Traditional Chinese medicine in osteoporosis: from pathogenesis to potential activity.

Osteoporosis characterized by decreased bone density and mass, is a systemic bone disease with the destruction of microstructure and increase in fragility. Osteoporosis is attributed to multiple causes, including aging, inflammation, diabetes mellitus, and other factors induced by the adverse effects of medications. Without treatment, osteoporosis will further progress and bring great trouble to human life. Due to the various causes, the treatment of osteoporosis is mainly aimed at improving bone metabolism, inhibiting bone resorption, and promoting bone formation. Although the currently approved drugs can reduce the risk of fragility fractures in individuals, a single drug has limitations in terms of safety and effectiveness. By contrast, traditional Chinese medicine (TCM), a characteristic discipline in China, including syndrome differentiation, Chinese medicine prescription, and active ingredients, shows unique advantages in the treatment of osteoporosis and has received attention all over the world. Therefore, this review summarized the pathogenic factors, pathogenesis, therapy limitations, and advantages of TCM, aiming at providing new ideas for the prevention and treatment of OP.

Effects of oropharyngeal administration of own mother's milk on oral microbial colonization in very low birth weight infants fed by gastric tube: A randomized controlled trial.

AIMS: The aim of the present study was to explore the effect of oropharyngeal mother's milk administration on oral microbial colonization in infants fed by gastric tube at different time points. METHODS: Infants (n = 116) with birth weight <1500 g were randomly allocated into two groups which both received breast milk for enteral nutrition. The control group (n = 51) accepted oropharyngeal normal saline administration. The experimental group (n = 53) accepted oropharyngeal mother's milk administration before fed by gastric tube once every 3 h over 21 days after birth. We analyzed the oral microbiota at initiation and 7 and 14 and 21 days later using 16S DNA amplicon sequencing. RESULTS: There were no difference in oral microbial diversity between the two groups at any time point, but diversity decreased significantly over time in both groups. On the first day of life, the oral microbiota of the infant in the experimental and control groups consisted mainly of Firmicutes (7.75%, 6.18%) and Proteobacteria (68.65%, 68.69%), respectively. As time increases to 21 days after birth, Firmicutes (77.67%, 77.66%) had replaced Proteobacteria (68.65%, 68.69%) as the predominant phylum. DISCUSSION: From birth to 21 days after birth, oropharyngeal mother's milk administration did not change the diversity and structural composition of the oral microbiota. The oral microbial diversity of infants declined significantly over time. Firmicutes had replaced Proteobacteria as the predominant phylum.

Transcriptomic profile of premature ovarian insufficiency with RNA-sequencing.

Introduction: This study aimed to explore the transcriptomic profile of premature ovarian insufficiency (POI) by investigating alterations in gene expression. Methods: A total of sixty-one women, comprising 31 individuals with POI in the POI group and 30 healthy women in the control group (HC group), aged between 24 and 40 years, were recruited for this study. The transcriptomic profiles of peripheral blood samples from all study subjects were analyzed using RNA-sequencing. Results: The results revealed 39 differentially expressed genes in individuals with POI compared to healthy controls, with 10 upregulated and 29 downregulated genes. Correlation analysis highlighted the relationship between the expression of SLC25A39, CNIH3, and PDZK1IP1 and hormone levels. Additionally, an effective classification model was developed using SLC25A39, CNIH3, PDZK1IP1, SHISA4, and LOC389834. Functional enrichment analysis demonstrated the involvement of these differentially expressed genes in the "haptoglobin-hemoglobin complex," while KEGG pathway analysis indicated their participation in the "Proteoglycans in cancer" pathway. Conclusion: The identified genes could play a crucial role in characterizing the genetic foundation of POI, potentially serving as valuable biomarkers for enhancing disease classification accuracy.

Cornus officinalis with high pressure wine steaming enhanced anti-hepatic fibrosis: Possible through SIRT3-AMPK axis.

Cornus officinalis, a medicinal and edible plant known for its liver-nourishing properties, has shown promise in inhibiting the activation of hepatic stellate cells (HSCs), crucial indicators of hepatic fibrosis, especially when processed by high pressure wine steaming (HPWS). Herein, this study aims to investigate the regulatory effects of cornus officinalis, both in its raw and HPWS forms, on inflammation and apoptosis in liver fibrosis and their underlying mechanisms. In vivo liver fibrosis models were established by subcutaneous injection of CCl4, while in vitro HSCs were exposed to transforming growth factor-ß (TGF-ß). These findings demonstrated that cornus officinalis with HPWS conspicuously ameliorated histopathological injury, reduced the release of proinflammatory factors, and decreased collagen deposition in CCl4-induced rats compared to its raw form. Utilizing ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometer (UHPLC-QTOF-MS) combined with network analysis, we identified that the pharmacological effects of the changed components of cornus officinalis before and after HPWS, primarily centered on the adenosine phosphate (AMP)-activated protein kinase (AMPK) pathway. Of note, cornus officinalis activated AMPK and Sirtuin 3 (SIRT3), promoting the apoptosis of activated HSCs through the caspase cascade by regulating caspase3, caspase6 and caspase9. siRNA experiments showed that cornus officinalis could regulate AMPK activity and its mediated-apoptosis through SIRT3. In conclusion, cornus officinalis exhibited the ability to reduce inflammation and apoptosis, with the SIRT3-AMPK signaling pathway identified as a potential mechanism underlying the synergistic effect of cornus officinalis with HPWS on anti-liver fibrosis.

Proteogenomic insights into early-onset endometrioid endometrial carcinoma: predictors for fertility-sparing therapy response.

Endometrial carcinoma remains a public health concern with a growing incidence, particularly in younger women. Preserving fertility is a crucial consideration in the management of early-onset endometrioid endometrial carcinoma (EEEC), particularly in patients under 40 who maintain both reproductive desire and capacity. To illuminate the molecular characteristics of EEEC, we undertook a large-scale multi-omics study of 215 patients with endometrial carcinoma, including 81 with EEEC. We reveal an unexpected association between exposome-related mutational signature and EEEC, characterized by specific CTNNB1 and SIGLEC10 hotspot mutations and disruption of downstream pathways. Interestingly, SIGLEC10Q144K mutation in EEECs resulted in aberrant SIGLEC-10 protein expression and promoted progestin resistance by interacting with estrogen receptor alpha. We also identified potential protein biomarkers for progestin response in fertility-sparing treatment for EEEC. Collectively, our study establishes a proteogenomic resource of EEECs, uncovering the interactions between exposome and genomic susceptibilities that contribute to the development of primary prevention and early detection strategies for EEECs.

Using Apparent Diffusion Coefficient (ADC) of Endometrial Cancer MRI to Determine P53 Molecular Subtypes.

BACKGROUND: Endometrial Cancer (EC) is a highly heterogeneous cancer comprising both histological and molecular subtypes. Using a non-invasive modality method to trigger these subtypes as early as possible can aid clinicians in establishing individualized treatment. PURPOSE: The study aimed to clarify the value of the Apparent Diffusion Coefficient (ADC) of EC MRI in determining molecular subtypes. MATERIAL AND METHODS: We retrospectively recruited 109 patients with pathologically proven EC (78 endometrioid cancers and 31 non-endometrioid cancers) with available molecular classification from a tertiary centre. MRI was prospectively performed a month prior to surgery; images were blindly interpreted by two experienced radiologists with consensus reading. The ADC value was measured by an experienced radiologist on the commercially available processing workstation. Interoperator measurement consistency was calculated. RESULTS: Our sample comprised 17 PLOE, 32 MSI-H, 31 NSMP, and 29 P53abn ECs. Clinical information did not differ significantly among the groups. The maximum diameter and volume of the lesions differed among the groups. The ADC value in the maximal area (ADCarea) or region of interest (ROI, ADCroi) in the P53abn group was higher than that in the other groups (894.0 ±12.6 and 817.5 ± 83.3 x10-6 mm2/s). The ADC mean values were significantly different between the P53abn group and the other groups (P = 0.000). The nomogram showed the highest discriminative ability to distinguish P53abn EC from other types (AUC: 0.859). CONCLUSION: Our results have suggested the quantitative MR characteristics (ADC values) derived from preoperative EC MRI to provide useful information in preoperatively determining P53abn cancer.

SIRT3: A potential therapeutic target for liver fibrosis.

Sirtuin3 (SIRT3) is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase located in the mitochondria, which mainly regulates the acetylation of mitochondrial proteins. In addition, SIRT3 is involved in critical biological processes, including oxidative stress, inflammation, DNA damage, and apoptosis, all of which are closely related to the progression of liver disease. Liver fibrosis characterized by the deposition of extracellular matrix is a result of long termed or repeated liver damage, frequently accompanied by damaged hepatocytes, the recruitment of inflammatory cells, and the activation of hepatic stellate cells. Based on the functions and pharmacology of SIRT3, we will review its roles in liver fibrosis from three aspects: First, the main functions and pharmacological effects of SIRT3 were investigated based on its structure. Second, the roles of SIRT3 in major cells in the liver were summarized to reveal its mechanism in developing liver fibrosis. Last, drugs that regulate SIRT3 to prevent and treat liver fibrosis were discussed. In conclusion, exploring the pharmacological effects of SIRT3, especially in the liver, may be a potential strategy for treating liver fibrosis.

Fully Automated Identification of Lymph Node Metastases and Lymphovascular Invasion in Endometrial Cancer From Multi-Parametric MRI by Deep Learning.

BACKGROUND: Early and accurate identification of lymphatic node metastasis (LNM) and lymphatic vascular space invasion (LVSI) for endometrial cancer (EC) patients is important for treatment design, but difficult on multi-parametric MRI (mpMRI) images. PURPOSE: To develop a deep learning (DL) model to simultaneously identify of LNM and LVSI of EC from mpMRI images. STUDY TYPE: Retrospective. POPULATION: Six hundred twenty-one patients with histologically proven EC from two institutions, including 111 LNM-positive and 168 LVSI-positive, divided into training, internal, and external test cohorts of 398, 169, and 54 patients, respectively. FIELD STRENGTH/SEQUENCE: T2-weighted imaging (T2WI), contrast-enhanced T1WI (CE-T1WI), and diffusion-weighted imaging (DWI) were scanned with turbo spin-echo, gradient-echo, and two-dimensional echo-planar sequences, using either a 1.5 T or 3 T system. ASSESSMENT: EC lesions were manually delineated on T2WI by two radiologists and used to train an nnU-Net model for automatic segmentation. A multi-task DL model was developed to simultaneously identify LNM and LVSI positive status using the segmented EC lesion regions and T2WI, CE-T1WI, and DWI images as inputs. The performance of the model for LNM-positive diagnosis was compared with those of three radiologists in the external test cohort. STATISTICAL TESTS: Dice similarity coefficient (DSC) was used to evaluate segmentation results. Receiver Operating Characteristic (ROC) analysis was used to assess the performance of LNM and LVSI status identification. P value <0.05 was considered significant. RESULTS: EC lesion segmentation model achieved mean DSC values of 0.700 ± 0.25 and 0.693 ± 0.21 in the internal and external test cohorts, respectively. For LNM positive/LVSI positive identification, the proposed model achieved AUC values of 0.895/0.848, 0.806/0.795, and 0.804/0.728 in the training, internal, and external test cohorts, respectively, and better than those of three radiologists (AUC = 0.770/0.648/0.674). DATA CONCLUSION: The proposed model has potential to help clinicians to identify LNM and LVSI status of EC patients and improve treatment planning. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 2.

Diagnosis of single umbilical artery and risk of foetal congenital malformations by prenatal ultrasound: a retrospective study.

BACKGROUND: Single umbilical artery (SUA) is strongly associated with foetal structural abnormalities; however, the exact pattern of this association has not been described. We aimed to investigate the occurrence of malformations in singleton pregnancies with SUA in China and to study the association between the absent side of the umbilical artery and foetal malformations. METHODS: This was a retrospective study of singleton pregnancies for which routine first-trimester anatomical screening was performed at 11+ 0-13+ 6 gestational weeks and, if the pregnancy continued, a second-trimester scan was performed at 20+ 0-24+ 0 weeks. Data were extracted from records at the referral centre, the Obstetrics and Gynecology Hospital of Fudan University, between January 2011 and April 2019 (n = 47,894). Using logistic regression, the odds ratios (OR) with 95% confidence intervals (CIs) were calculated for malformations associated with SUA. RESULTS: The incidence of SUA in our study was 2.0% (970/47,894). Of all foetuses with SUA, 387 (39.9%) had structural malformations. The malformation type varied, with cardiovascular complications being the most common. A robust association was observed between SUA and oesophageal stenosis or atresia (OR: 25.33), followed by cardiovascular (OR: 9.98-24.02), scoliosis (OR: 18.62), genitourinary (OR: 2.45-15.66), and brain malformations (OR: 4.73-9.12). The absence of the left umbilical artery (n = 445, 45.9%) was consistent with that of the right umbilical artery (n = 431, 44.4%). Furthermore, a significantly higher rate of an absent right than the left umbilical artery (p<0.01) was observed in SUA with foetal abnormalities than in SUA with no malformations. CONCLUSIONS: Overall, we observed a higher risk of various specific malformations in foetuses with SUA, and a strong association between SUA and oesophageal stenosis or atresia. The absence of the right umbilical artery was most common in foetuses with SUA and structural malformations. This study provides a reference for ultrasonographers in conducting foetal structural screening for pregnant women with SUA.

Determination of p53abn endometrial cancer: a multitask analysis using radiological-clinical nomogram on MRI.

OBJECTIVES: We aimed to differentiate endometrial cancer (EC) between TP53mutation (P53abn) and Non-P53abn subtypes using radiological-clinical nomogram on EC body volume MRI. METHODS: We retrospectively recruited 227 patients with pathologically proven EC from our institution. All these patients have undergone molecular pathology diagnosis based on the Cancer Genome Atlas. Clinical characteristics and histological diagnosis were recorded from the hospital information system. Radiomics features were extracted from online Pyradiomics processors. The diagnostic performance across different acquisition protocols was calculated and compared. The radiological-clinical nomogram was established to determine the nonendometrioid, high-risk, and P53abn EC group. RESULTS: The best MRI sequence for differentiation P53abn from the non-P53abn group was contrast-enhanced T1WI (test AUC: 0.8). The best MRI sequence both for differentiation endometrioid cancer from nonendometrioid cancer and high-risk from low- and intermediate-risk groups was apparent diffusion coefficient map (test AUC: 0.665 and 0.690). For all 3 tasks, the combined model incorporating all the best discriminative features from each sequence yielded the best performance. The combined model achieved an AUC of 0.845 in the testing cohorts for P53abn cancer identification. The MR-based radiomics diagnostic model performed better than the clinical-based model in determining P53abn EC (AUC: 0.834 vs 0.682). CONCLUSION: In the present study, the diagnostic model based on the combination of both radiomics and clinical features yielded a higher performance in differentiating nonendometrioid and P53abn cancer from other EC molecular subgroups, which might help design a tailed treatment, especially for patients with high-risk EC. ADVANCES IN KNOWLEDGE: (1) The contrast-enhanced T1WI was the best MRI sequence for differentiation P53abn from the non-P53abn group (test AUC: 0.8). (2) The radiomics-based diagnostic model performed better than the clinical-based model in determining P53abn EC (AUC: 0.834 vs 0.682). (3) The proposed model derived from multi-parametric MRI images achieved a higher accuracy in P53abn EC identification (AUC: 0.845).

Transcription factor PBX4 regulates limb development and haematopoiesis in mice.

The mammalian Pre-B cell leukaemia transcription factors 1-4 (PBX1-4) constitutes the PBC class of the homeodomain (HD)-containing proteins, which play important roles in diverse developmental processes. The functions and the underlying molecular mechanisms of PBX1-3 but not PBX4 have been extensively studied, and they have been reported to direct essential morphogenetic processes and organogenesis. In the present study, we generated knockin mice of FLAG-tagged PBX4 and the Pbx4 knockout (KO) mice and carried out in-depth characterisation of PBX4 expression and function. PBX4 was initially detected only in the testis among several organs of the adult mice and was expressed in spermatocytes and spermatids. However, no abnormality in spermatogenesis, but growth retardation and premature death after birth were observed in most adult Pbx4 KO mice. These animals were inactive and had shorter hindlimbs and lower numbers of reticulocytes and lymphocytes, probably caused by abnormalities at earlier developmental stages. Pbx4 mRNAs were indeed detected in several embryonic cell types related to limb development by in situ hybridisation and single-cell RNA-sequencing analysis. Pbx4 protein was also detected in the bone marrow of adult mice with a lower level compared with that in the testis. PBX4 preferentially binds to the promoters of a large number of genes including those for other HD-containing proteins and ribosomal proteins whose mutations are related to anaemia. PBX4-binding sites are enriched in motifs similar to those of other HD-containing proteins such as PKNOX1 indicating that PBX4 may also act as a co-transcription factor like other PBC proteins. Together, these results show that PBX4 participates in limb development and haematopoiesis while its function in spermatogenesis has not been revealed by gene KO probably due to the complementary effects of other genes.

Multiple intracellular pathogen infections with ocular pathologies associated with adult-onset immunodeficiency due to anti-interferon-γ autoantibodies: a case report.

BACKGROUND: Autoantibodies against interferon-γ (IFN-γ) can inhibit IFN-γ-dependent signal transducer and activator of transcription 1 phosphorylation and thus increase the risk of infection with intracellular pathogens, such as Talaromyces marneffei (TM), nontuberculous mycobacteria (NTMs), and Mycobacterium tuberculosis (TB). Here, we report a rare case of triple infection caused by TM, NTM, and TB in a human immunodeficiency virus-negative patient. CASE PRESENTATION: A middle-aged female was admitted to our hospital after experiencing recurrent rash, cough, and expectoration for 4 months. She was successively diagnosed with NTM, TM, and TB infections without conventional immunosuppression-associated factors. However, after effective anti-infective treatment, the patient was confirmed to have allergic conjunctivitis and was successfully treated with corticosteroids and immunosuppressants. The most conspicuous characteristics were recurrent infection and immune disorders. CONCLUSIONS: High-titer anti-IFN-γ autoantibodies are strongly associated with severe and disseminated infections, such as NTM, TM, and TB. It is characterized by persistently high degree of inflammation and high immunoglobin levels.

Mo-doping heterojunction: interfacial engineering in an efficient electrocatalyst for superior simulated seawater hydrogen evolution.

Exploring economical, efficient, and stable electrocatalysts for the seawater hydrogen evolution reaction (HER) is highly desirable but is challenging. In this study, a Mo cation doped Ni0.85Se/MoSe2 heterostructural electrocatalyst, Mox-Ni0.85Se/MoSe2, was successfully prepared by simultaneously doping Mo cations into the Ni0.85Se lattice (Mox-Ni0.85Se) and growing atomic MoSe2 nanosheets epitaxially at the edge of the Mox-Ni0.85Se. Such an Mox-Ni0.85Se/MoSe2 catalyst requires only 110 mV to drive current densities of 10 mA cm-2 in alkaline simulated seawater, and shows almost no obvious degradation after 80 h at 20 mA cm-2. The experimental results, combined with the density functional theory calculations, reveal that the Mox-Ni0.85Se/MoSe2 heterostructure will generate an interfacial electric field to facilitate the electron transfer, thus reducing the water dissociation barrier. Significantly, the heteroatomic Mo-doping in the Ni0.85Se can regulate the local electronic configuration of the Mox-Ni0.85Se/MoSe2 heterostructure catalyst by altering the coordination environment and orbital hybridization, thereby weakening the bonding interaction between the Cl and Se/Mo. This synergistic effect for the Mox-Ni0.85Se/MoSe2 heterostructure will simultaneously enhance the catalytic activity and durability, without poisoning or corrosion of the chloride ions.

Development of mobile health-based interventions to promote physical activity in patients with head and neck cancer: a qualitative study.

Background: Despite the well-grounded benefits of physical activity (PA), poor compliance with the PA guidelines has been reported among head and neck cancer (HNC) patients. Mobile health (mHealth)-based interventions can help cancer survivors increase their PA levels and increase the reach or efficiency of rehabilitation services. However, there is limited knowledge about the needs and perceptions of HNC patients regarding these interventions. This study explored the perceptions and needs of HNC patients regarding mHealth-based PA programs before developing such interventions to ensure their improved effectiveness. Study design: A constructivist qualitative study. Methods: We purposively selected 17 adult HNC patients aged 40-80 years to determine their needs and perceptions of future mHealth-based PA programs. Semi-structured face-to-face interviews were conducted, and the data were analyzed via thematic analysis. The report followed the Consolidated Criteria for Qualitative Research Reports guidelines. Results: Four themes were analyzed from the interview transcripts regarding the needs and perceptions of mHealth-based PA programs: (1) functionality needs; (2) system usage requirements; (3) social support; and (4) perceived barriers and facilitators. HNC patients expect highly customized and specialized mHealth interventions that consider individual factors, address their concerns about security, network, and cost, and prefer improved comfort. Moreover, they expect to receive support from their healthcare providers, families, and peers. Conclusion: The study provides pragmatic ready-to-use recommendations to design interventions for inactive HNC patients to achieve the recommended PA levels. Future mHealth interventions should be tailored according to the needs of the HNC patients by utilizing perceived facilitators and removing perceived barriers to help them engage in PA actively.

Sublingual immunotherapy adherence in patients with allergic rhinitis: Effects of an intervention based on the information-motivation-behavioral skills model.

Objective: This study aimed to confirm the efficacy of an intervention based on the information-motivation-behavior skills (IMB) model in improving the sublingual immunotherapy adherence score, medication beliefs score, self-efficacy score, and medication knowledge score of patients with allergic rhinitis. Methods: A total of 120 patients with allergic rhinitis from an otorhinolaryngology clinic were divided into the control group (n = 60) and experimental group (n = 60); the study was conducted from August 2021 to March 2022. The control group received routine intervention, whereas the experimental group received intervention based on the IMB model. The medication adherence, medication beliefs, self-efficacy, and medication knowledge levels of the two groups were evaluated at baseline, post-intervention, at 1-month follow-up, and at 3-month follow-up. Results: After intervention, a total of 116 patients completed the trial in the experimental and control groups (58 cases each). The results revealed differences in the scores of medication adherence, belief, self-efficacy, and knowledge between the two groups post-intervention, at 1-month follow-up, and at 3-month follow-up (P < 0.05). Further, the scores of the four indexes of the two groups were different with time, and better changes were noted among experimental group participants. Conclusion: Implementing interventions based on the IMB model for people receiving sublingual immunotherapy for allergic rhinitis can effectively improve patients' medication beliefs, self-efficacy, and knowledge of medication, thereby improving their medication adherence, ensuring efficacy, and providing medication care for outpatients.

Farnesoid X receptor: From Structure to Function and Its Pharmacology in Liver Fibrosis.

The farnesoid X receptor (FXR), a ligand-activated transcription factor, plays a crucial role in regulating bile acid metabolism within the enterohepatic circulation. Beyond its involvement in metabolic disorders and immune imbalances affecting various tissues, FXR is implicated in microbiota modulation, gut- to-brain communication, and liver disease. The liver, as a pivotal metabolic and detoxification organ, is susceptible to damage from factors such as alcohol, viruses, drugs, and high-fat diets. Chronic or recurrent liver injury can culminate in liver fibrosis, which, if left untreated, may progress to cirrhosis and even liver cancer, posing significant health risks. However, therapeutic options for liver fibrosis remain limited in terms of FDA- approved drugs. Recent insights into the structure of FXR, coupled with animal and clinical investigations, have shed light on its potential pharmacological role in hepatic fibrosis. Progress has been achieved in both fundamental research and clinical applications. This review critically examines recent advancements in FXR research, highlighting challenges and potential mechanisms underlying its role in liver fibrosis treatment.

SRSF1-mediated alternative splicing is required for spermatogenesis.

Alternative splicing (AS) plays significant roles in a multitude of fundamental biological activities. AS is prevalent in the testis, but the regulations of AS in spermatogenesis is only little explored. Here, we report that Serine/arginine-rich splicing factor 1 (SRSF1) plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf1 led to complete infertility by affecting spermatogenesis. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF1 affected the AS of Stra8 in a direct manner and Dazl, Dmc1, Mre11a, Syce2 and Rif1 in an indirect manner. Our findings demonstrate that SRSF1 has crucial functions in spermatogenesis and male fertility by regulating alternative splicing.

[Loss of RBFOX2 inhibits meiotic initiation in male mice].

Meiotic initiation is a critical step in gametogenesis. Recently, some genes required for meiotic initiation have been identified. However, meiosis-initiating factors and the underlying mechanisms are far from being fully understood. We have established a long-term culture system of spermatogonial stem cells (SSCs) and an in vitro model of meiotic initiation using mouse SSCs. Our previous study revealed that the RNA-binding protein RBFOX2 may regulate meiotic initiation, but the role and the mechanism need to be further elucidated. In this study, we constructed RBFOX2 knockdown SSC lines by using lentivirus-mediated gene delivery method, and found that the knockdown SSCs underwent normal self-renewal, mitosis and differentiation. However, they were unable to initiate meiosis when treated with retinoic acid, and they underwent apoptosis. These results indicate that RBFOX2 plays an essential role in meiotic initiation of spermatogonia. This work provides new clues for understanding the functions of RNA-binding proteins in meiotic initiation.

The regulation of tolerogenic dendritic cells by a Chinese herb formula improves abortion prone in mice.

BACKGROUND: Abortion prone (AP) is a common clinical event. The underlying mechanism remains unclear. Traditional Chinese formulas are known to be efficient in the management of abortion. The purpose of this study is to observe the effects of Anzitiaochongtang (AZT), a traditional formulation of Chinese medicine, on improving AP in mice by regulating immune tolerance. METHODS: An established abortion model (CBA/J×DBA/2) was employed. AZT was prepared and administered to mice in a manner consistent with clinical practice. Tolerogenic dendritic cells (tDC) and type 1 regulatory T cells (Tr1 cell) in mice were analyzed by immunological approaches to be used as representative immune tolerant parameters. RESULTS: An AP model was established with CBA/J × DBA/2 mice. The expression of IL-10 in tDC and Tr1 cell frequency in the mouse decidua tissues were lower in the AP group than that in the normal pregnancy (NP) group. Administration of AZT up regulated the expression of IL-10 in tDCs and Tr1 cell generation in the decidua tissues, and improved the pregnancy and tissue structure in AP mice. The main mechanism by which AZT improves pregnancy in AP mice is that AZT enhanced the expression of galectin-9 in the epithelial cells of decidua tissues. Galectin 9 activates TIM3 on DCs to promote the IL-10 expression. The DCs induced more Tr1 cells in the decidua tissues. CONCLUSIONS: Dysfunctional tDCs were detected in the AP decidua tissues. Administration of AZT improved pregnancy in AP mice by regulating tDC function and generation of Tr1 cells in the maternal-fetal interface.

The EQ-5D-3L Valuation Study in Pakistan.

BACKGROUND: To utilize EQ-5D in economic evaluations, a societal-based value set is needed. To date, no value sets exist for any EQ-5D instrument in Pakistan. Previous EQ-5D studies conducted in Pakistan 'borrowed' health preferences developed in other countries. However, for a value set to be valid for Pakistani population, it should represent the preferences of the Pakistani population, and culture and living standards of Pakistan. OBJECTIVE: The aim of this study was to derive a Pakistani EQ-5D-3L value set. METHODS: A moderately representative sample aged 18 years and over was recruited from the Pakistani general population. A multi-stage stratified quota method with respect to ethnicity, gender, age and religion was utilized. Two elicitation techniques, the composite time trade-off (cTTO) and discrete choice experiments (DCE) were applied. Interviews were undertaken by trained interviewers using computer-assisted face-to-face interviews with the EuroQol Portable Valuation Technology (EQ-PVT) platform. To estimate the value set, a hybrid regression model combining cTTO and DCE data was used. RESULTS: A total of 289 respondents who completed the interviews were included for the analysis. The hybrid model correcting for heteroskedasticity without a constant was selected as the final model for the value set. It is shown that being unable to do usual activities (level 3) was assigned the largest weight, followed by mobility level 3, self-care level 3, pain/discomfort level 3 and anxiety/depression level 3. The worst health state was assigned the value - 0.171 in the final model. CONCLUSIONS: A Pakistani country-specific EQ-5D-3L value set is now available. The availability of this value set may help promote and facilitate health economic evaluations and health-related quality-of-life (HRQoL) research in Pakistan.