Objective:To explore the genetic basis for a girl with primary microcephaly and growth retardation.Methods:A girl who was admitted to Guangdong Maternal and Child Health Care Hospital in was selected as the study subject. Peripheral blood samples were collected from the child and her parents. Trio whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethnics Committee of Guangdong Maternal and Child Health Care Hospital (Ethics No. 202201278).Results:DNA sequencing revealed that the child has harbored compound heterozygous variants of the WDR62 gene, including a frameshifting c. 2963delC (p.Pro988Argfs*80) variant in exon 24 which was inherited from the unaffected father, and a nonsense c.3163G>T (p.Glu1055*) variant in exon 26, which was inherited from her unaffected mother. Both variants were predicted to affect the reading frame of the WDR62 gene. Conclusion:Based on the clinical manifestations, results of genetic testing and pedigree analysis, the compound heterozygous variants were predicted to underlay the pathogenesis of microcephaly and growth retardation in this child. Above discovery has expanded the mutational spectrum for WDR62-associated Primary microcephaly type 2, and facilitated genetic counseling for the family.

OBJECTIVE: To explore the genetic basis for a girl with primary microcephaly and growth retardation. METHODS: A girl who was admitted to Guangdong Maternal and Child Health Care Hospital in was selected as the study subject. Peripheral blood samples were collected from the child and her parents. Trio whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethnics Committee of Guangdong Maternal and Child Health Care Hospital (Ethics No. 202201278). RESULTS: DNA sequencing revealed that the child has harbored compound heterozygous variants of the WDR62 gene, including a frameshifting c.2963delC (p.Pro988Argfs*80) variant in exon 24 which was inherited from the unaffected father, and a nonsense c.3163G>T (p.Glu1055*) variant in exon 26, which was inherited from her unaffected mother. Both variants were predicted to affect the reading frame of the WDR62 gene. CONCLUSION Based on the clinical manifestations, results of genetic testing and pedigree analysis, the compound heterozygous variants were predicted to underlay the pathogenesis of microcephaly and growth retardation in this child. Above discovery has expanded the mutational spectrum for WDR62-associated Primary microcephaly type 2, and facilitated genetic counseling for the family.
Female ; Humans ; Cell Cycle Proteins ; Heterozygote ; Microcephaly/genetics* ; Mutation ; Nerve Tissue Proteins/genetics* ; Pedigree

Objective:To analyze the characteristics of transabdominal bowel ultrasound (TBUS) in immune checkpoint inhibitor-related colitis (IRC) and their correlation with endoscopic manifestations.Methods:A cross-sectional study was conducted. Clinical data from 10 patients with IRC treated at Peking Union Medical College Hospital from January 2022 to January 2024 were collected. The ulcerative colitis endoscopic index of severity (UCEIS) and Limberg classification were used to assess the severity of colonoscopy and TBUS examinations, respectively. Kendall's tau-b method was applied for correlation analysis between UCEIS scores and Limberg classification.Results:All the 10 patients were male with a median age of 65 years (59-74 years). The majority had lung cancer (8 patients) and all were in advanced stages, with 6 patients in stage Ⅲ and 4 in stage Ⅳ. They all received anti-programmed death 1 (PD-1) /anti-programmed death ligand 1 (PD-L1) combined with chemotherapy, among whom 2 patients were combined with anti-angiogenic drug treatment. The median time from the first immunotherapy to the onset of IRC was 1.50 (0.25-12.00) months; the median time from IRC treatment to clinical symptom relief to G1 was 2.45 (0.50-8.00) weeks. Nine patients were in the active phase, mainly G3 (8 patients) ; 1 was in the remission phase after treatment. TBUS showed that among the 9 active IRC patients, the entire colon was mainly involved (7 patients), with combined small intestine involvement (3 patients) ; the main manifestations were thickening of the bowel wall, with the thickest bowel wall being 7.0 (5.0-8.0) mm, mainly located in the sigmoid colon (3 patients) and descending colon (3 patients) ; increased bowel wall blood flow signals (Limberg classification 2-4) occurred in 7 patients; 3 active patients had perienteric fat wrapping, and 2 had blurred bowel wall stratification. The Kendall's tau-b correlation coefficient r between the entire colon UCEIS scores and Limberg classification was 0.891 ( P = 0.003), and the Kendall's tau-b correlation coefficient r between the colon segment UCEIS scores and Limberg classification was 0.690 ( P < 0.001) . Conclusion:During the active phase, the left colon of IRC is more severe in TBUS, which mainly manifests as the thickening bowel wall and increased blood flow signals, and the TBUS has good correlation with colonoscopy evaluation.

Objective:To analyze the characteristics of transabdominal bowel ultrasound (TBUS) in immune checkpoint inhibitor-related colitis (IRC) and their correlation with endoscopic manifestations.Methods:A cross-sectional study was conducted. Clinical data from 10 patients with IRC treated at Peking Union Medical College Hospital from January 2022 to January 2024 were collected. The ulcerative colitis endoscopic index of severity (UCEIS) and Limberg classification were used to assess the severity of colonoscopy and TBUS examinations, respectively. Kendall's tau-b method was applied for correlation analysis between UCEIS scores and Limberg classification.Results:All the 10 patients were male with a median age of 65 years (59-74 years). The majority had lung cancer (8 patients) and all were in advanced stages, with 6 patients in stage Ⅲ and 4 in stage Ⅳ. They all received anti-programmed death 1 (PD-1) /anti-programmed death ligand 1 (PD-L1) combined with chemotherapy, among whom 2 patients were combined with anti-angiogenic drug treatment. The median time from the first immunotherapy to the onset of IRC was 1.50 (0.25-12.00) months; the median time from IRC treatment to clinical symptom relief to G1 was 2.45 (0.50-8.00) weeks. Nine patients were in the active phase, mainly G3 (8 patients) ; 1 was in the remission phase after treatment. TBUS showed that among the 9 active IRC patients, the entire colon was mainly involved (7 patients), with combined small intestine involvement (3 patients) ; the main manifestations were thickening of the bowel wall, with the thickest bowel wall being 7.0 (5.0-8.0) mm, mainly located in the sigmoid colon (3 patients) and descending colon (3 patients) ; increased bowel wall blood flow signals (Limberg classification 2-4) occurred in 7 patients; 3 active patients had perienteric fat wrapping, and 2 had blurred bowel wall stratification. The Kendall's tau-b correlation coefficient r between the entire colon UCEIS scores and Limberg classification was 0.891 ( P = 0.003), and the Kendall's tau-b correlation coefficient r between the colon segment UCEIS scores and Limberg classification was 0.690 ( P < 0.001) . Conclusion:During the active phase, the left colon of IRC is more severe in TBUS, which mainly manifests as the thickening bowel wall and increased blood flow signals, and the TBUS has good correlation with colonoscopy evaluation.

Objective:To explore the genetic basis for a girl with primary microcephaly and growth retardation.Methods:A girl who was admitted to Guangdong Maternal and Child Health Care Hospital in was selected as the study subject. Peripheral blood samples were collected from the child and her parents. Trio whole exome sequencing was carried out, and candidate variants were verified by Sanger sequencing and bioinformatic analysis. This study was approved by the Medical Ethnics Committee of Guangdong Maternal and Child Health Care Hospital (Ethics No. 202201278).Results:DNA sequencing revealed that the child has harbored compound heterozygous variants of the WDR62 gene, including a frameshifting c. 2963delC (p.Pro988Argfs*80) variant in exon 24 which was inherited from the unaffected father, and a nonsense c.3163G>T (p.Glu1055*) variant in exon 26, which was inherited from her unaffected mother. Both variants were predicted to affect the reading frame of the WDR62 gene. Conclusion:Based on the clinical manifestations, results of genetic testing and pedigree analysis, the compound heterozygous variants were predicted to underlay the pathogenesis of microcephaly and growth retardation in this child. Above discovery has expanded the mutational spectrum for WDR62-associated Primary microcephaly type 2, and facilitated genetic counseling for the family.

Objective To observe clinical efficacy and safety of less invasive surfactant administration(LISA)in treatment of respiratory distress syndrome(RDS)in extremely premature infants.Methods A total of 65 cases premature infants diagnosed with RDS admitted to neonatal intensive care unit of Xiaogan Central Hospital from January 2021 to December 2023,with gestational age of 28+0～31+6 weeks.They were divided into LISA group(n=33)and intubation administration of surfactant extubation(InSurE)group(n=32)using a random number table method.The incidence of adverse events,blood gas analysis before and after administration,pulse oxygen saturation(SpO2),changes in blood pressure,clinical efficacy,complications,and outcomes were compared between two groups.Results There was no statistically significant difference in the incidence of drug reflux,bradycardia,apnea,or SpO2＜80％between two groups of operations(P＞0.05).During the operation,SpO2 of LISA group was lower than that of InSurE group,and blood pressure monitoring at the 2nd and 4th minutes were lower than those of InSurE group at the corresponding time points,with statistically significant differences(P＜0.05).After 1 hour of treatment,arterial partial pressure of oxygen in LISA group was higher than that in InSurE group,and arterial partial pressure of carbon dioxide was lower than that in InSurE group,with statistically significant differences(P＜0.05).The mechanical ventilation ratio and oxygen therapy time within 72 hours in LISA group were lower than those in InSurE group,and the differences were statistically significant(P＜0.05).There was no statistically significant difference in reuse rate of pulmonary surfactant(PS),and hospitalization time between two groups(P＞0.05).The incidence of grade 3-4 periventricular intraventricular hemorrhage,P-IVH in LISA group was lower than that in InSurE group,and the difference was statistically significant(P＜0.05).There was no statistically significant difference in the incidence of other complications between two groups(P＞0.05).Conclusion Less invasive PS treatment for extremely premature infants with RDS can reduce the incidence of mechanical ventilation,shorten oxygen therapy time,and reduce the occurrence of severe P-IVH.

Objective To observe clinical efficacy and safety of less invasive surfactant administration(LISA)in treatment of respiratory distress syndrome(RDS)in extremely premature infants.Methods A total of 65 cases premature infants diagnosed with RDS admitted to neonatal intensive care unit of Xiaogan Central Hospital from January 2021 to December 2023,with gestational age of 28+0～31+6 weeks.They were divided into LISA group(n=33)and intubation administration of surfactant extubation(InSurE)group(n=32)using a random number table method.The incidence of adverse events,blood gas analysis before and after administration,pulse oxygen saturation(SpO2),changes in blood pressure,clinical efficacy,complications,and outcomes were compared between two groups.Results There was no statistically significant difference in the incidence of drug reflux,bradycardia,apnea,or SpO2＜80％between two groups of operations(P＞0.05).During the operation,SpO2 of LISA group was lower than that of InSurE group,and blood pressure monitoring at the 2nd and 4th minutes were lower than those of InSurE group at the corresponding time points,with statistically significant differences(P＜0.05).After 1 hour of treatment,arterial partial pressure of oxygen in LISA group was higher than that in InSurE group,and arterial partial pressure of carbon dioxide was lower than that in InSurE group,with statistically significant differences(P＜0.05).The mechanical ventilation ratio and oxygen therapy time within 72 hours in LISA group were lower than those in InSurE group,and the differences were statistically significant(P＜0.05).There was no statistically significant difference in reuse rate of pulmonary surfactant(PS),and hospitalization time between two groups(P＞0.05).The incidence of grade 3-4 periventricular intraventricular hemorrhage,P-IVH in LISA group was lower than that in InSurE group,and the difference was statistically significant(P＜0.05).There was no statistically significant difference in the incidence of other complications between two groups(P＞0.05).Conclusion Less invasive PS treatment for extremely premature infants with RDS can reduce the incidence of mechanical ventilation,shorten oxygen therapy time,and reduce the occurrence of severe P-IVH.

Hyperglycemia is a common complication of critical patients. Currently, clinical assessment of the changes in the blood glucose of critical patients is mainly based on the intermittent monitoring of peripheral blood glucose at a certain time point. This method cannot get the true blood glucose fluctuation, and it is more difficult to find asymptomatic hyperglycemia and hypoglycemia, so the guiding value of blood glucose control is limited. Arterial blood is the most accurate sample of blood glucose monitoring, so it is urgent to ensure the accuracy of arterial blood sample. A continuous arterial blood glucose monitoring equipment was independently developed by general surgical intensive care unit (ICU) of the First Affiliated Hospital of Nanjing Medical University, and National Utility Model Patent of China was obtained. It could greatly improve the efficiency of medical staff, and provide accurate and dynamic statistic data that would be an important basis for doctors' clinical decision-making. The continuous arterial blood glucose monitoring equipment was mainly composed of arterial pressure measuring monitor, program-controlled dynamic blood glucose meter, wire, electric switch, integrated collecting syringe, electric clip, rotary electric bracket, and blood glucose test strips, etc., which could be continuously and dynamically monitor patient blood glucose levels and perform various additional value-added functions such as automatic recording and alarming.

Objective: To investigate the influence of inhibiting expression of polyamine-modulated factor (PMF-1) on the antitumor effect of glucocorticoid dexamethasone (DEX) in human cervical cancer Caski cells. Methods: siRNAs which target human PMF-1 gene were designed and synthesized, and their effect on the expression of PMF-1 in Caski cells was evaluated by Western blotting. The PMF-1 down-regulated and control Caski cells were treated with DEX, and then the affect of PMF-1 down regulation on the sensitivity of the tumor cells to DEX was analyzed. MTT method was used to detect cell proliferation, flow cytometry was used to analyze cell cycle, Western blotting method was used to evaluate expression level of glucocorticoids receptor (GR), and HPLC was used to analyze intracellular polyamine content. Results: The transient transfection of Caski cells with siRNAwhich targets PMF-1 gene can significantly reduce the expression level of PMF-1 protein. Compared with the control cells, treating PMF-1 down-regulated Caski cells with DEX can more effectively inhibit cell proliferation（P<0.01), up regulate GR expression, arrest cell cycle at G2 stage（P<0.01), and also significantly reduce intracellular polyamine level（P<0.01). Conclusion：Inhibiting PMF-1 expression can enhance antitumor pharmacological activity of DEX against human cervical cancer cells, and the underlying mechanism may be related with enhanced cell cycle inhibition and decreased intracellular polyamine level.

Objective To explore the application of timing theory in home care of patients with acute coronary syndrome.Methods A total of 90 patients with acute coronary syndrome admitted to the Second People's Hospital of Wuxi in Jiangsu Province from February 2016 to February 2017 were selected, and randomly divided into control group and study group, with 45 cases each. The control group was given routine nursing intervention, while the study group was given home-based care intervention based on timing theory. The quality of life and negative emotions were compared between the two groups, using Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS), Seattle Angina Questionnaire (SAQ) and Athens Insomnia Scale (AIS).Results The scores of SAS and SDS of the control group after intervention were (61.7±2.0) and (52.4±1.3) respectively, which were both higher than those of the observation group, and the differences were statistically significant (t=27.295,23.129;P<0.001). After 3 months of nursing intervention, the quality of life of patients in both groups has been improved. SAQ scores in different division were as follow: limitation of physical activity (64.1±10.9), angina attack (89.7±12.0), stable angina pectoris (91.5±7.2), disease cognition (88.5±9.2) and satisfaction of treatment (91.6±10.8). Those scores were all higher than those of the control group. The differences were statistically significant (P<0.05). The score of sleeping time of the study group was (1.8±0.6), and that of the control group was (1.5±0.5). The difference in the sleeping quality between the two groups was statistically significant (t=2.577,P<0.05).Conclusions Home care intervention based on timing theory for patients with acute coronary syndrome can improve the quality of life and treatment effect, reduce anxiety and depression, and is worth popularizing and applying.