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Glioma is the common highly malignant primary brain tumor. However, the molecular pathways that result in the pathogenesis of glioma remain elusive. In this study, we found that microRNA-103 (miR-103), microRNA-195 (miR-195), or microRNA-15b (miR-15b), which all have the same 5′ “seed” miRNA portion and share common binding sites in the SALL4 3′-untranslated region (UTR), were downregulated in glioma tissues and cell lines. These miRNAs suppressed glioma cell proliferation, migration, and invasion, induced cell apoptosis, and decreased the level of the SALL4 protein, but not that of SALL4 mRNA, which was identified as a direct target of all three miRNAs. The caspase-3/7 activity expression in U251 cells overexpressing these miRNAs was rescued during SALL4 upregulation. An obvious inverse correlation was observed between SALL4 and miR-103 or miR-195 expression levels in clinical glioma samples. Moreover, enforced expression of SALL4 stimulated cell proliferation, migration, and invasion. In conclusion, these data suggest that miR-103, miR-195, and miR-15b post-transcriptionally downregulated the expression of SALL4 and suppressed glioma cell growth, migration, and invasion, and increased cell apoptosis. These results provide a potential therapeutic target that may downregulate SALL4 in glioma.

We performed this meta-analysis to evaluate the predictive value of different parameters in the sperm retrieval rate （SRR） of microdissection testicular sperm extraction （TESE） in patients with nonobstructive azoospermia （NOA）. All relevant studies were searched in PubMed, Web of Science, EMBASE, Cochrane Library, and EBSCO. We chose three parameters to perform the meta-analysis： follicle-stimulating hormone （FSH）, testicular volume, and testicular histopathological findings which included three patterns： hypospermatogenesis （HS）, maturation arrest （MA）, and Sertoli-cell-only syndrome （SCOS）. If there was a threshold effect, only the area under the summary receiver operating characteristic curve （AUSROC） was calculated. Otherwise, the pooled sensitivity, specificity, positive likelihood ratio （PLR）, negative likelihood ratio （NLR）, and the diagnostic odds ratio （DOR） were also calculated. Twenty-one articles were included in our study finally. There was a threshold effect among studies investigating FSH and SCOS. The AUSROCs of FSH, testicular volume, HS, MA, and SCOS were 0.6119, 0.6389, 0.6758, 0.5535, and 0.2763, respectively. The DORs of testicular volume, HS, and MA were 1.98, 16.49, and 1.26, respectively. The sensitivities of them were 0.80, 0.30, and 0.27, while the specificities of them were 0.35, 0.98, and 0.76, respectively. The PLRs of them were 1.49, 10.63, and 1.15, respectively. And NLRs were 0.73, 0.72, and 0.95, respectively. All the investigated factors in our study had limited predictive value. However, the histopathological findings were helpful to some extent. Most patients with HS could get sperm by microdissection TESE.

Background Infertility is associated with both physical and psychological challenges, and psychological distress is prevalent among infertility patients. To manage this, they may adopt a range of coping strategies—both adaptive and maladaptive—which can lead to varying outcomes. The choice of strategy will also be affected by many factors. Identifying the strategies and influencing factors of patients in coping with infertility and the infertility treatment process is helpful to help medical staff evaluate the coping effect of patients and give intervention. Methods A qualitative systematic review was conducted to explore the coping strategies and influencing factors of infertility patients in coping with infertility and infertility treatment. Twelve electronic databases were systematically searched: China National Knowledge Infrastructure, Wanfang, VIP, China Biomedical database, PubMed, Web of Science, Embase, Scopus, Proquest (Psychology Database), APA PsycINFO, CINAHL, Cochrane databases, and other resources. Study quality was assessed through The Joanna Briggs Institute’s Qualitative Assessment and Review Instrument by two researchers independently. Data synthesis was conducted using thematic analysis. The study employed the tool named Confidence in the Evidence from Reviews of Qualitative Research to grade the integrated evidence. Results There were 26 qualitative studies included and synthesized into two key themes and 11 sub-themes: (1) Coping strategies: Behavioral coping over verbal expression, blame-oriented coping strategy, developing emotional or psychological defenses, self-management, build inner mental strength, change cognition and behavior, and adopting compromising or adaptive strategies. (2) Influencing factors: individual internal resources, tolerance and rules, comprehensive support systems, and medical uncertainty. Conclusion Infertile patients will use positive and negative strategies to cope with infertility and infertility treatment. Coping strategies are dynamic and evolve over time, and influenced by a variety of personal, social, and clinical factors. Religion, notably, emerged as both a coping mechanism and an influencing factor. It is essential for healthcare professionals to assess coping strategies and their determinants in order. to provide timely and appropriate interventions.

Pregnancy is a complex biological process. The establishment and maintenance of foetal–maternal interface are pivotal events. Decidual immune cells and inflammatory cytokines play indispensable roles in the foetal–maternal interface. The disfunction of decidual immune cells leads to adverse pregnancy outcome. Tumour necrosis factor (TNF)-α, a common inflammatory cytokine, has critical roles in different stages of normal pregnancy process. However, the relationship between the disorder of TNF-α and adverse pregnancy outcomes, including preeclampsia (PE), intrauterine growth restriction (IUGR), spontaneous abortion (SA), preterm birth and so on, is still indefinite. In this review, we thoroughly reviewed the effect of TNF-α disorder on pathological conditions. Moreover, we summarized the reports about the adverse pregnancy outcomes (PE, IUGR, SA and preterm birth) of using anti-TNF-α drugs (infliximab, etanercept and adalimumab, certolizumab and golimumab) currently in the clinical studies. Overall, IUGR, SA and preterm birth are the most common adverse pregnancy outcomes of anti-TNF-α drugs. Our review may provide insight for the immunological treatment of pregnancy-related complication, and help practitioners make informed decisions based on the current evidences.

Background The hunt for the molecular markers with specificity and sensitivity has been a hot area for the tumor treatment. Due to the poor diagnosis and prognosis of pancreatic cancer (PC), the excision rate is often low, which makes it more urgent to find the ideal tumor markers. Methods Robust Rank Aggreg (RRA) methods was firstly applied to identify the differentially expressed genes (DEGs) between PC tissues and normal tissues from GSE28735, GSE15471, GSE16515, and GSE101448. Among these DEGs, the highly correlated genes were clustered using WGCNA analysis. The co-expression networks and molecular complex detection (MCODE) Cytoscape app were then performed to find the sub-clusters and confirm 35 candidate genes. For these genes, least absolute shrinkage and selection operator (lasso) regression model was applied and validated to build a diagnostic risk score model. Cox proportional hazard regression analysis was used and validated to build a prognostic model. Results Based on integrated transcriptomic analysis, we identified a 19 gene module ( SYCN , PNLIPRP1 , CAP2 , GNMT , MAT1A , ABAT , GPT2 , ADHFE1 , PHGDH , PSAT1 , ERP27 , PDIA2 , MT1H , COMP , COL5A2 , FN1 , COL1A2 , FAP and POSTN ) as a specific predictive signature for the diagnosis of PC. Based on the two consideration, accuracy and feasibility, we simplified the diagnostic risk model as a four-gene model: 0.3034*log 2 ( MAT1A )-0.1526*log 2 ( MT1H ) + 0.4645*log 2 ( FN1 ) -0.2244*log 2 ( FAP ), log 2 (gene count). Besides, a four-hub gene module was also identified as prognostic model = − 1.400*log 2 ( CEL ) + 1.321*log 2 ( CPA1 ) + 0.454*log 2 ( POSTN ) + 1.011*log 2 ( PM20D1 ), log 2 (gene count). Conclusion Integrated transcriptomic analysis identifies two four-hub gene modules as specific predictive signatures for the diagnosis and prognosis of PC, which may bring new sight for the clinical practice of PC.

Background This study aimed to obtain high-resolution endometrial gland images under high-definition hysteroscopy from in vitro fertilization and embryo transfer (IVF-ET) patients and perform image recognition to analyze their density and opening size. Concurrently, the number and morphology of pinopodes in the endometrial samples were observed using scanning electron microscopy (SEM). The objective was to compare the correlation between the two methods in evaluating endometrial receptivity and predicting pregnancy outcomes and to assess the consistency between the quantitative curves and pregnancy outcomes of the two methods in the cohort study. Methods 67 patients undergoing hysteroscopic surgery who had undergone controlled ovarian hyperstimulation treatment within 1–3 menstrual cycles before the surgery were selected. Hysteroscopic exploration was performed on the 3–5 days after ovulation (during the implantation window period). Endometrial images and tissues were collected under hysteroscopy. The endometrial glands were counted, the sizes of gland openings were calculated using an image recognition algorithm, and the number and morphology of endometrial pinopodes were observed through SEM. All patients underwent embryo transfer surgery within 1–3 menstrual cycles after hysteroscopy. Patients were divided into pregnancy and non-pregnancy groups based on pregnancy outcomes. The density and size of endometrial glands, as well as the number and morphology of pinopodes were compared between the two groups. Results The endometrial gland density and the size of the endometrial gland opening in the pregnancy group were higher than that in the non-pregnancy group ( P  < 0.05). In contrast, both the average pinopode count per image and the developmental maturity grading of pinopodes were significantly higher in the pregnancy group compared to the non-pregnancy group. Conclusions Both hysteroscopic endometrial gland image recognition technology and pinopode detection can effectively reflect endometrial receptivity and predict pregnancy outcomes. However, image recognition technology has clear economic and promotional advantages. Clinical trial number Not applicable.

Tumor metastasis to bone is often accompanied by a severe pain syndrome (cancer-induced bone pain, CIBP) that is frequently unresponsive to analgesics, which markedly reduces patient quality of life and cancer treatment tolerance in patients. Prolonged pain can induce hypersensitivity via spinal plasticity, and several recent studies have implicated the involvement of vascular endothelial growth factor-A (VEGF-A) signaling in this process. Here, we speculated that CIBP is associated with VEGF-A/VEGFR2 signaling in the spinal cord. A mouse model of CIBP was established by intramedullary injection of Lewis lung carcinoma (LLC) cells in the mouse femur. Pain sensitization and potential amelioration via VEGF-A/VEGFR2 blockade were measured using paw withdrawal threshold to mechanical stimulation and paw withdrawal latency to thermal. Spinal VEGF-A/VEGFR2 signaling was blocked by intrathecal injection of the VEGF-A antibody or the specific VEGFR2 inhibitor ZM323881. Changes in the expression levels of VEGF-A, VEGFR2, and other pain-related signaling factors were measured using western blotting and immunofluorescence staining. Mice after LLC injection demonstrated mechanical allodynia and thermal hyperalgesia, both of which were suppressed via anti-VEGF-A antibody or ZM323881. Conversely, the intrathecal injection of exogenous VEGF-A was sufficient to cause pain hypersensitivity in naïve mice via the VEGFR2-mediated activation of protein kinase C. Moreover, the spinal blockade of VEGF-A or VEGFR2 also suppressed N-methyl-D-aspartate receptor (NMDAR) activation and downstream Ca2+-dependent signaling. Thus, spinal VEGF-A/VEGFR2/NMDAR signaling pathways may be critical mediators of CIBP.

Singlet oxygen (1O2), a reactive oxygen species, can oxidize lipids, proteins, and DNA at high concentrations, leading to cell death. Despite its extremely short half-life (10−5 s), 1O2 acts as a critical signaling molecule, triggering a retrograde pathway from chloroplasts to the nucleus to regulate nuclear gene expression. In this study, rice seeds were treated with 0, 5, 20 and 80 μM Rose Bengal (RB, a photosensitizer) under moderate light for 3 days to induce 1O2 generation. Treatment with 20 μM RB reduced stomatal density by approximately 25% in three-leaf-stage rice seedlings, while increasing the contents of pectin, hemicellulose, and cellulose in root cell walls by 30–40%. Under drought, salinity, or shading stress, 20 μM RB treatment significantly improved rice tolerance, as evidenced by higher relative water contents (49–58%) and chlorophyll contents (60–76%) and lower malondialdehyde (37–43%) and electrolyte leakage (29–37%) compared to the control. Moreover, RT-qPCR analysis revealed that the significant up-regulation of stomatal development genes (OsTMM and OsβCA1) and cell wall biosynthesis genes (OsF8H and OsLRX2) was associated with RB-induced 1O2 production. Thus, under controlled environmental conditions, 1O2 may regulate stomatal development and cell wall remodeling to enhance rice tolerance to multiple abiotic stresses. These results provide new perspectives for the improvement of rice stress tolerance.

Initial tunnel support takes on a critical significance in the stability control of surrounding rocks and the core content of tunnel support design. Its stability and safety are essential to the tunnel. The support load was optimized using the active surrounding rock load intervention scheme in accordance with the section form and bearing characteristics of the support structure. The optimization scheme of active surrounding rock load was obtained by applying active intervention load to the initial support of the tunnel to minimize the peak moment of the support structure. An active adjustment system for tunnel-surrounding rock loads was developed using the function of hydraulic load transfer and transmission combined with load proportion control. Based on the actual project, the implementation effect of the surrounding rock load active intervention scheme was verified by analyzing the measurement results of the supporting structure in the test section and the comparison section. The results suggest that the application of active intervention load can effectively improve the stress state of the tunnel initial support structure, significantly reduce the tunnel surrounding rock bias pressure and the structural peak bending moment, and increase the stability of the support structure. To control the peak moment of the supporting structure, an active intervention method and its implementation scheme for the stress of the tunnel supporting structure were proposed, which reduces the deficiency in which the conventional supporting structure can only passively bear the deformation pressure of the surrounding rock, effectively improves the stress state of the supporting structure, and can provide a reference for the development of novel tunnel supporting forms.