Objective:To investigate the iodine nutrition level and thyroid function status of pregnant women in Hubei Province.Methods:According to the requirements of "the National Iodine Deficiency Disorders Monitoring Program (2016 Edition)", in 2020, using a cross-sectional survey method, two mountainous counties and two plain areas in Hubei Province were divided into five districts: east, west, south, north, and central. One township (street) was selected from each district, and 20 pregnant women were selected from each township (street) as survey subjects. Urine iodine content and thyroid function indicators [serum free triiodothyronine (FT 3), free thyroxine (FT 4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb)] were tested. Abnormal thyroid function rate and antibody positive rate were analyzed, and correlation analysis of thyroid function indicators was conducted (Spearman method). Results:A total of 321 pregnant women were included, including 43, 114, and 164 in early, middle, and late pregnancy, respectively; The median urinary iodine was 164.80 μg/L. The median serum FT 3, FT 4, TSH, TPOAb, TgAb levels were 4.10, 12.83 pmol/L, 1.85 mU/L, 15.84 and 13.35 U/ml, respectively. There were statistically significant differences in FT 3, FT 4, and TSH levels among different trimesters ( P < 0.05). According to Spearman's correlation analysis, FT 3 in early stage of pregnancy was negatively correlated with TSH and TPOAb levels ( r = - 0.46, - 0.33, P < 0.05), while TSH was positively correlated with TPOAb level ( r = 0.33, P = 0.032); there was a positive correlation between FT 4 and TgAb levels in middle stage of pregnancy ( r = 0.21, P = 0.032); there was a negative correlation between FT 3 and TPOAb levels in late stage of pregnancy ( r = - 0.19, P = 0.017); FT 3 and FT 4, TPOAb and TgAb levels were positively correlated throughout pregnancy ( P < 0.05). There was no correlation between urinary iodine content and thyroid function indicators ( P > 0.05). The total abnormal rate of thyroid function was 7.79% (25/321), with 16.28% (7/43), 5.26% (6/114), and 7.32% (12/164) in early, middle, and late pregnancy, respectively. There was no statistically significant difference in the abnormal rate of thyroid function among different pregnancy periods (χ 2 = 4.83, P = 0.097). The detection rates of hypothyroxinemia, hypothyroidism, subclinical hypothyroidism, hyperthyroidism, and subclinical hyperthyroidism were 4.36% (14/321), 0.31% (1/321), 2.49% (8/321), 0.31% (1/321), and 0.31% (1/321), respectively. The positive detection rate of autospecific antibodies was 10.28% (33/321), with a TPOAb positive detection rate of 9.97% (32/321) and a TgAb positive detection rate of 5.30% (17/321). Conclusions:The iodine nutrition level of pregnant women in Hubei Province is at a suitable level, and the rates of abnormal thyroid function and thyroid autospecific antibody positive are relatively low. It is necessary to continuously monitor the iodine nutrition and thyroid function indexes of pregnant women, strengthen health education on the hazards of iodine deficiency during pregnancy, and minimize the harm to maternal and infant health caused by iodine deficiency.

Effective supervision of the clinical research management department can guarantee and improve the quality of the investigator initiated trials(IIT). The authors analyzed relevant clinical research regulations and literature and summarized the current situation of risk-based IIT project process quality management. On such basis, they determined the risk-based IIT project process quality management method in combination with the previous research of the research group.From 2021 to 2022, this method was used to implement process quality management for 353 IIT projects in Shanghai′s tertiary hospitals. More than 3 000 risk points were identified through centralized supervision, and then on-site supervision was carried out to correct the problems found. As proven by the results, the method could find existing problems in time and define the risk level of the project, and also formulate an individualized risk supervision plan accordingly, so as to effectively ensure the data reliability and scientific results. It is suggested that the clinical research management department implement risk based management for the whole process of IIT projects, increase funding and staffing, and implement hierarchical management for the projects by research types, so as to promote the sustainable development of IITs.

Objective:To assess possible risk factors and their respective levels in the whole process of investigator initiated trial(IIT)projects proposed in the proposal stage, for reference in formulation of risk management plans.Methods:Through literature analysis and research group discussions, the risk factors of IIT projects and risk level assessment criteria were preliminarily identified, and a consultation questionnaire was developed as a result. Delphi method was used to further optimize the risk factors and determine their risk levels. Data obtained from the consulfation were analysied by descriptive.Results:The recovery rates of two rounds of expert consultation were both 100%, and the degree of expert authority was 0.942. The survey finalized 38 risk factors, including extremely high risk, high risk, medium risk, low risk and very low risk factors of 17(44.7%), 15(39.5%), 3(7.9%), 2(5.3%) and 1(2.6%) respectively.Conclusions:This study determined a risk evaluation system of IIT projects in the proposal stage. This system can identify risks of IIT projects at an early stage, facilitating early intervention of problems existing in such projects, and minimize risks to the rights and safety of patients.

Purpose: Pyrotinib is a newly-developed irreversible pan-ErbB receptor tyrosine kinase inhibitor. This study reported the first real-world data of pyrotinib-based therapy in metastatic human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC), focusing on efficacy in lapatinib-treated patients and in brain metastasis. Materials and Methods: One hundred thirteen patients with metastatic HER2-positive BC treated with pyrotinib-based therapy in Fudan University Shanghai Cancer Center under non-clinical trial settings from September 1, 2018 to March 1, 2019 were included. Results: Over half patients have received more than two lines of systematic therapy and exposed to two or more kinds of anti-HER2 agents. Most patients received a combined therapy, commonly of pyrotinib plus capecitabine, or vinorelbine or trastuzumab. Median progression-free survival (PFS) was 6.3 months (range, 5.54 to 7.06 months) and objective response rate (ORR) was 29.5%, with two patients (1.9%) achieving complete response. Lapatinib-naïve patients had significantly longer PFS than lapatinib-treated patients (9.0 months vs. 5.4 months, p=0.001). ORR for lapatinib-treated patients was 23.2%. Thirty-one of 113 patients have brain metastasis. Median PFS was 6.7 months and intracranial ORR was 28%. For patients without concurrent radiotherapy and/or brain surgery, the ORR was very low (6.3%). But for patients receiving concurrent radiotherapy and/or brain surgery, the ORR was 66.7%, and three patients achieved complete response. Most common adverse event was diarrhea. Conclusion Pyrotinib-based therapy demonstrated promising effects in metastatic HER2-positive BC and showed activity in lapatinib-treated patients. For patients with brain metastasis, pyrotinib-based regimen without radiotherapy showed limited efficacy, but when combined with radiotherapy it showed promising intracranial control.

Objective:To investigate the clinical feature, diagnosis, treatment and prognosis of childhood acute lymphoblastic leukemia (ALL) complicated with candida tropicalis bloodstream infection (CTBI), so as to improve the understanding of this disease.Methods:The general information, clinical manifestation, auxiliary examination, treatment and outcome of 14 childhood ALL who were diagnosed with tropical candidemia between January 2015 and December 2018 in 6 hospitals were analyzed retrospectively. Clinical data of non invasive fungal disease (IFD) ALL (28 cases) and other IFD children (9 cases) admitted in the same period were collected as control group. Logistic regression model was used to analyze the risk factor of CTBI.Results:Among 14 cases, there were 7 males and 7 females, with the age ranged from 17 months to 13 years. All the cases had fever, 9 cases had digestive system symptoms and stool fungal culture were positive in 3 of them; 7 cases had respiratory system symptoms and sputum fungal culture was positive in 1 of them; 2 cases had central nervous system symptoms and 10 cases progressed into septic shock. All 14 cases had neutropenia and the neutropenia duration was 1 to 53 days. Among 14 cases, the C-reactive protein was>50 mg/L in 8 cases, in which the proportion was significantly higher than that in other invasive fungal disease(IFD) (8/14 vs. 1/9, P<0.05), meanwhile the 1, 3-β-D-glucan detection, galactomannan detection and pulmonary imaging were not remarkable in all 14 cases. The blood culture results of 14 cases were all candida tropicalis, among which 13 cases finished drug susceptibility tests, the isolates of all cases were sensitive to flucytosine and amphotericin B, and the isolates of 4 cases were sensitive to fluconazole, voriconazole and itraconazole. Among 14 cases, 1 case lost to follow-up after giving up treatment, 1 case died before antifungal therapy and the remaining 12 cases received antifungal therapy; 7 of the 14 cases died. Univariate analysis showed that between ALL with CTBI group (14 cases) and ALL without invasive fungal disease (IFD) group (28 cases), the differences in variables such as ALL not in remission (χ2=37.847, P<0.01), length of hospital stay>15 days (χ 2=8.351, P=0.004), neutropenia (χ2=14.280, P<0.01), neutropenia duratio n>10 days (χ2=10.254, P=0.001), use of broad-spectrum antibiotics (χ2=13.888, P<0.01), skin and mucous membrane damage (χ2= 5.923, P=0.015) were statistically significant. Conclusions:In childhood ALL complicated with tropical candidemia, the drug resistance rate and mortality rate were high. For azole-resistant tropical candida, amphotericin B liposome or echinocandins(caspofungin) -fluorocytosine combined therapy was recommended to reduce treatment-related deaths.

Objective To assess the efficacy of immunoprophylaxis against mother-to-infant transmission of hepatitis B virus (HBV) in a real-world setting since the implementation of charge-free hepatitis B immunoglobulin (HBIG) and hepatitis B vaccine in China. Methods The screening rate and the prevalence of hepatitis B surface antigen (HBsAg) in 61 790 puerperants, and the administration of combined immunoprophylaxis in infants of HBsAg-positive mothers in Rugao City of Jiangsu Province from July 1, 2011 to June 30, 2016 were retrospectively analyzed. HBV infection status of infants born to HBV infected mothers was followed up after 7 months of age. HBsAg-positive infants and their mothers were followed up again for HBV markers in April 2018. Fisher's exact test and Cochran-Armitage trend test were used to statistically analyze the differences between groups and various years, respectively. Results All 61 790 puerperants were screened for HBsAg and the prenatal screen rate was 98.6% (60 937/61 790) with an increasing trend over time (χ2trend=750.908, P<0.001). HBsAg-positive puerperants accounted for 5.5% (3 397/61 790) with a decreasing trend over time (χ2trend=32.667, P<0.001). In total, 778 offspring (399 boys and 379 girls) of 759 HBsAg-positive mothers were followed up at (13.7±6.9) months of age, among which 751 (96.5%) were administered and 25 (3.2%) were probably administered standard combined immunoprophylaxis after birth, and the rest two (0.3%) were not. Fourteen infants (1.8%) were HBsAg positive and all born to mothers with positive hepatitis B e antigen (HBeAg). None of the 538 infants born to HBeAg-negative mothers was HBsAg-positive. HBsAg-positive rate in infants born since 2013 was lower than those in 2011 and 2012 (χ2trend=13.352, P=0.000 3). Eleven HBsAg-positive mothers and their children were followed up again 4–5 years later in April 2018. HBV DNA levels of all mothers were within the range of (7.34–28.2)×107 IU/ml except one case of spontaneous HBeAg seroconversion. One out of the 11 infected children also had HBeAg seroconversion. Phylogenetic analysis of HBV S gene showed that the 11 pairs of mothers and children were all infected with HBV of genotype C. Conclusions The implementation of charge-free HBIG and hepatitis B vaccine for newborns achieves fruitful results in Rugao city as the mother-to-infant transmission of HBV in the real-world had been further reduced to a similar level reported in literature survey.

In the original publication the grant number is incorrectly published. The correct grant number should be read as "17140901600". The corrected contents are provided in this correction article. This work was partially supported by grants from the National Natural Science Foundation of China (Nos. 81670470 and 81600149), a grant from the Shanghai Municipal Commission for Science and Technology (17140901600, 18411953500 and 15JC1400201) and a grant from National Key Research and Development Program (2016YFC0905100).

Adenosine ; genetics ; Adenosine Deaminase ; genetics ; metabolism ; Animals ; CRISPR-Associated Protein 9 ; genetics ; metabolism ; CRISPR-Cas Systems ; genetics ; Embryo, Mammalian ; metabolism ; Gene Editing ; Genetic Variation ; genetics ; Mice ; Mice, Inbred C57BL ; Rats ; Rats, Sprague-Dawley

Objective: To evaluate the characteristics and performance of various prediction models for early-onset preeclampsia, and to provide a reference for further study of preeclampsia prediction methods. Methods: (1) Databases of PubMed, Medline, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang Database were searched since their inception to October 2016. Studies in models for predicting early-onset preeclampsia during the first trimester were included. (2) Two reviewers independently checked potentially eligible articles, assessed risk of bias and extracted data. (3) Subtotals for the performance of different models were created and their properties were analyzed. Differences between simple models (based upon high risk factors such as demographic figures, medical history and family history, etc) and complex models (based upon blood pressure, uterine artery Doppler and biomarkers) were compared by analyzing forest plot created by SAS 9.4. Results: (1) Seventeen studies met the inclusion criteria were screened out, including nine prospective cohort studies, two case-control studies and six nested case-control studies. A total of 76 436 gravidas from tendifferent populations were assessed by the established models in these studies. (2) The area under the curve (AUC) of 13 simple models ranged from 0.64 to 0.81 with the sensitivity of 21%-60% when the false positive rate (FPR) was 10%. The AUC of 17 complex models ranged from 0.77 to 0.98 and the sensitivity was between 48.0% and 95.2% at a fixed FPR of 10%. (3) Compared with the simple models, the best complex models could ensure a promotion of 0.171 (range from 0.060 to 0.245) in median AUC, and a promotion of 40.8% (16.0% to 52.2%) in sensitivity at a FPR of 10%. Based on the simple models, additional mean arterial pressure (MAP) would increase the AUC and sensitivity by 0.092 (0.079 to 0.104) and 28.7% (16.2% to 55.0%), respectively, while additional uterine artery pulsatility index (UtA-PI) would bring an increase of 0.106 (0 to 0.137) and 31.8% (-1.0% to 41.9%), respectively. Moreover, when both MAP and UtA-PI were included into the simple models, the AUC and sensitivity would increase by 0.157 (0.094 to 0.218) and 31.6% (12.0% to 52.2%). Conclusions Complex prediction models perform better than simple models in prediction of early-onset preeclampsia. However, further confirmation is required in different population.

Objective To explore the influence of delivery mode and feeding pattern on cytomegalovirus (CMV) infection on infants born ≥ 32 gestational weeks,and to observe the outcomes after CMV infection.Methods In this retrospective study,378 pregnant women with positive CMV IgG and negative CMV IgM,and their offsprings (384 cases,including six pairs of twins),who got visited at five hospitals of our collaboration group during March 2013 and February 2016,were enrolled.Serum samples were retrieved from a previous study of these participants for CMV IgM and IgG detection with enzyme-linked immunosorbent assay.All participants were divided into exclusive artificial feeding (EAF) and breastfeeding groups (BF),and the latter included exclusive breastfeeding (EBF) and mixed feeding (MF).T or Chi-square or Fisher's exact tests were performed for statistical analysis.Results (1) Among the 378 pregnant women,there were 186 mothers and 190 infants (4 pairs of twins) in BF group,and the other 192 mothers and 194 infants (2 pairs of twins) in EAF group.The percentage of male infants were 54.7％(104/186) and 56.2％(109/194) in the BF and EAF group,respectively.The mean birth age was (38.9± 1.4) and (38.7± 1.7) weeks,and the age at followingup was (9.8± 2.2) and (10.5± 2.9) months,respectively.(2) The CMV IgG positive rate of infants in BF group was higher than in the EAF group [62.6％(119/190) vs 29.9％ (58/194),x2=41.403,P＜0.001].CMV IgG levels in infants were higher than the mothers [(537.1 ±249.5) vs (416.2±241.2) U/ml,t=4.609,P＜0.001].In infants with positive CMV IgG,the positive rates of CMV IgM were similar in the two groups [21.0％(25/119) vs 19.0％ (11/58),x2=0.101,P=0.751].(3) The positive rate of CMV IgG in vaginally born infants was higher than those born by caesarean section [55.2 (95/172) vs 38.7％ (82/212),x2=10.472,P=0.001].Further analysis in the EAF group showed that those infants born vaginally had a higher positive rate ofCMV IgG than those born by caesarean section [42.9％ (33/77) vs 21.4％ (25/117),~=10.231,P=0.001],while this figure did not show statistical difference in the BF group.(4) Infants with positive or negative CMV IgG were in similar age and gender proportion,as well as their height and weight.Among 36 infants with both positive CMV IgG and IgM,three failed in alanine aminotransferase (ALT) test due to hemolysis.However,among the other 33 cases,15.1％ (five cases) presented with lightly elevated ALT (42-107.2 U/L),which was similar to those infants with positive CMV IgG and negative CMV IgM (14/98,14.3％) and those with both negative CMV IgG and IgM (20/144,13.9％),(x2=0.036,P=0.982).Conclusions Although breastfeeding and vaginal birth may increase CMV infection rate in neonates and infants,but no obviously adverse prognosis was reported in those born over 32 gestational weeks.So we should encourage vaginal birth and breastfeeding in these population.