Dental pulp and periapical diseases make patients suffer from acute pain and economic loss. Although root canal therapies, as demonstrated through evidence-based medicine, can relieve symptoms and are commonly employed by dentists, it is still difficult to fully restore a dental pulp's nutrition, sensory, and immune-regulation functions. In recent years, researchers have made significant progress in tissue engineering to regenerate dental pulp in a desired microenvironment. With breakthroughs in regenerative medicine and material science, bioactive scaffolds play a pivotal role in creating a suitable microenvironment for cell survival, proliferation, and differentiation, following dental restoration and regeneration. This article focuses on current challenges and novel perspectives about bioactive scaffolds in creating a microenvironment to promote dental pulp regeneration. We hope our readers will gain a deeper understanding and new inspiration of dental pulp regeneration through our summary.

Dental pulp tissue engineering is a promising alternative treatment for pulpitis and periapical periodontitis, and dental pulp stem cells (DPSCs) are considered to be the gold standard for dental seed cell research. Periapical lesions harbor mesenchymal stem cells with the capacity for self‐renewal and multilineage differentiation. However, it remains unknown whether these periapical lesion‐derived stem cells (PLDSCs) are suitable for dental pulp tissue engineering. To investigate this possibility, PLDSCs and DPSCs were isolated using the tissue outgrowth method and cultured under identical conditions. We then performed in vitro experiments to investigate their biological characteristics. Our results indicate that PLDSCs proliferate actively in vitro and exhibit similar morphology, immunophenotype and multilineage differentiation ability as DPSCs. Simultaneously, PLDSCs exhibit stronger migrative ability and express more vascular endothelial growth factor and glial cell line‐derived neurotrophic factor than DPSCs, and PLDSC‐derived conditioned medium was more effective in tube formation assay. The mRNA expression levels of immunomodulatory genes HLA‐G , IDO and ICAM‐1 were also higher in PLDSCs. However, regarding osteo/odontogenic differentiation, PLDSCs showed weaker alkaline phosphatase staining and lower calcified nodule formation compared to DPSCs, as well as lower expression of ALP , RUNX2 and DSPP , as confirmed by a quantitative RT‐PCR. The osteo/odontogenic protein expression levels of DSPP, RUNX2, DMP1 and SP7 were also higher in DPSCs. The present study demonstrates that PLDSCs demonstrate potential use as seed cells for dental pulp regeneration, especially for achieving enhanced neurovascularization.

OBJECTIVE Human dental pulp stem cells (hDPSCs) constitute a promising source of stem cells in tissue engineering. However, the molecular mechanism of differentiation in hDPSCs remains largely unclear. MicroRNAs (miRNAs) play crucial roles in lineage-specific differentiation of stem cells. The present study investigated the function of miRNA-342-5p in the odonto/osteogenic differentiation of hDPSCs. METHODS The miRNA array profiling and quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) revealed the expression of miR-342-5p during odonto/osteogenic differentiation of hDPSCs. hDPSCs were treated with miR-342-5p mimic and inhibitor to investigate the regulatory roles of miR-342-5p in the differentiation of hDPSCs. Moreover, miR-342-5p inhibitor and small interference RNA (siRNA) targeting Wnt7b were applied to explore the regulatory mechanism of miR-342-5p. RESULTS Downregulated miR-342-5p was observed during odonto/osteogenic differentiation of hDPSCs. The overexpression of miR-342-5p inhibited the odonto/osteogenic potential of DPSCs, as indicated by low levels of alkaline phosphatase activity, calcium deposition formation, and odonto/osteogenic differentiation markers, whereas silencing of miR-342-5p exhibited the opposite effect. When co-treated with siRNA targeting Wnt7b and miR-342-5p inhibitor in hDPSCs, the odonto/osteogenic potential and activation of Wnt7b/β-catenin pathway were attenuated. CONCLUSIONS This study showed that miR-342-5p inhibits the odonto/osteogenic differentiation of hDPSCs by interfering with Wnt/β-catenin signaling via targeting Wnt7b.

目的:分析三甲综合医院中层管理人员对医院多院区协同管理的认知和评价,并提出相关建议.方法:基于协同理论,自制结构式问卷,以三甲综合医院中层管理人员为调查对象,进行问卷调查.运用方差分析、卡方检验、描述性统计等方法对数据进行统计分析.结果:调查对象对"多院区协同管理有利于医院发展"的总体认同度较高,认为多院区协同管理的利好面和关键点集中在宏观和中观协同要素;对于多院区中观层面协同要素设置倾向于集中管理下的协调一致,认为多院区协同管理的不利在于多院区协调困难和运营成本增加等微观层面.结论:多院区协同管理应从一体化的顶层设计出发,重视宏观协同能力;多院区协同管理中观面要素应采用集中管理原则进行设置;多院区协同管理微观面应着眼于常态化交流机制建立和降本增效.

目的 了解医院中层管理人员对医院学科建设及多学科协作诊疗(multi-disciplinary diagnosis and treatment,MDT)的认知现状及影响要素,挖掘两者联动发展的共同点,为其联动发展提供针对性建议.方法 自制结构式问卷,以医院中层管理人员为调查对象.运用方差分析、χ2检验、描述性统计等方法对数据进行统计分析.结果 学科建设的资源投入要素主要为平台建设和人才经费,成果产出要素主要为专科声誉和科研成果.80％以上的调查对象对于MDT的理解和源动力集中于疑难杂症的诊疗.调查对象对于MDT难点的选择比较分散,仅"医生等人员(精力)的短缺"和"MDT的文化氛围"选择占比超过了50％.临床科主任对于将MDT纳入科主任考核和学科建设评价指标的认同度得分分别为3.53和3.59分,低于另外两类人员.结论 平台建设和人才经费是学科建设和MDT联动发展的共同要素.MDT应纳入医院层面考核评价体系和院内优势学科的学科建设评价指标.

在全面深化改革的大背景下,以国内大型多院区公立医院为主要对象,运用SWOT分析法对新形势下其发展态势进行全面剖析,科学制定大型公立医院多院区协同发展策略,旨在解决多院区运营管理面临的重点难点,为促进大型公立医院可持续发展提供借鉴.

OBJECTIVE:Preeclampsia (PE) is a severe complication in pregnancy and a leading cause of maternal and infant mortality. However, the exact underlying etiology of PE remains unknown. Emerging evidence indicates that the cause of PE is associated with genetic factors. Therefore, the aim of this study is to identify susceptibility genes to PE.MATERIALS AND METHODS:Human Exome BeadChip assays were conducted using 370 cases and 482 controls and 21 loci were discovered. A further independent set of 958 cases and 1007 controls were recruited for genotyping to determine whether the genes of interest ROS1 and PTPRK are associated with PE. Immunohistochemistry was used for localization. Both qPCR and Western blotting were utilized to investigate the levels of PTPRK in placentas of 20 PE and 20 normal pregnancies.RESULTS:The allele frequency of PTPRK rs3190930 differed significantly between PE and controls and was particularly significant in severe PE subgroup and early-onset PE subgroup. PTPRK is primarily localized in placental trophoblast cells. The mRNA and protein levels of PTPRK in PE were significantly higher than those in controls.CONCLUSION:These results suggest that PTPRK appears to be a previously unrecognized susceptibility gene for PE in Han Chinese women, and its expression is also associated with PE, while ROS1 rs9489124 has no apparent correlation with PE risk.

The interplay between genetic and environmental risk factors contributes to the pathogenesis of metabolic disease. Polycystic ovary syndrome (PCOS) is the most common endocrine and metabolic disorder in women of reproductive age. Circadian rhythm disruption is an important risk factor for PCOS. In this study, we evaluated the effect of circadian disorder on reproduction as well as metabolism, and determined its influence on gut microbiota in a rat model. Female Sprague Dawley (SD) rats were kept under continuous light exposure (12-h:12-h light/light cycle, L/L group) or a control cycle (12-h:12-h light/dark cycle, L/D group) for four consecutive weeks. Manifestations in endocrine hormones and metabolism were detected and gut microbiota were analyzed with the 16s rRNA gene sequencing technique. To our knowledge, this is the first study to report PCOS-like reproductive manifestation, such as anti-Müllerian hormone (AMH) elevation induced by continuous light exposure. Moreover, continuous light resulted in abnormal glucose metabolism and gut microbial community variations, including enrichment of the microbial genus of Parasutterella and reduced abundance of genus Corynebacterium, genus Odoribacter, and genus Acinetobacter. Increased Parasutterella abundance was positively correlated with serum testosterone level. A PICRUSt analysis revealed that reproductive and metabolic-related genes were enriched in rats of L/D group. In conclusion, the present study demonstrates that continuous light exposure, an important environmental factor, contributes to the occurrence and developmental progress of PCOS and changes in microbial component and structure. Continuous light exposure is one of vital causes of PCOS, which is closely related to microbial structure and functions.

Problem For women of reproductive age, achieving a successful pregnancy requires both the normal functioning of reproductive endocrine and the health of the reproductive tract environment. We aimed to study how these fertility factors, such as female age, baseline sexual hormone levels, tubal patency, and vaginal pH, affect the composition of vaginal microbiome. Method of study The 16S rRNA sequencing was carried on vaginal microbiome samples from 85 women of reproductive age without vaginal infections or reproductive endocrine diseases. The detailed correlations between fertility factors and vaginal microbiome were quantified by Spearman's rank tests. A linear discriminant analysis was carried out to explore the effects of fertility factors on the relative abundances of vaginal bacterial species. Results The vaginal pH, levels of basal E2, LH, and FSH all had significant effects on the distribution of vaginal microbiome. The relative abundances of vaginal bacterial species, including Escherichia coli , Streptococcus agalactiae , and Prevotella intermedia , were significantly different due to the host's state of reproductive endocrine and tubal patency. It was worth noting that women with tubal obstruction, or prolonged menstrual cycle, or antral follicle count >15, or vaginal pH > 4.5 all had a higher abundance of Escherichia coli in vagina. Conclusion The fertility factors associated with the reproductive endocrine and the genital tract environment affected vaginal microbiome in women of reproductive age. The species Escherichia coli , Streptococcus agalactiae , Prevotella intermedia , etc could be used as biomarkers to reflect the pathological state of reproductive endocrine and genital tract.

Polycystic ovary syndrome is a complex endocrine condition with chronic inflammation. Prostaglandin E2 (PGE2) is a proinflammatory factor with an increased expression in the serum of women with polycystic ovary syndrome. Zinc finger gene 217 ( ZNF217 ) is known as a candidate gene for polycystic ovary syndrome. We aimed to investigate the relation between ZNF217 and PGE2 in polycystic ovary syndrome. We used a rat model of dehydroepiandrosterone-induced polycystic ovary syndrome and human granulosa cells both of women with polycystic ovary syndrome and of women without the syndrome to measure ZNF217 and other target gene expressions. In addition, we performed in vitro experiments with KGN human granulosa-like tumor cells to verify the molecular mechanisms. ZNF217 was decreased in the granulosa cells both of dehydroepiandrosterone-treated rats and of women with polycystic ovary syndrome. Cyclooxygenase 2, a key enzyme of PGE2 synthesis, was highly expressed in the granulosa cells of rats and women with the syndrome, and PGE2 concentration was increased in the follicular fluid. Furthermore, decreased ZNF217 expression was supposed to inhibit estradiol synthesis, which further promoted cyclooxygenase 2 and PGE2 synthesis. At the same time, PGE2 had an inhibitory effect on ZNF217 expression in a dose-dependent manner in KGN cells. Decreased ZNF217 expression in granulosa cells of women with polycystic ovary syndrome induced inflammation via PGE2, and PGE2 inhibited ZNF217 expression to establish a feedback loop. This mechanism might account for the pathogenesis of polycystic ovary syndrome.

Because of the complexity of cancer, a combination of chemotherapy and gene therapy is an emerging treatment modality. To realize the full potential of this strategy, a smart, highly biocompatible nanosystem that enables the precise co-delivery of small-molecule anticancer drugs and small interfering RNA (siRNA) is urgently needed. This study aimed to improve the therapeutic effect against cervical cancer by using cancer cell membrane-camouflaged nanoparticles for simultaneous delivery of paclitaxel (PTX) and siRNA targeting E7. Methods: By camouflaging HeLa cell membranes onto siRNA/PTX co-loaded (lactic-co-glycolic acid) (PLGA) nanoparticles, a biomimetic dual-drug delivery system (Si/PNPs@HeLa) was developed to simultaneously deliver PTX and siRNA targeting E7. After evaluating the physicochemical characteristics as well as their cell uptake and biodistribution behavior, studies on the RNA interference efficiency and antitumor ability of Si/PNPs@HeLa in vitro and in vivo were further carried out. Results: The Si/PNPs@HeLa was capable of delivering PTX and siRNA simultaneously to HeLa cells both in vitro and in vivo. Moreover, benefiting from the recognition and adhesion molecules on the surface of HeLa cells, Si/PNPs@HeLa exhibited an improved immune escape ability and an increased tumor region accumulation (3-fold higher than bare nanoparticles). As a result, an excellent synergistic anti-tumor effect was observed in the HeLa tumor-bearing mice, with tumor volume inhibiting rates of 83.6% and no side effects in major organs. The mechanistic studies confirmed that E7 knockdown sensitized HeLa cells to PTX chemotherapy, mainly by inhibiting PTX-induced AKT pathway activation. Conclusion: Si/PNPs@HeLa, by integrating immune escape and tumor-homing ability, can serve as an efficient dual-drug delivery system to achieve precise treatment of cervical cancer through chemo-gene combined therapy.

Introduction Polycystic ovary syndrome is a complex endocrine condition with chronic inflammation. Prostaglandin E2 (PGE2) is a proinflammatory factor with an increased expression in the serum of women with polycystic ovary syndrome. Zinc finger gene 217 (ZNF217) is known as a candidate gene for polycystic ovary syndrome. We aimed to investigate the relationship between ZNF217 and PGE2 in polycystic ovary syndrome. Material and methods We used a rat model of dehydroepiandrosterone-induced polycystic ovary syndrome and human granulosa cells both of women with polycystic ovary syndrome and of women without the syndrome to measure ZNF217 and other target gene expressions. In addition, we performed in vitro experiments with KGN human granulosa-like tumor cells to verify the molecular mechanisms. Results ZNF217 was decreased in the granulosa cells both of dehydroepiandrosterone-treated rats and of women with polycystic ovary syndrome. Cyclooxygenase 2, a key enzyme of PGE2 synthesis, was highly expressed in the granulosa cells of rats and women with the syndrome, and PGE2 concentration was increased in the follicular fluid. Furthermore, decreased ZNF217 expression was supposed to inhibit estradiol synthesis, which further promoted cyclooxygenase 2 and PGE2 synthesis. At the same time, PGE2 had an inhibitory effect on ZNF217 expression in a dose-dependent manner in KGN cells. Conclusions Decreased ZNF217 expression in granulosa cells of women with polycystic ovary syndrome induced inflammation via PGE2, and PGE2 inhibited ZNF217 expression to establish a feedback loop. This mechanism might account for the pathogenesis of polycystic ovary syndrome.

从人工智能的相关概念、常见应用场景、应用类型、挑战与困境等方面对临床应用现状进行综述,以期为人工智能的进一步研究提供借鉴。

Melatonin is an important factor in regulating numerous processes in human female reproduction. The aim of the present study was to compare melatonin levels in the follicular fluid (FF) of ovarian hyperstimulation syndrome (OHSS) women with those of non-OHSS women undergoing in vitro fertilization (IVF)-embryo transfer and to evaluate the relationship between FF melatonin levels and IVF outcomes in these women.

Obesity is a worldwide health problem with rising incidence and results in reproductive difficulties. Elevated saturated free fatty acids (FFAs) in obesity can cause insulin resistance (IR) in peripheral tissues. The high intra-follicular saturated FFAs may also account for IR in ovarian granulosa cells (GCs). In the present study, we investigated the relationship between saturated FFAs and IR in GCs by the use of palmitic acid (PA). We demonstrated that the glucose uptake in cultured GCs and lactate accumulation in the culture medium were stimulated by insulin, but the effects of insulin were attenuated by PA treatment. Besides, insulin-induced phosphorylation of Akt was reduced by PA in a dose- and time-dependent manner. Furthermore, PA increased phosphorylation of JNK and JNK blockage rescued the phosphorylation of Akt which was downregulated by PA. These findings highlighted the negative effect of PA on GCs metabolism and may partially account for the obesity-related reproductive disorders.

Objective: To identify different microbial species in women with polycystic ovary syndrome (PCOS) and reveal a possible relationship between gut dysbiosis and pathological changes. Design: Cross-sectional study. Setting: Academic institution. Patient(s): Reproductive-aged women with PCOS (n = 14) and controls (n = 14) from the Centre for Reproductive Medicine. Intervention(s): Shotgun metagenomic sequencing on fecal samples from patients, and clinical parameters (including body mass index, endocrine hormone levels, and glycemia level) gathered for correlation analysis. Main Outcome Measure(s): Identification of different gut microbial strains and relativity between microbiota and clinical parameters. Result(s): We found several microbial strains were statistically significantly more abundant in the PCOS group, including Parabacteroides merdae, Bacteroides fragilis, and strains of Escherichia and Shigella, whereas Faecalibacterium prausnitzii was enriched in the control group. Metagenomic species (MGS) analysis revealed that the microbes of the PCOS group were negatively correlated with those of the control group. Of note, we observed a positive correlation between MGS relevant to PCOS and endocrine disorders, including body mass index and elevated levels of serum testosterone, luteinizing hormone, and antimullerian hormone. Functional alterations, reflected by Kyoto Encyclopedia of Genes and Genomes orthologues, could imply potential mechanisms of microbial involvement in the developmental progress of PCOS. Conclusion(s): Our findings suggest an intimate association and potential mechanisms linking microbial dysbiosis and the pathophysiologic changes of PCOS. We address the importance of monitoring and modulating microbial composition and functional shifts in future clinical practice. ((C) 2020 by American Society for Reproductive Medicine.)

Objective: To evaluate the impact of unicornuate uterus on perinatal outcomes after in vitro fertilization and/or intracytoplasmic sperm injection (IVF/ICSI) cycles. Methods: We performed a retrospective cohort study including 160 women with unicornuate uterus and 1:1 matched controls with normally shaped uterus. They received IVF/ICSI treatment during January 2009 and December 2011. The perinatal outcomes were followed up till December 2014. Results: There were no significant differences in pregnancy rate, clinical pregnancy rate or live birth rate (53.6 versus 52.7, 41.4 versus 43.5, 33.8% versus 31.8%) between unicornuate uterus group and controls. Their biochemical pregnancy rate (22.8 versus 17.5%) and miscarriage rate (16.0 versus 18.8%) were similar. No significant differences were identified in preterm birth rate (18.3 versus 11.8%), birthweight (3.24 +/- 0.60 versus 3.33 +/- 0.54 kg) or birth length (50.47 +/- 2.33 versus 50.06 +/- 2.40 cm) among the singletons. However, lower gestational age (35.56 +/- 2.68 versus 36.71 +/- 1.73, p = .019), higher preterm birth rate (55.0 versus 34.4%, p = .038), lower birthweight (2.33 +/- 0.58 versus 2.69 +/- 0.38 kg, p = .001), lower birth length (45.33 +/- 2.46 versus 48.88 +/- 2.06 cm, p = .000), as well as higher rate of very low birthweight (13.2% versus 0, p = .007) were found for the twins from unicornuate uterus group. Conclusions: The results indicated unimpaired pregnancy and perinatal outcomes for women with unicornuate uterus conceiving one fetus. However, close attention should be paid to twin pregnancy in unicornuate uterus owing to increased risks of prematurity and low birthweight. Selected single embryo transfer is recommended for women with unicornuate uterus undergoing IVF/ICSI cycles.

OBJECTIVE:The purpose of this study was to observe the efficacy of Danefukang (DEFK) soft extract for the treatment of symptoms associated with endometriosis, and its effect on quality of life, the Self-rating Anxiety Scale (SAS) and Self-rating Depression Scale (SDS) scores, and on levels of carbohydrate antigen (CA)-125, tumor necrosis factor (TNF)-α, and interleukin (IL)-6. MATERIALS AND METHODS:A total of 174 patients with endometriosis treated from January 2010 to December 2013 were randomly divided into a control group treated with mifepristone (n = 87) or DEFK (n = 87). Both groups were treated for 3 months. Symptoms, quality of life, SAS, SD scores, and levels of CA-125, TNF-α, and IL-6 were evaluated before and after treatment. RESULTS:The effectiveness rate was 93.10% in the DEFK group and 81.61% in the mifepristone control group (χ2 = 4.215, P < 0.05). Treatment with DEFK resulted in a greater improvement in quality of life, SDS, and SAS scores compared with mifepristone (all, P < 0.05). DEFK treatment also resulted in a greater decrease of CA-125, TNF-α, and IL-6 levels compared with mifepristone (all, P < 0.05). CONCLUSION:Based on the current results - improved symptoms, attenuated depression and anxiety, and reduced the levels of pro-inflammatory cytokines and CA-125 -treatment with DEFK is a meaningful option for patients with endometriosis. DEFK fills an unmet need in the pharmacologic treatment of endometriosis.