The development of chimeric antigen receptor T-cells against CD70 for renal cell carcinoma treatment.

In this study, we investigated CD70 as a promising target for renal cell carcinoma (RCC) therapy and developed a potent chimeric antigen receptor T (CAR-T) cells for potential clinical testing. CD70, found to be highly expressed in RCC tumors, was associated with decreased survival. We generated CAR-T cells expressing VHH sequence of various novel nanobodies from immunized alpaca and a single-chain variable fragment (scFv) derived from human antibody (41D12). In our in vitro experiments, anti-CD70 CAR-T cells effectively eliminated CD70-positive tumor cells while sparing CD70-negative cells. The nanobody-based CAR-T cells demonstrated significantly higher production of cytokines such as IL-2, IFN-γ and TNF-ɑ during co-culture, indicating their potential for enhanced functionality. In xenograft mouse model, these CAR-T cells exhibited remarkable anti-tumor activity, leading to the eradication of RCC tumor cells. Importantly, human T cell expansion after infusion was significantly higher in the VHH groups compared to the scFv CAR-T group. Upon re-challenging mice with RCC tumor cells, the VHH CAR-T treated group remained tumor-free, suggesting a robust and long-lasting anti-tumor response. These findings provide strong support for the potential of nanobody-based CD70 CAR-T cells as a promising therapeutic option for RCC. This warrants further development and consideration for future clinical trials and applications.

Clinical evidence of hyperbaric oxygen therapy for Alzheimer's disease: a systematic review and meta-analysis of randomized controlled trials.

Objective: To evaluate the potential benefits of hyperbaric oxygen intervention on people with Alzheimer's disease (AD) based on the existing randomized controlled trials (RCTs). Methods: A systematic search was conducted in nine databases until November 17, 2023, for RCTs assessing the effect of hyperbaric oxygen intervention for AD. The primary outcomes included Mini-Mental State Examination (MMSE), Alzheimer's Disease Assessment Scale-Cognitive (ADAS-Cog), activities of daily living (ADL), and adverse events. All results were shown in forest plots, and sensitivity analysis was adopted to further verify the robustness of the pooled results. Results: A total of 11 RCTs recruiting 847 participants were included in this meta-analysis. Based on the pooled evidence, hyperbaric oxygen could remarkably ameliorate MMSE [MD = 3.08, 95%CI (2.56, 3.61), p < 0.00001], ADAS-Cog [MD = -4.53, 95%CI (-5.05, -4.00), p < 0.00001], ADL [MD = 10.12, 95%CI (4.46, 15.79), p = 0.0005], MDA levels [SMD = -2.83, 95%CI (-5.27, -0.38), p = 0.02], SOD levels [SMD = 2.12, 95%CI (1.10, 3.15), p < 0.0001], IL-1-ß levels [SMD = -1.00, 95%CI (-1.48, -0.53), p < 0.0001], and TGF-ß1 levels [MD = 4.87, 95%CI (3.98, 5.76), p < 0.00001] without adverse events [OR = 1.17, 95%CI (0.68, 2.03), p = 0.58] for people with AD. The pooled results were robust after checking by sensitivity analysis. Conclusion: These evidences suggest that hyperbaric oxygen is an effective and safe intervention for the treatment of AD. Further studies with more rigorous design will help to fully evaluate the clinical value of hyperbaric oxygen on cognition function in people with AD. Systematic review registration: https://www.crd.york.ac.uk, identifier CRD42023483726.

The effect of ovarian injection of autologous platelet rich plasma in patients with poor ovarian responder: a systematic review and meta-analysis.

Objective: To evaluate the effects of ovarian injection of autologous platelet rich plasma (aPRP) on patients with poor ovarian responder (POR) based on the existing clinical evidence. Methods: According to systematic review and meta-analysis, we comprehensively searched nine databases established as of September 6, 2023, and evaluated the impact of ovarian PRP infusion on poor ovarian responder. The research results include serum follicle-stimulating hormone(FSH) and anti-Mullerian hormone(AMH) levels, antral Follicle Count(AFC), oocyte number, and embryo number. The Newcastle Ottawa Scale (NOS) was used to evaluate the quality of inclusion in trials. Results: Add up to 10 studies consisting of 793 participants were included in the meta-analysis. A review of existing evidence showed that intraovarian injection of PRP has significant therapeutic effects in increasing levels of anti-Müllerian hormone (AMH) (SMD=0.44,95% CI [0.07,0.81], p=0.02), antral follicle count (AFC) (MD=1.15,95% CI [0.4,1.90], p=0.003), oocyte count (MD=0.91, 95% CI [0.40, 1.41], p=0.0004), and embryo number (MD=0.78, 95% CI [0.5,1.07], p<0.0001). We compared the relevant data of patients before and after treatment after 2 months of intervention. It can be seen that ovarian injection of PRP treatment for 2 months has better effects in reducing FSH levels, increasing AMH levels, increasing antral follicle count, and increasing the number of oocytes and embryos (p<0.05). When the dose of PRP injected into each ovary was ≥ 4ml, there was also a significant correlation (p<0.05) with improving the number of AFC, oocytes and embryos. Significant heterogeneity existed among the studies. Conclusion: The pooled results suggest that intra-ovarian injection of PRP can promote ovarian regeneration and improve the reproductive outcomes of patients with ovarian dysfunction. This therapy may have significant clinical potential in improving sex hormone levels, increasing AFC, oocyte count, and embryo count. However, this findings still requires more rigorous and extensive trials worldwide to determine the value of intra-ovarian injection of PRP in POR patients. Systematic review registration: https://www.crd.york.ac.uk, Identifier CRD42023451232.

Correlation between long non-coding RNA MAFG-AS1 and cancer prognosis: a meta-analysis.

Background: MAF transcription factor G antisense RNA 1 (MAFG-AS1), a novel long non-coding RNA discovered recently, was proved to be useful in predicting malignancy prognosis. Nevertheless, its association with cancer prognosis has been inconsistent. Therefore, this meta-analysis aimed to explore the clinicopathological and prognostic significance of MAFG-AS1 in diverse carcinomas. Methods: Studies focused on MAFG-AS1 expression as a prognostic role in cancers were thoroughly searched in six electronic databases. The value of MAFG-AS1 in malignancies was assessed by hazard ratios (HRs) or odds ratios (ORs). Additionally, the GEPIA database was utilized to further strengthen our conclusion. Results: A total of 15 studies involving 1187 cases and nine types of cancers were recruited into this meta-analysis. High MAFG-AS1 expression was significantly related to advanced tumor stage (OR = 0.52, 95%CI [0.39, 0.69], P < 0.00001), earlier lymph node metastasis (OR = 3.62, 95%CI [2.19, 5.99], P < 0.00001), worse tumor differentiation (OR = 0.64, 95%CI [0.43, 0.95], P = 0.03), and poor overall survival (HR = 1.94, 95%CI [1.72, 2.19], P < 0.00001). No significant heterogeneity and publication bias was detected across studies. Meanwhile, MAFG-AS1 was significantly elevated in ten kinds of cancers based on the validation of the GEPIA database. Conclusion: The results of this meta-analysis indicated that high MAFG-AS1 expression is dramatically correlated with unfavorable prognosis in cancers. MAFG-AS1 may be served as a promising biomarker for malignancies.

Clinical evidence of growth hormone for infertile women with diminished ovarian reserve undergoing IVF: a systematic review and meta-analysis.

Objective: To appraise the current randomized clinical trials (RCTs) for evidence of the association of growth hormone (GH) with improved outcomes in infertile women with diminished ovarian reserve (DOR) undergoing in vitro fertilization (IVF). Methods: Relevant RCTs published in Chinese or English were identified through a comprehensive search of nine databases from the period of database inception to April 20, 2023. We included trials investigating adjuvant GH during ovarian stimulation and reported the subsequent outcomes. The group with adjuvant GH treatment and the group without adjuvant GH treatment were set up as the trial and control groups, respectively. The quality of RCTs was measured according to the Cochrane Collaboration Handbook. Results: Of the 579 studies initially identified, 10 RCTs comprising 852 infertile women with DOR were included. The GH dose of individual trials ranged between 3 and 5 IU/day. Overall, we judged the trials to be at high risk of bias in the blinding domain. Pooled results showed that GH was associated with an increased clinical pregnancy rate (RR = 1.63, 95%CI [1.31, 2.03], p < 0.0001) and a greater number of oocytes retrieved (MD = 0.91, 95%CI [0.47, 1.35], p < 0.0001). Favorable associations were also observed when ovarian stimulation was combined with GH therapy for improving the optimal embryos rate (RR = 1.84, 95%CI [1.30, 2.59], p = 0.0005) and the number of optimal embryos (MD = 0.28, 95%CI [0.08, 0.48], p = 0.005) along with reducing the cycle cancellation rate (RR = 0.46, 95%CI [0.24, 0.89], p = 0.02). Moreover, GH resulted in an increase in the fertilization rate (RR = 1.33, 95%CI [1.18, 1.50], p < 0.00001) and the embryo implantation rate (RR = 1.56, 95%CI [1.21, 2.01], p = 0.0006). In addition, there was a significant enhancement in estradiol levels (SMD = 1.18, 95%CI [0.46, 1.91], p = 0.001) and endometrial thickness (MD = 0.75, 95%CI [0.41, 1.09], p < 0.0001) on the day of hCG. With regard to the total number of days and total dose of gonadotrophins used, GH treatment was correlated with shorter days (MD = -0.26, 95%CI [-0.46, -0.06], p = 0.01) and lower dose (MD = -460.97, 95%CI [-617.20, -304.73], p < 0.00001) of gonadotrophins applied during ovarian stimulation. Furthermore, GH in conjunction with the GnRH antagonist protocol was more conducive to improving the number of oocytes retrieved when compared with the GnRH agonist protocol (p < 0.0001). Moreover, a notable association was also seen in IVF combined with GH more than or equal to 4.5 IU/day to increase the number of optimal embryos and estradiol levels on the day of hCG (p < 0.05). Conclusion: For infertile women with DOR undergoing IVF, adjuvant treatment with GH during ovarian stimulation protocols showed better clinical outcomes, shorter days and lower dosages of gonadotrophin required. Furthermore, well-designed RCTs are needed to verify our results in the future. Systematic review registration: https://www.crd.york.ac.uk PROSPERO (CRD42023421739).

The clinical value of progestin-primed ovarian stimulation protocol for women with diminished ovarian reserve undergoing IVF/ICSI: a systematic review and meta-analysis.

Background: To determine whether progestin-primed ovarian stimulation (PPOS) is more effective for women with diminished ovarian reserve (DOR) than clomiphene citrate (CC)/letrozole (LE) plus gonadotropin in IVF or ICSI treatment. Methods: Nine databases were searched until May 24, 2023, to identify relevant studies. Forest plots were used to present the results of this meta-analysis. Begg's and Egger's tests were applied to estimate publication bias. Subgroup and sensitivity analysis were performed to check the potential sources of heterogeneity and verify the robustness of the pooled results, respectively. Results: A total of 14 studies with 4182 participants were included for meta-analysis. There was evidence of a statistically notable increase in clinical pregnancy rate (OR = 1.39, 95%CI [1.01, 1.91], p = 0.05), optimal embryos rate (OR = 1.50, 95%CI [1.20, 1.88], p = 0.0004), and cumulative pregnancy rate (OR = 1.73, 95%CI [1.14, 2.60], p = 0.009), the duration and the amount of gonadotropin required (MD = 1.56, 95%CI [0.47, 2.66], p = 0.005; SMD = 1.51, 95%CI [0.90, 2.12], p < 0.00001), along with decrease cycle cancellation rate (OR = 0.78, 95%CI [0.64, 0.95], p = 0.02), luteinizing hormone (LH) level on the day of hCG (SMD = -0.81, 95%CI [-1.10, -0.53], p < 0.00001), and premature LH surge rate (OR = 0.10, 95%CI [0.07, 0.15], p < 0.00001) when PPOS was used. No evidence for publication bias within results was revealed. Conclusions: Based on evidence-based results, PPOS protocol seems to improve IVF/ICSI outcomes for women with DOR. More research with larger sample sizes and rigorous designs are required to further explore the value of PPOS among women diagnosed with DOR. Systematic review registration: www.crd.york.ac.uk, identifier CRD42023430202.

Gaussian optics optimization of an optical particle counter for measurement in high-pressure gas.

An optimization model for the parameters of the pressure-resistant lens of an optical particle counter, based on Gaussian optics theory, was established to increase the measurement accuracy of the counter for high-pressure natural gas. Comparing the experimental and calculated values of the calibrated model, when the pressure-resistant lens is displaced by 2 mm under atmospheric pressure, the relative error of the measured body deformation is 0.15%. When the air pressure varies in the range 0.10-5.09 MPa, the maximum relative error of optical measurement volume deformation with the change of refractive index is 0.13%, which shows that the model has high reliability and accuracy.

Prognostic significance of long noncoding RNA TTN-AS1 in various malignancies.

BACKGROUND: Increasing evidence has demonstrated that high TTN-AS1 expression is highly related to poor prognosis in diverse human cancers. However, the findings concerning the prognostic value of TTN-AS1 were inconsistent, as these conclusions were usually drawn with relatively small sample sizes. Hence, this meta-analysis proposes to investigate the prognostic significance of TTN-AS1 in multiple malignancies systematically. METHODS: Web of Science, Springer, Embase, PubMed, Cochrane Library, and Scopus databases were comprehensively searched to retrieve studies related to the TTN-AS1 expression with the prognosis of malignancies. The significance of the TTN-AS1 in cancers was estimated by hazard ratios (HRs) or odds ratios (ORs). Additionally, the Gene Expression Profiling Interactive Analysis (GEPIA) analysis tool was used to strengthen our results further. RESULTS: Twenty studies involving 17 different cancers and 1330 patients were recruited into this meta-analysis. The research revealed that high TTN-AS1 expression was remarkably associated with unfavorable overall survival (OS) (HR = 2.07, 95%CI [1.78, 2.41], p < .00001) when compared with low TTN-AS1 expression in malignancies. Additionally, elevated TTN-AS1 expression significantly contributed to lymph node metastasis (OR = 4.09, 95%CI [3.08, 5.44], p < .0001), larger tumor size (OR = 2.42, 95%CI [1.56, 3.77], p < .0001), worse tumor differentiation (OR = 0.36, 95%CI [0.22, 0.59], p < .0001) and more advanced tumor stage (OR = 0.29, 95%CI [0.22, 0.38], p < .0001) with low or no heterogeneity existing. Moreover, high TTN-AS1 expression  was connected with worse disease-free survival in five different cancers based on the GEPIA online database. CONCLUSIONS: The results of this meta-analysis support that high TTN-AS1 expression significantly correlates with worse prognosis in various cancers. Therefore, TTN-AS1 may be considered as a novel biomarker for malignancies.

Clinical efficacy of acupuncture for diminished ovarian reserve: a systematic review and meta-analysis of randomized controlled trials.

Objective: To evaluate the clinical efficacy of acupuncture for the treatment of diminished ovarian reserve (DOR) based on the existing randomized controlled trials (RCTs). Methods: Nine databases from their inception to December 6th, 2022, were comprehensively searched to retrieve RCTs related to the clinical efficacy of acupuncture for the treatment of DOR. The outcomes of interest were sex hormones level and antral follicle count (AFC). Risk of Bias (RoB) was adopted to assess the quality of the included trials. Results: A total of 13 RCTs involving 787 patients were included in this meta-analysis. The review of available evidence revealed acupuncture produced a significant efficacy in decreasing follicle-stimulating hormone (FSH) levels (SMD = -1.07, 95%CI [-1.79, -0.36], p = 0.003), FSH/LH ratio (MD = -0.31, 95%CI [-0.54, -0.09], p = 0.006) and increasing anti-Müllerian hormone (AMH) levels (SMD = 0.25, 95%CI [-0.00, 0.49], p = 0.05), along with AFC (MD = 1.87, 95%CI [0.96, 2.79], p < 0.0001) compared to controls. Compared with electro-acupuncture treatment, manual acupuncture was superior in reducing FSH levels, FSH/LH ratio, and increasing AMH levels and AFC (p < 0.05). A notable association was also seen when acupuncture was combined with traditional Chinese medicine therapy for improving FSH levels, FSH/LH ratio, and AFC (p < 0.05). Besides, a high dose of acupuncture (≥10 acupoints) was more conducive to ameliorating FSH levels, FSH/LH ratio, and AFC (p < 0.05) than a low dose of acupuncture (<10 acupoints). Substantial heterogeneity existed among studies. Conclusion: Acupuncture may have significant clinical potential for patients with DOR in terms of improving sex hormones level and increasing AFC, although the evidence is drawn with high heterogeneity. This finding suggests that more rigorous trials conducted in diverse regions worldwide are necessary to identify the efficacy of acupuncture for patients diagnosed with DOR. Systematic review registration: https://www.crd.york.ac.uk, identifier CRD42023402336.

Prognostic effect of lncRNA BBOX1-AS1 in malignancies: a meta-analysis.

Background: With the increasing number of new cancer cases and mortality rates, cancer has become a serious global health problem, but there are no ideal cancer biomarkers for effective diagnosis. Currently, mounting evidence demonstrates that lncRNAs play a fundamental role in cancer progression. BBOX1 anti-sense RNA 1 (BBOX1-AS1) is a recently clarified lncRNA and has been identified as dysregulated in various carcinomas, and it contributes to poor survival in cancer patients. Methods: We thoroughly searched six databases for eligible articles published as of 27, April 2023. The association of BBOX1-AS1 expression levels with prognostic and clinicopathological parameters was assessed by odds ratios (OR) and hazard ratios with 95% CIs. Additionally, we further validated our results utilizing the GEPIA online database. Results: Eight studies comprising 602 patients were included in this analysis. High BBOX1-AS1 expression indicated poor overall survival (OS) (hazard ratios = 2.30, 95% Cl [1.99, 2.67], p < 0.00001) when compared with low BBOX1-AS1 expression. Furthermore, BBOX1-AS1 expression was positively correlated with lymph node metastasis (OR = 3.00, 95% CI [1.71-5.28], p = 0.0001) and advanced tumor stage (OR = 3.74, 95% CI [2.63-5.32], p < 0.00001) for cancer patients. Moreover, BBOX1-AS1 was remarkably upregulated in 12 malignancies, and the elevated BBOX1-AS1 expression predicted poorer OS and worse disease-free survival (DFS) confirmed through the GEPIA online gene analysis tool. Conclusion: The findings highlight that BBOX1-AS1 was significantly associated with detrimental overall survival, disease-free survival, lymph node metastasis and tumor stage; thus, it could act as a novel promising biomarker to predict the clinicopathological characteristics and prognosis for various cancers.

Cognitive impairment and factors influencing depression in adolescents with suicidal and self-injury behaviors: a cross-sectional study.

BACKGROUND: Non-suicidal self-injury (NSSI) and suicide attempts (SAs) by adolescent patients with depression have become serious public health problems. There is still insufficient research evidence on the effects of NSSI and SAs on neurocognitive functioning in adolescents. Cognitive function alterations may be associated with SAs and self-injury. NSSI and SAs have different influencing factors. METHODS: Participants were recruited from outpatient clinics and included 142 adolescent patients with depression (12-18 years old). This cohort included the SAs group (n = 52), NSSI group (n = 65), and depression without SAs/NSSI control group (n = 25). All participants underwent a clinical interview and neuropsychological assessment for group comparisons, and post-hoc tests were performed. Finally, partial correlation analysis was used to explore factors related to changes in cognitive function. RESULTS: The SAs group performed significantly worse than the control group in executive function and working memory. The depression score was directly proportional to the executive function of the SAs group, whereas cognitive functioning in the NSSI group was associated with borderline traits and rumination. CONCLUSIONS: These findings suggest that impairment of executive function and working memory may be a common pattern in adolescent depressed patients with SAs. However, borderline traits and rumination may be indicative of NSSI but not SAs.

Diagnostic value of plasma D-dimer and serum lipoprotein phospholipase A2 in patients with cerebral small vessel disease and their association with severity of the disease.

OBJECTIVE: To determine the diagnostic value of plasma D-dimer (DD) and serum lipoprotein phospholipase A2 (Lp-PLA2) in patients with cerebral small vessel disease (CSVD) and their association with severity of the disease. METHODS: In this retrospective analysis, 84 patients with CSVD treated in Shangqiu First People's Hospital from February 2020 to November 2021 were included in the study group, and 75 healthy individuals were assigned into the control group. The DD and Lp-PLA2 levels in the two groups were compared, and the diagnostic value of the two in CSVD was evaluated via receiver operating characteristic (ROC) curves. Patients were assigned to a mild group or a severe group based on Fazekas scale scores. Then, the two groups were compared in terms of the DD and Lp-PLA2 levels, and the association of the two with the severity of CSVD was determined through ROC curves. With the Montreal cognitive assessment (MoCA) scale, the patients were assigned to a cognitive impairment group or a non-cognitive impairment group. Then the two groups were compared in terms of the DD and Lp-PLA2 levels, and the association of the two with the cognitive function of CSVD patients was also determined by ROC curves. RESULTS: The research group showed higher DD and Lp-PLA2 levels than the control group; the severe group showed higher DD and Lp-PLA2 levels than the mild group; the cognitive impairment group showed higher DD and Lp-PLA2 levels than the non-cognitive impairment group (all P < 0.001). The areas under the curves (AUCs) of DD and Lp-PLA2 in CSVD diagnosis were 0.902 and 0.907, respectively; the AUCs of DD and Lp-PLA2 in CSVD severity determination were 0.747 and 0.704, respectively; the AUCs of DD and Lp-PLA2 in cognitive impairment diagnosis were 0.736 and 0.725, respectively. CONCLUSION: Plasma DD and Lp-PLA2 possess good diagnostic value in patients with CSVD, and also has certain clinical value in diagnosing patients' severity and cognitive impairment.

The role of family and peer factors in the development of early adolescent depressive symptoms: A latent class growth analysis.

Few studies have explored the trajectories of Chinese early adolescent depressive symptoms or comprehensively considered the factors of family and peers. The present study aimed to identify the trajectories of depressive symptoms in early adolescence using a school-based sample assessed in three waves. The study also examined whether family and peer factors were significant predictors. A total of 586 Chinese primary and middle school students participated in the survey. A growth mixture model was used to find the trajectories of depressive symptoms, and multinominal logistic regression was used to identify the predictors. Three trajectories were identified, including a stable-low class, an increasing class, and a high-decreasing class. Results indicated that gender, parental psychological aggression and neglect, parental psychological control, traditional bullying/cyberbullying victimization, and friendship quality were significant predictors. However, witnessing intimate partner violence, parental behavior control, and traditional bullying/cyberbullying perpetration could not significantly predict the trajectories. The findings of this study can provide an empirical basis for teachers and clinical interveners to determine different development trajectories of depressive symptoms and carry out prevention and intervention.

Diagnostic value of cardiac magnetic resonance imaging for myocardial fibrosis in patients with heart failure and its predictive value for prognosis.

OBJECTIVE: To determine the diagnostic value of cardiac magnetic resonance imaging (CMRI) for myocardial fibrosis (MF) in patients with heart failure (HF) and its predictive value for prognosis. METHODS: A total of 180 patients with heart failure who were hospitalized in the Cardiology Department of The First People's Hospital of Shangqiu City from September 2019 to May 2021 were selected and assigned to Group B (n=80) given levosimendan and Group A (n=100) given levosimendan combined with ivabradine hydrochloride. The cardiac function indicators (left ventricular end-systolic volume (LVESV), left ventricular ejection fraction (LVEF), and left ventricular end-systolic diameter (LVESD) were measured by nuclear magnetic resonance (MRI). Myocardial fibrosis (MF)-related indicators (pyridinoline cross-linked carboxy-terminal telopeptide of type I collagen (ICTP), N-terminal propeptide of procollagen type III (PIIINP), connective tissue growth factor (CTGF), and hyaluronic acid (HA), inflammatory factors (Hs-CRP and IL-8) were measured using ELISA. Quality of life (QoL) and physical recovery (6-min walking test (6MWT), Fugl-Meyer Assessment (FMA), and Barthel index) of the two groups were compared. The late gadolinium enhancement (LGE) was used to analyze the occurrence of MF in patients. The patients were further divided into the LGE (+) group (cases) and LGE (-) group (cases). The changes of cardiac function indicators before treatment were analyzed, and their predictive value was analyzed. RESULTS: Compared with Group B, Group A showed a lower incidence of complications, and presented a higher LVEF level and lower levels of LVESV, LVESD, ICTP, PIIINP, CTGF, HA, LN, and inflammatory factors. The area under the curves of LVESV, LVESD, and LVEF in predicting MF were all >0.7. CONCLUSION: Levosimendan combined with ivabradine hydrochloride can effectively alleviate MF in patients with MF, and CMRI has a good predictive value for MF in such patients, which is worthy of clinical promotion.

Isochlorogenic Acid C Alleviates High-Fat Diet-Induced Hyperlipemia by Promoting Cholesterol Reverse Transport.

Background: Promoting cholesterol reverse transport (RCT) has been proven to be a promising hyperlipidemia therapy since it is more effective for the treatment of atherosclerosis (AS) caused by hyperlipidemia. Liver X receptor (LXR) agonists can accelerate RCT, but most of them trigger undesirable liver steatosis due to the activation of liver LXRα. Aim: We aim to figure out whether isochlorogenic acid C (ICAC) facilitates RCT without causing hepatic steatosis. Methods: In vitro study, we established foam macrophages and macrophages with loaded NBD-cholesterol models to investigate the competence of RCT promoting ICAC. RT-qPCR and Western blot were used to verify ICAC's regulation of RCT and NF-κB inflammatory pathways. In this in vivo study, male 6-week-old C57BL/6 mice were fed a high-fat diet (HFD) to investigate ICAC's anti-hyperlipidemic effect and its functions in regulating RCT. The anti-hyperlipidemic effect of ICAC was evaluated by blood and liver lipid levels, liver hematoxylin, oil red o staining, and liver coefficient. Finally, mRNA levels of genes involved in RCT and inflammation pathways in the liver and intestine were detected by RT-qPCR. Results: ICAC prevented macrophages from foaming by up-regulating the LXRα mediated RCT pathway and down-regulating expression of the cholesterol absorption genes LDLR and CD36, as well as suppressing iNOS, COX2, and IL-1ß inflammatory factors. In HFD-fed mice, ICAC significantly lowered the lipid level both in the serum and the liver. Mechanistic studies showed that ICAC strengthened the RCT pathway in the liver and intestine but didn't affect liver LXRα. Furthermore, ICAC impeded both adipogenesis and the inflammatory response in the liver. Conclusion: ICAC accelerated RCT without affecting liver LXRα, thus resulting in a lipid-lowering effect without increasing liver adipogenesis. Our results indicated that ICAC could be a new RCT promoter for hyperlipidemia treatment without causing liver steatosis.

Clinical and prognostic value of CT perfusion imaging parameters in patients with primary liver cancer after therapy.

OBJECTIVE: To explore the value of arterial enhancement fraction (AEF) of CT perfusion in evaluating the postoperative treatment efficacy on liver cancer (LC). METHODS: Clinical data of 60 patients with LC who were treated with transcatheter arterial chemoembolization for LC in our hospital from Jan. 2015 to Jan. 2017 were analyzed retrospectively. They underwent CT scanning before and after surgery. The change of arterial enhancement fraction (AEF) was analyzed, and its value in efficacy evaluation was assessed. RESULTS: After surgery, the AEF value of the effective group decreased greatly (P<0.05) and was significantly lower than that of the ineffective group (P<0.05). Alpha fetal protein (AFP) of both groups decreased after surgery, with a significantly lower AFP level in the effective group than that in the ineffective group (P<0.05). AEF and AFP were positively correlated. According to the follow-up results, patients with a low AEF level showed a higher survival rate than those with a high level. Cox regression analysis revealed that AEF was an independent factor for patients' prognosis. CONCLUSION: CT perfusion imaging parameters are of high clinical value for patients with primary LC after therapy and can be used as independent factors for their prognosis.

Granular cell tumor of the vulva: Case report and systematic review of the literature.

RATIONALE: Granular cell tumor (GCT) of the vulva is an exceptionally rare female genital tract tumor. The majority of these are benign and there are no standardized surgical techniques for the special site to reduce tension of the wound. PATIENT CONCERNS: A 47-years-old Chinese woman experienced a nodule on her right vulva with itch sometimes in late 2018. DIAGNOSES: Magnetic resonance imaging showed a high possibility of vulvar cancer. While Chest X-ray, abdominal sonography, and cystoscopy examination were unremarkable. INTERVENTIONS: The patient underwent local complete resection of vulvar tumor under general anesthesia on March 24, 2022. The resection scope was approximately 4 cm × 3 cm × 3 cm. Due to the large surgical incision, Z-plasty was performed to achieve the primary closure for decreasing wound tension and improving aesthetic reduction. OUTCOMES: The final pathological diagnosis was benign GCT of the vulva and surgical margins were uninvolved. At 8 months follow-up, no new lesions were detected. LESSONS: Surgery with negative resection margins is the mainstay for benign GCT of the vulva, while Z-plasty is appropriate for decreasing the tension of the wound and improving aesthetic reduction.

How mobile phone addiction is associated with suicidal ideation in university students in China: Roles of depression and online social support.

Background: Recent studies have highlighted mobile phone addiction (MPA) as a potential risk of suicidal ideation. However, the mechanisms underlying that association require attention. Objective: This investigation aims to examine whether the relationship between MPA and suicidal ideation would be mediated by depression, and buffered by online social support (OSS) in university students. Methods: A convenient sample of 1,042 Chinese university students completed the measures of mobile phone addiction, depression, suicidal ideation, OSS in classroom settings. Moderated mediation analyses were performed to test the roles of depression and OSS in the association between MPA and suicidal ideation. Results: MPA was positively associated with suicidal ideation through depression (indirect effect =. 23, 95% CI: 0.18, 0.28, p < 0.001); OSS moderated the association between depression and suicidal ideation (B = - 0.09, 95% CI: -0.13, -0.04, p < 0.001). Specifically, the effect of depression on suicidal ideation was weaker in individuals with high (versus low) OSS. OSS moderated the association between MPA and suicidal ideation (B = 0.06, 95% CI: 0.02, 0.10, p = 0.001). The influence of MPA on suicidal ideation was non-significant among individuals with high OSS but negatively significant among students with low OSS. Conclusion: The results enrich the understanding of how MPA may increase suicidal ideation, and highlight the potential importance of reducing depression and enhancing OSS to prevent suicidal ideation in university students.

High-Throughput Screening Campaign Identified a Potential Small Molecule RXFP3/4 Agonist.

Relaxin/insulin-like family peptide receptor 3 (RXFP3) belongs to class A G protein-coupled receptor family. RXFP3 and its endogenous ligand relaxin-3 are mainly expressed in the brain with important roles in the regulation of appetite, energy metabolism, endocrine homeostasis and emotional processing. It is therefore implicated as a potential target for treatment of various central nervous system diseases. Since selective agonists of RXFP3 are restricted to relaxin-3 and its analogs, we conducted a high-throughput screening campaign against 32,021 synthetic and natural product-derived compounds using a cyclic adenosine monophosphate (cAMP) measurement-based method. Only one compound, WNN0109-C011, was identified following primary screening, secondary screening and dose-response studies. Although displayed agonistic effect in cells overexpressing the human RXFP3, it also showed cross-reactivity with the human RXFP4. This hit compound may provide not only a chemical probe to investigate the function of RXFP3/4, but also a novel scaffold for the development of RXFP3/4 agonists.

Deleterious mutation V369M in the mouse GCGR gene causes abnormal plasma amino acid levels indicative of a possible liver-α-cell axis.

Glucagon plays an important role in glucose homeostasis and amino acid metabolism. It regulates plasma amino acid levels which in turn modulate glucagon secretion from the pancreatic α-cell, thereby establishing a liver-α-cell axis described recently. We reported previously that the knock-in mice bearing homozygous V369M substitution (equivalent to a naturally occurring mutation V368M in the human glucagon receptor, GCGR) led to hypoglycemia with improved glucose tolerance. They also exhibited hyperglucagonemia, pancreas enlargement and α-cell hyperplasia. Here, we investigated the effect of V369M/V368M mutation on glucagon-mediated amino acid metabolism. It was found that GcgrV369M+/+ mice displayed increased plasma amino acid levels in general, but significant accumulation of the ketogenic/glucogenic amino acids was observed in animals fed with a high-fat diet (HFD), resulting in deleterious metabolic consequence characteristic of α-cell proliferation and hyperglucagonemia.