AIM:To investigate the interaction mechanisms of estrogen receptor β(ERβ),nuclear factor-κB(NF-κB)and activator protein-1(AP-1)in colorectal cancer by analyzing the transcriptome data after tumor necrosis fac-tor α(TNF-α)treatment and combining it with NF-κB/p65 and ERβ cistrome data in colon cancer cell lines HT29 and SW480.METHODS:The TNF-α transcriptome was integrated with p65 and ERβ cistrome data.Protein interaction net-works of TNF-α,NF-κB/p65 and ERβ were constructed in colon cancer cell lines HT29 and SW480 using R.RE-SULTS:TNF-α regulated genes through p65 DNA binding,which were mainly enriched in the NF-κB and mitogen-acti-vated protein kinase(MAPK)pathways.Components of the NF-κB/p65 and MAPK pathways had potential interactions with AP-1 family proteins.ERβ overexpression did not significantly affect TNF-α-mediated gene regulation but may regu-late AP-1 activity through the MAPK and phosphatidylinositol 3-kinase(PI3K)/Akt pathways.Furthermore,ERβ de-creased p65 DNA binding sites in HT29 but increased p65 binding sites in SW480,suggesting cell line-specific regulation of NF-κB by ERβ.CONCLUSION:In colorectal cancer,NF-κB,ERβ and AP-1 have potential interactions:TNF-α can regulate AP-1 through NF-κB,while ERβ overexpression can alter NF-κB-mediated regulation,and the influence of ERβ on NF-κB may be gender-related.

ObjectiveTo explore the clinical features and causative genes of short stature children with unknown etiology， providing evidence for precise clinical diagnosis and treatment. MethodsThe study recruited children with suspected but undiagnosed short stature from the pediatric endocrinology department in our hospital between January 2018 and August 2022. A retrospective analysis was performed on the clinical manifestations， laboratory test and whole exome sequencing （WES） results. Causative genes were classified and analyzed according to different pathogenic mechanisms. ResultsA total of 48 children （30 boys and 18 girls） were enrolled， aged 7.73 ± 3.97 years， with a height standard deviation score （ HtSDS） of -3.63 ± 1.67. Of the patients， 33 （68.8%） suffered from facial anomalies， 31 （64.6%） from skeletal abnormalities， 26 ［54.2%， 61.5% of whom born small for gestational age （SGA）］ from perinatal abnormalities， 24 ［50.0%， 87.5% of whom with growth hormone （GH） peak concentration below normal］ from endocrine disorders and 21（43.8%） had a family history of short stature. Laboratory tests showed that GH peak concentration following stimulation test was （9.72 ± 7.25） ng/mL， IGF-1 standard deviation score was -0.82 ± 1.42， the difference between bone age and chronological age was -0.93 ± 1.39 years. Of the 25 cases with mutant genes found by WES， 14 （56.0%） had pathogenic mutation， 6 （24.0%） likely pathogenic mutation， and 5 （20.0%） mutation of uncertain significance. Pathogenic and likely pathogenic variants were identified in 14 genes， including 10 affecting intracellular signaling pathways （PTPN11， RAF1， RIT1， ARID1B， ANKRD11， CSNK2A1， SRCAP， CUL7， SMAD4 and FAM111A） and 4 affecting extracellular matrix （ECM） components or functions （ACAN， FBN1， COL10A1 and COMP）. ConclusionsA rare monogenic disease should be considered as the possible etiology for children with severe short stature accompanied by facial anomalies， disproportionate body types， skeletal abnormalities， SGA， GH peak concentration below normal and a family history of short stature. WES played an important role in identifying the monogenic causes of short stature. This study indicated that affecting growth plate cartilage formation through intracellular signaling pathways and ECM components or functions was the main mechanism of causative genes leading to severe short stature in children. Further research may help discover and study new pathogenic variants and gene functions.

Objective To analyze the effect of preoperative nutritional status on the intraoperative un-expected hypothermia in elderly patients with laparoscopic gastrointestinal tumor radical operation and its risk factors.Methods The clinical case data in 282 elderly patients with laparoscopic gastrointestinal tumor radical surgery in the Fourth Affiliated Hospital of Nanjing Medical University from February 2021 to December 2023 were analyzed retrospectively.The mini nutritional assessment short form(MNA-SF)was adopted to e-valuate the preoperative nutritional status of the patients.The intraoperative unexpected hypothermia occur-rence were statistically analyzed.The univariate and multivariate logistic regression was used to analyze the in-fluencing factors.Results Among 282 patients,104 cases(36.88％)had unexpected hypothermia during op-eration.The incidence rate of intraoperative unexpected hypothermia in the patients with complicating malnu-trition or malnutritional risk was significantly higher than that in the patients with normal nutritional status(P＜0.05).The multivariate logistic regression analysis showed that the age ≥70 years old,body mass index(BMI)＜18.5 kg/m2,progressive weight loss appearance before surgery,preoperative MNA-SF score＜12 points,CO2 pneumoperitoneum time＞4 h and complicating hypoalbuminemia were the independent risk fac-tors for intraoperative unexpected hypothermia occurrence in the elderly patients with laparoscopic gastroin-testinal tumor radical operation(P＜0.05),while the use of heating device for initiatively maintaining tem-perature during surgery was the protective factor for avoiding intraoperative unexpected hypothermia occur-rence(P＜0.05).Conclusion The elderly patients with poor nutritional status undergoing laparoscopic gas-trointestinal tumor radical surgery are more likely to develop unexpected hypothermia.There are many influ-encing factors,so close attention should be paid to.

Hematopoietic stem cell transplantation, applied in the treatment of blood tumors and non-tumor diseases in children, has improved the survival rate and life span of the patients.However, with the extension of survival time, various endocrine complications will appear in these survivors of childhood cancer and reduce the quality of life.Complications related to hematopoietic stem cell transplantation in children are caused by primary disease and/ or treatments before and after transplantation, including abnormal glucose and lipid metabolism, hypogonadism, short stature and so on.Regular endocrine evaluations can help physicians find the endocrine dysfunctions of children with hematopoietic stem cell transplantation as soon as possible.This review summarizes the common endocrine complications and follow-up evaluation of children with thalassemia and acute leukemia after hematopoietic stem cell transplantation, in order to provide reference for the monitoring of endocrine function in children after hematopoietic stem cell transplantation.

As one of the common endocrine diseases in children, the incidence of type 1 diabetes mellitus(T1DM)is increasing year by year.T1DM is an autoimmune disease.It is generally believed that the pathogenesis of T1DM is that the immune disorder of genetically susceptible individuals under the action of environmental factors causes immune damage, leading to islet inflammation and the production of autoantibodies, and the destruction of β cells of the islet, leading to insufficient insulin secretion to absolute deficiency.Although there is no effective radical cure for T1DM at present, more and more research on stem cell therapy has been conducted.Umbilical cord blood, as an important source of stem cells, is expected to make the radical cure of T1DM possible in the future.In this paper, the mechanism of immune injury in T1DM and the progress of umbilical cord blood stem cell therapy are reviewed.

OBJECTIVE: To analyze pathogenic variant of CSNK2A1 gene in a boy with Okur-Chung neurodevelopmental syndrome (OCNS). METHODS: The 8-year-old boy presented with growth retardation, intellectual disability and spells of breath holding. With genomic DNA extracted from peripheral blood samples of the patient and his parents, whole exome sequencing was carried out. Putative pathogenic variants were verified with Sanger sequencing. The nature and impact of detected variants were predicted through bioinformatic analysis. RESULTS: A novel de novo missense variant c.149A>G (p.Tyr50Cys) of the CSNK2A1 gene was identified, which was unreported previously. The variant was predicted to be pathogenic by PolyPhen-2, Mutation Taster and SIFT software. Based on a HomoloGene system, 50 loci within the CK2alpha protein are highly conserved. The change of amino acid (Cys) at position 50 has destroyed the ATP binding loop domain, causing serious damage to its function. As predicted by a Swiss PDB viewer, the variant can significantly alter the spatial structure of CK2alpha, resulting in loss of protein function. CONCLUSION The patient's condition may be attributed to the novel de novo missense variant c.149A>G (p.Tyr50Cys) of the CSNK2A1 gene.

OBJECTIVE: To detect pathogenic variant in a juvenile with severe type Cornelia de Lange syndrome (CdLS). METHODS: A 12-year-old female presented with comprehensive developmental retardation and deformity of lower limbs. Genomic DNA was extracted from peripheral blood sample of the patient. Whole exome sequencing was performed to identify pathogenic variants. Putative variant was verified by Sanger sequencing. The impact of variants was predicted and validated by bioinformatic analysis. RESULTS: A de novo missense variant, c.1507A>G (p. Lys503Glu), was found in the NIPBL gene of the proband. The variant was unreported previously and predicted to be pathogenic by PolyPhen-2, MutationTaster and SIFT. Using HomoloGene system, the 503 loci in the NIPBL protein are highly conserved. The change of amino acid (Glu), locating in 503 locus, was found to cause the Neuromodulin_N superfamily domain destroyed, resulting in severe damage to the function of NIPBL protein. CONCLUSION The de novo missense variant c.1507A>G (p. Lys503Glu) of the NIPBL gene probably underlies the disease in this patient.
Cell Cycle Proteins ; genetics ; Child ; De Lange Syndrome ; genetics ; Developmental Disabilities ; genetics ; Female ; Humans ; Mutation, Missense ; Phenotype

Objective:To explore effects of four postures nursing on oxygen partial pressure, pain and comfort degree of affected limbs in patients with lower extremity atherosclerotic occlusive disease (LEAOD) .Methods:A total of 357 patients with LEAOD who were admitted in Henan Provincial People's Hospital of Henan University from March 2018 to February 2019 were selected as the research objects by convenient sampling. All patients were respectively treated with four postural nursing methods, including supine position, sitting position, lower limb ptosis position and lower limb elevation position. The differences in oxygen partial pressure, pain value and comfort level of patients in different posture nursing states were compared.Results:Among 357 patients, 106 patients had no pain. Compared with the other three positions, the oxygen partial pressure level of the lower limb elevated position was the lowest, and the pain score and comfort score were the highest. The differences among the groups were statistically significant ( P<0.01) . The oxygen partial pressure level of lower limb ptosis position was the highest, and the pain score and comfort score were significantly lower than the other three positions. The differences were all statistically significant ( P<0.01) . Among the four postures, the changes of oxygen partial pressure in sitting position and lower limb ptosis position were the most significant, and the differences were statistically significant ( Z=145.433, P<0.01) . Conclusions:In the nursing of supine position, sitting position, lower limb ptosis position and lower extremity elevation position, lower extremity ptosis position has a more obvious improvement effect on oxygen partial pressure, comfort degree and pain value of patients with LEAOD compared with the other three positions. However, long-term prolapse of the affected limbs can easily cause blood stasis and discomfort symptoms. Therefore, it is necessary to set a reasonable nursing method and time for the affected limbs according to the condition of patients.

OBJECTIVE: To analyze the current status of diagnosis and management of acute appendicitis (AA) in China. METHODS: Questionnaire survey was used to retrospectively collect data of hospitalized patients with AA from 43 medical centers nationwide in 2017 (Sort by number of cases provided: Jinling Hospital of Medical School of Nanjing University, The First Affiliated Hospital of Xinjiang Medical University, Lu'an People's Hospital, Tengzhou Central People's Hospital, Dalian Central Hospital, The Affiliated Hospital of Xuzhou Medical University, Dongying People's Hospital, Jinjiang Hospital of Traditional Chinese Medicine, Huangshan Shoukang Hospital, Xuyi People's Hospital, Nanjing Jiangbei People's Hospital, Lanzhou 940th Hospital of PLA, Heze Municipal Hospital, The First College of Clinical Medical Science of China Three Gorges University, Affiliated Jiujiang Hospital of Nanchang University, The Second People's Hospital of Hefei, Affiliated Central Hospital of Shandong Zaozhuang Mining Group, The Third People's Hospital of Kunshan City, Xuzhou First People's Hospital, The 81st Group Army Hospital of PLA, Linyi Central Hospital, The General Hospital of Huainan Eastern Hospital Group, The 908th Hospital of PLA, Liyang People's Hospital, The 901th Hospital of Joint Logistic Support Force, The Third Affiliated Hospital of Chongqing Medical University, The Fourth Hospital of Jilin University, Harbin Acheng District People's Hospital, The First Affiliated Hospital of Zhengzhou University, Nanjing Luhe People's Hospital, Taixing Municipal People's Hospital, Baotou Central Hospital, The Affiliated Hospital of Nantong University, Linyi People's Hospital, The 72st Group Army Hospital of PLA, Zaozhuang Municipal Hospital, People's Hospital of Dayu County, Taixing City Hospital of Traditional Chinese Medicine, Suzhou Municipal Hospital, Beijing Guang'anmen Hospital, Langxi County Hospital of Traditional Chinese Medicine, Nanyang Central Hospital, The Affiliated People's Hospital of Inner Mongolia Medical University).The diagnosis and management of AA were analyzed through unified summary. Different centers collected and summarized their data in 2017 and sent back the questionnaires for summary. RESULTS: A total of 8 766 AA patients were enrolled from 43 medical centers, including 4 711 males (53.7%) with median age of 39 years and 958 (10.9%) patients over 65 years old. Of 8 776 patients, 5 677 cases (64.6%) received one or more imaging examinations, and the other 3 099 (35.4%) did not receive any imaging examination. A total of 1 858 (21.2%) cases received medical treatment, mainly a combination of nitroimidazoles (1 107 cases, 59.8%) doublet regimen, followed by a single-agent regimen of non-nitroimidazoles (451 cases, 24.4%), a nitroimidazole-free doublet regimen (134 cases, 7.2%), a triple regimen of combined nitroimidazoles (116 cases, 6.3%), nitroimidazole alone (39 cases, 2.1%) and nitroimidazole-free triple regimen (3 cases, 0.2%). Of the 6 908 patients (78.8%) who underwent surgery, 4 319 (62.5%) underwent laparoscopic appendectomy and 2589 (37.5%) underwent open surgery. Ratio of laparotomy was higher in those patients under 16 years old (392 cases) or over 65 years old (258 cases) [15.1%(392/2 589) and 10.0%(258/2 589), respectively, compared with 8.5%(367/4 316) and 8.0%(347/4 316) in the same age group for laparoscopic surgery, χ²=91.415, P<0.001; χ²=15.915,P<0.001]. Patients with complicated appendicitis had higher ratio of undergoing open surgery as compared to those undergoing laparoscopic surgery [26.7%(692/2 589) vs. 15.6%(672/4 316), χ²=125.726, P<0.001].The cure rates of laparoscopic and open surgery were 100.0% and 99.8%(2 585/2 589) respectively without significant difference (P=0.206). Postoperative complication rates were 4.5%(121/2 589) and 4.7%(196/4 316) respectively, and the difference was not statistically significant (χ²=0.065, P=0.799). The incidence of surgical site infection was lower (0.6% vs. 1.7%, χ²=17.315, P<0.001), and hospital stay was shorter [6(4-7) days vs. 6(5-8) days, U=4 384 348.0, P<0.001] in the laparoscopic surgery group, while hospitalization cost was higher (median 12 527 yuan vs. 9 342 yuan, U=2 586 809.0, P<0.001). CONCLUSIONS The diagnosis of acute appendicitis is still clinically based, supplemented by imaging examination. Appendectomy is still the most effective treatment at present. Laparoscopic appendectomy has become the main treatment strategy, but anti-infective drugs are also very effective.
Acute Disease ; Adolescent ; Adult ; Aged ; Anti-Bacterial Agents ; therapeutic use ; Appendectomy ; Appendicitis ; diagnosis ; therapy ; China ; Female ; Health Care Surveys ; Humans ; Laparoscopy ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult

Objective To analyze the clinical manifestations and gene mutations of rare causes of primary adrenal insufficiency (PAI) in childhood.Methods The clinical features,laboratory tests and gene mutation of 13 patients with PAI in our hospital from September 2010 to August 2017 were analyzed retrospectively.Patients with congenital adrenal hyperplasia,X-linked adrenoleukodystrophy with neurological onset or a clear family history,and autoimmune adrenal insufficiency were excluded.Results The median age of 13 cases (12 males,1 female) was 3 years and 10 months.Medical history or clinical manifestations on the first visit included hyperpigmentation,electrolyte imbalance/salt-wasting crisis,gastrointestinal symptoms,and fatigue,etc.All developments of external genitalia were normal.All cases presented with decreased serum cortisol and increased ACTH levels.Some of the cases showed decreased aldosterone level and plasma renin activity,while 17α-hydroxyprogesterone,testosterone,and androstenedione were in the normal range.Part of cases revealed delayed bone age and adrenal atrophy.Three gene mutations were detected in 13 patients,including NR0B 1 gene (9/13),ABCD 1 gene (3/13),and CYP 11A 1 gene (1/13).NR0B1,and ABCD1 gene mutations were pathogenic mutations,consistent with clinical characteristics.CYP11A1 gene mutation was heterozygote,which cannot fully explain the clinical features.Conclusion PAI in childhood presents common clinical manifestations of adrenal insufficiency,e.g.hyperpigmentation and electrolyte imbalance/sah-wasting crisis,but without specificity.Gene mutational analysis is necessary for precise diagnosis and prognosis estimation.NR0B1 and ABCD1 gene mutations were common in childhood with rare causes of PAI.