Objective:To explore the clinical phenotype and genetic characteristics of a pediatric child with RELA-associated autoinflammatory disease (RAID) caused by a RELA gene variant, and to review the reported cases in the literature. Methods:A pediatric child with RAID who presented with recurrent fever, vomiting, and oral ulcers for over 5 years was selected as the study subject. The child visited the Women and Children′s Hospital of Ningbo University in August 2023. Clinical data were collected, and peripheral blood samples were obtained from the child and his family members for whole exome sequencing (WES) and Sanger sequencing to identify and validate candidate variants. The pathogenicity of the variants was analyzed accordingly. Using the keywords " RELA" " NF-κB" " autoinflammatory disease" " tofacitinib" " sulfasalazine" a literature search was conducted in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed from January 1, 2000 to December 13, 2023. This study was approved by the Medical Ethics Committee of the Women and Children′s Hospital of Ningbo University (Ethics No. EC2020-048).Results:① The child primarily manifested with recurrent fever, vomiting, and oral ulcers. ② WES identified a heterozygous nonsense variant c. 985C>T (p.Arg329Ter) in the RELA gene, which was inherited from the mother. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants and the Clinical Genome Resource (ClinGen) recommendations for PVS1, this variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP4). ③ Despite treatment with adalimumab and tocilizumab, the child′s symptoms persisted. Switching to tofacitinib improved oral ulcers, but fever and vomiting continued. The addition of thalidomide significantly alleviated fever and vomiting, and the patient′s growth and development remained normal. ④ A literature review identified 14 unrelated RAID families, including a total of 35 cases (including the present child). The main clinical features were recurrent oral ulcers, genital ulcers, skin problems, fever, diarrhea, abdominal pain, and vomiting. Conclusion:The nonsense variant c. 985C>T (p.Arg329Ter) in the RELA gene is likely the genetic cause of the child′s recurrent fever, vomiting, and oral ulcers. WES is valuable for timely diagnosis of RAID and provides a basis for clinical treatment strategies.

OBJECTIVE: To explore the clinical phenotype and genetic characteristics of a pediatric child with RELA-associated autoinflammatory disease (RAID) caused by a RELA gene variant, and to review the reported cases in the literature. METHODS: A pediatric child with RAID who presented with recurrent fever, vomiting, and oral ulcers for over 5 years was selected as the study subject. The child visited the Women and Children's Hospital of Ningbo University in August 2023. Clinical data were collected, and peripheral blood samples were obtained from the child and his family members for whole-exome sequencing (WES) and Sanger sequencing to identify and validate candidate variants. The pathogenicity of the variants was analyzed accordingly. Using the keywords "RELA" "NF-κB" "autoinflammatory disease" "tofacitinib" "sulfasalazine" a literature search was conducted in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed from January 1, 2000 to December 13, 2023. This study was approved by the Medical Ethics Committee of the Women and Children's Hospital of Ningbo University (Ethics No. EC2020-048). RESULTS: The child primarily manifested with recurrent fever, vomiting, and oral ulcers. WES identified a heterozygous nonsense variant c.985C>T (p.Arg329Ter) in the RELA gene, which was inherited from the mother. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants and the Clinical Genome Resource (ClinGen) recommendations for PVS1, this variant was classified as pathogenic (PVS1+PM2_Supporting+PP4). Despite treatment with adalimumab and tocilizumab, the child's symptoms persisted. Switching to tofacitinib improved oral ulcers, but fever and vomiting continued. The addition of thalidomide significantly alleviated fever and vomiting, and the patient's growth and development remained normal. A literature review identified 14 unrelated RAID families, including a total of 35 cases (including the present child). The main clinical features were recurrent oral ulcers, genital ulcers, skin problems, fever, diarrhea, abdominal pain, and vomiting. CONCLUSION The nonsense variant c.985C>T (p.Arg329Ter) in the RELA gene is likely the genetic cause of the child's recurrent fever, vomiting, and oral ulcers. WES is valuable for timely diagnosis of RAID and provides a basis for clinical treatment strategies.
Humans ; Male ; Transcription Factor RelA/genetics* ; Female ; Hereditary Autoinflammatory Diseases/genetics* ; Child ; Pedigree ; Exome Sequencing

Objective:To explore the clinical phenotype and genetic characteristics of a pediatric child with RELA-associated autoinflammatory disease (RAID) caused by a RELA gene variant, and to review the reported cases in the literature. Methods:A pediatric child with RAID who presented with recurrent fever, vomiting, and oral ulcers for over 5 years was selected as the study subject. The child visited the Women and Children′s Hospital of Ningbo University in August 2023. Clinical data were collected, and peripheral blood samples were obtained from the child and his family members for whole exome sequencing (WES) and Sanger sequencing to identify and validate candidate variants. The pathogenicity of the variants was analyzed accordingly. Using the keywords " RELA" " NF-κB" " autoinflammatory disease" " tofacitinib" " sulfasalazine" a literature search was conducted in the China National Knowledge Infrastructure, Wanfang Data Knowledge Service Platform, and PubMed from January 1, 2000 to December 13, 2023. This study was approved by the Medical Ethics Committee of the Women and Children′s Hospital of Ningbo University (Ethics No. EC2020-048).Results:① The child primarily manifested with recurrent fever, vomiting, and oral ulcers. ② WES identified a heterozygous nonsense variant c. 985C>T (p.Arg329Ter) in the RELA gene, which was inherited from the mother. According to the American College of Medical Genetics and Genomics (ACMG) Standards and Guidelines for the Interpretation of Sequence Variants and the Clinical Genome Resource (ClinGen) recommendations for PVS1, this variant was classified as pathogenic (PVS1+ PM2_Supporting+ PP4). ③ Despite treatment with adalimumab and tocilizumab, the child′s symptoms persisted. Switching to tofacitinib improved oral ulcers, but fever and vomiting continued. The addition of thalidomide significantly alleviated fever and vomiting, and the patient′s growth and development remained normal. ④ A literature review identified 14 unrelated RAID families, including a total of 35 cases (including the present child). The main clinical features were recurrent oral ulcers, genital ulcers, skin problems, fever, diarrhea, abdominal pain, and vomiting. Conclusion:The nonsense variant c. 985C>T (p.Arg329Ter) in the RELA gene is likely the genetic cause of the child′s recurrent fever, vomiting, and oral ulcers. WES is valuable for timely diagnosis of RAID and provides a basis for clinical treatment strategies.

Objective:To discuss the effect of human umbilical cord mesenchymal stem cells culture supernatant(hUCMSCs-Sup)on the proliferation,apoptosis,and endometrium receptivity of the human endometrial stromal cells(hEndoSCs)treated with mifepristone(Ms),and to clarify the possible mechanism.Methods:The hEndoSCs were cultured in vitro and divided into control group and 40,60,80,and 100 μmol·L-1 Ms groups.The survival rates of the cells in various groups were detected by MTT assay.The hEndoSCs were divided into control group,40 μmol·L-1 Ms group,and 60 μmol·L-1 Ms group.The apoptotic rates of the cells in various groups were detected by flow cytometry;the expression levels of apoptosis-related protein B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)proteins in the cells in various groups were detected by Western blotting method,and the ratio of Bcl-2/Bax was calculated.After treated with hUCMSCs-Sup,the hEndoSCs were divided into control group,Ms group,Ms+hUCMSCs-Sup group,and Ms+hUCMSCs-Sup+3-methyladenine(3-MA)group.The survival rates of the cells in various groups were detected by MTT assay;the apoptotic rates of the cells in various groups were detected by flow cytometry;the expression levels of microtubule-associated protein 1 light chain 3B-Ⅱ(LC3B-Ⅱ)and microtubule-associated protein 1 light chain 3B-I(LC3B-Ⅰ)proteins in the cells in various groups were detected by Western blotting method,and the ratio of LC3B-Ⅱ/LC3B-Ⅰwas calculated;the expression levels of endometrium receptivity marker molecules mRNA in the cells in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.Results:Compared with control group,the survival rates of the cells in 40,60,80,and 100 μmol·L-1 Ms groups were significantly decreased(P<0.05)in a time-dependent and dose-dependent manner.Compared with control group,the apoptotic rates of the cells in 40 and 60 μmol·L-1 Ms groups were significantly increased(P<0.05),and the ratios of Bcl-2/Bax were significantly decreased(P<0.05).After treated with hUCMSCs-Sup,compared with control group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms group were significantly decreased(P<0.05),the apoptotic rate was significantly increased(P<0.05),and the expression levels of homeobox A10(HOXA10),leukemia inhibitory factor(LIF),and integrin subunit beta 3(ITGB3)mRNA in the cells were significantly decreased(P<0.05);compared with Ms group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰin the cells in Ms+hUCMSCs-Sup group were significantly increased(P<0.05),the apoptotic rate was significantly decreased(P<0.05),and the expression levels of HOXA10,LIF,and ITGB3 mRNA in the cells were significantly increased(P<0.05);compared with Ms+hUCMSCs-Sup group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms+hUCMSCs-Sup+3-MA group were significantly decreased(P<0.05).Conclusion:hUCMSCs-Sup can increase the survival rate and decrease the apoptotic rate of the hEndoSCs after treated with Ms,and increase the endometrium receptivity,and its mechanism may be associated with the activation of autophagy of the hEndoSCs by hUCMSCs-Sup.

Objective:To observation the application of multimedia combined with health education manuals in asthma children.Methods:A total of 192 asthma children who were admitted to Haikou Hospital of the Maternal and Child Health between January and December 2019 were enrolled. They were divided into observation group and control group by random number table method, 96 cases in each group. The control group was given routine health education based on oral education, while observation group was additionally given multimedia intervention. Both groups were continuously intervened for 4 weeks. After intervention, treatment compliance was evaluated. The health behaviors and quality of life before and after intervention in both groups were recorded. Both groups were followed up after 6 months of intervention. The number of cases with acute asthma attacks, and number of re-admission and hospitalization cases due to asthma in both groups were statistically analyzed.Results:The compliance of observation group was significantly better than that of control group in terms of quantitative medication on time, inhaler usage and recording asthma diary ( Z values were 9.809, 10.082, 10.287, P<0.05). After intervention, health behaviors such as keeping away from allergens, medication following doctor's advice, paying attention to keep warm, diet control, exercise training and inhaler usage in observation group were significantly higher than those in control group ( χ 2 values were 5.169-19.006, P<0.05). After intervention, scores of symptoms, activities and emotion, and total score of Pediatric Asthma Quality of Life Questionnaire (PAQLQ) in observation group were (48.52±7.46), (25.16±4.83) (110.32±20.64) and (36.57±5.64) points, significantly higher than (42.17±7.12), (18.65±3.72), (29.86±5.48) and (85.06±16.23) points in control group ( t values were 6.146-10.463, P<0.05). During follow-up, the incidence rates of acute asthma attack, re-admission and re-hospitalization due to asthma in observation group were 21.89% (20/91), 15.38% (14/91), 9.89% (9/91), which were lower than 39.33% (35/89), 23.58% (29/89), 25.84% (23/89) in control group ( χ 2 values were 6.381, 7.321, 7.833, P<0.05). Conclusion:The multimedia combined health education manuals can effectively improve treatment compliance, health behaviors and quality of life in asthma children, and reduce incidence of asthma related events.

Objective:To analyze the factors influencing clinical pregnancy outcomes after single embryo transfer (SET) undergoing in vitro fertilization-embryo transfer (IVF-ET) treatment cycles. Methods:A retrospective cohort analysis was carried out on SET cycles of Center for Reproductive Medicine in Nanfang Hospital from September 1st, 2013 to December 31st, 2019. Totally 2734 SET cycles were assigned to day 3 (D3) group, day 4 (D4) group, day 5 (D5) group, day 6 (D6) group according to the different stages of embryo development and analyzed for the relation of clinical pregnancy outcomes to ages, different embryo stages and quality.Results:The total clinical pregnancy rate (CPR) was 39.8% (1098/2734) and the live birth rate (LBR) was 30.5% (842/2734) in the 2761 SET cycles. The significant differences were observed among four groups in CPR [D3 group, D4 group, D5 group and D6 group: 33.3% (264/793), 36.4% (142/390), 52.5% (492/937) and 32.6% (200/614), respectively, P<0.001] and LBR [24.8% (203/793), 30.5% (119/390), 40.9% (383/937) and 22.3% (137/614), respectively, P<0.001]. In D3 group, significantly higher CPR and LBR were observed after transfer of top-quality cleavage embryos (8-cell I, 7-cell I, 8-cell II) than those in other cleavage embryos [CPR: 41.7% (207/496) vs. 19.2% (57/297), P<0.001; LBP: 32.1% (159/496) vs. 14.8% (441/297), P<0.001]. In D4 group, significantly higher CPR and LBR were observed after transfer of embryo with entirely compaction than partial compaction [CPR: 40.4% (134/332) vs. 13.8% (8/58), P<0.001; LBR: 34.0% (113/332) vs. 10.3% (113/332), P=0.001]. In slow-growing blastocysts group, fresh transfer of embryos which began blastulation but did not reach Gardner stage III by D5 resulted in similar outcomes to the transfer of fully expanded blastocysts by D6 [CPR: 30.6% (22/72) vs. 32.6% (200/614), P>0.05; LBR: 27.8% (20/72) vs. 22.3% (137/614), P>0.05]. Conclusion:SET of a top-quality D5 blastocyst or D4 morula can reduce the incidence of multiple pregnancies and obtain the best pregnancy outcome. For slow-growing D5 blastocysts, it may be a strategy to improve pregnancy outcome to continue culture until D6 fully expanded blastocysts and then perform subsequent frozen-thawed embryo transfer. For cleavage embryo, SET of top-quality cleavage embryos (8-cell I, 7-cell I, 8-cell II) also achieved satisfactory pregnancy outcome.

Objective:To analyze the factors influencing clinical pregnancy outcomes after single embryo transfer (SET) undergoing in vitro fertilization-embryo transfer (IVF-ET) treatment cycles. Methods:A retrospective cohort analysis was carried out on SET cycles of Center for Reproductive Medicine in Nanfang Hospital from September 1st, 2013 to December 31st, 2019. Totally 2734 SET cycles were assigned to day 3 (D3) group, day 4 (D4) group, day 5 (D5) group, day 6 (D6) group according to the different stages of embryo development and analyzed for the relation of clinical pregnancy outcomes to ages, different embryo stages and quality.Results:The total clinical pregnancy rate (CPR) was 39.8% (1098/2734) and the live birth rate (LBR) was 30.5% (842/2734) in the 2761 SET cycles. The significant differences were observed among four groups in CPR [D3 group, D4 group, D5 group and D6 group: 33.3% (264/793), 36.4% (142/390), 52.5% (492/937) and 32.6% (200/614), respectively, P<0.001] and LBR [24.8% (203/793), 30.5% (119/390), 40.9% (383/937) and 22.3% (137/614), respectively, P<0.001]. In D3 group, significantly higher CPR and LBR were observed after transfer of top-quality cleavage embryos (8-cell I, 7-cell I, 8-cell II) than those in other cleavage embryos [CPR: 41.7% (207/496) vs. 19.2% (57/297), P<0.001; LBP: 32.1% (159/496) vs. 14.8% (441/297), P<0.001]. In D4 group, significantly higher CPR and LBR were observed after transfer of embryo with entirely compaction than partial compaction [CPR: 40.4% (134/332) vs. 13.8% (8/58), P<0.001; LBR: 34.0% (113/332) vs. 10.3% (113/332), P=0.001]. In slow-growing blastocysts group, fresh transfer of embryos which began blastulation but did not reach Gardner stage III by D5 resulted in similar outcomes to the transfer of fully expanded blastocysts by D6 [CPR: 30.6% (22/72) vs. 32.6% (200/614), P>0.05; LBR: 27.8% (20/72) vs. 22.3% (137/614), P>0.05]. Conclusion:SET of a top-quality D5 blastocyst or D4 morula can reduce the incidence of multiple pregnancies and obtain the best pregnancy outcome. For slow-growing D5 blastocysts, it may be a strategy to improve pregnancy outcome to continue culture until D6 fully expanded blastocysts and then perform subsequent frozen-thawed embryo transfer. For cleavage embryo, SET of top-quality cleavage embryos (8-cell I, 7-cell I, 8-cell II) also achieved satisfactory pregnancy outcome.

Objective To analyze the clinical features of patients with acute stage brucellosis in Shenzhen,and provide a scientific basis for prevention and control of brucellosis in immigrant city.Methods A retrospective analysis was conducted to collect clinical data of patients with brucellosis admitted to the Department of Infectious Diseases,Shenzhen People's Hospital from May 2013 to May 2018.The patient's epidemiology manifestations,pathogen and laboratory examination results,diagnosis and treatment outcomes and prognosis were analyzed.Results Among the 39 patients with brucellosis,males were predominant,with a male to female ratio of 1.4 ∶ 1.0 (23 ∶ 16),an age of (44.91 ± 17.18) years and 24 cases were non-Guangdong natives.There were 23 cases with epidemiological history,including 14 cases with mutton,sheep viscera and goat milk history;the disease occurred throughout the year,mainly from February to July,a total of 26 cases.The clinical manifestations of the patients were mainly fever,sweating,fatigue,joint and muscle pain,weight loss,and liver or spleen or lymph nodes swelling.The blood culture was identified as 38 cases of Brucella melitensis and 1 case of Brucella suis.All strains were sensitive to common antibiotics in vitro.All cases were diagnosed as acute stage of brucellosis,2 cases with orchitis,1 case with brucellosis meningoencephalitis,3 cases with spondylitis,and 3 cases with misdiagnosis.Thirty-nine patients were cured according to the "Brucellosis Diagnosis and Treatment Guidelines (Trial)" and were followed up for 1 year.Conclusions Patients with brucellosis in Shenzhen are mainly infected with Brucella melitensis;fever,sweating,joint and muscle pain are the main clinical symptoms;the patient's efficacy and prognosis are better after treatment;for the occurrence of occasional misdiagnosis,it is recommended that in immigrant cities,medical staff should strengthen their understanding of brucellosis.

OBJECTIVE: To explore the causes of oocyte vitrification and its application in assisted reproduction. METHODS: We retrospectively analyzed the data of 26 patients with 27 cycles of oocyte vitrification cryopreservation undergoing intracytoplasmic sperm injection (ICSI) and embryo transfer between January, 2008 and October, 2018. The causes of oocyte vitrification and the outcomes of ICSI and clinical pregnancy were analyzed. RESULTS: The causes of oocytes vitrification included mainly azoospermia or severe spermatogenesis disorder of the husband, failure to obtain sperms from the husband, failure of the husband to be present on the day of oocyte retrieval and acute diseases of the husband to not allow sperm collection. A total of 274 oocytes were frozen in 27 oocyte retrieval cycles, and 217 eggs were thawed in 19 cycles with a survival rate of 81.11% (176/217). The normal fertilization rate, cleavage rate and high-quality embryo rate was 74.81% (98/131), 89.80% (88/98) and 36.73% (36/98), respectively. Fifteen patients underwent embryo transfer, and the clinical pregnancy rate and live birth rate was 53.33% (8/15) and 33.33% (5/15), respectively. Compared with patients below 35 years of age, the patients aged above 35 years had significantly lower oocyte survival rate after thawing (82.76% 74.42%, =0.211), clinical pregnancy rate (77.78% 16.67%, =0.041) and live birth rate (55.56% 0, =0.044). CONCLUSIONS Oocytes vitrification can be used as a remedy for infertile couples who fail to provide sperms due to male factors on the day of oocyte retrieval. Vitrification of the oocytes does not significantly affect the fertilization rate or the clinical pregnancy rate. The survival rate of the thawed oocytes is related to the age of the wife, and an age younger than 35 years can be optimal for achieving favorable clinical pregnancy outcomes after oocyte vitrification.
Adult ; Cryopreservation ; Embryo Transfer ; Female ; Humans ; Male ; Oocytes ; Pregnancy ; Pregnancy Rate ; Retrospective Studies ; Vitrification

Objective: To understand the epidemiological and clinical features of patients with hemorrhagic fever and renal syndrome (HFRS) in Shenzhen, and to accumulate experience in the diagnosis and treatment of HFRS in this area. Methods: A retrospective analysis was conducted by collecting the clinical data from 46 patients who were confirmed with HFRS and admitted to the Department of Infectious Diseases of Shenzhen People's Hospital from January 2015 to December 2018. The demographic characteristics, epidemiological, clinical manifestations, examinations, treatments and prognosis, and other characteristics were analyzed. Results: All the 46 patients with HFRS were residens in Shenzhen, with a male-to-female ratio of 6.67∶1.00(40∶6), aged (40.18 ± 15.63) years old, and 38 patients (82.61%) aged 23-45 years old. There were 41 patients (89.13%) with a history of HFRS epidemiology, and there were mice in their houses or workplaces. The houses of 39 patients (84.78%) were rented, and 34 patients(87.18%) rented their houses in urban villages. There were morbidity throughout the year, and 33 patients (71.74%) were ill from January to June. In clinical classification, 44 cases (95.65%) were mild, 2 cases (4.35%) were medium, and there were no severe or critical cases. The clinical manifestations were that all patients were hospitalized due to fever mainly with hyperthermia. Thirty-nine patients (84.78%) were presented with systemic aches, headaches, low back pain and eyelid pain, and 28 patients (60.87%) had skin and mucous membrane hyperemia flushing. Clinical stages showed that all patients had pyretogenesis stage and polyuria stage, including pyretogenesis stage [(7.34 ± 6.82) d], polyuria stage [(9.94 ± 5.77) d], only 4.35% (2/46) patients with hypotension shock stage, all patients did not have oliguric stage. On the next day of admission, the number of white blood cells in 46 patients was (8.17 ± 3.19) × 10⁹/L, and 38 cases (82.61%) in the normal range; platelet was (61.92 ± 32.53) × 10⁹/L, and 42 cases (91.30%) were decreased; the procalcitonin was (1.62 ± 0.38) ng/ml, and 41 cases (89.13%) were increased; C-reactive protein was (74.33 ± 30.48) mg/L, and 46 patients (100.00%) were elevated; creatinine was (176.25 ± 55.15) μmol/L, and 19 cases (41.30%) were increased. Abnormal liver function was manifested by increased enzymology, alanine aminotransferase was (137.58 ± 46.76) U/L, and aspartate aminotransferase was (129.82 ± 40.29) U/L. All patients were positive for Hantavirus IgM. B-ultrasound results showed that in 58.70% (27/46) patients, both kidneys were plump and the parenchymal echo was enhanced. Liver injury occurred in 39 patients (84.78%) and sinus bradycardia in 2 patients (4.35%). All the 46 patients were clinically cured. Conclusion The epidemiological characteristics of patients with HFRS in Shenzhen are typical, the clinical manifestations are mild, and the curative effect and prognosis are good.