Objective To analyze the prognosis and influencing factors in patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). Methods A retrospective analysis was conducted on 52 patients with RAIR-DTC who underwent ineffective ¹³¹I therapy at the Department of Nuclear Medicine, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to January 2020. Patients were categorized into progression and stable groups based on disease progression within five years post-treatment. Differences between groups were analyzed using chi-square test and logistic regression. Independent prognostic risk factors were identified using a Cox proportional hazards model. The Kaplan-Meier method with log-rank test was used to evaluate the impact of treatment on the prognosis of the progression group. Results The 3-year and 5-year survival rates of the 52 patients with RAIR-DTC were 88.5% and 73.1%, respectively. In the progression group, the rates were 81.8% and 57.6%. In the stable group, the rates were 100% and 100%. There were significant differences between the two groups in terms of age, presence of extrathyroidal extension, and the initial ¹³¹I treatment dose (P < 0.05). Univariate analysis indicated that the age, pre-ablation stimulated thyroglobulin level before the first ¹³¹I treatment, the neutrophil-to-lymphocyte ratio before the first treatment, and the sites of recurrence and metastasis were significantly associated with overall survival (P < 0.05). Multivariate analysis showed that age > 55 years (HR=12.40, 95% CI= 2.09-73.57, P=0.001) and distant metastasis (HR=24.47, 95% CI=4.17-143.75, P < 0.001) were independent risk factors for poor prognosis. Kaplan-Meier curve analysis showed that local surgery and/or targeted therapy significantly prolonged progression-free survival in the progression group (P < 0.001). Conclusion The prognosis for RAIR-DTC is poor, with advanced age and distant metastasis significantly associated with unfavorable outcomes. In elderly patients and those with extrathyroidal invasion, the treatment dose during initial ¹³¹I therapy may be appropriately increased to delay disease progression. For patients with disease progression, prompt local surgical intervention and/or targeted therapy is recommended.

Objective To analyze the prognosis and influencing factors in patients with radioiodine-refractory differentiated thyroid cancer (RAIR-DTC). Methods A retrospective analysis was conducted on 52 patients with RAIR-DTC who underwent ineffective ¹³¹I therapy at the Department of Nuclear Medicine, Cancer Hospital, Chinese Academy of Medical Sciences from October 2016 to January 2020. Patients were categorized into progression and stable groups based on disease progression within five years post-treatment. Differences between groups were analyzed using chi-square test and logistic regression. Independent prognostic risk factors were identified using a Cox proportional hazards model. The Kaplan-Meier method with log-rank test was used to evaluate the impact of treatment on the prognosis of the progression group. Results The 3-year and 5-year survival rates of the 52 patients with RAIR-DTC were 88.5% and 73.1%, respectively. In the progression group, the rates were 81.8% and 57.6%. In the stable group, the rates were 100% and 100%. There were significant differences between the two groups in terms of age, presence of extrathyroidal extension, and the initial ¹³¹I treatment dose (P < 0.05). Univariate analysis indicated that the age, pre-ablation stimulated thyroglobulin level before the first ¹³¹I treatment, the neutrophil-to-lymphocyte ratio before the first treatment, and the sites of recurrence and metastasis were significantly associated with overall survival (P < 0.05). Multivariate analysis showed that age > 55 years (HR=12.40, 95% CI= 2.09-73.57, P=0.001) and distant metastasis (HR=24.47, 95% CI=4.17-143.75, P < 0.001) were independent risk factors for poor prognosis. Kaplan-Meier curve analysis showed that local surgery and/or targeted therapy significantly prolonged progression-free survival in the progression group (P < 0.001). Conclusion The prognosis for RAIR-DTC is poor, with advanced age and distant metastasis significantly associated with unfavorable outcomes. In elderly patients and those with extrathyroidal invasion, the treatment dose during initial ¹³¹I therapy may be appropriately increased to delay disease progression. For patients with disease progression, prompt local surgical intervention and/or targeted therapy is recommended.

Objective:To investigate the application of sentinel lymph node biopsy (SLNB) in early-staged cervical cancer by laparoscopy.Methods:It was a prospective, single-arm, single-center clinical study. Seventy-eight cases of cervical cancer patients were collected from July 2015 to December 2018 at the Fourth Hospital of Hebei Medical University. All the patients were injected with tracer into the disease-free block of cervical tissue after anesthesia by the same surgeon who learned sentinel lymph node (SLN) mapping technique in Memorial Sloan-Kettering Cancer Center, and underwent SLN mapping followed by complete pelvic lymphadenectomy. Moreover, all the dissected lymph nodes were stained with hematoxylin eosin staining (HE) pathological examination. Besides, the negative SLN on hematoxylin-eosin staining were detected by immunohistochemistry cytokeratin staining micro-metastasis. To analyze the distribution, detection rate, false negative rate the sensitivity and negative predictive value of the SLN in early-staged cervical cancer by laparoscopy, and explore the value of SLN mapping in predicting the lymph nodes metastasis in early-staged cervical cancer.Results:The overall detection rate of SLN in cervical cancer was 99% (77/78), bilateral detection rate was 87% (68/78). The average of 12.4 lymph node (LN) and 3.6 SLN were dissected for each patients each side. SLN of cervical cancer were mainly distributed in the obturator space (61.5%, 343/558), followed by external iliac (23.5%, 131/558), common iliac (7.3%, 41/558), para-uterine (3.8%, 21/558), internal iliac (2.2%, 12/558), para abdominal aorta (1.1%, 6/558), and anterior sacral lymphatic drainage area (0.7%, 4/558). Fourteen cases of LN metastasis were found among all 78 cases. There were a total of 38 positive LN, including 26 SLN metastasis and 12 none sentinel LN metastasis. Through immunohistochemical staining and pathological ultra-staging, 1 SLN was found to be isolated tumor cells (ITC), and 5 SLNs were found to be micro-metastases (MIC), accounting for 23% (6/26) of positive SLN. SLN mapping with pathological ultra-staging improved the prediction of LN metastasis in cervical cancer (2/14). Metastatic SLN mainly distributed in the obturator space (65%, 17/26), peri-uterine region (12%, 3/26), common iliac region (15%, 4/26), and external iliac region (8%, 2/26). The consistency of the diagnosis of lymph node metastasis by SLN biopsy and postoperative retroperitoneal lymph node metastasis showed that the Kappa value was 1.000 ( P<0.001), indicated that the metastasis status of SLN and retroperitoneal lymph node were completely consistent. The sensitivity, specificity, accuracy, false-negative rate, and negative predictive value of SLN biopsy in the diagnosis of lymph node metastasis were 100%, 100%, 100%, 0, and 100%, respectively. Conclusions:SLN in early-staged cervical cancer patients were mainly distributed in the obturator and external iliac space, pathalogical ultra-staging of SLN could improve the prediction of LN metastasis. Intraoperative SLN mapping is safe, feasible and could predict the state of retroperitoneal LN metastasis in early-staged cervical cancer. SLNB may replace systemic pelvic lymphadenectomy.

OBJECTIVE: To study the influence of maternal sex chromosomal abnormalities on the prediction of fetal sex chromosome abnormalities (SCAs) by non-invasive prenatal testing (NIPT). METHODS: Thirty-six pregnant women with a prediction for fetal SCAs by NIPT were verified as false positive after prenatal diagnosis using amniotic fluid samples. With informed consent, these women were subjected to chromosomal karyotyping or copy number variations (CNVs) analysis through high-throughput sequencing. RESULTS: Sex chromosomal abnormalities were found in 8 women, which yielded an abnormal rate of 22.22% (8/36). Among these, 3 had sex chromosome aneuploidies (47, XXX), 4 had sex chromosome mosaicisms, and 1 carried structural chromosomal abnormalities. Reanalysis of the results of NIPT were consistent with the maternal CNVs by large. With the ratio of cffDNA (ChrX)/cffDNA was more than 2, 6 of the eight women were found to harbor sex chromosome abnormalities, and the fetal karyotype was normal. However, with a ratio of less than 2, only 2 of the 38 pregnant women had sex chromosome abnormalities, and 10 of the fetuses were confirmed as positive. CONCLUSION The presence of maternal sex chromosomal abnormalities can greatly influence the result of NIPT, which may also be an important reason for false prediction for fetal SCAs by NIPT. When NIPT indicates abnormal SCAs, it is necessary to analyze maternal sex chromosomes. The ratio of cffDNA(ChrX)/cffDNA may help to determine the source of abnormal signals.

Objective To explore the changes in gravida's age and its influences on maternal and neonatal complications under China's two-child policy.Methods This study retrospectively analyzed the clinical data such as adverse gestational complications and fetal condition of 42 771 gravidas delivering at Changzhou Maternity and Child Health Care Hospital Affiliated to Nanjing Medical University from July 2013 to December 2017.According to their age at delivery,they were divided into three groups:the younger maternal age group (1 140 cases,＜20 years),the advanced maternal age group (4 307 cases,≥ 35 years) and the median maternal age group (37 324 cases,≥ 20 and ＜35 years).Chi-square test was used to compare the differences among groups.Cochran-Armitage test was used for trend analysis.The risks of various complications in younger and advanced maternal age groups were analyzed by binary logistic regression analysis.Results (1) The proportion of advanced maternal age pregnancies tended to rise gradually year by year (Z=-9.909,P＜0.001).However,the figure of younger gravidas remained low and presented a downward trend (Z=10.685,P＜0.001).(2) The incidence of pregnant complications in the younger,advanced and the median maternal age groups were 52.8％ (602/1 140),72.3％ (3 116/4 307) and 56.5％ (21 091/37 324),respectively.Compared with the median maternal age group,the advanced maternal age group was at greater risks of premature delivery [9.0％ (3 343/37 324) vs 11.6％ (499/4 307),x2=124.233,P＜0.001],fetal growth restriction (FGR) [0.6％ (218/37 324) vs 1.2％ (50/4 307),x2=20.087,P＜0.001],postpartum hemorrhage [5.7％ (2 120/37 324) vs 7.8％ (336/4 307),x2=31.299,P＜0.05],hypertensive disorders in pregnancy(HDP) [4.2％ (1 561/37 324) vs 8.7％ (376/4 307),x2=180.013,P＜0.001],gestational diabetes mellitus (GDM) [7.6％ (2 845/37 324) vs 15.1％ (650/4 307),x2=280.126,P＜0.001]and placenta previa [1.7％ (621/37 324) vs 3.8％ (165/4 307),x2=97.904,P＜0.001],and the younger maternal age group was at greater risks of HDP [4.2％ (1 561/37 324) vs 5.9％ (67/1 140),x2=4.234,P=0.040],fetal distress [3.5％ (1 325/37 324) vs 5.1％ (58/1 140),x2=7.546,P=0.006],premature delivery [9.0％ (3 343/37 324) vs 15.0％ (171/1 140),22=48.668,P＜0.001] and FGR [0.6％ (218/37 324) vs 1.1％ (12/1 140),x2=4.086,P=0.043].(3) Gestational complications in the younger maternal age group were mainly related to the fetuses such as premature rupture of membranes (PROM) and premature delivery,while the advanced maternal age group had a higher incidence of maternal complications,especially GDM and HDP.(4) Most of the gravidas of advanced maternal age with HDP developed severe preeclampsia (47.9％,180/376),while mild preeclampsia was dominant in the median maternal aged HDP women (45.4％,708/1 561).(5) The advanced maternal age group had higher risk of stillbirth,premature delivery,FGR,placenta previa,GDM,HDP and postpartum hemorrhage [OR(95％CI):1.91 (1.29-2.84),1.33 (1.21-1.46),1.66 (1.21-2.28),2.56 (2.15-3.04),2.39 (2.19-2.61),2.36 (2.11-2.65),1.46 (1.31-1.62);all P＜0.05],but lower risks of fetal distress and PROM [OR(95％CI):0.79 (0.65-0.95) and 0.88 (0.81-0.96);both P＜0.05].The younger maternal age group had a higher risk of premature delivery [OR(95％CI):1.97 (1.61-2.40);P＜0.001],but significant lower risks of PROM and GDM [OR(95％CI):0.77 (0.62-0.95) and 0.05 (0.02-0.16);both P＜0.05].Conclusions Maternal age is closely related to the adverse outcomes of pregnancy.Two-child policy in China will bring about changes in maternal age and composition of pregnant complications.

OBJECTIVETo explore the cause of failure of non-invasive prenatal testing (NIPT) using cell-free fetal DNA from peripheral maternal blood.

METHODSA total of 31 832 cases of NIPT were retrospectively analyzed. The clinical data of pregnant women were analyzed and the outcome of pregnancy was followed up.

RESULTSAmong the 31 832 cases, 200 patients have failed for the first NIPT test. Second test has succeeded in 171 (85.9%) of 199 cases, while 28 cases (14.1%) still yielded no effective results. This gave rise for a total failure rate of 0.088%. Of the 28 cases, 11 (39.2%) were due to high content of total free DNA and could not be sequenced, 17 (60.7%) were found to have the fetal DNA content of less than 4%. Among the 171 cases which have obtained a valid result, NIPT showed that there were 4 patients with high risk of trisomy 21, 18 cases with high risk of 18 trisomy and 1 case with high risk of 13 trisomy. Karyotyping analysis of the amniocytic chromosomes has identified 3 cases with 47,XN,+21, 1 case with 46,XN,rob(21;21), 1 case with 47,XN,+18, while the 13 trisomy case was found to be false positive. For the 28 cases with failed NIPT retest, 14 had normal delivery, with no anomaly noticed in the neonates. Nine patients had opted for artificial abortion during middle or late pregnancy due to maternal factors (4 cases) or fetal factors (5 cases). Four patients developed complications of pregnancy. One case was in good condition upon follow-up. Four cases were lost during follow-up. Of the 11 pregnant women who had failed the NIPT test due to high content of total free DNA, 6 (54.5%) had opted for artificial abortion during midterm pregnancy, which was significantly higher than that of pregnant women with low free DNA content (17.6%).

CONCLUSIONFailure of NIPT testing should attract attention from researchers. Failure of single NIPT test should not be regarded as a high risk signal for fetal chromosomal aneuploidies. For those where the test has failed again, genetic counseling and strengthened perinatal care should be provided for the pregnant women.

Objective To explore the correlations of lung resistance protein (LRP) and glutathione S transferase π (GST-π) to chemotherapy resistance and prognosis of epithelial ovarian cancer.Methods The expressions of LRP and GST-π in epithelial ovarian cancer were examined with immunohistochemistry.Correlations of LRP and GST-π to chemotherapy efficacy and survival time after operation were analyzed.Results The short-term efficacy rates of ovarian cancer were lower in patients with positive expressions of LRP and GST-π than those with negative expressions [61.2％,61.7％ vs 94.1％,89.5％,x2 =6.47,4.94,P =0.011,P =0.026].The positive rates of LRP and GST-π were significant higher in patients with chemotherapy resistance than in those sensitive to chemotherapy [91.3％,87.0％ vs 65.1％,62.8％,P ＜ 0.05].Log-rank test showed that patients with positive LRP and GST-π had shorter survival time than those negative,and patients with both positive LRP and GST-π had shorter survival time than those both negative (P ＜ 0.05).Conclusions The expressions of LRP and GST-π in epithelial ovarian cancer could be used to predict chemotherapy resistance and prognosis of patients.

Objective To investigate the effect of bioactivity glass 45S5-silk fibroin(BG45S5-SF) membrane on growth, proliferation and differentiation of human dental pulp stem cells(hDPSC), and to provide new ideas and method for the regeneration of pulp-dentine complex.Methods hDPSC seed on pure silk fibroin membrane (protein membrane group) and BG45S5-SF membrane with different concentrations(1 000, 5 000 mg/L, composite membrane group A and B, respectively) were prepared, and the materials were incubated in cell culture fluid for 24 h.No material membrane orifice plate was used as blank control group.Contact angle meter was used to measure surface contact angle of protein membrane and composite membrane group(each group had three repeated holes).Cell proliferation was assessed by cell counting kit-8 on the 4, 7, 14, and 21 days.The state of adhesion and growth of hDPSC on the materials surface was evaluated by scanning electron microscopy and cytoskeleton staining;and alkaline phosphatase (ALP) activity was measured to evaluate the cell differentiation potential.The expression of odontoblastic differentiation-related genes was measured by real-time PCR.Results Surface contact angle of the protein membrane group and composite membrane group A and group B were 89.51°±0.12°, 70.32°±0.07° and 71.31°±0.09° respectively.hDPSC adhered well on each materials surface on the 7, 14, 21 days, ALP activity and differentiation genes of composite membrane group A and B rised more significantly than the blank control group and protein membrane group did (P＜0.05).Dentin matrix protein1(DMP-1), dentin sialoprotein(DSP), ALP, osteoealcin(OC) mRNA expression reached peak on the 14 days in group A, and in group B on the 21 days.Bone sialoprotein(BSP) mRNA expression in both group A and B reached peak on the 21 days.Conclusions BG45S5-SF membrane is able to support the proliferation and showed the potential of odontoblastic differentiation for hDPSC.This finding suggests that BG45S5-SF membrane was a kind of tissue engineering film material with the regeneration potential for pulp-dentine complex.

Objective To establish a method for detecting 3 common toxigenic molds (Aspergillus, Penicillium, and Fusarium) based on non-modified magnetic beads coupled with multiple real-time PCR (NMB-multiple qPCR). Methods The primers and genus-specific probes were designed based on the rDNA sequences to develop a multiple real-time PCR using non-modified magnetic bead to enrichment of fungal spores. The sensitivity, specificity and repeatability of this assay were evaluated. Results The detection limit of this assay for spiked samples was 104 CFU/g, demonstrating a 10-fold greater detection sensitivity of this assay than that of real-time PCR. The NMB-multiple qPCR assay also showed good specificity and reproducibility and yielded comparable results with those by traditional colony counting method for spiked samples (P>0.05). Conclusion NMB-multiple qPCR assay we established allows rapid and sensitive detection of common mycotoxigenic fungi in paprika.

Objective To establish a method for detecting 3 common toxigenic molds (Aspergillus, Penicillium, and Fusarium) based on non-modified magnetic beads coupled with multiple real-time PCR (NMB-multiple qPCR). Methods The primers and genus-specific probes were designed based on the rDNA sequences to develop a multiple real-time PCR using non-modified magnetic bead to enrichment of fungal spores. The sensitivity, specificity and repeatability of this assay were evaluated. Results The detection limit of this assay for spiked samples was 104 CFU/g, demonstrating a 10-fold greater detection sensitivity of this assay than that of real-time PCR. The NMB-multiple qPCR assay also showed good specificity and reproducibility and yielded comparable results with those by traditional colony counting method for spiked samples (P>0.05). Conclusion NMB-multiple qPCR assay we established allows rapid and sensitive detection of common mycotoxigenic fungi in paprika.