Association between late sleeping and major adverse cardiovascular events in patients with percutaneous coronary intervention.

BACKGROUND: Sleeping late has been a common phenomenon and brought harmful effects to our health. The purpose of this study was to investigate the association between sleep timing and major adverse cardiovascular events (MACEs) in patients with percutaneous coronary intervention (PCI). METHODS: Sleep onset time which was acquired by the way of sleep factors questionnaire in 426 inpatients was divided into before 22:00, 22:00 to 22:59, 23:00 to 23:59 and 24:00 and after. The median follow-up time was 35 months. The endpoints included angina pectoris (AP), new myocardial infarction (MI) or unplanned repeat revascularization, hospitalization for heart failure, cardiac death, nonfatal stroke, all-cause death and the composite endpoint of all events mentioned above. Cox proportional hazards regression was applied to analyze the relationship between sleep timing and endpoint events. RESULTS: A total of 64 composite endpoint events (CEEs) were reported, including 36 AP, 15 new MI or unplanned repeat revascularization, 6 hospitalization for heart failure, 2 nonfatal stroke and 5 all-cause death. Compared with sleeping time at 22:00-22:59, there was a higher incidence of AP in the bedtime ≥ 24:00 group (adjusted HR: 5.089; 95% CI: 1.278-20.260; P = 0.021). In addition, bedtime ≥ 24:00 was also associated with an increased risk of CEEs in univariate Cox regression (unadjusted HR: 2.893; 95% CI: 1.452-5.767; P = 0.003). After multivariable adjustments, bedtime ≥ 24:00 increased the risk of CEEs (adjusted HR: 3.156; 95% CI: 1.164-8.557; P = 0.024). CONCLUSION: Late sleeping increased the risk of MACEs and indicated a poor prognosis. It is imperative to instruct patients with PCI to form early bedtime habits.

Huang-Lian-Jie-Du decoction alleviates depressive-like behaviors in dextran sulfate sodium-induced colitis mice via Trem2/Dap12 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Huang-Lian-Jie-Du decoction (HLJD), a traditional Chinese medicine prescription, has been implicated as effective in treating colitis, depression and inflammation-related diseases. Whether HLJD decoction could ameliorate colitis-induced depression was still unknown and the underlying mechanism was needed to be clarified. AIM OF THE STUDY: Our study aimed to explore the effect and the underlying mechanism of HLJD treatment on colitis-induced depression and the involvement of the inflammatory factors and microglial-activated related genes. MATERIALS AND METHODS: The chronic colitis model was established by treating male mice with 1% dextran sulfate sodium (DSS) for 8 weeks. One week after DSS-treated, HLJD decoction was administered orally with 2 and 4 g/kg daily for 7 weeks. Behavior tests (Open field/Elevated plus maze/Novel object recognition) and TUNEL staining were then assessed. The expression of inflammatory-related genes and microglial dysregulation were measured by RT-PCR and the expression of Trem2, Danp12 and Iba1 were assessed by immunofluorescence methods. RESULTS: Depressive-like behaviors were observed in mice treated with DSS, which suffered colitis. Compared to normal control (NC-V) mice, the density of TUNEL + cells in the habenula (Hb), hippocampus (HIP), and cortex were significantly higher in colitis (DSS-V) mice, especially in Hb. Compared to NC-V and several brain regions, the expression levels of the Il-1ß, Il-10 and Dap12 mRNA were significantly increased in the lateral habenula (LHb) of colitis mice. Moreover, the expression of Trem2, Dap12 and Iba1 were increased in LHb of DSS-V mice. HLJD treatment could alleviate depressive-like behaviors, reduce the density of TUNEL + cells in Hb and the expression of Il-6, Il-10 and Dap12 mRNA in LHb of DSS-V mice. The overexpression of Trem2, Dap12 and Iba1 in LHb of DSS-V mice were reversed after HLJD treatment. CONCLUSION: These results reveal LHb is an important brain region during the process of colitis-induced depression. HLJD treatment could alleviates depressive-like behaviors in colitis mice via inhibiting the Trem2/Dap12 pathway in microglia of LHb, which would contribute to the precise treatment. It provides a potential mechanistic explanation for the effectiveness of HLJD treatment in colitis patients with depression.

Functional Analysis of Serum Long Noncoding RNAs in Patients with Atrial Fibrillation.

Objectives: Long noncoding RNAs (lncRNAs) are closely related to diverse diseases. However, its role in atrial fibrillation (AF) pathogenesis needs further exploration. Design: We performed microarray analysis on the serum samples from 70 healthy volunteers and 70 AF patients. This study was aimed at detecting the levels of serum lncRNAs and mRNAs and bioinformatically analyze them to establish potential marker(s) for AF diagnosis. Receiver operating curve (ROC) and area under the curve (AUC) were employed to address the AF diagnostic power of lncRNAs. Results: In the AF serum samples, 753 lncRNAs and 802 mRNAs (p ≤ 0.05; fold change ≥ 2) were upregulated, and 315 lncRNAs and 153 mRNAs were downregulated, as opposed to healthy serum samples. Using bioinformatic analysis, we analyzed the top 4 differentially expressed (DE) lncRNAs, namely, NR-001587, NR-015407, NR-038455, and NR-038894, and found that the PI3K-AKT cell proliferation signaling pathway was most affected. This was in accordance with our functional analysis of DE mRNAs and adjacent lncRNAs. Notably, the elevated serum NR-001587 levels were strongly associated with AF incidence. Conclusions: Our work highlights the role of lncRNAs in AF pathogenesis and provides a novel serum biomarker for AF diagnosis.

Strike Velocity Prediction of Stick Blunt Instruments Based on Backpropagation Neural Network / 法医学杂志

OBJECTIVES@#To analyze and predict the striking velocity range of stick blunt instruments in different populations, and to provide basic data for the biomechanical analysis of blunt force injuries in forensic identification.@*METHODS@#Based on the Photron FASTCAM SA3 high-speed camera, Photron FASTCAM Viewer 4.0 and SPSS 26.0 software, the tester's maximum striking velocity of stick blunt instruments and related factors were calculated and analyzed, and inputed to the backpropagation (BP) neural network for training. The trained and verified BP neural network was used as the prediction model.@*RESULTS@#A total of 180 cases were tested and 470 pieces of data were measured. The maximum striking velocity range was 11.30-35.99 m/s. Among them, there were 122 female data, the maximum striking velocity range was 11.63-29.14 m/s; there were 348 male data, the maximum striking velocity range was 20.11-35.99 m/s. The maximum striking velocity of stick blunt instruments increased with the increase of weight and height, but there was no obvious increase trend in the male group; the maximum striking velocity decreased with age, but there was no obvious downward trend in the female group. The maximum striking velocity of stick blunt instruments has no significant correlation with the material and strike posture. The root mean square error (RMSE), the mean absolute error (MAE) and the coefficient of determination (R2) of the prediction results by using BP neural network were 2.16, 1.63 and 0.92, respectively.@*CONCLUSIONS@#The prediction model of BP neural network can meet the demand of predicting the maximum striking velocity of different populations.

Reconstruction and Quantitative Evaluation of Blunt Injury Cases by Finite Element Method / 法医学杂志

OBJECTIVES@#To reconstruct the cases of acceleration craniocerebral injury caused by blunt in forensic cases by finite element method (FEM), and to study the biomechanical mechanism and quantitative evaluation method of blunt craniocerebral injury.@*METHODS@#Based on the established and validated finite element head model of Chinese people, the finite element model of common injury tool was established with reference to practical cases in the forensic identification, and the blunt craniocerebral injury cases were reconstructed by simulation software. The cases were evaluated quantitatively by analyzing the biomechanical parameters such as intracranial pressure, von Mises stress and the maximum principal strain of brain tissue.@*RESULTS@#In case 1, when the left temporal parietal was hit with a round wooden stick for the first time, the maximum intracranial pressure was 359 kPa; the maximum von Mises stress of brain tissue was 3.03 kPa at the left temporal parietal; the maximum principal strain of brain tissue was 0.016 at the left temporal parietal. When the right temporal was hit with a square wooden stick for the second time, the maximum intracranial pressure was 890 kPa; the maximum von Mises stress of brain tissue was 14.79 kPa at the bottom of right temporal lobe; the maximum principal strain of brain tissue was 0.103 at the bottom of the right temporal lobe. The linear fractures occurred at the right temporal parietal skull and the right middle cranial fossa. In case 2, when the forehead and left temporal parietal were hit with a round wooden stick, the maximum intracranial pressure was 370 kPa and 1 241 kPa respectively, the maximum von Mises stress of brain tissue was 3.66 kPa and 26.73 kPa respectively at the frontal lobe and left temporal parietal lobe, and the maximum principal strain of brain tissue was 0.021 and 0.116 respectively at the frontal lobe and left temporal parietal lobe. The linear fracture occurred at the left posterior skull of the coronary suture. The damage evaluation indicators of the simulation results of the two cases exceeded their damage threshold, and the predicted craniocerebral injury sites and fractures were basically consistent with the results of the autopsy.@*CONCLUSIONS@#The FEM can quantitatively evaluate the degree of blunt craniocerebral injury. The FEM combined with traditional method will become a powerful tool in forensic craniocerebral injury identification and will also become an effective means to realize the visualization of forensic evidence in court.

Analysis of clinical phenotype and genotype of Chinese children with disorders of sex development / 中华儿科杂志

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.

Correlation between severity of diabetic retinopathy and corneal SNP changes / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To investigate the correlation between severity of diabetic retinopathy(DR)and corneal sub-basal nerve plexus(SNP)changes. METHODS: There were 132 patients with 132 eyes in type 2 diabetes(T2DM)and 80 patients with 80 eyes in age-related cataract selected in our hospital from January 2018 to May 2021, among them, there were 52 non-diabetic retinopathy(NDR)patients with 52 eyes, 40 non proliferative diabetic retinopathy(NPDR)patients with 40 eyes and 40 proliferative diabetic retinopathy(PDR)patients with 40 eyes in T2DM. The general data and corneal laser scanning confocal microscopy were analyzed. Spearman rank correlation analysis was used to evaluate the correlation between DR clinical stage and nerve fiber length. RESULTS: There were no differences in gender and age comparisons among 4 groups(P>0.05). The diabetes duration in PDR group was significantly longer than NPDR group and NDR group(P<0.05). The diabetes duration in NPDR group was significantly longer than NDR group(P<0.05). The levels of fasting blood glucose and glycosylated hemoglobin in age-related cataract group were significantly lower than other three groups(P<0.05). The best corrected visual acuity in PDR group was significantly lower than NPDR group and NDR group(P<0.05). The best corrected visual acuity in NPDR group was significantly lower than NDR group(P<0.05). The length of nerve fibers in age-related cataract group was significantly higher than NDR group, NPDR group and PDR group(P<0.05). The length of nerve fibers in PDR group was significantly shorter than NPDR group(P<0.05). Spearman rank correlation analysis showed that there was a negative correlation between DR stage and nerve fiber length(rs=-0.347, P<0.001).CONCLUSION: There was a correlation between the severity of DR and the changes of corneal SNP. The length of nerve fibers in patients with PDR was significantly shorter than patients with NPDR; Both PDR and NPDR have a loss of neural structure and should pay attention to the evaluation and treatment of ocular surface lesions in the treatment of T2DM fundus lesions.

Study on the Intervention Effect of Qi Gong Wan Prescription on Patients with Phlegm-Dampness Syndrome of Polycystic Ovary Syndrome Based on Intestinal Flora.

OBJECTIVE: This was a population-based cohort study, to compare the type and structure of intestinal flora in patients with polycystic ovary syndrome (PCOS) with phlegm-dampness syndrome, nonphlegm-dampness syndrome, and normal population. Besides, changes in the intestinal flora and the clinical curative effects of Jiawei Qi Gong Wan on phlegm-dampness syndrome in patients with polycystic ovary syndrome (PCOS) were evaluated. Patients and Methods. A total of 22 patients with PCOS with phlegm-dampness syndrome, 21 PCOS patients with nonphlegm-dampness syndrome, and 20 control volunteers were selected for this study. The general index, sex hormone index, fasting blood glucose (FPG), and serum fasting insulin (FINS) were determined in each of the groups. The intestinal flora of each group was determined by the 16s rDNA high-throughput sequencing technique. Besides, the PCOS with phlegm-dampness syndrome group was treated with Jiawei Qi Gong Wan, and the changes in TCM syndrome, sex hormone index, BMI, WHR, FPG, FINS, HOMA-IR, and intestinal flora were determined before and after treatment. RESULTS: PCOS patients with phlegm-dampness syndrome showed characteristics of obesity and insulin resistance. There were several differences in both structure and function of the intestinal flora between PCOS patients with phlegm-dampness syndrome, PCOS patients with nonphlegm-dampness syndrome, and the control group. An imbalance in the intestinal flora may be a key factor in the pathogenesis of PCOS with phlegm-dampness syndrome and also has a specific influence on glucose and lipid metabolism, obesity, and the menstrual cycle in PCOS patients with phlegm-dampness syndrome. Besides, the imbalance is associated with a decrease in the number of butyrate-producing bacteria, an increase in the number of lipopolysaccharide-producing bacteria, and an increase in proinflammatory bacteria. The intestinal flora in PCOS patients with phlegm-dampness syndrome was found to be linked to obesity, impaired glucose tolerance, and hyperandrogenemia. Treatment with Jiawei Qi Gong Wan was found to increase the diversity of intestinal flora, increase the number of intestinal probiotics, and improve the structure and functional genes of intestinal flora which improved the state of insulin resistance, regulated endocrine metabolism, and improved the overall symptoms. CONCLUSIONS: Intestinal flora imbalance is a key factor in the pathogenesis of PCOS with phlegm-dampness syndrome. Besides, Jiawei Qi Gong Wan improves insulin resistance which is linked to the status of the intestinal flora in PCOS patients with phlegm-dampness syndrome.

Comparative efficacy and safety of PD-1/PD-L1 Inhibitors versus platinum-based chemotherapy for the first-line treatment of advanced non-small cell lung cancer: a meta analysis of randomized controlled trials.

OBJECTIVE: The main aim of this study was to systematically evaluate the efficacy and safety of inhibitors of programmed cell death receptor 1 (PD-1) and its ligand, programmed cell death ligand-1 (PD-L1), in the treatment of advanced non-small cell lung cancer (NSCLC). METHODS: Randomized controlled trials assessing the efficacy of PD-1/PD-L1 inhibitors relative to platinum-based chemotherapy for advanced NSCLC in PubMed, EMBASE, and Cochrane libraries from 2015 to 2020 were searched, along with review of studies at American Society of Clinical Oncology (ASCO) and European society for Medical Oncology (ESMO). Pooled hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) and odds ratios (OR) for adverse events (AE) were calculated using STATA and Revman software. RESULTS: PD-1/PD-L1 inhibitors alone or combined with chemotherapy significantly improved OS (HR = 0.82, 95% CI:0.74-0.91, P = 0.01 or HR = 0.74, 95% CI:0.67-0.82, P = 0.001). PD-1/PD-L1 inhibitors alone did not benefit PFS (HR = 0.99, 95% CI: 0.89-1.10, P = 0.892), while combination therapy led to prolonged PFS (HR = 0.61, 95% CI: 0.56-0.67, P < 0.001). Subgroup analysis showed that in NSCLC with PD-L1 ≥ 50%, treatment with PD-1/PD-L1 inhibitors alone significantly improved both PFS and OS. In patients subjected to the combined treatment regimen, we observed significant differences in PFS among groups stratified by PD-L1 expression (p < 0.001), immune drug type (p = 0.029), gender (p = 0.014) and liver metastasis (p = 0.035) and OS among groups stratified by immune drug type (p < 0.001), gender (P = 0.001) and smoking status (P = 0.041). Safety analysis showed that combination therapy increased chemotherapy-induced adverse events (AE), while PD-1/PD-L1 inhibitors alone were associated with a lower incidence of any grade of treatment-related AEs (TRAE). A higher incidence of Grade 3-5 TRAEs and hypothyroidism was observed with PD-1 inhibitors than PD-L1 inhibitors. CONCLUSIONS: First-line treatment of advanced NSCLC with immune monotherapy or immunochemotherapy confers a greater survival benefit than chemotherapy alone. Combination of chemotherapy with PD-1/PD-L1 inhibitors leads to an increase in adverse events, and PD-1 inhibitors offer enhanced survival benefits and fewer adverse events than PD-L1 inhibitors. Remarkably, female patients undergoing combination therapy had longer overall survival than male patients.

Bone morphogenetic protein 6 affects cell-cell communication by altering the expression of Connexin43 in human granulosa-lutein cells.

Connexin 43 (Cx43)-coupled gap junctions in granulosa cells play an important role in follicular development, oocyte maturation, and corpus luteum maintenance. Bone morphogenetic protein 6 (BMP6) is highly expressed in human oocytes and granulosa cells and is involved in the regulation of female reproduction. Currently, whether oocyte- and granulosa cell-derived BMP6 affects the expression of Cx43 and its related gap junction intercellular communication (GJIC) activity in human granulosa cells remains unknown. In this study, we demonstrate that BMP6 treatment significantly suppressed the expression of Cx43 in both primary and immortalized (SVOG) human granulosa-lutein cells. Using both pharmacological inhibitors and small interfering RNA-mediated knockdown approaches, we demonstrate that ALK2 and ALK3 BMP type I receptors are involved in BMP6-induced suppressive effects on Cx43 expression and GJIC activity in SVOG cells. Furthermore, these cellular activities are most likely mediated by the SMAD1/SMAD5-SMAD4-dependent signaling pathway. Notably, the ChIP analyses demonstrated that phosphorylated SMADs could bind to human Cx43 promoter. Our findings provide new insight into the molecular mechanisms by which an intrafollicular growth factor regulates cell-cell communication in human granulosa cells.

Effects of Electroacupuncture on Expression of PI3K/Akt/Foxo3a in Granulosa Cells from Women with Shen (Kidney) Deficiency Syndrome Undergoing in vitro Fertilization-Embryo Transfer.

OBJECTIVE: To observe the effects of electroacupuncture (EA) on reproductive outcomes in women with Shen (Kidndy) deficiency syndrome after in vitro fertilization-embryo transfer (IVF-ET), and explore the underlying molecular mechanism. METHODS: Sixty-six infertile patients with Shen deficiency syndrome undergoing IVF-ET were divided into EA or control groups according to a random table, 33 cases in each group. Before undergoing IVF, patients in the EA and control groups received EA therapy and placebo needle puncture, respectively, for 3 menstrual cycles. Shen deficiency syndrome scores were assessed. Other outcome measures included the number of retrieved oocytes and fertilization, high-quality embryo and clinical pregnancy rates. Follicular fluid was collected on the day of oocyte retrieval, and granulosa cell expression of phosphatidylinositide 3-kinases (PI3K), serine-threonine kinase (Akt) and forkhead box O3 (Foxo3a) mRNA were measured by reverse transcribed and quantitative real-time polymerase chain reaction. RESULTS: Syndrome scores for pre- versus post-treatments decreased significantly (16.53±1.75 to 8.67±1.61) in the EA group (P<0.05), but showed no significant change in the control group (17.18±1.58 to 14.74±1.58). A significant difference in score change was found between the EA and control groups (P<0.05). High-quality embryo and clinical pregnancy rates were both increased in the EA group compared with the control group [69.15% (195/282) vs. 60.27% (176/292) and 66.67% (22/33) vs. 42.42% (14/33), respectively, P<0.05]. The fertilization rate was equivalent in EA and control groups. No difference was found in the number of retrieved oocytes between the two groups. Granulosa cell expression levels of PI3K and Akt mRNA were significantly increased in the EA group compared with the control group, while the expression of Foxo3a was reduced (all P<0.05). CONCLUSIONS: For infertile patients with Shen deficiency syndrome undergoing IVF, EA for tonifying Shen as an adjunct treatment may alleviate clinical symptoms and improve the high-quality embryo rate. The EA-induced mechanism may involve regulation of PI3K/Akt/Foxo3a expression in granulosa cells to improve the developmental microenvironment of oocytes and inhibit granulosa cell apoptosis, possibly contributing to the improved clinical pregnancy rate (Registration No. ChiCTR 1800016217).

Effect of CD44st and HER2 expression on the postoperative prognosis of breast cancer patients.

OBJECTIVE: CD44st is a member of the CD44 family; abnormal expression of some CD44 isoforms are closely associated with axillary lymph node metastasis, cancer progression, and patients' prognosis. The objective of this study is to investigate the correlation between the expression of CD44st and HER2 in breast cancer and the effect on patients' prognosis. METHODS: Primers were designed to target the CD44st mRNA (Gene Bank No FJ216964) which has been newly identified in a drug-resistant breast cancer cell line. The expression of CD44st and HER2 mRNA and proteins in cancerous and paracancerous tissue of postoperative breast cancer patients was detected and compared. Tissue samples were obtained from 102 cases of invasive ductal carcinoma, 19 cases of intraductal carcinoma, and 11 cases of medullary carcinoma. The correlation between CD44st and HER2 expression and clinical pathological features was examined. RESULTS: The expression rate of CD44st mRNA and protein in breast cancer tissue was 64.4% (85/132), while HER2 mRNA and protein was expressed in 22.0% (29/106) of the samples. The expression of CD44st and HER2 were low in paracancerous tissue. In breast cancer tissue, the expression rate of HER2 mRNA and protein in the CD44st-positive group was 28.2% (24/85), and 10.6% (5/47) in the CD44st-negative group. This difference was statistically significant (P=0.015). Sequencing analysis showed that the amplified CD44st gene in this study was the same as that which was previously discovered in the drug-resistant breast cancer cell line. A linear correlation was found between the expression of CD44st and HER2 (r=0.972, r2=0.945, F=2,213.51, P<0.001). The expression of CD44st and HER2 was also closely associated with luminal cancer subtypes, lymph node metastasis, and TNM stage (P<0.05), but not associated with age, pathological type, or tumor size (P>0.05). The median overall survival in the CD44st high-expression group was 51.85 months (95% CI: 48.48-55.22), which was significantly shorter than that in the CD44st low-expression group (57.61 months; 95% CI: 55.54-59.68, P=0.032). CONCLUSION: CD44st is closely related to the expression of HER2. The expression of CD44st affects patient prognosis and is associated with lymph node metastasis, TNM staging, and molecular subtyping.

Neurotrophins and glial cell line-derived neurotrophic factor in the ovary: physiological and pathophysiological implications.

BACKGROUND: Neurotrophins [nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4)] and glial cell line-derived neurotrophic factor (GDNF) are soluble polypeptide growth factors that are widely recognized for their roles in promoting cell growth, survival and differentiation in several classes of neurons. Outside the nervous system, neurotrophin (NT) and GDNF signaling events have substantial roles in various non-neural tissues, including the ovary. OBJECTIVE AND RATIONALE: The molecular mechanisms that promote and regulate follicular development and oocyte maturation have been extensively investigated. However, most information has been obtained from animal models. Even though the fundamental process is highly similar across species, the paracrine regulation of ovarian function in humans remains poorly characterized. Therefore, this review aims to summarize the expression and functional roles of NTs and GDNF in human ovarian biology and disorders, and to describe and propose the development of novel strategies for diagnosing, treating and preventing related abnormalities. SEARCH METHODS: Relevant literature in the English language from 1990 to 2018 describing the role of NTs and GDNF in mammalian ovarian biology and phenotypes was comprehensively selected using PubMed, MEDLINE and Google Scholar. OUTCOMES: Studies have shown that the neurotrophins NGF, BDNF, NT-3 and NT-4 as well as GDNF and their functional receptors are expressed in the human ovary. Recently, gathered experimental data suggest putative roles for NT and GDNF signaling in the direct control of ovarian function, including follicle assembly, activation of the primordial follicles, follicular growth and development, oocyte maturation, steroidogenesis, ovulation and corpus luteum formation. Additionally, crosstalk occurs between these ovarian regulators and the endocrine signaling system. Dysregulation of the NT system may negatively affect ovarian function, leading to reproductive pathology (decreased ovarian reserve, polycystic ovary syndrome and endometriosis), female infertility and even epithelial ovarian cancers. WIDER IMPLICATIONS: A comprehensive understanding of the expression, actions and underlying molecular mechanisms of the NT/GDNF system in the human ovary is essential for novel approaches to therapeutic and diagnostic interventions in ovarian diseases and to develop more safe, effective methods of inducing ovulation in ART in the treatment of female infertility.

Effects of Electroacupuncture on Expression of PI3K/Akt/Foxo3a in Granulosa Cells from Women with Shen (Kidney) Deficiency Syndrome Undergoing in vitro Fertilization-Embryo Transfer / 中国结合医学杂志

OBJECTIVE@#To observe the effects of electroacupuncture (EA) on reproductive outcomes in women with Shen (Kidndy) deficiency syndrome after in vitro fertilization-embryo transfer (IVF-ET), and explore the underlying molecular mechanism.@*METHODS@#Sixty-six infertile patients with Shen deficiency syndrome undergoing IVF-ET were divided into EA or control groups according to a random table, 33 cases in each group. Before undergoing IVF, patients in the EA and control groups received EA therapy and placebo needle puncture, respectively, for 3 menstrual cycles. Shen deficiency syndrome scores were assessed. Other outcome measures included the number of retrieved oocytes and fertilization, high-quality embryo and clinical pregnancy rates. Follicular fluid was collected on the day of oocyte retrieval, and granulosa cell expression of phosphatidylinositide 3-kinases (PI3K), serine-threonine kinase (Akt) and forkhead box O3 (Foxo3a) mRNA were measured by reverse transcribed and quantitative real-time polymerase chain reaction.@*RESULTS@#Syndrome scores for pre- versus post-treatments decreased significantly (16.53±1.75 to 8.67±1.61) in the EA group (P<0.05), but showed no significant change in the control group (17.18±1.58 to 14.74±1.58). A significant difference in score change was found between the EA and control groups (P<0.05). High-quality embryo and clinical pregnancy rates were both increased in the EA group compared with the control group [69.15% (195/282) vs. 60.27% (176/292) and 66.67% (22/33) vs. 42.42% (14/33), respectively, P<0.05]. The fertilization rate was equivalent in EA and control groups. No difference was found in the number of retrieved oocytes between the two groups. Granulosa cell expression levels of PI3K and Akt mRNA were significantly increased in the EA group compared with the control group, while the expression of Foxo3a was reduced (all P<0.05).@*CONCLUSIONS@#For infertile patients with Shen deficiency syndrome undergoing IVF, EA for tonifying Shen as an adjunct treatment may alleviate clinical symptoms and improve the high-quality embryo rate. The EA-induced mechanism may involve regulation of PI3K/Akt/Foxo3a expression in granulosa cells to improve the developmental microenvironment of oocytes and inhibit granulosa cell apoptosis, possibly contributing to the improved clinical pregnancy rate (Registration No. ChiCTR 1800016217).

Effect of Yangjing Zhongyu Tang in Treating Kidney-Yin Deficiency Due to Repeated Implantation Failure and on LIF,VEGF,IL-1β,MCP-1 Levels / 中国实验方剂学杂志

Objective:To explore the clinical efficacy of Yangjing Zhongyu Tang in treating kidney-Yin deficiency due to repeated implantation failure (RIF). Method:Totally 70 patients with kidney yin deficiency due to repeated implantation failure (RIF) who received the periodic Frozen thawed embyo (FET) after in vitro fertilization (IVF) embryo cryopreservation were selected from the Integrative Medicine Reproductive and Genetics Center of Affiliated Hospital of Shandong University of Traditional Chinese Medicine(TCM). They were randomly divided into observation group and control group, with 35 cases in each group. All patients were received long protocol controlled ovarian hyperstimulation. Observation group was given Yangjing Zhongyu Tang from the 5th day to the 14th day of the menstrual cycle 1 month before transplantation, and continued to take it on the 5th day of the menstrual cycle in the month of the transplantation. Control group did not given TCM. After treatment, TCM syndrome scores, endometrial thickness, typing, uterine artery pulsation index (PI) and resistance index (RI) of HCG, endometrial secretion leukemia inhibitory factor (LIF), blood vessels endothelial growth factor (VEGF), interleukin-1β (IL-1β) and monocyte chemoattractant protein-1 (MCP-1), number of eggs obtained, fertilization rate and embryo transfer results were observed. Result:After treatment, the scores of TCM syndromes in observation group were significantly improved, with statistically significant difference (PPPβ and LIF of observation group were higher than those of control group, and the MCP-1 was lower than that of control group (PPConclusion:Yangjing Zhongyu Tang can significantly alleviate the clinical symptoms of patients with kidney-Yin deficiency due to RIF, effectively improve the type A endometrial morphology of RIF patients, reduce the uterine artery blood flow resistance, optimize endometrial implantation, and significantly improve the clinical pregnancy rate.

A correlation study of the expression of HA-CD44st and HER-2 in breast cancer.

BACKGROUND: This study investigated the effect of hyaluronic acid (HA)-CD44st on the invasive ability of human breast cancer MCF-7 cells and the correlation between the expression of CD44st and human epidermal growth factor receptor-2 (HER-2) in postoperative breast cancer patients. MATERIALS AND METHODS: MCF-7 cells transfected with the eukaryotic expression vector pcDNA3.1-CD44st (MCF/CD44st) were used to examine the effect of the activation of the HA-CD44st-transforming growth factor ß (TGFß)-phosphatidylinositol-3-kinase (PI3K) signaling pathway on the invasive ability of MCF-7 cells. The expression of proteins related to this signaling pathway was assessed by flow cytometry, reverse transcription-polymerase chain reaction, and Western blotting, and the role of AP-1 in the pathway was investigated by electrophoretic mobility shift assay. The effect of pathway activation on the invasion of MCF-7 cells was assessed by Transwell assay, and CD44 expression in breast cancer tissue was detected by immunohistochemistry. Quantitative reverse transcription-polymerase chain reaction was used to detect the expression of CD44st and HER-2 in breast cancer tissue and their correlation was investigated. RESULTS: HA significantly upregulated HER-2 and TGFß in MCF-7/CD44st cells, increased p-AKT expression and AP-1 activity, and promoted the invasive ability of tumor cells. CD44st mRNA expression had significant difference between breast cancer tissues and adjacent normal tissues (P < 0.05), and high expression of CD44st mRNA was closely correlated with HER-2 expression in breast cancer tissues. CONCLUSION: Binding of HA to the CD44st receptor may regulate the invasiveness of MCF-7 cells through the CD44st/TGFß/PI3K/AP-1 signaling pathway with increased expression of TGFß and HER-2. The expression of CD44st mRNA is correlated with HER-2 expression in postoperative breast cancer patients.

Streaming potential method for characterizing interaction of electrical double layers between rice roots and Fe/Al oxide-coated quartz in situ.

The interaction between rice roots and Fe/Al oxide-coated quartz was investigated through zeta potential measurements and column leaching experiments in present study. The zeta potentials of rice roots, Fe/Al oxide-coated quartz, and the binary systems containing rice roots and Fe/Al oxide-coated quartz were measured by a specially constructed streaming potential apparatus. The interactions between rice roots and Fe/Al oxide-coated quartz particles were evaluated/deduced based on the differences of zeta potentials between the binary systems and the single system of rice roots. The zeta potentials of the binary systems moved in positive directions compared with that of rice roots, suggesting that there were overlapping of diffuse layers of electric double layers on positively charged Fe/Al oxide-coated quartz and negatively charged rice roots and neutralization of positive charge on Fe/Al oxide-coated quartz with negative charge on rice roots. The greater amount of positive charges on Al oxide led to the stronger interaction of Al oxide-coated quartz with rice roots and the more shift of zeta potential compared with Fe oxide. The overlapping of diffuse layers on Fe/Al oxide-coated quartz and rice roots was confirmed by column leaching experiments. The greater overlapping of diffuse layers on Al oxide and rice roots led to more simultaneous adsorptions of K+ and NO3- and greater reduction in leachate electric conductivity when the column containing Al oxide-coated quartz and rice roots was leached with KNO3 solution, compared with the columns containing rice roots and Fe oxide-coated quartz or quartz. When the KNO3 solution was replaced with deionized water to flush the columns, more K+ and NO3- were desorbed from the binary system containing Al oxide-coated quartz and rice roots than from other two binary systems, suggesting that the stronger electrostatic interaction between Al oxide and rice roots promoted the desorption of K+ and NO3- from the binary system and enhanced overlapping of diffuse layers on these oppositely charged surfaces compared with other two binary systems. In conclusion, the overlapping of diffuse layers occurred between positively charged Fe/Al oxides and rice roots, which led to neutralization of opposite charge and affected adsorption and desorption of ions onto and from the charged surfaces of Fe/Al oxides and rice roots.

Effects of adhesions of amorphous Fe and Al hydroxides on surface charge and adsorption of K+ and Cd2+ on rice roots.

Iron (Fe) and aluminum (Al) hydroxides in variable charge soils attached to rice roots may affect surface-charge properties and subsequently the adsorption and uptake of nutrients and toxic metals by the roots. Adhesion of amorphous Fe and Al hydroxides onto rice roots and their effects on zeta potential of roots and adsorption of potassium (K+) and cadmium (Cd2+) by roots were investigated. Rice roots adsorbed more Al hydroxide than Fe hydroxide because of the greater positive charge on Al hydroxide. Adhesion of Fe and Al hydroxides decreased the negative charge on rice roots, and a greater effect of the Al hydroxide. Consequently, adhesion of Fe and Al hydroxides reduced the K+ and Cd2+ adsorption by rice roots. The results of attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR) and desorption of K+ and Cd2+ from rice roots indicated that physical masking by Fe and Al hydroxides and diffuse-layer overlapping between the positively-charged hydroxides and negatively-charged roots were responsible for the reduction of negative charge on roots induced by adhesion of the hydroxides. Therefore, the interaction between Fe and Al hydroxides and rice roots reduced negative charge on roots and thus inhibited their adsorption of nutrient and toxic cations.

Expression of Novel CD44st and MMP2 in NSCLC Tissues and Their Clinical Significance.

BACKGROUND: Abnormal expression of some CD44 molecules in tumor tissues can induce the degradation of the extracellular matrix, and is closely associated with axillary lymph node metastasis, angiogenesis, cancer progression, and drug resistance. PATIENTS AND METHODS: We measured and confirmed the expression of CD44st and MMP2 mRNAs and proteins in the cancer tissues and adjacent normal tissues of postoperative non-small cell lung cancer (NSCLC) patients with either adenocarcinoma (n = 72) or squamous cell carcinoma (n = 53) using quantitative reverse transcription polymerase chain reaction, gene sequencing, and immunohistochemical analysis. RESULTS: CD44st and MMP2 expression were closely associated with the histopathological classification, lymph node metastasis, and TNM stage of the tumors, and the difference was statistically significant (p < 0.05). The median overall survival (OS) for the high CD44st expression group was 30.52 months (95% confidence interval (CI) 24.02-36.15); for the low expression group it was 43.23 months (95% CI 31.81-52.02) (p = 0.020). The median OS for the high MMP-2 expression group was 30.53 months (95% CI 26.69-33.31); for the low expression group it was 40.06 months (95% CI 33.55-46.45) (p = 0.022). CONCLUSION: The rates of CD44st and MMP2 expression were higher in squamous cell carcinomas than in adenocarcinomas, were closely associated with lymph node metastasis and TNM stage, and affected patients' prognoses.

Analysis of growth plate material property effect on knee injury of six-year-old child occupant / 医用生物力学

Objective To develop the finite element model of six-year-old child occupant lower extremity with higher biofidelity and validate the model of knee joints,as well as analyze the biomechanical responses of growth plate under frontal impact load and injury mechanisms of the knee joint by using this model.Methods The sixyear-old child occupant lower extremity with growth plate was modeled based on children's anatomy and CT images,and corresponding material properties of the lower extremity model were assigned.The model was validated according to biomechanical experiments by Kerrigan et aL and Haut et aL and then was used to analyze the injury results of growth plate with different material properties.Results The model validation was qualified by comparing the curves from the experimental and simulation results.The growth plates at knee regions could change injury patterns of the child occupant lower extremity fracture.The material properties of growth plate could affect threshold of axial damage of the femur as well as relative position of the fracture.Conclusions The validated model can be used for related study and application on biomechanical responses and injury mechanisms of sixyear-old child occupant lower extremities.