Background::While type 2 diabetes mellitus (T2DM) is considered a putative causal risk factor for coronary artery disease (CAD), the intrinsic link underlying T2DM and CAD is not fully understood. We aimed to highlight the importance of integrated care targeting both diseases by investigating the phenotypic and genetic relationships between T2DM and CAD.Methods::We evaluated phenotypic associations using data from the United Kingdom Biobank ( N = 472,050). We investigated genetic relationships by leveraging genomic data conducted in European ancestry for T2DM, with and without adjustment for body mass index (BMI) (T2DM: Ncase/ Ncontrol = 74,124/824,006; T2DM adjusted for BMI [T2DM adjBMI]: Ncase/ Ncontrol = 50,409/523,897) and for CAD ( Ncase/ Ncontrol = 181,522/984,168). We performed additional analyses using genomic data conducted in multiancestry individuals for T2DM ( Ncase/ Ncontrol = 180,834/1,159,055). Results::Observational analysis suggested a bidirectional relationship between T2DM and CAD (T2DM→CAD: hazard ratio [HR] = 2.12, 95% confidence interval [CI]: 2.01–2.24; CAD→T2DM: HR = 1.72, 95% CI: 1.63–1.81). A positive overall genetic correlation between T2DM and CAD was observed ( rg = 0.39, P = 1.43 × 10 -75), which was largely independent of BMI (T2DM adjBMI–CAD: rg = 0.31, P = 1.20 × 10 –36). This was corroborated by six local signals, among which 9p21.3 showed the strongest genetic correlation. Cross-trait meta-analysis replicated 101 previously reported loci and discovered six novel pleiotropic loci. Mendelian randomization analysis supported a bidirectional causal relationship (T2DM→CAD: odds ratio [OR] = 1.13, 95% CI: 1.11-1.16; CAD→T2DM: OR = 1.12, 95% CI: 1.07-1.18), which was confirmed in multiancestry individuals (T2DM→CAD: OR = 1.13, 95% CI: 1.10-1.16; CAD→T2DM: OR = 1.08, 95% CI: 1.04-1.13). This bidirectional relationship was significantly mediated by systolic blood pressure and intake of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, with mediation proportions of 54.1% (95% CI: 24.9-83.4%) and 90.4% (95% CI: 29.3-151.5%), respectively. Conclusion::Our observational and genetic analyses demonstrated an intrinsic bidirectional relationship between T2DM and CAD and clarified the biological mechanisms underlying this relationship.

Objective:To explore the effect of ultraviolet-C (UV-C) combined with Kangfuxin liquid wet compress and oxygen blowing method on the post chemotherapy oral mucositis (OM) in patients with hematological malignancies.Methods:From January 2022 to February 2023, convenience sampling was used to select 120 patients with post chemotherapy OM in the Department of Hematology of the Affiliated Huai'an First People's Hospital of Nanjing Medical University. The patients were randomly divided into a control group and an observation group, with 60 cases in each group. The control group received Kangfuxin liquid wet compress, while the observation group carried out a combination of UV-C irradiation and oxygen oral blowing method on the basis of the control group. This study compared the Visual Analogue Scale (VAS) score before and two days after treatment, the healing status of OM after treatment on the 5th day, and the healing time of OM between the two groups of patients.Results:A total of 108 patients completed the study, with 52 in the control group and 56 in the observation group. After two days of treatment, the VAS scores of both groups of patients were lower than those before treatment, and those of the observation group were lower than those of the control group, with statistically significant differences ( P<0.05). On the 5th day of treatment, the healing rate of OM in the observation group was higher than that in the control group, and the difference was statistically significant (χ 2=5.425, P<0.05). The healing time of OM in the observation group was shorter than that in the control group, and the difference was statistically significant ( t=2.458, P<0.05) . Conclusions:The combination of UV-C, Kangfuxin liquid and oxygen blowing method can alleviate pain, improve the healing rate of OM, and shorten the healing time of post chemotherapy OM in patients with hematological malignancies, which is worthy of clinical promotion.

Objective To employ a mouse model of ABI3BP gene deletion for the detection of postnatal changes in body weight and glucose metabolism and establish a different method of creating a mouse model of low birth weight.Methods Heterozygote mice were mated to produce ABI3BP gene knockout homozygote(ABI3BP-/-)mice,heterozygote(ABI3BP+/)mice,and wild-type(WT)mice.Adult mice from all three groups were evaluated for glucose metabolism markers,including the fasting blood glucose level,glucose tolerance,and insulin tolerance.Additionally,body weight was measured at various postnatal time periods,and the weight ratio of critical organs in adulthood was calculated.Results The gene sequencing result of the polymerase chain reaction product of ABI3BP-/-mice showed that frameshift mutations occurred in the knockout region,with quantitative reverse-transcription polymerase chain reaction analysis demonstrating significantly reduced ABI3BP expression in ABI3BP-/-mice compared with that in WT mice.Notably,the birth weight of ABI3BP-/-mice(1.25±0.08 g)was markedly lower than that of WT mice(1.34±0.12 g)(P＜0.05).Conversely,the weight of adult(120 d)ABI3BP-/mice(27.70±1.93 g)was significantly higher than that of WT mice(23.64±1.34 g)(P＜0.01).The ratios of key organ weights to body weight were not significantly different between the groups(P＞0.05).Fasting blood glucose and insulin tolerance tests showed no significant variations between the groups.However,glucose tolerance tests indicated that ABI3BP-/-mice had lower blood glucose levels(15.68±7.04 mmol/L)than WT mice(23.01±5.75 mmol/L).Conclusions Deletion of the ABI3BP gene result in mice with low birth weight,poor growth recuperation,and inadequate glucose tolerance in adulthood,similar to the clinical growth traits of low-birth-weight human neonates.Therefore,this mouse model is a promising choice for the study of low birth weight.

Objective:To investigate the relationship between gestational weight gain (GWG) in twin pregnancies and adverse perinatal outcomes.Methods:This retrospective study included twin pregnant women with live births at≥25 weeks of gestation and their offspring, who delivered at Peking University People's Hospital from January 2012 to October 2022. Total GWG was standardized according to gestational age and categorized into three groups based on the 2009 Institute of Medicine (IOM) guidelines: insufficient GWG (GWG below IOM recommendations), appropriate GWG (GWG within IOM recommendations), and excessive GWG (GWG above IOM recommendations). Comparisons between data of the three groups used analysis of variance, Kruskal-Wallis test or Bonferroni correction or Chi-square partitions. Multivariable logistic regression models and generalized estimating equations with logistic regression models were used to analyze the independent effects of GWG on maternal and neonatal outcomes. Results:A total of 794 twin pregnant women and their 1 588 live-born neonates were included in the study. There were 360 women (45.3%) with appropriate GWG, 356 (44.8%) with insufficient GWG, and 78 (9.8%) with excessive GWG. Both insufficient and excessive GWG were associated with an increased risk of preterm birth [adjusted ORs of 1.39 (95% CI: 1.04-1.88) and 1.70 (95% CI: 1.05-2.78), respectively]. Insufficient GWG was associated with an increased risk of gestational diabetes mellitus (adjusted OR=1.42, 95% CI: 1.00-2.01) and low birth weight infants (adjusted OR=2.04, 95% CI: 1.57-2.66). Insufficient GWG was also associated with a reduced risk of eclampsia or preeclampsia (adjusted OR=0.50, 95% CI: 0.33-0.75), cesarean section (adjusted OR=0.48, 95% CI: 0.30-0.77), discordant twin growth (adjusted OR=0.56, 95% CI: 0.37-0.85), and large for gestational age infants (adjusted OR=0.46, 95% CI: 0.35-0.61). Excessive GWG was associated with an increased risk of eclampsia or preeclampsia (adjusted OR=2.85, 95% CI: 1.65-4.91), and large for gestational age infants (adjusted OR=2.49, 95% CI: 1.60-3.86), while with a decreased risk of low birth weight infants (adjusted OR=0.42, 95% CI: 0.27-0.65). Conclusions:More than half of the twin pregnancies have GWG outside the recommended range of the IOM guidelines. Both insufficient and excessive GWG are associated with adverse perinatal outcomes, particularly an increased risk of preterm birth.

Objective To propose strategies for developing clinical predictive models,aiming to assist researchers in conducting standardized clinical prediction model studies.Methods Literature review was conducted to summarize the operational steps and content for developing clinical predictive models.Then,a methodological framework was summarized and refined through expert consultation.Results The 11-step methodological framework for developing clinical predictive models was obtained by synthesizing the experience of 456 clinical predictive modeling studies and expert consultation,and the details were analyzed and elaborated.Conclusions This study presents methodological strategies and recommendations for the development of clinical predictive models,intended to serve as a guide for researchers.

Objective:To discuss the effect of human umbilical cord mesenchymal stem cells culture supernatant(hUCMSCs-Sup)on the proliferation,apoptosis,and endometrium receptivity of the human endometrial stromal cells(hEndoSCs)treated with mifepristone(Ms),and to clarify the possible mechanism.Methods:The hEndoSCs were cultured in vitro and divided into control group and 40,60,80,and 100 μmol·L-1 Ms groups.The survival rates of the cells in various groups were detected by MTT assay.The hEndoSCs were divided into control group,40 μmol·L-1 Ms group,and 60 μmol·L-1 Ms group.The apoptotic rates of the cells in various groups were detected by flow cytometry;the expression levels of apoptosis-related protein B-cell lymphoma-2(Bcl-2)and Bcl-2-associated X protein(Bax)proteins in the cells in various groups were detected by Western blotting method,and the ratio of Bcl-2/Bax was calculated.After treated with hUCMSCs-Sup,the hEndoSCs were divided into control group,Ms group,Ms+hUCMSCs-Sup group,and Ms+hUCMSCs-Sup+3-methyladenine(3-MA)group.The survival rates of the cells in various groups were detected by MTT assay;the apoptotic rates of the cells in various groups were detected by flow cytometry;the expression levels of microtubule-associated protein 1 light chain 3B-Ⅱ(LC3B-Ⅱ)and microtubule-associated protein 1 light chain 3B-I(LC3B-Ⅰ)proteins in the cells in various groups were detected by Western blotting method,and the ratio of LC3B-Ⅱ/LC3B-Ⅰwas calculated;the expression levels of endometrium receptivity marker molecules mRNA in the cells in various groups were detected by real-time fluorescence quantitative PCR(RT-qPCR)method.Results:Compared with control group,the survival rates of the cells in 40,60,80,and 100 μmol·L-1 Ms groups were significantly decreased(P<0.05)in a time-dependent and dose-dependent manner.Compared with control group,the apoptotic rates of the cells in 40 and 60 μmol·L-1 Ms groups were significantly increased(P<0.05),and the ratios of Bcl-2/Bax were significantly decreased(P<0.05).After treated with hUCMSCs-Sup,compared with control group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms group were significantly decreased(P<0.05),the apoptotic rate was significantly increased(P<0.05),and the expression levels of homeobox A10(HOXA10),leukemia inhibitory factor(LIF),and integrin subunit beta 3(ITGB3)mRNA in the cells were significantly decreased(P<0.05);compared with Ms group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰin the cells in Ms+hUCMSCs-Sup group were significantly increased(P<0.05),the apoptotic rate was significantly decreased(P<0.05),and the expression levels of HOXA10,LIF,and ITGB3 mRNA in the cells were significantly increased(P<0.05);compared with Ms+hUCMSCs-Sup group,the survival rate of the cells and ratio of LC3B-Ⅱ/LC3B-Ⅰ in the cells in Ms+hUCMSCs-Sup+3-MA group were significantly decreased(P<0.05).Conclusion:hUCMSCs-Sup can increase the survival rate and decrease the apoptotic rate of the hEndoSCs after treated with Ms,and increase the endometrium receptivity,and its mechanism may be associated with the activation of autophagy of the hEndoSCs by hUCMSCs-Sup.

ObjectiveTo explore the effect of Qingre Huayu Jianpi prescription （QHJ） on colitis-associated colorectal cancer （CAC） in mice， and its related mechanism. MethodC57BL/6 mice were randomly divided into four groups including the normal， model， QHJ low-dose （QHJ-L， 10 g·kg^-1）， and QHJ high-dose （QHJ-H， 40 g·kg^-1） groups. Azoxymethane （AOM） and dextran sodium sulfate （DSS） were combined to chemically build a CAC mouse model for 14 weeks. Each drug group was given intragastrically from the 5^th week to the 14^th week， once per day. An equal volume of water was fed to the normal and model groups. The mouse survival rate， colon length， weight， and pathological alterations were assessed. The protein expressions of Wnt-3a protein signaling （Wnt3a）， β-catenin， Non-phosphor-β-catenin （Non-p-β-catenin）， and cholesterol-binding glycoproteins 133 （CD133） were detected by Western blot. The localization and expression of the cluster of differentiation （CD） 80 and CD11 antigen-like family member B （CD11b） were detected by immunohistochemistry （IHC）. The colon organoids derived from CAC mice were isolated and cultured to detect the expression of Wnt signaling pathway-related proteins. ResultThe survival rate of the CAC mice was improved by QHJ treatment and the number of colon tumors was inhibited significantly. Compared with those in the normal group， the expression levels of Wnt3a， β-catenin， Non-p-β-catenin， and CD133 in colon tissues in the model group were significantly increased （P<0.05， P<0.01）. Compared with those in the model group， the levels of Wnt3a and β-catenin in the QHJ-L group were significantly decreased （P<0.01）， and the protein levels of Wnt3a， β-catenin， Non-p-β-catenin， and CD133 in the QHJ-H group were significantly decreased （P<0.05， P<0.01）. Meanwhile， the expression level of CD11b in the model group was significantly increased compared with that in the normal group while the CD80 level was significantly decreased （P<0.05， P<0.01）. Compared with those in the model group， CD11b in QHJ-L and QHJ-H groups was significantly decreased， and CD80 was significantly increased（P<0.05， P<0.01）. The expressions of Non-p-β-catenin and CD133 in colonic organoids of CAC model mice were significantly increased， while QHJ treatment could inhibit the expressions of Non-p-β-catenin and CD133 in colonic organoids （P<0.01）. ConclusionQHJ could inhibit the inflammation-cancer development in CAC mice， the mechanism of which might be related to regulating the microenvironment and inhibiting the over-activation of Wnt signaling.

ObjectiveTo explore the differences between the ancient decocting methods and modern decocting method of Yihuangtang by taking the dry extract rate， the content of active ingredients and the fingerprint information as indicators， so as to provide reference for the preparation of benchmark samples and the development of compound preparations of this famous classical formula. MethodAccording to the three decocting methods recorded in Paozhi Dafa and Jianming Yigou and Management Specifications of Traditional Chinese Medicine Decoction Chambers in Medical Institutions， the Yihuangtang was decocted respectively. The polysaccharide content in the samples was determined by ultraviolet spectrophotometer （UV） at 488 nm， and the contents of alkaloids （berberine hydrochloride， phellodendrine chloride and magnoflorine） in the samples and their fingerprint profiles were determined by high performance liquid chromatography （HPLC）， and the dry extract rate was combined to compare the differences of the three decocting methods of Yihuangtang. Among them， the fingerprint was gradient eluted with acetonitrile （A） -0.1% phosphoric acid aqueous solution （B） as mobile phase （0-10 min， 5%-8%A； 10-35 min， 8%A； 35-45 min， 8%-12% A； 45-75 min， 12%-17%A； 75-105 min， 17%-35%A； 105-110 min， 35%-100%A； 110-112 min， 100%-5%A； 112-122 min， 5%A）， and the detection wavelength was 230 nm. ResultWhen the decoction was carried out according to the method described in Paozhi Dafa， the content of polysaccharides was higher than that of the modern decocting method and the method described in Jianming Yigou. However， the contents of berberine hydrochloride， phellodendrine chloride and magnoflorine were the highest in the modern decocting method. Meanwhile， the number of peaks in fingerprint of the samples prepared by the three decocting methods was basically the same， and 13 common peaks were matched， and the three common peaks of berberine hydrochloride， phellodendrine chloride and magnoflorine were identified. However， the relative peak areas of the common peaks in the fingerprint of the samples prepared by the three decocting methods varied greatly， suggesting that there were differences in the extracting effects of different decocting methods. In addition， there were also differences in the dry extract rate among the three decocting methods of Yihuangtang， and the highest value was obtained by decocting the samples according to the method recorded in Paozhi Dafa. ConclusionDecocting method can affect the dry extract rate， fingerprint information and active ingredient content of Yihuangtang， among which the modern decocting method is conducive to the extraction of alkaloids and the preparation transformation of this famous classical formula， and it is recommended to determine its preparation process by optimizing the modern decocting method.

OBJECTIVE: To assess the value of single sperm sequencing in preimplantation genetic testing for monogenic disease (PGT-M). METHODS: A Chinese couple with two children whom had died of Spinal muscular atrophy (SMA) and attended the Jiangxi Provincial Maternal and Child Health Care Hospital in June 2020 was selected as the subject. Eleven single sperm samples were isolated by mechanical immobilization and subjected to whole genome amplification. Real-time PCR and Sanger sequencing were used to detect the SMN1 variants in the single sperm samples. Genomic DNA of the wife, her parents and the husband, as well as one single sperm sample harboring the SMN1 variant and two single sperm samples without the variant were used for the linkage analysis. Targeted capture and high-throughput sequencing were carried out to test 100 single nucleotide polymorphisms distributed within 2 Mb up- and downstream the variant site. The haplotypes linked with the SMN1 variants were determined by linkage analysis. Blastocyst embryos were harvested after fertilizing by intracytoplasmic sperm injection. Cells from the trophoblasts of each embryo were biopsied and subjected to whole genome amplification and targeted capture and high-throughput sequencing to determine their carrier status. Chromosomal aneuploidy of wild-type embryos was excluded. An euploid embryo of high quality was transferred. Amniotic fluid sample was taken at 18 weeks of gestation to confirm the status of the fetus. RESULTS: Genetic testing showed that the couple both had deletion of exons 7 ~ 8 of the SMN1 gene. The wife has inherited the deletion from her father, while the husband was de novo. The haplotypes of the husband were successfully constructed by single sperm sequencing. Preimplantation genetic testing has indicated that 5 embryos had harbored the heterozygous variant, 4 embryos were of the wild type, among which 3 were euploid. Prenatal diagnosis during the second trimester of pregnancy has confirmed that the fetus did not carry the deletion. CONCLUSION By single sperm sequencing and PGT-M, the birth of further affected child has been successfully avoided.
Humans ; Pregnancy ; Female ; Child ; Male ; Preimplantation Diagnosis ; East Asian People ; Semen ; Genetic Testing ; Muscular Atrophy, Spinal/genetics* ; Aneuploidy ; Blastocyst/pathology* ; High-Throughput Nucleotide Sequencing ; Spermatozoa

Objective:In order to explore the impact of corona virus disease 2019(COVID-19)on the hospitalization of children with bronchiolitis and to improve clinicians′ understanding of the characteristics of bronchiolitis during the COVID-19 epidemic.Methods:This was a multicenter clinical study, and the data have been collected from 23 children′s medical centers in China.All the clinical data were retrospectively collected from children with bronchiolitis who were hospitalized at each study center from January 1, 2019 to December 31, 2021.The results included gender, age at hospitalization, length of stay, respiratory syncytial virus(RSV) test results, severity rating, ICU treatment, and the total number of children hospitalized with respiratory tract infection during the same period.The clinical data of children with bronchiolitis in 2019 before COVID-19 epidemic and in 2020、2021 during COVID-19 epidemic were statistically analyzed and compared.Results:According to a summary of data provided by 23 children′s medical centers, there were 4 909 cases of bronchiolitis in 2019, 2 654 cases in 2020, and 3 500 cases in 2021.Compared with 2019, the number of bronchiolitis cases decreased by 45.94% in 2020 and 28.70% in 2021.In 2019, 2020 and 2021, there were no significant differences in gender ratio, age, and duration of hospitalization.Compared with 2019, the ratio of bronchiolitis to the total number of hospitalizations for respiratory tract infection decreased significantly in 2020 and 2021( χ2=12.762, P<0.05; χ2=84.845, P<0.05).The proportion of moderate to severe bronchiolitis cases in both 2020 and 2021 was lower than that in 2019, and the difference was statistically significant ( χ2=4.054, P<0.05; χ2=8.109, P<0.05).There was no statistically significant difference in the proportion of bronchiolitis cases requiring ICU treatment between 2019, 2020, and 2021 ( χ2=1.914, P>0.05).In 2019, a total of 52.60%(2 582/4 909) of children with bronchiolitis underwent RSV pathogen testing, and among them, there were 708 cases with RSV positive, accounting for 28.00%.In 2020, 54.14%(1 437/2 654) of children with bronchiolitis underwent RSV pathogen testing, and there were 403 cases with RSV positive, accounting for 28.04%.In 2021, 66.80%(2 238/3 500) of children with bronchiolitis underwent RSV pathogen testing, and there were 935 cases with RSV positive, accounting for 41.78%.Compared with 2019 and 2020, the RSV positive rate in 2021 showed a significant increase( χ2=99.673, P<0.05; χ2=71.292, P<0.05). Conclusion:During the COVID-19 epidemic, the implementation of epidemic prevention and control measures reduced the hospitalization rate and severity of bronchiolitis, but did not reduce the positive rate of RSV detection.