Anti-CD20 monoclonal antibodies for the treatment of refractory nephrotic syndrome （RNS） in children. The first- generation rituximab is the most widely used in clinical practice； it shows definite efficacy in children with RNS， is recommended by guidelines， particularly for achieving a high remission rate in minimal change nephrosis， and can significantly reduce the cumulative use of glucocorticoids and immunosuppressants. The second-generation ofatumumab has potential as an alternative treatment for patients who are intolerant or resistant to rituximab， while the third-generation obinutuzumab has shown efficacy in complex cases such as rituximab resistance or post-transplant recurrence. However， there is still controversy regarding the optimization of rituximab treatment dosage and whether ofatumumab and obinutuzumab offer greater advantages than rituximab for the treatment of RNS in children. The most common adverse reaction induced by anti-CD20 monoclonal antibodies is infusion reactions， and long-term adverse events mainly include increased risks of sustained immunosuppression and infections. Rituximab has significant economic advantages for the treatment of RNS， but additional pharmacoeconomic research based on China’s healthcare environment is needed to evaluate the cost-effectiveness of ofatumumab and obinutuzumab in this population. Given that the current use of ofatumumab and obinutuzumab in this field is considered off-label use， clinical application should only proceed after a rigorous evaluation of the patient’s benefits and risks.

ObjectiveTo explore the effects of genetic variation of obesity-related biological pathways and gene-obesity interactions on the incidence of gastric cancer, so as to better understand the pathogenesis of gastric cancer and help identify high-risk populations for individualized prevention of gastric cancer. MethodsA case-control study based on the Shanghai Suburban Adult Cohort and Biobank study (SSACB) was conducted on the cases with gastric cancer. A total of 267 cases with gastric cancer and 267 healthy controls matched 1∶1 by age and gender using propensity score were included in the study. After genome-wide genotyping, quality control and imputation, 19 250 single nucleotide polymorphism (SNP) sites from 115 genes in 4 obesity-related biological pathways were extracted. Univariate and multivariate logistic regression analyses were used to evaluate the association between these SNP sites and the risk of gastric cancer, and false positive report probability (FPRP) was used for multiple test correction.Data from Biobank Japan (BBJ) and FinnGen public accessible databases were used to validate significant SNP sites. For validated sites, expression quantitative trait loci (eQTL) analysis and differentially expressed genes analysis were further performed. Additive and multiplicative interactions were used to evaluate the gene-obesity interactions on the incidence of gastric cancer. Additive interaction evaluation indicators included relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP) and synergy index (SI), while multiplicative interaction evaluation indicators include OR_GxE and P_inter. ResultsA total of 41 SNP sites were significantly associated with the onset of gastric cancer (P_adj<0.05, FPRP_0.1<0.1), among which 7 groups of haplotype blocks were formed. ACACB/ rs2268401 [SSACB: P=0.005, BBJ: P=0.049], HRAS/ rs12785860 (SSACB: P<0.001, FinnGen: P=0.045), and PTPN1/ rs6095985 (SSACB: P<0.001, FinnGen: P=0.023) were significantly associated with the risk of gastric cancer after validation in different populations. Among which, the G allele of HRAS/ rs12785860 was correlated with the downregulation of HRAS mRNA expression (P<0.001), and the expression level of HRAS in gastric cancer tissues was higher than that in adjacent normal tissues (P<0.001). Additionaly, JAK1/rs11208559 showed a positive additive interaction with waist circumstance (WC) on the risk of gastric cancer [RERI=2.29(0.06~4.53), AP=0.57(0.23~0.90), SI=4.03(2.20~5.87)]. ConclusionObesity-related biological pathway SNP sites and their haplotypes are associated with the risk of gastric cancer, suggesting that genetic variations in obesity pathways may affect gastric cancer. The HRAS/ rs12785860 is significantly associated with downregulation of HRAS gene expression, which may serve as a potential genetic marker for gastric cancer. JAK1/rs11208559 interacts with obesity additively on the risk of gastric cancer. Individuals with GC+CC genotypes and pre-central or central obesity have an increased risk of gastric cancer, providing clues and evidences for individualized prevention of gastric cancer.

BACKGROUND: Massive bleeding is the main concern for the management of placenta percreta (PP). Intra-abdominal aortic balloon occlusion (IABO) is one method for pelvic devascularization, but the efficacy of IABO is uncertain. This study aims to investigate the outcomes of IABO in PP patients. METHODS: We retrospectively reviewed the clinical data of PP cases from six tertiary centers in China between January 2011 and December 2015. PP cases with/without the use of IABO were analyzed. Propensity score matching analysis was performed to reduce the effect of selection bias. Postpartum hemorrhage (PPH) and the rate of hysterectomy, as well as neonatal outcomes, were analyzed. RESULTS: One hundred and thirty-two matched pairs of patients were included in the final analysis. Compared with the control group, maternal outcomes, including PPH (68.9% vs. 87.9%, χ2 = 13.984, P < 0.001), hysterectomy (8.3% vs. 65.2%, χ2 = 91.672, P < 0.001), and repeated surgery (1.5% vs. 12.1%, χ2 = 11.686, P = 0.001) were significantly reduced in the IABO group. For neonatal outcomes, Apgar scores at 1 minute (8.67 ± 1.79 vs. 8.53 ± 1.68, t = -0.638, P = 0.947) and 5 minutes (9.43 ± 1.55 vs. 9.53 ± 1.26, t = 0.566, P = 0.293) were not significantly different between the two groups. CONCLUSIONS IABO can significantly reduce blood loss, hysterectomies, and repeated surgeries. This procedure has not shown harmful effects on neonatal outcomes.
Aorta ; Balloon Occlusion/methods* ; Blood Loss, Surgical ; Female ; Humans ; Hysterectomy ; Infant, Newborn ; Placenta Accreta/surgery* ; Placenta Previa/surgery* ; Postpartum Hemorrhage ; Pregnancy ; Retrospective Studies

Objective To evaluate the risk factors and sonographic findings of pregnancies complicated by placenta increta or placenta percreta. Methods Totally, 2219 cases were retrospectively analyzed from 20 tertiary hospitals in China from January 2011 to December 2015. The data were collected based on the original case records. All cases were divided into two groups, the placenta increta (PI) group (79.1％, 1755/2219) and the placenta percreta (PP) group (20.9％, 464/2219), according to the degree of placental implantation. The risk factors and sonographic findings of placenta increta or percreta were analyzed by uni-factor and logistic regression statistic methods. Results The risk factors associated with the degree of placental implantation were age, gravida, previous abortion or miscarriage, previous cesarean sections, and placenta previa (all P<0.05), especially, previous cesarean sections (χ2=157.961) and placenta previa (χ2=91.759). Sonographic findings could be used to predict the degree of placental invasion especially the boundaries between placenta and uterine serosa, the boundary between placenta and myometrium, the disruption of the placental-uterine wall interface and loss of the normal retroplacental hypoechoic zone(all P<0.01). Conclusions Previous cesarean sections and placenta previa are the main independent risk factors associated with the degree of placenta implantation. Ultrasound could be used to make a prenatal suggestive diagnosis of placenta accreta spectrum disorders.

Objective To investigate the level of mammalian target of rapamycin (mTOR) in serum and the expression of mTOR,nuclear factor-κ B (NF-κ B) and sterol regulatory element binding protein 2 (SREBP2) in placenta among gravidas with preeclampsia.Methods From August 2015 to August 2017,60 gravidas including 40 with severe preeclampsia (SPE) and 20 with mild preeclampsia (MPE) who underwent regular prenatal care and delivered by caesarean section were selected from the Second Xiangya Hospital of Central South University.According to the ratio of 2:1,30 gravidas who delivered through caesarean section due to cephalopelvic disproportion,abnormal fetal position or social factors during the same period were enrolled as the control group.Peripheral blood samples were obtained to determine the concentrations of serum mTOR,high density lipoprotein-cholesterol (HDL-C),low density lipoprotein-cholesterol (LDL-C),triglyceride (TG) and total cholesterol (TC) by enzyme linked immunosorbent assay (ELISA).The expression of mTOR,phospho-mTOR (p-mTOR),NF-κ B and SREBP2 in placenta were measured by Western blot.Clinical datas were statistically analyzed using one-way ANOVA,Bonferroni or Dunnett's T3 test,and Pearson's correlation analysis.Results (1) The serum levels of mTOR and LDL-C in the SPE and MPE group were both higher than that in the control group [mTOR:(11 765.56± 1 698.95) and (8 278.56±1 106.59) vs (4 366.19±716.43) pg/ml;LDL-C:(7.81 ±1.90) and (4.11 ±0.75) vs (2.42±0.45) mmol/L,all P＜0.05].Furthermore the serum levels of mTOR and LDL-C in the SPE group were both higher than those in the MPE group (both P＜0.05).The serum level of HDL-C in the SPE and MPE group were lower than that in the control group [(0.36±0.12) and (0.85±0.11) vs (1.33± 0.16) mmol/L,both P＜0.05],and that in the SPE group was lower than that in the MPE group (P＜0.05).Women in the SPE group showed higher TG level when comparing with the MPE and control group [(46.19± 18.92)vs (35.55±6.54) and (33.24±9.78) nmol/L,both P＜0.05],while the TC levels in the SPE and MPE group were higher than that in the control group[(24.72±7.17) and (21.83±4.19) vs (16.32±3.88) nmol/L,both P＜0.05].(2) The placental expressions of mTOR,p-mTOR,NF-κ B and SREBP2 protein in the SPE and MPE group were higher compared with that in the control group [mTOR:(0.52±0.09) and (0.38±0.08) vs (0.24±0.05);p-mTOR:(0.42±0.08) and (0.26±0.05) vs (0.14±0.03);NF-κ B:(0.58±0.10) and (0.36±0.05) vs (0.21 ± 0.03);SREBP2:(0.52 ± 0.08) and (0.33 ± 0.05) vs (0.20 ± 0.05);all P＜0.05],and those expressions of the SPE group also higher comparing with the MPE group.Otherwise the p-mTOR/mTOR ratios in the SPE group and MPE group were higher than that in the control group [(0.75±0.10) and (0.69±0.14) vs (0.59 ±0.13),both P＜0.05].(3) Pearson's correlation analysis showed that serum level of mTOR and placental expressions of mTOR and p-mTOR in the SPE group were positively correlated with serum LDL-C (r=0.682,0.584 and 0.504,all P＜0.05),TG (r=0.612,0.658 and 0.422,all P＜0.05),while serum level of mTOR and placental expressions of mTOR in the SPE group were positively correlated with TC (r=0.598 and 0.452,all P＜0.05),but were negatively correlated with serum HDL-C (r=-0.375,-0.442 and-0.390,all P＜0.05).The NF-κ B expression in placenta of the SPE group was significantly positively correlated with the mTOR expression in placenta and serum LDL-C (r=0.375 and 0.391,both P＜0.05).Moreover,in the SPE group,the SREBP2 level in placenta was significantly positively correlated with placental expression of mTOR and serum TC level (r=0.364 and 0.392,both P＜0.05).(4) In the MPE group,mTOR level in serum and levels of mTOR and p-mTOR in placenta were significantly positively correlated with serum LDL-C (r=0.813,0.641 and 0.465,all P＜0.05),TG (r=0.646,0.529 and 0.502,all P＜0.05) and TC (r=0.558,0.482 and 0.483,all P＜0.05),while the level of serum mTOR was negatively correlated with the level of serum HDL-C (r=-0.606,P＜0.05).The NF-κ B level in placenta in MPE group was positively correlated with the mTOR in placenta and the serum LDL-C (r=0.458 and 0.595,both P＜0.05),while the SREBP2 level in placenta was significantly positively correlated with mTOR in placenta and serum TC (r=0.580,0.560,respectively;both P＜0.05) in the MPE group.Conclusions mTOR,NF-κ B and SREBP2 may play important roles in the onset and development of preeclampsia by interfering lipid metabolism.

Orthodontic treatment is more complicated when both soft and hard tissues must be considered because an impacted maxillary canine has important effects on function and esthetics. Compared with extraction of impacted maxillary canines, exposure followed by orthodontic traction can improve esthetics and better protect the patient's teeth and alveolar bone. Therefore, in order to achieve desirable tooth movement with minimal unexpected complications, a precise diagnosis is indispensable to establish an effective and efficient force system. In this report, we describe the case of a 31-year-old patient who had a labio-palatal horizontally impacted maxillary left canine with a severe occlusal alveolar bone defect and a missing maxillary left first premolar. Herein, with the aid of three-dimensional imaging, sequential traction was performed with a three-directional force device that finally achieved acceptable occlusion by bringing the horizontally impacted maxillary left canine into alignment. The maxillary left canine had normal gingival contours and was surrounded by a substantial amount of regenerated alveolar bone. The 1-year follow-up stability assessment demonstrated that the esthetic and functional outcomes were successful.

Objective To evaluate the protective effect of Bletilla striata polysaccharide ( BSPS) on immunological and chemical liver injury in mice. Methods Thirty Kunming male mice were randomly divided into five groups, including the normal control group,model control group,and low-,middle-,and high-dose BSPS groups (n=6 each).Tail vein injection of ConA was carried out to establish the ConA-induced liver injury model.After different treatments,all the animals were sacrificed,and the plasma levels of ALT and AST were tested.Additionally,sixty Kunming male mice were randomly divided into six groups,including the normal control group,model control group,silymarin group,and low-,middle-,and high-dose BSPS groups (n=10 each).Tail vein injection of CCl4 was performed to establish the CCl4-induced acute liver injury model.After different treatments,the plasma levels of ALT and GSH were tested.The effects of BSPS on the weights of the liver and spleen were examined. Results The levels of ALT and AST were reduced in BSPS-treated mice when compared with those experiencing only ConA-induced liver injury ( model control group) ,and significant difference was found between the middle-and high-dose BSPS groups and the model control group (P<0.01,P<0.05).The weights of the liver and spleen and the level of ALT were reduced in BSPS-treated mice as compared with those with only CCl4-induced acute liver injury (model control group),while the level of GSH was significantly increased in middle-and high-dose BSPS groups (P<0.05). Conclusion BSPS at low,middle,and high doses can prevent against the ConA-induced immunological liver injury and CCl4-induced acute liver injury in mice.

Objective To investigate the efficacy of endovascular stenting for aortic arch artery stenosis after nasopharyngeal carcinoma radiotherapy. Methods The clinical data of 8 patients with symptomatic severe aortic arch artery stenosis after nasopharyngeal carcinoma radiotherapy were analyzed retrospectively. The patients were all received endovascular stenting,and their improvement of cerebral ischemic symptoms was observed. They were followed up by cervical color Doppler ultrasound.Results The whole brain vascular DSA confirmed that there were 24 severe arterial stenoses on the aortic arch arteries of extracranial segments in 8 patients,including 11 in internal carotid artery,2 in common carotid artery,10 in vertebral artery and 1 in subclavian artery. The patients were treated with vascular angioplasty and stenting respectively. All the patients were followed up for 1 year;there were no recurrence of cerebral ischemic symptoms.Cervical color Doppler ultrasound did not reveal any obvious restenosis. Conclusion Endovascular stent angioplasty for the treatment of aortic arch artery stenosis after nasopharyngeal carcinoma radiotherapy is relatively safe and feasible.

OBJECTIVE: To evaluate the safety, effectiveness and complications of serial invasive prenatal diagnostic techniques, and to investigate the prenatal diagnosis indication as well as to analyze the abnormal chromosomal karyotype. METHODS: We retrospectively studied all patients from March 2005 to May 2012 who received amniocentesis and cordocentesis in the prenatal diagnosis center of Second Xiangya Hospital. The indication of the procedure, successful rate and complications were evaluated, and 25 abnormal chromosome nuclear types were analyzed. RESULTS: A total of 669 patients received invasive prenatal diagnosis from March 2005 to May 2012 in Second Xiangya Hospital: 598 received amniocentesis and 71 cordocentesis carried out. Compared with the cordocentesis group, the amniocentesis group had higher achievement ratio (91.54% vs 100%, P<0.05), lower spontaneous abortion rate (1.41% vs 0.33%, P<0.05), fewer abnormal karyotypes (11.27% vs 2.84%, P<0.05) and lower expenditure (880 yuan vs 800 yuan, P<0.05). Positive screening, advanced maternal age, and ultrasonography abnormality were the top 3 indications of amniocentesis and cordocentesis. We found 25 abnormal karyotypes, including 6 cases of trisomy 21, 4 sex chromosomal abnormalities, 7 autosomal balanced translocations, 1 marker chromosome, and 7 mosaics. CONCLUSION As a widely used invasive prenatal diagnosis, amniocentesis is safe and effective. The complications of cordocentesis are much higher than those of amniocentesis, which is not a proper routine procedure for prenatal diagnosis of abnormal karyotype. The analysis of karyotype not only can identify fetal chromosome abnormality, but also provide the scientific basis for pregnancy continuation, thus reducing the ratio of birth defect.
Abnormal Karyotype ; statistics & numerical data ; Adult ; Amniocentesis ; methods ; Cordocentesis ; adverse effects ; methods ; Evaluation Studies as Topic ; Female ; Humans ; Karyotyping ; methods ; Pregnancy ; Prenatal Diagnosis ; methods ; Retrospective Studies

OBJECTIVE: To determine the effect of human corticotrophin-releasing hormone (CRH) on the expression of connexin-43 phosphate (P-Cx43) in human myometrial smooth muscle cells (SMCs) and the function of cell gap junction intercellular communication in SMCs. METHODS: Human non-conceive myometial SMCs were cultured with different concentrations of CRH (0, 5.85, 58.5, 585 and 5850 pmol/L). Western blot was used to test P-Cx43 and Cx43 non-phosphate (NP-Cx43) of protein expression. Cell scratch was used to test cell gap junction intercellular communication opening status in human myometrial SMCs. RESULTS: Compared with the control group, the expression of P-Cx43 was higher in the CRH groups (P<0.01), and was concentration-dependent. There was no significant difference in NPCx43 between the control group and the CRH groups (P>0.05). The transmission of cell layers in the CRH groups was higher than that in the control group (P<0.01), and as the concentration of CRH increased, the time was concentration-dependent (P<0.01). CONCLUSION CRH can enhance the expression of P-Cx43 and the function of gap junction intercellular communication in the primary cultured myometrial SMCs.
Cell Communication ; drug effects ; Cells, Cultured ; Connexin 43 ; metabolism ; Corticotropin-Releasing Hormone ; pharmacology ; Female ; Gap Junctions ; drug effects ; Humans ; Myocytes, Smooth Muscle ; metabolism ; Myometrium ; cytology ; Phosphorylation ; drug effects