Single cell transcriptomics reveals distinct transcriptional responses to oxycodone and buprenorphine by iPSC-derived brain organoids from patients with opioid use disorder.

The opioid epidemic represents a national crisis. Oxycodone is one of the most prescribed opioid medications in the United States, whereas buprenorphine is currently the most prescribed medication for opioid use disorder (OUD) pharmacotherapy. Given the extensive use of prescription opioids and the global opioid epidemic, it is essential to understand how opioids modulate brain cell type function at the single-cell level. We performed single nucleus RNA-seq (snRNA-seq) using iPSC-derived forebrain organoids from three male OUD subjects in response to oxycodone, buprenorphine, or vehicle for seven days. We utilized the snRNA-seq data to identify differentially expressed genes following drug treatment using the Seurat integrative analysis pipeline. We utilized iPSC-derived forebrain organoids and single-cell sequencing technology as an unbiased tool to study cell-type-specific and drug-specific transcriptional responses. After quality control filtering, we analyzed 25787 cells and identified sixteen clusters using unsupervised clustering analysis. Our results reveal distinct transcriptional responses to oxycodone and buprenorphine by iPSC-derived brain organoids from patients with OUD. Specifically, buprenorphine displayed a significant influence on transcription regulation in glial cells. However, oxycodone induced type I interferon signaling in many cell types, including neural cells in brain organoids. Finally, we demonstrate that oxycodone, but not buprenorphine activated STAT1 and induced the type I interferon signaling in patients with OUD. These data suggest that elevation of STAT1 expression associated with OUD might play a role in transcriptional regulation in response to oxycodone. In summary, our results provide novel mechanistic insight into drug action at single-cell resolution.

Ectopic breast tissue of the vulva.

Ectopic mammary gland tissue in the vulva is an exceptionally rare disease. We present a case of a 62-year-old woman with a left vulvar mass of 30 years duration that progressively increased in size. The patient reported having pressure and discomfort, especially during movement. Surgical excision was performed, and a histopathological examination revealed a well-differentiated ectopic breast. We also review other cases of vulvar ectopic breast to further comprehend the characteristics of this rare disease.  Clinicians and pathologists should always consider it as a differential diagnosis when presented with a vulvar mass.

The pheromone affects reproductive physiology and behavior by regulating hormone in juvenile mice.

Pheromones could promote hormone secretions and regulate sexual behavior. It was unclear whether multiparous pheromone could induce variations in puberty. The aim was to ascertain whether pheromone in urine of multiparous females induced central precocious puberty (CPP) in juvenile C57BL/6J females. The precocious puberty was examined by vaginal smear, lordosis reaction, HE stain, and ELISA analysis. Results suggested that the first vaginal opening and the first estrus were significantly earlier. The time interval of the first vaginal opening and estrus was significantly shortened. It was interesting that the first estrus was significantly correlated with the first vaginal opening and the time interval of the first estrus. In the first estrus, female lordosis reaction, the number of mature follicles, and the weight of the ovary and uterus significantly increased. The level of luteinizing hormones also significantly increased. Thus, multiparous pheromone can regulate sex hormone to induce CPP in juvenile C57BL/6J females.

Cooperation of ATF4 and CTCF promotes adipogenesis through transcriptional regulation.

Adipogenesis is a multi-step process orchestrated by activation of numerous TFs, whose cooperation and regulatory network remain elusive. Activating transcription factor 4 (ATF4) is critical for adipogenesis, yet its regulatory network is unclarified. Here, we mapped genome-wide ATF4 binding landscape and its regulatory network by Chip-seq and RNA-seq and found ATF4 directly modulated transcription of genes enriching in fat cell differentiation. Motifs of TFs especially CTCF were found from ATF4 binding sites, suggesting a direct role of ATF4 in regulating adipogenesis associated with CTCF and other TFs. Deletion of CTCF attenuated adipogenesis while overexpression enhanced adipocyte differentiation, indicating CTCF is indispensable for adipogenesis. Intriguingly, combined analysis of Chip-seq data of these two TFs showed that ATF4 co-localized with CTCF in the promoters of key adipogenic genes including Cebpd and PPARg and co-regulated their transactivation. Moreover, ATF4 directly regulated CTCF expression and interacted with CTCF in differentiated 3T3-L1 cells. In vivo, downregulation of ATF4 suppressed the expression of CTCF, Cebpd, and PPARg, leading to reduced adipose tissue expansion in refeeding mice. Consistently, mRNA expression of ATF4 and CTCF was positively correlated with each other in human subcutaneous adipose tissue and inversely associated with BMI, indicating a possible involvement of these two TFs in adipose development. Taken together, our data propose for the first time that ATF4 and CTCF work cooperatively to control adipogenesis and adipose development via orchestrating transcription of adipogenic genes. Our findings reveal novel therapeutic targets in obesity treatment.

[Progress in genetic research on tooth agenesis associated with Wnt/beta-catenin signaling pathway].

Tooth agenesis is the most common form of congenital craniofacial dysplasia seen in stomatology clinics, which may be caused by genetic and/or environmental factors. Tooth development is regulated by a series of signaling pathways, and variants in any of these strictly balanced signaling cascades can result in tooth agenesis and/or other oral defects. Notably, variants of genes of the Wnt/beta-catenin signaling pathway are important cause for both non-syndromic and syndromic tooth agenesis. This article has provided a review for the molecular genetics of tooth agenesis associated with Wnt/beta-catenin signaling pathway, which may shed lights on the etiology and molecular mechanism of this disease.

Elevated C-reactive protein and complement C3 levels are associated with preterm birth: a nested case-control study in Chinese women.

BACKGROUND: Currently, there are many studies researched the associations between maternal serum inflammatory indicators (i.e. ferritin, C-reactive protein [CRP], C3 and C4) and preterm birth (PTB). The results, however, are inconsistent. Therefore, the aim of this study was to estimate the relationship between maternal serum inflammatory indicators and PTB in a nested case-control (NCC)study. METHODS: A NCC study was conducted by Guangxi Birth Cohort Study which enrolled a total of 6203 pregnant women between 50/7 and 346/7 weeks of gestational age (wGA) from six cities in China between 2015 and 2016. There were 206women who delivered preterm (< 370/7 wGA), and 412 women who delivered term birth, those women were matched by maternal age, birth place, gender of infants, and wGA at blood collection. The inflammatory indicators were quantified by immunoturbidimetric methods. RESULTS: Highest quartile concentrations of all inflammatory indicators were determined versus median. After adjusting for maternal age, high levels of CRP (CRP > 16.60 mg/L) are related to the risk of PTB (OR = 2.16, 95% CI: 1.02-4.56, p = 0.044) in the first trimester. The association of C3 was extremely related to those who delivered PTB (OR = 2.53, 95% CI: 1.14-5.64, p = 0.023) in the first trimester. Moreover, no significant associations were found in C4 (p = 0.079) and ferritin (p = 0.067) between PTB. CONCLUSIONS: Elevated concentrations of CRP and C3 in the first trimester were associated with increased risk of PTB. Inflammatory indicators may act a pivotal part in early diagnosis and prognosis of PTB.

Relationships of Cadmium, Lead, and Mercury Levels With Albuminuria in US Adults: Results From the National Health and Nutrition Examination Survey Database, 2009-2012.

In this cross-sectional study, we evaluated associations between cadmium, lead, and mercury levels and the presence of albuminuria in US adults who participated in the National Health and Nutrition Examination Survey during the period 2009-2012. A total of 2,926 adults aged ≥20 years were included, representing a population-based sample of 18,264,307 persons. Data on blood and urinary levels of cadmium, lead, and mercury and urinary albumin concentration (albuminuria, measured as albumin:creatinine ratio (ACR) ≥30 mg/g) were obtained. Multivariate linear regression was used to analyze associations between log-transformed cadmium, lead, and mercury levels and the presence of albuminuria. Urinary ACR was significantly higher among participants with a blood cadmium level of 0.349-0.692 µg/L (quartile 3) than in those with a blood cadmium level less than or equal to 0.243 µg/L (quartile 1) (crude ß = 0.15, 95% confidence interval (CI): 0.01, 0.28). Participants with a urinary cadmium level greater than or equal to 0.220 µg/L had a significantly higher ACR (0.220-0.403 µg/L (quartile 3): crude ß = 0.12 (95% CI: 0.03, 0.21); ≥0.404 µg/L (quartile 4): crude ß = 0.29 (95% CI: 0.18, 0.39)) than those with a urinary cadmium level less than or equal to 0.126 µg/L (quartile 1). In conclusion, only blood and urinary cadmium levels, not mercury or lead levels, were associated with albuminuria among adults in this population.

Protein phosphatase 2A modulates podocyte maturation and glomerular functional integrity in mice.

BACKGROUND: Protein phosphorylation & dephosphorylation are ubiquitous cellular processes that allow for the nuanced and reversible regulation of protein activity. Protein phosphatase 2A (PP2A) is a multifunction phosphatase that is well expressed in all cell types of kidney during early renal development, though its functions in kidney remains to be elucidated. METHODS: PP2A conditional knock-out mice was generated with PP2A fl/fl mice that were crossed with Podocin-Cre mice. The phenotype of Pod-PP2A-KO mice (homozygous for the floxed PP2A allele with Podocin-Cre) and littermate PP2A fl/fl controls (homozygous for the PP2A allele but lacking Podocin-Cre) were further studied. Primary podocytes isolated from the Pod-PP2A-KO mice were cultured and they were then employed with sing label-free nano-LC - MS/MS technology on a Q-exactive followed by SIEVE processing to identify possible target molecular entities for the dephosphorylation effect of PP2A, in which Western blot and immunofluorescent staining were used to analyze further. RESULTS: Pod-PP2A-KO mice were developed with weight loss, growth retardation, proteinuria, glomerulopathy and foot process effacement, together with reduced expression of some slit diaphragm molecules and cytoskeleton rearrangement of podocytes. Y box protein 1 (YB-1) was identified to be the target molecule for dephosphorylation effect of PP2A. Furthermore, YB-1 phosphorylation was up-regulated in the Pod-PP2A-KO mice in contrast to the wild type controls, while total and un-phosphorylated YB-1 both was moderately down-regulated in podocytes from the Pod-PP2A-KO mice. CONCLUSION: Our study revealed the important role of PP2A in regulating the development of foot processes and fully differentiated podocytes whereas fine-tuning of YB-1 via a post-translational modification by PP2A regulating its activity might be crucial for the functional integrity of podocytes and glomerular filtration barrier.

Low serum folate status in the second trimester increase the risk of low birthweight in Chinese women.

AIM: This study aimed to explore the influence of maternal folate and vitamin B12 (B12) status during pregnancy on the incidence of low birthweight (LBW) infants. METHODS: A total of 6203 eligible women registered in seven hospitals in southern China, and 230 cases with singleton live births and 382 controls were matched for further analyses. The concentrations of serum folate and B12 were detected with chemiluminescence microparticle immunoassay on ARCHITECT i2000-1. Conditional logistic regression was used to evaluate the effects of folate and B12 levels on LBW. RESULTS: Maternal serum folate levels increased basically with increasing the period of folic acid supplementation (P trend <0.001). Moreover, maternal serum folate and B12 levels gradually decreased with the increase of gestational age (P < 0.001). Conditional logistic regressions analysis results showed increased odds ratios (OR) for LBW from the fourth to first folate quartiles (P trend <0.01) in the second trimester. Compared with the women in the highest quartile, those in the lowest quartile of serum folate in the second trimester were found with higher risk of LBW (adjusted OR = 1.67, 95% confidence interval [CI]: 1.02-2.73). However, no significant association was observed between serum folate and LBW in the first trimester or third trimester. In addition, serum B12 exhibited no significant association with LBW. CONCLUSIONS: Low serum folate levels in the second trimester significantly increases the risk of LBW amongst Chinese women with singleton pregnancies.

EBV-HLH children with reductions in CD4+ T cells and excessive activation of CD8+ T cells.

BackgroundIn this report, we analyzed the number and activation profiles of T cells in Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) patients and assessed their value for the diagnosis of EBV-HLH.MethodsWe compared the quantity of CD4+ T cells and CD8+ T cells in peripheral blood among HLH patients, a sepsis group, and healthy controls. We then analyzed variations in the activation marker in CD4+ T and CD8+ T cells.ResultsThe percentage of CD4+ T cells decreased in the EBV-HLH patients when compared with healthy controls, which induced significant differences in the ratio of CD4+ T cells/CD8+ T cells. The percentage of CD4+HLA-DR+ T cells, CD8+CD69+ T cells, CD8+HLA-DR+ T cells, and CD8+HLA-DR+ T cells/CD4+CD25+ T cells increased in EBV-HLH patients when compared with that in healthy controls. Compared with EBV-HLH survivors, the median percentage of CD4+CD25+ T cells (7.9 vs. 3.0) were decreased, but the ratios of CD8+HLA-DR+T cells/CD4+CD25+T cells (6.3 vs. 20.3) were increased in the dead patients.ConclusionsThere was a reduction in CD4+ T cells and abnormal activation of CD8+ T cells in the EBV-HLH patients. The percentage of CD4+CD25+ T cells and the ratios of CD8+HLA-DR+ T cells/CD4+CD25+ T cells in EBV-HLH patients had a relation to the prognosis of the disease.

TS Gene Polymorphisms Correlate with Susceptibility to Acute Lymphocytic Leukemia in Children.

BACKGROUND Acute lymphocytic leukemia (ALL) in children is a clonal disease of bone marrow hematopoietic stem cells. This study aimed to explore the associations between MTHFR or TS genetic polymorphisms and susceptibility to acute lymphocytic leukemia (ALL) in children. MATERIAL AND METHODS This case-control study included 79 ALL patients (case group) and 102 non-ALL patients (control group). Post-PCR genomic DNA sequencing revealed MTHFR C677T and MTHFR A1298C genotypes and TS polymorphisms. The χ² test was used to compare differences in MTHFR and TS polymorphisms (including genotypic and allelic distributions) between groups. Logistic regression analysis was used to determine genetic polymorphisms and ALL risk associations. RESULTS The results indicated that TS 3R allele frequency was significantly higher in the case group than in the control group (χ²=7.45, P<0.05). The MTHFR C677T and MTHFR A1298C polymorphisms were not associated with ALL risk. Compared to the TS 2R/2R genotype, subjects carrying TS 2R/3R were twice as likely to develop ALL, and the TS 3R/3R+3R/4R genotype carried a 4-fold higher risk of developing ALL (OR=1.96, CI: 1.14-3.36). CONCLUSIONS The TS genetic polymorphisms increase the ALL risk. The TS 3R allele was a risk factor for ALL. There were no associations between MTHFR C677T or MTHFR A1298C polymorphisms and ALL susceptibility.

Subcellular quantitative proteomic analysis reveals host proteins involved in human cytomegalovirus infection.

Viral replication requires host cell macromolecules and energy, although host cells can alter their protein expression to restrict viral replication. To study the host cell response to human cytomegalovirus (HCMV) infection, a stable isotope labeling by amino acids in cell culture (SILAC)-based subcellular quantitative proteomic study of HCMV-infected human embryo lung fibroblast (HEL) cells was performed, and a total of 247 host proteins were identified as differentially regulated by HCMV. Western blotting and immunofluorescence confocal microscopy were performed to validate the data sets. Gene Ontology analysis indicated that cellular processes involving the metabolism, localization and immune system were regulated as a result of HCMV infection. Functional analysis of selected regulated proteins revealed that knockdown of HNRPD, PHB2 and UB2V2 can increase HCMV replication, while knockdown of A4 and KSRP resulted in decreased HCMV replication. Our study may improve our understanding of the dynamic interactions between HCMV and its host and provide multiple potential targets for anti-HCMV agent research.

Evaluation of mycophenolate mofetil or tacrolimus in children with steroid sensitive but frequently relapsing or steroid-dependent nephrotic syndrome.

AIM: Approximately 30-40% of children with steroid sensitive nephrotic syndrome have frequently relapsing nephrotic syndrome (FRNS) or steroid-dependent nephrotic syndrome (SDNS). Mycophenolate mofetil (MMF) and tacrolimus (TAC) are often alternative treatment choices for these patients. METHODS: A single-center prospective study was conducted to compare the efficacy of MMF or TAC in reducing relapses and maintaining remission in children with FRNS or SDNS. Of the 72 recruited patients, either MMF (20∼30 mg/kg/d, n = 34) or TAC (0.05∼0.15 mg/kg/d, n = 38) was administered for 12 months. RESULTS: The mean 6-month relapse rates decreased from 2.56 episodes before therapy to 0.76 episodes in the first 6 months after therapy (c(2) = 44.362, p < 0.001) and 0.67 in the next 6 months (c(2) = 37.817, p < 0.001) in the MMF group. In the TAC group, the mean 6-month relapse rates decreased from 2.39 episodes before therapy to 0.41 episodes in the first 6 months after therapy (c(2) = 62.242, p < 0.001) and 0.42 in next 6 months (c(2) = 67.482, p < 0.001). No significant difference in the relapse rate was found between the groups (before therapy, c(2) = 0.902, p = 0.637; first 6 months, c(2) = 5.358, p = 0.147; second 6 months, c(2) = 4.089, p = 0.252). And there was also no significant difference in cumulative sustained remission and the incidence of adverse events between two groups. CONCLUSIONS: In combination with low-dose steroids, MMF or TAC presented similar efficacy in maintaining remission in children with FRNS/SDNS in the present study. Therapy with MMF or TAC is a promising strategy with a moderate risk of side effects in children who are steroid sensitive but have FRNS/SDNS.

Analysis of EV71 infection progression using triple-SILAC-based proteomics approach.

Enterovirus 71 (EV71), a member of Picornaviridae, causes severe neurological and systemic illness in children. To better understand the virus-host cell interactions, we performed a triple-SILAC-based quantitative proteomics study monitoring host cell proteome changes after EV71 infection. Based on the quantitative data for more than 4100 proteins, ∼17% of the proteins were found as significantly changed (p<0.01) at either 8 or 20 hours post infection. Five biological processes and seven protein classes showed significant differences. Functional screening of nine regulated proteins discovered the regulatory role of CHCH2, a mitochondrial protein known as a transcriptional activator for cytochrome c oxidase, in EV71 replication. Further studies showed that CHCH2 served as a negative regulator of innate immune responses. All MS data have been deposited in the ProteomeXchange with identifier PXD002483 (http://proteomecentral.proteomexchange.org/dataset/PXD002483).

Serum suPAR levels help differentiate steroid resistance from steroid-sensitive nephrotic syndrome in children.

BACKGROUND: Soluble urokinase plasminogen activator receptor (suPAR) has been regarded as a permeability factor in proteinuria, though its role in primary nephrotic syndrome remains to be elucidated further. METHODS: Plasma samples and clinical information from 176 children with primary nephrotic syndrome were collected and concentrations of suPAR were measured. We evaluated the correlation between suPAR concentrations and clinical features, and the value of the plasma suPAR level in predicting steroid-resistant nephrotic syndrome (SRNS). RESULTS: There is a significant difference in plasma suPAR concentration between SRNS and steroid-sensitive nephrotic syndrome (SSNS) groups (3,744.1 ± 2,226.0 vs. 2,153.5 ± 1,167.0, p < 0.05). The area under the curve (AUC) was 0.80, with p < 0.001 for the receiver operating characteristic (ROC) curve analysis using suPAR to predict SRNS. The suspicious range for predicting SRNS was estimated to be 1,907.0 pg/ml to 3,043.5 pg/ml (χ(2) = 14.775, p = 0.001). CONCLUSIONS: From ROC curve analysis, we demonstrated the significance of the suPAR level in predicting SRNS with a high specificity but low sensitivity. However, the clinical value of suPAR to predict steroid resistance and guide therapy remains to be investigated further.

[Influence of thymidylate synthase gene polymorphisms on high-dose methotrexate-related toxicities in childhood acute lymphoblastic leukemia].

OBJECTIVE: To investigate the influence of thymidylate synthase (TS) gene polymorphisms on high-dose methotrexate (HD-MTX)-related toxicities in childhood acute lymphoblastic leukemia (ALL). METHODS: A total of 73 children who were diagnosed with ALL between March 2011 and March 2013 were included into this study. Genomic DNAs were extracted from their peripheral blood. And then the genotypes of TS 5'-UTR were determined by direct DNA sequencing after PCR. The toxicity response of 73 patients receiving HD-MTX chemotherapy were observed and recorded, and plasma MTX concentrations at 42-48 hours after chemotherapy were measured. RESULTS: The main HD-MTX-related toxicities of 73 patients receiving HD-MTX chemotherapy were neutropenia, decreased hemoglobin level, thrombocytopenia, liver toxicity, mucosal damage, and gastrointestinal reactions. There were no significant differences in the incidence rate of HD-MTX-related toxicities between children with different TS 5'-UTR genotypes after chemotherapy (P>0.05). TS 5'-UTR genotype was not significantly correlated with plasma MTX concentrations at 42-48 hours after chemotherapy (P>0.05). CONCLUSIONS: TS gene polymorphisms have no influence on the incidence of HD-MTX-related toxicities in childhood ALL.

A Bi-GRU-attention neural network to identify motor units from high-density surface electromyographic signals in real time.

To utilize surface electromyographics (sEMG) for control purposes, it is necessary to perform real-time estimation of the neural drive to the muscles, which involves real-time decomposition of the EMG signals. In this paper, we propose a Bidirectional Gate Recurrent Unit (Bi-GRU) network with attention to perform online decomposition of high-density sEMG signals. The model can give different levels of attention to different parts of the sEMG signal according to their importance using the attention mechanism. The output of gradient convolutional kernel compensation (gCKC) algorithm was used as the training label, and simulated and experimental sEMG data were divided into windows with 120 sample points for model training, the sampling rate of sEMG signal is 2048 Hz. We test different attention mechanisms and find out the ones that could bring the highest F1-score of the model. The simulated sEMG signal is synthesized from Fuglevand method (J. Neurophysiol., 1993). For the decomposition of 10 Motor Units (MUs), the network trained on simulated data achieved an average F1-score of 0.974 (range from 0.96 to 0.98), and the network trained on experimental data achieved an average F1-score of 0.876 (range from 0.82 to 0.97). The average decomposition time for each window was 28 ms (range from 25.6 ms to 30.5 ms), which falls within the lower bound of the human electromechanical delay. The experimental results show the feasibility of using Bi-GRU-Attention network for the real-time decomposition of Motor Units. Compared to the gCKC algorithm, which is considered the gold standard in the medical field, this model sacrifices a small amount of accuracy but significantly improves computational speed by eliminating the need for calculating the cross-correlation matrix and performing iterative computations.

Systematic analysis of palatal transcriptome to identify cleft palate genes within TGFß3-knockout mice alleles: RNA-Seq analysis of TGFß3 Mice.

BACKGROUND: In humans, cleft palate (CP) accounts for one of the largest number of birth defects with a complex genetic and environmental etiology. TGFß3 has been established as an important regulator of palatal fusion in mice and it has been shown that TGFß3-null mice exhibit CP without any other major deformities. However, the genes that regulate cellular decisions and molecular mechanisms maintained by the TGFß3 pathway throughout palatogenesis are predominantly unexplored. Our objective in this study was to analyze global transcriptome changes within the palate during different gestational ages within TGFß3 knockout mice to identify TGFß3-associated genes previously unknown to be associated with the development of cleft palate. We used deep sequencing technology, RNA-Seq, to analyze the transcriptome of TGFß3 knockout mice at crucial stages of palatogenesis, including palatal growth (E14.5), adhesion (E15.5), and fusion (E16.5). RESULTS: The overall transcriptome analysis of TGFß3 wildtype mice (C57BL/6) reveals that almost 6000 genes were upregulated during the transition from E14.5 to E15.5 and more than 2000 were downregulated from E15.5 to E16.5. Using bioinformatics tools and databases, we identified the most comprehensive list of CP genes (n = 322) in which mutations cause CP either in humans or mice, and analyzed their expression patterns. The expression motifs of CP genes between TGFß3+/- and TGFß3-/- were not significantly different from each other, and the expression of the majority of CP genes remained unchanged from E14.5 to E16.5. Using these patterns, we identified 8 unique genes within TGFß3-/- mice (Chrng, Foxc2, H19, Kcnj13, Lhx8, Meox2, Shh, and Six3), which may function as the primary contributors to the development of cleft palate in TGFß3-/- mice. When the significantly altered CP genes were overlaid with TGFß signaling, all of these genes followed the Smad-dependent pathway. CONCLUSIONS: Our study represents the first analysis of the palatal transcriptome of the mouse, as well as TGFß3 knockout mice, using deep sequencing methods. In this study, we characterized the critical regulation of palatal transcripts that may play key regulatory roles through crucial stages of palatal development. We identified potential causative CP genes in a TGFß3 knockout model, which may lead to a better understanding of the genetic mechanisms of palatogenesis and provide novel potential targets for gene therapy approaches to treat cleft palate.

Impact of endometriosis on female sexual function: an updated systematic review and meta-analysis.

Introduction: Endometriosis can lead to a state of chronic inflammation marked by the presence of scarring and adhesions within the pelvis and/or other parts of the body. Recent estimates suggest that globally this condition affects approximately 10% of women in the reproductive age group. Aims: In this study we sought updated evidence on the association between endometriosis and sexual function in female patients. Methods: We used standard assessment tools to conduct a systematic search of the PubMed, EMBASE, and Scopus databases for observational studies that documented the association of endometriosis with female sexual function. A random-effects model was used for the analysis, and effect sizes were reported as the weighted mean difference (WMD) or OR with 95% CIs. Results: A total of 13 studies were selected for inclusion in our investigation. All of the included studies were cross-sectional in design. The data on sexual function in most of the studies were collected by using the Female Sexual Function Index (FSFI) tool, for which higher scores suggest better sexual function. The risk of sexual dysfunction (based on specific cutoffs for the FSFI score) was higher in women with than in women without endometriosis (OR 1.71; 95% CI, 1.21-2.43). In addition, when we used continuous scores to examine the risk of sexual dysfunction, diagnosis of endometriosis was associated with significantly lower overall FSFI scores (WMD, -3.40; 95% CI, -5.13 to -1.66) and lower scores on all of its 6 domains, ie, desire (WMD, -0.27; 95% CI, -0.53 to -0.02), arousal (WMD, -0.43; 95% CI, -0.79 to -0.07), lubrication (WMD, -0.49; 95% CI, -0.66 to -0.31), orgasm (WMD, -0.65; 95% CI, -1.07 to -0.23), satisfaction (WMD, -0.52; 95% CI, -0.77 to -0.26), and pain (WMD, -1.06; 95% CI, -1.57 to -0.55). Conclusion: The findings of this study suggest that female patients with endometriosis have suboptimal sexual function compared with healthy female subjects. Patients with endometriosis should be offered sexual counseling and supportive care by a multidisciplinary team of gynecologists, psychologists, and sexual therapists.

Comparative Study on MNVT of OPV Type I and III Reference Products in Different Periods.

Widespread vaccination using the oral live attenuated polio vaccine (OPV) and Sabin strain inactivated vaccine (sIPV) have greatly reduced the incidence of polio worldwide. In the period post-polio, the virulence of reversion of the Sabin strain makes the use of OPV gradually becoming one of the major safety hazards. The verification and release of OPV has become the top priority. The monkey neurovirulence test (MNVT) is the gold standard for detecting whether OPV meets the criteria, which are recommended by the WHO and Chinese Pharmacopoeia. Therefore, we statistically analyzed the MNVT results of type I and III OPV at different stages: 1996-2002 and 2016-2022. The results show that the upper and lower limits and C value of the qualification standard of type I reference products in 2016-2022 have decreased compared with the corresponding scores in the 1996-2002 period. The upper and lower limit and C value of the qualified standard of type III reference products were basically the same as the corresponding scores in the 1996-2002. We also found significant differences in the pathogenicity of the type I and III in the cervical spine and brain, with the decreasing trend in the diffusion index of the type I and type III in the cervical spine and brain. Finally, two evaluation criteria were used to judge the OPV test vaccines from 2016 to 2022. The vaccines all met the test requirements under the evaluation criteria of the above two stages. Based on the characteristics of OPV, data monitoring was one of the most intuitive methods to judge changes in virulence.