Objective: Depression was common during coronavirus disease-2019 (COVID-19) pandemic, while the association of perceived stress with depression among vaccinated healthcare workers has not been investigated. This study aimed to address this issue. Methods: We included a total of 898 fully vaccinated healthcare workers during the outbreak of severe acute respiratory syndrome coronavirus 2 Delta variant in Nanjing, 2021. Depression was ascertained by Patient Health Questionnaire-9, with a cut-off score of ≥5 indicative of mild-to-severe depression. Perceived stress, resilience, and compassion fatigue were assessed by Perceived Stress Scale-10, Resilience Scale-25, and Professional Quality of Life Scale version-5, respectively. Logistic regression analyses were used to estimate the odds ratio (OR) and 95% confidence interval (CI), along with subgroup and mediation analyses. Results: The prevalence of mild-to-severe depression was 41.1% in vaccinated healthcare workers. The odd of mild-to-severe depression was increased with higher perceived stress. Compared with vaccinated healthcare workers with the lowest tertile of perceived stress, those with the highest tertile had increased odds of mild-to-severe depression by 120% (OR 2.20, 95% CI 1.46 to 3.31) after multivariable-adjustment. However, perceived stress was not associated with mild-to-severe depression in vaccinated healthcare workers with strong resilience, but was in those with weak resilience (pinteraction=0.004). Further analysis showed that compassion fatigue mediated the relationship between perceived stress and mild-to-severe depression, with a mediating effect of 49.7%. Conclusion Perceived stress was related to an increased odd of mild-to-severe depression in vaccinated healthcare workers during COVID-19 pandemic, and this relationship might be explained by compassion fatigue.

Through bioinformatics predictions, we identified that GTF2I and FAT1 were downregulated in thyroid carcinoma (TC). Further, Pearson's correlation coefficient revealed a positive correlation between GTF2I expression and FAT1 expression. Therefore, we selected them for this present study, where the effects of bone marrow mesenchymal stem cell-derived EVs (BMSDs-EVs) enriched with GTF2I were evaluated on the epithelial-to-mesenchymal transition (EMT) and stemness maintenance in TC. The under-expression of GTF2I and FAT1 was validated in TC cell lines. Ectopically expressed GTF2I and FAT1 were found to augment malignant phenotypes of TC cells, EMT, and stemness maintenance. Mechanistic studies revealed that GTF2I bound to the promoter region of FAT1 and consequently upregulated its expression. MSC-EVs could shuttle GTF2I into TPC-1 cells, where GTF2I inhibited TC malignant phenotypes, EMT, and stemness maintenance by increasing the expression of FAT1 and facilitating the FAT1-mediated CDK4/FOXM1 downregulation. In vivo experiments confirmed that silencing of GTF2I accelerated tumor growth in nude mice. Taken together, our work suggests that GTF2I transferred by MSC-EVs confer antioncogenic effects through the FAT1/CDK4/FOXM1 axis and may be used as a promising biomarker for TC treatment.
Mice ; Animals ; Cell Line, Tumor ; Cell Proliferation ; Mice, Nude ; Epithelial-Mesenchymal Transition ; Thyroid Neoplasms/pathology* ; Extracellular Vesicles/pathology* ; Mesenchymal Stem Cells ; Transcription Factors, TFIII/metabolism* ; Neoplastic Stem Cells/pathology*

OBJECTIVE: To explore the genetic basis for a patient with Alport syndrome (AS) and confirm the existence of a splicing variant. METHODS: An AS patient diagnosed at the Affiliated Hospital of Inner Mongolia Medical University on January 8, 2021 for significant proteinuria and occult hematuria was selected as the study subject. Clinical data was collected. Peripheral blood samples were collected for the extraction of genomic DNA. Whole exome sequencing and Sanger sequencing were carried out to identify potential genetic variants. An in vitro experiment was also conducted to verify the abnormal mRNA splicing. Bioinformatic software was used to analyze the conservation of amino acids of the variant sites and simulate the 3D structure of the variant collagen IV protein. Immunofluorescence and immunohistochemistry were carried out on renal tissues from the patient to confirm the presence of AS kidney injury. RESULTS: The patient, a 21-year-old male, had a 24-hour urine protein of 3.53 g/24 h, which fulfilled the diagnostic criteria for proteinuria. His blood uric acid has also increased to 491 μmol/L. DNA sequencing revealed that he has harbored a c.835-9T>A splice variant of the COL4A5 gene, which was not found in either of his parents. In vitro experiment confirmed that the variant has removed 57 bp from the exon 15 of the mRNA of the COL4A5 gene. The deletion may cause loss of amino acid residues from positions 279 to 297, which in turn may affect the stability of the secondary structure of the α5 chain encoded by the COL4A5 gene. The amino acids are conserved across various species. The result of homology modeling indicated that the trimerization of Col-IV with the mutated α5 chain could be achieved, however, the 3D structure was severely distorted. The AS kidney damage was confirmed through immunofluorescence assays. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.835-9T>A variant was classified as likely pathogenic (PVS1_Moderate+PS3_Moderate+PM2_Supporting+PS2+PP3+PP4). CONCLUSION The c.835-9T>A variant of the COL4A5 gene probably underlay the AS in this patient. In vitro experiment has confirmed the abnormal splicing caused by the variant. Histopathological examination of the kidney tissue has provided in vivo evidence for its pathogenicity. Above finding has expanded the mutational spectrum of the COL4A5 gene.
Humans ; Male ; Young Adult ; Amino Acids ; China ; Collagen Type IV/genetics* ; Exons ; Nephritis, Hereditary/genetics* ; RNA Splicing

BACKGROUND: Gestational diabetes mellitus (GDM) brings health issues for both mothers and offspring, and GDM prevention is as important as GDM management. It was shown that a history of GDM was significantly associated with a higher maternal risk for GDM recurrence. The incidence of GDM recurrence was unclear because of the incidence of second-child was low before 2016 in China. We aim to investigate the prevalence of GDM recurrence and its associated high-risk factors which may be useful for the prediction of GDM recurrence in China. METHODS: A retrospective study was conducted which enrolled participants who underwent regular prenatal examination and delivered twice in the same hospital of 18 research centers. All participants were enrolled from January 2018 to October 2018, where they delivered the second baby during this period. A total of 6204 women were enrolled in this study, and 1002 women with a history of GDM were analyzed further. All participants enrolled in the study had an oral glucose tolerance test (OGTT) result at 24 to 28 weeks and were diagnosed as GDM in the first pregnancy according to the OGTT value (when any one of the following values is met or exceeded to the 75-g OGTT: 0 h [fasting], ≥5.10 mmol/L; 1 h, ≥10.00 mmol/L; and 2 h, ≥8.50 mmol/L). The prevalence of GDM recurrence and development of type 2 diabetes mellitus were calculated, and its related risk factors were analyzed. RESULTS: In 6204 participants, there are 1002 women (1002/6204,16.15%) with a history of GDM and 5202 women (5202/6204, 83.85%) without a history of GDM. There are significant differences in age (32.43 ± 4.03 years vs. 33.00 ± 3.34 years vs. 32.19 ± 3.37 years, P  < 0.001), pregnancy interval (4.06 ± 1.44 years vs. 3.52 ± 1.43 years vs. 3.38 ± 1.35 years, P  = 0.004), prepregnancy body mass index (BMI) (27.40 ± 4.62 kg/m2vs. 23.50 ± 3.52 kg/m2vs. 22.55 ± 3.47 kg/m2, P < 0.001), history of delivered macrosomia (22.7% vs. 11.0% vs. 6.2%, P < 0.001) among the development of diabetes mellitus (DM), recurrence of GDM, and normal women. Moreover, it seems so important in the degree of abnormal glucose metabolism in the first pregnancy to the recurrence of GDM and the development of DM. There are significant differences in OGTT levels of the first pregnancy such as area under the curve of OGTT value (18.31 ± 1.90 mmol/L vs. 16.27 ± 1.93 mmol/L vs. 15.55 ± 1.92 mmol/L, P < 0.001), OGTT fasting value (5.43 ± 0.48 mmol/L vs. 5.16 ± 0.49 mmol/L vs. 5.02 ± 0.47 mmol/L, P < 0.001), OGTT 1-hour value (10.93 ± 1.34 mmol/L vs. 9.69 ± 1.53 mmol/L vs. 9.15 ± 1.58 mmol/L, P < 0.001), OGTT 2-hour value (9.30 ± 1.66 mmol/L vs. 8.01 ± 1.32 mmol/L vs. 7.79 ± 1.38 mmol/L, P < 0.001), incidence of impaired fasting glucose (IFG) (fasting plasma glucose ≥5.6 mmol/L) (31.3% vs. 14.6% vs. 8.8%, P < 0.001), and incidence of two or more abnormal OGTT values (68.8% vs. 39.7% vs. 23.9%, P < 0.001) among the three groups. Using multivariate analysis, the factors, such as age (1.07 [1.02-1.12], P = 0.006), prepregnancy BMI (1.07 [1.02, 1.12], P  = 0.003), and area under the curve of OGTT in the first pregnancy (1.14 [1.02, 1.26], P  = 0.02), have an effect on maternal GDM recurrence; the factors, such as age (1.28 [1.01-1.61], P  = 0.04), pre-pregnancy BMI (1.26 [1.04, 1.53], P = 0.02), and area under the curve of OGTT in the first pregnancy (1.65 [1.04, 2.62], P = 0.03), have an effect on maternal DM developed further. CONCLUSIONS The history of GDM was significantly associated with a higher maternal risk for GDM recurrence during follow-up after the first pregnancy. The associated risk factors for GDM recurrence or development of DM include age, high pre-pregnancy BMI, history of delivered macrosomia, the OGTT level in the first pregnancy, such as the high area under the curve of OGTT, IFG, and two or more abnormal OGTT values. To prevent GDM recurrence, women with a history of GDM should do the preconception counseling before preparing next pregnancy.
Adult ; Blood Glucose/metabolism* ; China/epidemiology* ; Diabetes Mellitus, Type 2/epidemiology* ; Diabetes, Gestational ; Female ; Fetal Macrosomia ; Glucose Intolerance ; Humans ; Male ; Pregnancy ; Retrospective Studies

Objective:To analyze the health fitness and its influencing factors among urban elderly residents in Lanzhou city.Methods:A multi-stage sampling method was used to survey urban elderly residents in Lanzhou city with self-designed questionnaire from July 17th to August 3rd, 2020. The questionnaire included general information, life habits and Healthy Fitness Measurement Scale Version 1.0 (HFMS V 1.0), a total of 1 124 questionnaires were distributed and 1 124 were collected, including 1 043 valid questionnaires (92.8%). The HFMS V 1.0 was scored with Likert 5-point scale, positive and negative scoring method. The health fitness status of the subjects was divided into low, medium and high levels according to the norms of HFMS V 1.0 for Chinese urban elderly residents. The influencing factors were analyzed by using the chi-square test and ordinal logistic regression.Results:The conversion score of HFMS V 1.0 for the urban elderly residents in Lanzhou city was 61.99±14.20, and the physical fitness score was the lowest (57.84±16.98); of the 1 043 subjects, 332 (31.83%), 360 (34.52%) and 351 (33.65%) subjects were classified with low, medium, and high health fitness levels, respectively. Chronic diseases and poor dietary habits were the risk factors for the health fitness of urban elderly residents in Lanzhou city (both P<0.05); more adequate sun exposure, physical exercise, sufficient sleep, high self-health concern and high frustration quotient were protective factors for health fitness in those subjects (all P<0.05). Conclusion:The overall level of health fitness in urban elderly residents in Lanzhou city is moderate, and chronic disease, dietary habits, sun exposure, physical exercise, length of sleep, self-health concern and frustration quotient are the main influencing factors.

Objective:To investigate the changes of various cytokines and coagulation function in B cell acute lymphoblastic leukemia(ALL) patients with different CRS scores during CD19-CAR-T cell immunotherapy.Methods:87 patients with B-ALL hospitalized in the First Affiliated Hospital of Soochow University and 30 normal controls were enrolled into this study from July 2018 to October 2020. The age of the patients was 32(20, 56) years old and 36(41.4%) were female. All these coagulation indicators, prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer, fibrinogen (Fg) were analyzed by automatic blood coagulation in B-ALL patients before and after treated with CAR-T cell. The ratio of CD19-CAR-T cells and the expression of IL-6, IL-10, IFN-γ, TFN-α, IL-2, IL-4, and IL-17A were analyzed using flow cytometry. The patients′ clinical parameters were detected, and the CRS classification of severity was made according to the standard of consensus.Results:Patients with CRS>3 had prolonged PT and APTT, increased D-dimer, and decreased fibrinogen ( P<0.05). The levels of cytokines of IFN-γ, IL-6, and IL-10 were significantly higher in patients with CRS>3 than that in controls ( P<0.05).The D-dimer level is positively correlated with IL-10. Conclusion:Patients with severe CRS grading have significant coagulation dysfunction in CD19-CAR-T cell immunotherapy. Cytokines IFN-γ, IL-6, and IL-10 may affect coagulation function and CRS grading during CD19-CAR-T cell immunotherapy.

BACKGROUND: Recombinant human thrombopoietin (rh-TPO) and eltrombopag are two distinct TPO receptor agonists (TPO-RAs) with different mechanisms. During the pandemic, when immunosuppressive medications are controversial, switching to another TPO-RA may be worth exploring in patients who do not benefit from their first TPO-RA. We investigated the outcomes of switching from rh-TPO to eltrombopag or vice versa in immune thrombocytopenia (ITP) patients. METHODS: This prospective, open-label, observational investigation included 96 adult ITP patients who needed to switch between rh-TPO and eltrombopag between January 2020 and January 2021 at Peking University People's Hospital in China. The study evaluated response rates and platelet counts at different time points after the switch, bleeding events, time to response, duration of response, and adverse events. RESULTS: At 6 weeks after switching, response was observed in 21/49 patients (43%) who switched for inefficacy and 34/47 patients (72%) who switched for non-efficacy-related issues. In the inefficacy group, 9/27 patients (33%) responded to eltrombopag, and 12/22 patients (55%) responded to rh-TPO. In the non-efficacy-related group, 21/26 (81%) and 13/21 (62%) patients in the eltrombopag and rh-TPO groups maintained their response rates at 6 weeks after switching, respectively. Response at 6 months was achieved in 24/49 patients (49%) switching for inefficacy and 37/47 patients (79%) switching for non-efficacy issues. In the inefficacy group, 13/27 patients (48%) responded to eltrombopag, and 11/22 patients (50%) responded to rh-TPO. In the non-efficacy-related group, 22/26 patients (85%) and 15/21 patients (71%) in the eltrombopag and rh-TPO groups maintained their response rates at 6 months after switching, respectively. Both eltrombopag and rh-TPO were well tolerated. CONCLUSIONS: Our study confirmed the safety and effectiveness of switching between rh-TPO and eltrombopag for ITP patients who had no response to or experienced adverse events with their first TPO-RA. When the switch was motivated by other reasons, including patient preference and platelet count fluctuations, the probability of response was high. REGISTRATION ClinicalTrials.gov, NCT04214951.
Adult ; Humans ; Purpura, Thrombocytopenic, Idiopathic ; Thrombopoietin/adverse effects* ; Prospective Studies ; Recombinant Fusion Proteins ; Receptors, Fc/therapeutic use* ; Receptors, Thrombopoietin/therapeutic use* ; Thrombocytopenia/chemically induced* ; Benzoates/adverse effects* ; Hydrazines/adverse effects*

Objective:To explore the effects of interpregnancy interval (IPI) on pregnancy outcomes of subsequent pregnancy.Methods:A multicenter retrospective study was conducted in 21 hospitals in China. Information of age, height, pre-pregnancy weight, IPI, history of diseases, complications of pregnancy, gestational age of delivery, delivery mode, and pregnancy outcomes of the participants were collected by consulting medical records of pregnant women who had two consecutive deliveries in the same hospital during 2011 to 2018. The participants were divided into 4 groups according to IPI:<18 months, 18-23 months, 24-59 months and ≥60 months. According to the WHO′s recommendation, with the IPI of 24-59 months group as a reference, to the effects of IPI on pregnancy outcomes of subsequent pregnancy were analyzed. Stratified analysis was further carried out based on age, history of gestational diabetes mellitus (GDM), macrosomia, and premature delivery, to explore the differences in the effects of IPI on pregnancy outcomes among women with different characteristics.Results:A total of 8 026 women were included in this study. There were 423, 623, 5 512 and 1 468 participants in <18 months group, 18-23 months group, 24-59 months group and ≥60 months group, respectively. (1) The age, pre-pregnancy body mass index (BMI), history of cesarean section, GDM, gestational hypertension and cesarean section delivery rate of <18 months group, 18-23 months group, 24-59 months group and ≥60 months group were gradually increased, and the differences were statistically significant ( P<0.05). (2) After adjusting for potential confounding factors, compared with women in the IPI of 24-59 months group, the risk of premature delivery, premature rupture of membranes, and oligohydramnios were increased by 42% ( OR=1.42, 95% CI: 1.07-1.88, P=0.015), 46% ( OR=1.46, 95% CI: 1.13-1.88, P=0.004), and 64% ( OR=1.64, 95% CI: 1.13-2.38, P=0.009) respectively for women in the IPI≥60 months group. No effects of IPI on other pregnancy outcomes were found in this study ( P>0.05). (3) After stratified by age and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of oligohydramnios for women with advanced age ( OR=2.87, 95% CI: 1.41-5.83, P=0.004); and <18 months could increase the risk of premature rupture of membranes for women under the age of 35 ( OR=1.59, 95% CI: 1.04-2.43, P=0.032). Both the risk of premature rupture of membranes ( OR=1.58, 95% CI: 1.18-2.13, P=0.002) and premature delivery ( OR=1.52, 95% CI: 1.07-2.17, P=0.020) were significantly increased in the IPI≥60 months group. After stratified by history of GDM and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would lead to an increased risk of postpartum hemorrhage for women with a history of GDM ( OR=5.34, 95% CI: 1.45-19.70, P=0.012) and an increased risk of premature rupture of membranes for women without a history of GDM ( OR=1.44, 95% CI: 1.10-1.90, P=0.009). After stratified by history of macrosomia and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months could increase the proportion of cesarean section for women with a history of macrosomia ( OR=4.11, 95% CI: 1.18-14.27, P=0.026) and the risk of premature rupture of membranes for women without a history of macrosomia ( OR=1.46, 95% CI: 1.12-1.89, P=0.005). After stratified by history of premature delivery and adjusted for confounding factors, compared with women in the IPI of 24-59 months group, IPI≥60 months would significantly increase the risk of premature rupture of membranes for women without a history of premature delivery ( OR=1.47, 95% CI: 1.13-1.92, P=0.004). Conclusions:Both IPI≥60 months and <18 months would increase the risk of adverse pregnancy outcomes in the subsequent pregnancy. Healthcare education and consultation should be conducted for women of reproductive age to maintain an appropriate IPI when they plan to pregnant again, to reduce the risk of adverse pregnancy outcomes in the subsequent pregnancy.

Objective:To explore the application of home nutrition support in children with intestinal failure.Methods:Children with intestinal failure admitted to Division of Pediatric Gastroenterology and Nutrition and Department of Pediatric Surgery in Xinhua Hospital were retrospectively enrolled since January 2009. The details of home nutrition support, nutritional status and home parenteral nutrition (HPN) associated complications were collected.Results:A total of 10 children received HPN support, 7 of whom were with short bowel syndrome (SBS) and the other 3 with pediatric intestinal pseudo-obstruction. The average length of remnant small bowel in 7 SBS children was (36.7±32.4) cm. The average age at HPN onset was (5.4±4.7) years. The average duration of follow-up was (3.1±2.1) years. The average duration of HPN was (619.5±669.1) days after (391.8±340.1) days of parenteral nutrition support in our hospital. All 10 cases started home enteral nutrition (HEN) with tube feeding (3 cases transited to oral feeding during treatment). The average duration of HEN was (536.1±429.6) days. Daily calorie intake was 104.0%±39.0% of the recommended intake according to the guideline, with 46.5%±21.3% via HPN and 57.5%±29.2% via HEN. During follow-up, 3 cases were found with severe malnutrition, 5 with moderate malnutrition and 2 with mild malnutrition. Four children suffered from catheter-related thrombosis and five children were identified with catheter-related blood stream infection. No intestinal failure associated liver disease was observed.Conclusions:HPN is feasible but needs the support of national medical insurance policy. At present, there are still frequent nutritional deficiencies and complications in HPN. Nutrition support team (NST) should provide guidance for more scientific nutrition screening and nutrition management.

Hypoparathyroidism during pregnancy is an uncommon clinical problem, By presenting a case of post-surgical hypoparathyroidism during pregnancy, this paper reviewed calcium physiology in pregnancy, as well as characteristics of pregnant women with hypoparathyroidism which differ from those of normal pregnant women in order to help readers better undarstand the complexity of this problem and management of hypoparathyroidism during pregnancy.