This report describes a case of maturity-onset diabetes of the young(MODY)type 3(MODY3)complicated with type 5(MODY5),including the patient's clinical features,diagnosis,and treatment,and reviews relevant literature.Using next-generation sequencing of MODY(types 1-14)gene exons and Sanger sequencing for verification,the patient and her mother were assessed.Based on the clinical phenotype and genetic test results,the patient was diagnosed as MODY3 combined with MODY5.Treatment included insulin and linagliptin,with monitoring of blood glucose changes.Clinicians should enhance their understanding of MODY clinical phenotypes.In adolescents with diabetes who have congenital pancreatic and renal developmental defects,elevated high-density lipoprotein cholesterol,no spontaneous ketosis,insulin secretion defects,negative pancreatic autoantibodies,no significant insulin resistance,and who are not obese,gene testing should be conducted to screen for MODY.Accurate diagnosis and personalized treatment can aid in achieving glycemic control,improving quality of life,and optimizing reproductive planning.

Purpose To analyze the impact of clinicopatho-logical factors on residual tumor burden(RCB)grading system and Miller-Payne(MP)grading system in non-specific invasive breast cancer patients after neoadjuvant chemotherapy,and to explore the predictive value of the two grading systems for patient survival.Methods The clinical data of 177 patients with non-specific invasive breast cancer diagnosed by preoperative punc-ture and treated with neoadjuvant chemotherapy were retrospec-tively analyzed.The relationship of RCB grading system or MP grading system with disease free survival(DFS)and overall sur-vival(OS)was studied,and the value of the two systems in predicting prognosis was analyzed and compared.Results RCB grading was related to menstrual status,histological grading be-fore treatment,and lymph node metastasis after treatment;MP grading was related to pre-treatment histological grading,post-treatment lymph node metastasis,and pre-treatment molecular typing.By evaluating the ROC curve of recurrence and survival and comparing the area under curve(AUC),it was shown that RCB grading system was superior to MP grading system in pre-dicting recurrence and evaluating survival.Univariate and multi-variate survival analysis showed that pre-treatment clinical stag-ing,post-treatment lymph node metastasis,and RCB grading were independent factors for DFS.Pre-treatment clinical stag-ing,pre-treatment molecular typing,and RCB grading were in-dependent factors for OS,while MP grading was not an inde-pendent factor for DFS and OS.Conclusion RCB grading sys-tem has a higher predictive value for patient survival than MP grading system.RCB grading evaluation system is recommended as evaluation system for non-specific invasive breast cancer after neoadjuvant chemotherapy.

China prospective multicenter birth cohort (Prospective Omics Health Atlas birth cohort, POHA birth cohort) study was officially launched in 2022. This study, in collaboration with 12 participating units, aims to establish a high-quality, multidimensional cohort comprising 20 000 naturally conceived families and assisted reproductive families. The study involves long-term follow-up of parents and offspring, with corresponding biological samples collected at key time points. Through multi-omics testing and analysis, the study aims to conduct multi-omics big data research across the entire maternal and infant life cycle. The goal is to identify new biomarkers for maternal and infant diseases and provide scientific evidence for risk prediction related to maternal diseases and neonatal health.

Objective:To establish a disease risk prediction model for the newborn screening system of inherited metabolic diseases by artificial intelligence technology.Methods:This was a retrospectively study. Newborn screening data ( n=5 907 547) from February 2010 to May 2019 from 31 hospitals in China and verified data ( n=3 028) from 34 hospitals of the same period were collected to establish the artificial intelligence model for the prediction of inherited metabolic diseases in neonates. The validity of the artificial intelligence disease risk prediction model was verified by 360 814 newborns ' screening data from January 2018 to September 2018 through a single-blind experiment. The effectiveness of the artificial intelligence disease risk prediction model was verified by comparing the detection rate of clinically confirmed cases, the positive rate of initial screening and the positive predictive value between the clinicians and the artificial intelligence prediction model of inherited metabolic diseases. Results:A total of 3 665 697 newborns ' screening data were collected including 3 019 cases ' positive data to establish the 16 artificial intelligence models for 32 inherited metabolic diseases. The single-blind experiment ( n=360 814) showed that 45 clinically diagnosed infants were detected by both artificial intelligence model and clinicians. A total of 2 684 cases were positive in tandem mass spectrometry screening and 1 694 cases were with high risk in artificial intelligence prediction model of inherited metabolic diseases, with the positive rates of tandem 0.74% (2 684/360 814)and 0.46% (1 694/360 814), respectively. Compared to clinicians, the positive rate of newborns was reduced by 36.89% (990/2 684) after the application of the artificial intelligence model, and the positive predictive values of clinicians and artificial intelligence prediction model of inherited metabolic diseases were 1.68% (45/2 684) and 2.66% (45/1 694) respectively. Conclusion:An accurate, fast, and the lower false positive rate auxiliary diagnosis system for neonatal inherited metabolic diseases by artificial intelligence technology has been established, which may have an important clinical value.

Objective:To investigate the etiology of necrotizing pneumonia (NP) in children and the clinical characteristics of NP caused by different pathogens in China.Methods:A retrospective, case-control study was performed in children with NP who were admitted to 13 hospitals in China from January 2008 to December 2019. The demographic and clinical information, laboratory data, etiological and radiological findings were analyzed. The data were divided into three groups based on the following years: 2008-2011, 2012-2015 and 2016-2019, and the distribution characteristics of the pathogens in different period were compared. Meanwhile, the pathogens of pediatric NP in the southern and northern China were compared. And the clinical characteristics of the Mycoplasma pneumoniae (MP) NP and the bacterial NP were also compared. T-test or Mann-Whitney nonparametric test was used for comparison of numerical variables, and χ 2 test was used for categorical variables. Results:A total of 494 children with NP were enrolled, the median ages were 4.7 (0.1-15.3) years, including 272 boys and 222 girls. Among these patients, pathogens were identified in 347 cases and the pathogen was unclear in the remaining 147 cases. The main pathogens were MP (238 cases), Streptococcus pneumoniae (SP) (61 cases), Staphylococcus aureus (SA) (51 cases), Pseudomonas aeruginosa (13 cases), Haemophilus influenzae (10 cases), adenovirus (10 cases), and influenza virus A (7 cases), respectively. MP was the most common pathogen in all three periods and the proportion increased yearly. The proportion of MP in 2016-2019 was significantly higher than that in 2012-2015 (52.1% (197/378) vs. 36.8% (32/87), χ 2= 6.654, P=0.010), while there was no significant difference in the proportion of MP in 2012-2015 and that in 2008-2011 (36.8% (32/87) vs. 31.0% (9/29), χ2=0.314, P=0.575).Regarding the regional distribution, 342 cases were in the southern China and 152 in the northern China. Also, MP was the most common pathogen in both regions, but the proportion of MP was higher and the proportion of SP was lower in the north than those in the south (60.5% (92/152) vs. 42.7% (146/342), χ 2=13.409, P<0.010; 7.9% (12/152) vs. 14.3% (49/342), χ 2= 4.023, P=0.045). Comparing the clinical characteristics of different pathogens, we found that fever and cough were the common symptoms in both single MP and single bacterial groups, but chest pain was more common (17.0% (34/200) vs. 6.1% (6/98), χ 2=6.697, P=0.010) while shortness of breath and wheezing were less common in MP group (16.0% (32/200) vs. 60.2% (59/98), χ 2=60.688, P<0.01; 4.5% (9/200) vs. 21.4% (21/98), χ 2=20.819, P<0.01, respectively). The white blood cell count, C-reactive protein and procalcitonin in the bacterial group were significantly higher than those in the MP group (14.7 (1.0-67.1)×10 9/L vs. 10.5 (2.5-32.2)×10 9/L, 122.5 (0.5-277.3) mg/L vs. 51.4 (0.5-200.0) g/L, 2.13 (0.05-100.00) μg/L vs. 0.24 (0.01-18.85) μg/L, Z=-3.719, -5.901 and -7.765, all P<0.01). Conclusions:The prevalence of pediatric NP in China shows an increasing trend during the past years. MP, SP and SA are the main pathogens of NP, and the most common clinical symptoms are fever and cough. The WBC count, C-reactive protein and procalcitonin in bacterial NP are significantly higher than those caused by MP.

Objective:To explore the effect of irinotecan combined with apatinib on the prognosis of patients with advanced gastric cancer.Methods:Sixty-two patients with advanced gastric cancer who were admitted to Shanghai Minhang District Cancer Hospital from January 2016 to October 2018 were selected. Among them, 30 patients were treated with apatinib (control group), and 32 cases were treated with irinotecan combined with apatinib(observation group). Before administration, the two groups were given routine symptomatic intervention, including prevention of vomiting, improvement of leukocyte, nutrition supplement, etc. During the treatment, routine blood examination, liver and kidney function examination were carried out regularly, and the drug dosage was adjusted according to the situation. The chemotherapy regimen was given once every 3 weeks, and both groups received 4 cycles of treatment. After 3 months of treatment, the short-term efficacy was evaluated, and the therapeutic effects of the two groups were compared. The incidence of side effects was analyzed. After 12 months of follow-up, the survival curves were drawn by Kaplan-Meier method, and the progression-free survival (PFS) and overall survival (OS) of the two groups were analyzed.Results:The recent overall remission rates of the observation group and the control group were 9.38% (3/32) and 3.33% (1/30), and the difference was not statistically significant ( χ2 = 0.203, P = 0.652). The disease progression rate of the observation group was lower than that of the control group, and the difference was statistically significant [28.13% (9/32) vs. 53.33% (16/30), χ2 = 4.089, P = 0.043]. There was no statistical difference in the incidence of platelet decline, hemoglobin decline, white blood cell decline, diarrhea, nausea and vomiting, liver damage, and bone marrow suppression between the two groups (both P > 0.05). The median PFS and OS time in the observation group were 5.8 months (5.0-6.3 months) and 8.1 months (7.2-9.3 months), respectively, which were longer than those in the control group [4.9 months (4.7-5.1 months) and 6.0 months (5.2-6.9 months), and the differences were statistically significant (both P < 0.01). Conclusion:The combination of irinotecan and apatinib can reduce the disease progression rate, prolong the survival time, and does not increase the adverse reactions.

Objective: To evaluate the outcomes of myelodysplastic syndromes (MDS) patients who received HLA-matched sibling donor allogeneic peripheral blood stem cell transplantation (MSD-PBSCT) . Methods: The clinical data of 138 MDS patients received MSD-PBSCT from Sep. 2005 to Dec. 2017 were retrospectively analyzed, and the overall survival (OS) rate, disease-free survival (DFS) rate, relapse rate (RR) , non-relapse mortality (NRM) rate and the related risk factors were explored. Results: ①After a median follow-up of 1 050 (range 4 to 4 988) days, the 3-year OS and DFS rates were (66.6±4.1) % and (63.3±4.1) %, respectively. The 3-year cumulative incidence of RR and NRM rates were (13.9±0.1) % and (22.2±0.1) %, respectively. ②Univariate analysis showed that patients with grade Ⅲ-Ⅳ acute graft-versus-host disease (aGVHD) or hematopoietic cell transplantation comorbidity index (HCT-CI) ≥2 points or patients in very high-risk group of the Revised International Prognostic Scoring System (IPSS-R) had significantly decreased OS[ (42.9±13.2) %vs (72.9±4.2) %, χ²=8.620, P=0.003; (53.3±7.6) %vs (72.6±4.7) %, χ²=6.681, P=0.010; (53.8±6.8) %vs (76.6±6.2) %vs (73.3±7.7) %, χ²=6.337, P=0.042]. For MDS patients with excess blasts-2 (MDS-EB2) and acute myeloid leukemia patients derived from MDS (MDS-AML) , pre-transplant chemotherapy or hypomethylating agents (HMA) therapy could not improve the OS rate[ (60.4±7.8) %vs (59.2±9.6) %, χ²=0.042, P=0.838]. ③Multivariate analysis indicated that the HCT-CI was an independent risk factor for OS and DFS (P=0.012, HR=2.108, 95%CI 1.174-3.785; P=0.008, HR=2.128, 95%CI 1.219-3.712) . Conclusions HCT-CI was better than the IPSS-R in predicting the outcomes after transplantation. The occurrence of grade Ⅲ-Ⅳ aGVHD is a poor prognostic factor for OS. For patients of MDS-EB2 and MDS-AML, immediate transplantation was recommended instead of receiving pre-transplant chemotherapy or HMA therapy.

Objective:To investigate the expressions of HIF-1α, BRD4, Beclin1, LC3B and p62 in breast cancer tissues and their clinicopathological significance, and to study alterations of their expression in breast cancer cells under hypoxic microenvironment.Methods:Immunohistochemistry was used to detect HIF-1α, BRD4, Beclin1, LC3B and p62 protein expressions in 125 breast cancer tissues and 50 para-cancer normal breast tissues, and their correlation with clinicopathologic characteristics were analyzed. The expression of these proteins were also measured after 24 hours of hypoxia stimulation was detected in different breast cancer cell lines and normal breast epithelial cells.Results:The expression of HIF-1α, BRD4, Beclin1 and LC3B proteins in breast cancer tissues were significantly higher than in para-cancer normal breast tissues ( P<0.05). There was a positive association between histologic grade, the expression of HIF-1α, BRD4, Beclin1 and LC3B ( P<0.05). High expressions of HIF-1a and Beclin1 were often correlated with lymph node metastasis and lymphatic invasion ( P<0.05). Increased HIF-1α, BRD4, Beclin1 and LC3B expression was associated with ER or PR negativity, but only HIF-1α was associated with HER2 positivity ( P<0.05). HIF-1α, BRD4, Beclin1, and LC3B were positively correlated with each other in breast cancer tissues ( P<0.01). After 24 hours of hypoxic stimulation, the expression of HIF-1α, BRD4, Beclin1 and LC3B was up-regulated in breast cancer cells. Conclusions:Hypoxia induces autophagy in breast cancer tissues. HIF-1α is positively correlated with BRD4, suggesting that BRD4 is involved in the regulation of autophagy by hypoxic microenvironment in breast cancer. High expression of HIF-1α, BRD4 and autophagy may play an important role in the development of breast cancer.

Objective: To investigate the effects of donor-specific HLA antibodies(DSA) for graft failure in un-manipulated haploidentical hematopoietic stem cell transplantation(haplo-HSCT) and the feasible treatment for DSA. Methods: HLA antibodies were examined using the Luminex-based single Ag assay for 92 patients who were going on haplo-SCT and the correlations of graft failure and DSA among the patients who had finished SCT were analyzed. Results: Of the total 92 patients who were going on haplo-HSCT, sixteen (17.4%) patients were HLA Ab-positive, including six (6.5%) patients with antibodies corresponding to donor HLA Ags (DSA-positive). Among the patients who had finished the haplo-HSCT with conventional myeloablative conditioning regimen, the engraftment rate was significantly higher in DSA (-) patients than that in DSA (+) patients [92.3% (24/26) vs 25.0%(1/4), χ²=8.433, P=0.004] and DSA was the only factor relevant with graft failure in multiple-factor analysis [OR=12.0(95% CI 1.39-103.5), P=0.024]. Strategies to decrease antibody levels were taken for 4 patients, two were their first transplantations, and the other two patients were their second haplo-HSCT. Three of the four patients were HLA-I-DSA positive and had gained donor engraftment by means of donor platelet transfusions to decreased the level of DSA, the fourth patient with both HLA-I and HLA-II DSA also gained engraftment with the treatments of TBI, rituximab and donor platelet transfusion. Conclusion DSA is one of the key factors of graft failure in haplo-HSCT. Donors should be selected on the basis of an evaluation of HLA antibodies before transplantation. If haplo-HSCT from donors with DSA must be performed, then recipients should be treated for DSA to improve the chances of successful engraftment.

Polycystic ovary syndrome (PCOS) is a common disease that lead to endocrine disorders and infertility in women of child-bearing age.A large number of studies have shown that the pathogenesis of PCOS is related to insulin resistance (IR),hyperandrogenism and high body mass index.At present,remarkable progress has been made in the study of conception methods and the reduction of multiple pregnancies in PCOS patients.However,there is relatively little research on the adverse pregnancy outcomes after conception.Therefore,this study will use evidence-based medicine to make a review of complications in maternal.For instance,pregnancy-induced hypertension syndrome (PIH),gestational diabetes mellitus (G DM),miscarriage,premature delivery and so on.This study provides an overall basis for early prevention and intervention in clinical work through discussing the pathophysiology of PCOS,the risk factors of its occurrence and development,and the management strategies of pre-pregnancy and gestation period.