms as “pembrolizumab”， “keytruda”， “anemia” and “aplastic anemia” in both Chinese and English， the literature related to AA/PRCA induced by pembrolizumab were retrieved from PubMed， Embase， CNKI， Wanfang and VIP databases， and then analyzed descriptively and statistically. RESULTS A total of 10 patients were included from 10 literature； among these 10 patients， there were 5 males and 5 females， with 5 patients being aged 65 or above. The primary disease was mainly metastatic melanoma （4 cases）. AA/PRCA occurred 13 d-3 years after the first dose of pembrolizumab. The main clinical manifestations included fatigue， dyspnea， oral/nasal bleeding， diffuse purpura， etc.； 8 cases developed moderate anemia and 2 cases developed severe anemia. After discontinuation and receiving supportive therapy， 5 cases improved， 1 case worsened in anemia， and 4 cases died. CONCLUSIONS When using pembrolizumab in clinical practice， blood routine should be regularly monitored. When AA/PRCA and other related symptoms occur， pembrolizumab should be stopped in time and a therapy regimen should be formulated according to the patient’ condition， to ensure the safety of medication.

Objective    To retrospectively analyze the surgical treatment of Stanford type A aortic dissection after coronary artery stenting, and to explore the surgical techniques and surgical indications. Methods    Clinical data of 1 246 consecutive patients who underwent operations on Stanford type A aortic dissection from April 2016 to July 2019 in Beijing Anzhen Hospital were retrospectively analyzed. Patients with Stanford type A aortic dissection after coronary artery stenting were enrolled. Results    Finally 19 patients were collected, including 16 males and 3 females with an average age of 54±7 years ranging from 35 to 66 years. There were 11 patients in acute phase, 15 patients with AC (DeBakey Ⅰ) type and 4 patients with AS (DeBakey Ⅱ) type. In AC type, there were 10 patients receiving Sun's surgery and 5 patients partial arch replacement. Meanwhile, coronary artery bypass grafting was performed in 7 patients and mitral valve replacement in 1 patient. Stents were removed from the right coronary artery in 4 patients. In this group, 1 patient died of multiple organ failure in hospital after operation combined with malperfusion of viscera. Eighteen patients recovered after treatment and were discharged from hospital. The patients were followed up for 30 (18-56) months. One patient underwent aortic pseudoaneurysm resection, one thoracic endovascular aortic repair, one emergency percutaneous coronary intervention due to left main artery stent occlusion, and one underwent femoral artery bypass due to iliac artery occlusion. Conclusion    Iatrogenic aortic dissection has a high probability of coronary artery bypass grafting at the same time in patients with Stanford type A aortic dissection after coronary artery stenting. Complicated type A aortic dissection after percutaneous coronary intervention should be treated with surgery aggressively.

Objective:To summarize the clinical and genetic features of children with intellectual developmental disorder with seizures and language delay (IDDSELD) due to 12q24.31 deletion and SETD1B locus variants. Methods:The clinical data of a child with 12q24.31 deletion diagnosed in the Department of Pediatric Neurology of the Third Affiliated Hospital of Zhengzhou University in September 2022 were retrospectively analyzed. Trio-whole exome sequencing (trio-WES) and copy number variations sequencing (CNV-seq) were used for genetic analysis. The relevant literatures were reviewed to summarize the clinical features of the disease.Results:The proband was a 7 years and 9 month old girl who had clinical features of global developmental delay, epilepsy, hyperactivity, hypertonia, gait disorder, special facial features (high eyebrow arch, big ears, upper lip protrusion), funnel chest, lumbar lordosis. Karyotypic analysis showed 46XX in the proband. CNV-seq showed 12q24.31 (chr12: 121895654-122449092) position had a deletion of about 553.44 kb which contained the SETD1B gene. Trio-WES showed deletion of all exons 1-16 of the SETD1B gene. CNV-seq results of her parents were normal: the SETD1B gene was wild-type. This type has not been reported in China. Four children with IDDSELD caused by 12q24.31 deletion (including the SETD1B gene) were retrieved (totally 5 cases including this case), with male to female ratio of 1∶4, all with de novo mutations, and all with mental retardation, cephalo-facial and skeletal malformations. Three cases had seizures, 2 cases still had developmental backwardness after treatment, and 1 case was seizure controlled. Forty-seven cases of IDDSELD due to point mutation in the SETD1B gene were retrieved: male to female ratio was 31∶16, missense mutations (38/47) were predominant, most were de novo mutations (36/47), and a few were inherited from their fathers/mothers (6/47) or of unknown origin (5/47), with clinical manifestations of speech delay (43/47), growth retardation (43/47), intellectual disability (37/41), behavioral problems (37/47), facial malformations (34/47), skeletal malformations (23/47), obesity (16/47), skin abnormalities (11/47), etc. Thirty-nine cases were combined with seizures, 23 of whom were under control after treatment, and 8 cases were recorded as still having developmental backwardness after treatment. Conclusions:IDDSELD patients are rare at home and abroad, with diverse clinical phenotypes and difficult diagnosis. Symptomatic treatment is the main approach. And the patients can leave behind seizures and varying degrees of developmental backwardness. Among them, patients with 12q24.31 deletion are relatively rare and have not been reported in China, and this type is more common in females, all of whom have de novo mutations, and genetic testing is helpful for the early diagnosis of IDDSELD.

Traditional Chinese medicine injections for the prevention and treatment of cardiotoxicity of antineoplastic drugs was summarized, including Shengmai injection, Shenmai injection, Shenfu injection, Shenqi Fuzheng injection, Kangai injection, Huangqi injection, Xinmailong injection, Danhong injection, Danshen injection, Honghua injection, Kushen injection, Cinobufacin injection and Yinxingdamo injection. The mechanism of effect mainly includes inhibition of lipid peroxidation, reduction of calcium overload and anti-cardiomyocyte apoptosis, which provides the basis for the prevention and treatment of cardiotoxicity of antitumor drugs by traditional Chinese medicine.

Traditional Chinese medicine(TCM)plays a unique role in preventive treatment of disease,treatment of chronic disease and recovery.Integrating modern science and technology and methods to carry out integrated and innovative research will help to bring the value of traditional Chinese medicine into full play.In recent years,with the rapid development of digital therapeutics such as artificial intelligence and wearable devices,digital therapeutics have emerged.Under the guidance of TCM theory,TCM integrates digital therapeutics technology methods,personalized treatment of patients through advanced program-driven software or combined with hardware devices,and improves patient compliance,gives full play to the advantages of TCM.This paper uses CiteSpace to visualize the research hotspots of digital therapeutics,combined with the literature and the website data of the Food and Drug Administration and the National Medical Products Administration,to sort out the application of digital therapeutics in the prevention,treatment and recovery of diseases,analyze the key technologies and core theories in the current application of digital therapeutics.And taking TCM pentatotherapy,kinesiatrics and aromatherapy as examples,this paper discusses the application forms of digital therapeutics under the guidance of TCM theory,and provides a preliminary paradigm for TCM digital therapeutics.

Objective:To provide molecular evidence for clinical diagnosis and genetic counseling by analyzing the clinical characteristics and identifying the pathogenic genes in a SPONASTRIME-type spondyloepimetaphyseal dysplasia(SEMDSP)family.Methods:Clinical data of the family members was collected and analyzed. Case 2 was identified as the proband for whole-exome sequencing and variant analysis. Suspected variants were validated across family numbers using Sanger sequencing.Results:The two affected individuals in this family, a brother and a sister, both presented as short stature. The initial diagnosis for the sister(case 1)was made at the age of 4 years and 2 months(height: 88.6 cm), and for the brother(case 2)at 4 years and 4 months(height: 81.6 cm). Both individuals exhibited distinctive facial features, including frontal bossing, midface hypoplasia with depressed nasal bridge, upturned nostrils, ocular hypertelorism, and epicanthus, thick hair, short lingual frenulum, stubby fingers and palms, and absence of scoliosis. The parents displayed normal phenotypes. Laboratory tests indicated growth hormone deficiency in both affected individuals. Imaging studies revealed significant bone age delay in case 2, while case 1 showed longitudinal striations at the distal radius but with bone age matching their actual age(5 years and 11 months). Despite receiving recombinant human growth hormone treatment, both patients had inadequate responses. Genetic testing identified compound heterozygous mutations in the TONSL gene shared by the two siblings. These mutations included a paternally inherited c. 1291-14_1291-11delCCTC and a maternally inherited c. 1909_1920delACGCTGCAGCAG. Notably, SEMDSP families have not been reported in China, and the c. 1909_1920delACGCTGCAGCAG mutation is a novel variant.Conclusion:Two patients were diagnosed as spondyloepimetaphyseal dysplasia, SPONASTRIME type, and the compound heterozygous variant was the genetic cause of this family.

BACKGROUND: The relationship between quality of life at three months after lung cancer surgery and different surgical approaches is remains unclear. This study aimed to compare the quality of life of patients three months after uniportal and multiportal thoracoscopic lobectomy. METHODS: Data from patients who underwent lung surgery at the Department of Thoracic Surgery, Sichuan Cancer Hospital between April 2021 and October 2021 were collected. The European Organization for Research and Treatment of Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30) and Quality of Life Questionnaire-Lung Cancer 29 (EORTC QLQ-LC29) were used to collect quality of life data of the patients. Potential confounding factors in the baseline data were included in a multivariate regression model for adjustment, and the quality of life of the two groups three months postoperatively was compared with traditional clinical outcomes. RESULTS: A total of 130 lung cancer patients were included, with 57 males (43.8%) and 73 females (56.2%), and an average age of (57.1±9.5) yr. In the baseline data of the two groups, there was a statistical difference in the number of chest drainage tubes placed (P<0.001). After adjustment with the regression model, at three months postoperatively, there were no significant differences in all symptoms and functional status scores between the two groups (all P>0.05). The multiportal group had longer surgery time (120.0 min vs 85.0 min, P=0.001), postoperative hospital stay (6.0 d vs 4.0 d, P=0.020), and a higher incidence of early ≥ grade 2 complications (39.0% vs 10.1%, P=0.011) compared to the uniportal group. CONCLUSIONS Patients undergoing uniportal and multiportal thoracoscopic lobectomy have similar quality of life at three months postoperatively. The uniportal group may have certain advantages in terms of traditional clinical outcome indicators such as operation time, postoperative hospital stay, and early postoperative complications.
Male ; Female ; Humans ; Lung Neoplasms/surgery* ; Quality of Life ; Thoracic Surgery, Video-Assisted/adverse effects* ; Pneumonectomy/adverse effects* ; Postoperative Complications/surgery* ; Retrospective Studies

OBJECTIVE: To explore the genetic basis for an infant with permanent neonatal diabetes mellitus (PNDM). METHODS: Clinical data of the child was collected. Targeted capture-next generation sequencing was carried out to identify the potential variants. Candidate variant was verified by Sanger sequencing of her family members. RESULTS: The child was a 4-month-and-26-day female featuring onset of ketoacidosis accompanied with fasting blood glucose of 24.4 mmol/L, positive urine glucose, decreased serum C-peptide, HbA1c of 9.58%, and negative diabetes autoantibody. Genetic testing revealed that she has carried a heterozygous c.314T>G (p.L105R) variant of the INS gene. Sanger sequencing verified that neither of her parents has carried the same variant, which was also unreported in the literature. The variant was classified as likely pathogenic based on the ACMG guidelines. CONCLUSION The c.314T>G (P.L105R) variant of the INS gene probably underlay the genetic etiology in this child. Genetic testing should be conducted for children with suspected PNDM for early diagnosis and appropriate treatment.
Humans ; Infant ; Child ; Infant, Newborn ; Female ; Mutation ; Insulin/genetics* ; Diabetes Mellitus/genetics* ; Genetic Testing

Objective:To explore the clinical and molecular genetic characteristics of patients with maturity-onset diabetes of the young type 2(MODY2).Methods:Clinical data and laboratory results were collected from five MODY2 patients and their family members diagnosed in the Department of Endocrinology, Genetics, and Metabolism of Xi ′an Children′s Hospital in the recent two years. Whole exome sequencing was carried out on every proband to identify potential variants, then the suspected variants were verified with Sanger sequencing in family numbers.Results:Among the 5 probands, except for proband 4 who presented with polydipsia and polyuria, hyperglycemia in the rest of the children was accidentally identified. Urine routine, urinary protein, and blood lipid of the five probands were all normal, and HbA 1C was between 5.96% and 8.15%. Moreover, an important discovery in this study was that proband 5 had insulin resistance(IRS), which was different from previous studies. It was confirmed by genetic analysis that a glucokinase(GCK) gene variant existed in every MODY2 pedigree. There were four GCK variants in this study, including c. 146C>T(p.T49I), c. 1237T>G(p.Y413D), c. 683C>T(p.T228M) and c. 952G>T(p.G318W), among which the C. 1237T>G(P.y413d) and C. 952G>T(P.G318W) had not been reported till now. All probands received lifestyle intervention, and the blood glucose control was relatively stable. Conclusion:There is MODY2 patient complicated with IRS. MODY2 patients can be controlled well by lifestyle interventions. In addition, we discovered two novel variants of GCK, which extend the mutation spectrum of this gene.

Objective:To explore the clinical manifestations and genetic characteristics of Wolf-Hirschhorn syndrome (WHS) to improve the ability of diagnosis and differential diagnosis of the disease.Methods:The clinical features and auxiliary examinations and treatment of a proband with WHS caused by microdeletion of 4p16.3 segment who admitted to the Third Affiliated Hospital of Zhengzhou University in December 2021 were recorded, and whole exome sequencing (WES) of the family was performed. The prognosis was followed up.Results:The female proband, 11 months old, presented with convulsions at the age of 8 months, with the characteristics of heat sensitivity and cluster seizures, and her identical twin sister had a similar medical history. Physical examination found malnutrition, retarded development, special face, prominent forehead, wide nasal bridge, small jaw, precordial murmur and grade 3/6 murmur in the whole period, hyperactivity of P2, and low limb muscle tone. The whole exon and copy number variation (CNV) test of the family revealed that the proband had a 1.99 Mb heterozygous deletion in the chromosome 4p16.3 segment, including WHSC1 (NSD2), WHSC2 (NEFLA) and other genes. Copy number variation sequencing (CNV-Seq) of the proband and her sister showed 1.97 and 1.92 Mb heterozygous deletion of chromosome 4p16.3, respectively. Genealogical analysis by quantitative polymerase chain reaction revealed that the CNV was de novo, and it was determined to be a pathogenic variant according to the American College of Medical Genetics and Genomics guidelines. The proband took sodium valproate orally, and her sister took oral sodium valproate, zonisamide, and levetiracetam successively, and at the same time they received family rehabilitation training. The age at the last follow-up was 1 year and 8 months. Neither of them had convulsions again in the past 3 months, but the developmental delay was obvious. Conclusion:WHS patients may present with growth retardation, epilepsy, Greek warrior helmet-like special face, and congenital heart disease, and may have microdeletions in the chromosome 4p16.3 segment.