Time-dependent progress of lower urinary tract dysfunction in streptozotocin-induced diabetic rats with or without low-dose insulin treatment.

Objectives: To examine time-dependent functional and structural changes of the lower urinary tract in streptozotocin-induced diabetic rats with or without low-dose insulin treatment and explore the pathophysiological characteristics of insulin therapy on lower urinary tract dysfunction (LUTD) caused by diabetes mellitus (DM). Methods: Female Sprague-Dawley rats were divided into five groups: normal control (NC) group, 4 weeks insulin-treated DM (4-DI) group, 4 weeks DM (4-DM) group, 8 weeks insulin-treated DM (8-DI) group and 8 weeks DM (8-DM) group. DM was initially induced by i.p. injection of streptozotocin (65 mg/kg), and then the DI groups received subcutaneous implantation of insulin pellets under the mid dorsal skin. Voiding behavior was evaluated in metabolic cages. The function of bladder and urethra in vivo were evaluated by simultaneous recordings of the cystometrogram and urethral perfusion pressure (UPP) under urethane anesthesia. The function of bladder and urethra in vitro were tested by organ bath techniques. The morphologic changes of the bladder and urethra were investigated using Hematoxylin-Eosin and Masson's staining. Results: Both 4-and 8-weeks diabetic rats have altered micturition patterns, including increased 12-h urine volume, urinary frequency/12 hours and voided volume. In-vivo urodynamics showed the EUS bursting activity duration is longer in 4-DM group and shorter in 8-DM group compared to NC group. UPP change in 8-DM were significantly lower than NC group. While none of these changes were found between DI and NC groups. Organ bath showed the response to Carbachol and EFS in bladder smooth muscle per tissue weights was decreased significantly in 4- and 8-weeks DM groups compared with insulin-treated DM or NC groups. In contrast, the contraction of urethral muscle and maximum urethral muscle contraction per gram of the tissue to EFS stimulation were significantly increased in 4- and 8-weeks DM groups. The thickness of bladder smooth muscle was time-dependently increased, but the thickness of the urethral muscle had no difference. Conclusions: DM-induced LUTD is characterized by time-dependent functional and structural remodeling in the bladder and urethra, which shows the hypertrophy of the bladder smooth muscle, reduced urethral smooth muscle relaxation and EUS dysfunction. Low-dose insulin can protect against diuresis-induced bladder over-distention, preserve urethral relaxation and protect EUS bursting activity, which would be helpful to study the slow-onset, time-dependent progress of DM-induced LUTD.

[Retracted] Liraglutide repairs the infarcted heart: The role of the SIRT1/Parkin/mitophagy pathway.

Following the publication of this paper, it was drawn to the Editors' attention by a concerned reader that the immunofluorescence data shown in Fig. 2G, the mitochondria­ and lysosome­stained images in Fig. 3C, the JC­1 staining images in Fig. 4C and the immunofluorescence data in Fig. 5G were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had either already been published elsewhere prior to the submission of this paper to Molecular Medicine Reports, or were under consideration for publication at around the same time. In view of the fact that certain of the abovementioned data had already apparently been published previously, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal. After having been in contact with the authors, they agreed with the decision to retract the paper. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 17: 3722­3734, 2018; DOI: 10.3892/mmr.2018.8371].

Motility and tumor infiltration are key aspects of invariant natural killer T cell anti-tumor function.

Dysfunction of invariant natural killer T (iNKT) cells contributes to immune resistance of tumors. Most mechanistic studies focus on their static functional status before or after activation, not considering motility as an important characteristic for antigen scanning and thus anti-tumor capability. Here we show via intravital imaging, that impaired motility of iNKT cells and their exclusion from tumors both contribute to the diminished anti-tumor iNKT cell response. Mechanistically, CD1d, expressed on macrophages, interferes with tumor infiltration of iNKT cells and iNKT-DC interactions but does not influence their intratumoral motility. VCAM1, expressed by cancer cells, restricts iNKT cell motility and inhibits their antigen scanning and activation by DCs via reducing CDC42 expression. Blocking VCAM1-CD49d signaling improves motility and activation of intratumoral iNKT cells, and consequently augments their anti-tumor function. Interference with macrophage-iNKT cell interactions further enhances the anti-tumor capability of iNKT cells. Thus, our findings provide a direction to enhance the efficacy of iNKT cell-based immunotherapy via motility regulation.

High-throughput sequencing reveals hub genes for human early embryonic development arrest in vitro fertilization: a pilot study.

Many clinical studies have shown that embryos of in vitro fertilization (IVF) are often prone to developmental arrest, which leads to recurrent failure of IVF treatment. Early embryonic arrest has always been an urgent clinical problem in assisted reproduction centers. However, the molecular mechanisms underlying early embryonic development arrest remain largely unknown. The objective of this study is to investigate potential candidate hub genes and key signaling pathways involved in early stages of embryonic development. RNA-seq analysis was performed on normal and arrest embryos to study the changes of gene expression during early embryonic development. A total of 520 genes exhibiting differential expression were identified, with 174 genes being upregulated and 346 genes being downregulated. Upregulated genes show enrichment in biosynthesis, cellular proliferation and differentiation, and epigenetic regulation. While downregulated genes exhibit enrichment in transcriptional activity, epigenetic regulation, cell cycle progression, cellular proliferation and ubiquitination. The STRING (search tool for the retravel of interacting genes/proteins) database was utilized to analyze protein-protein interactions among these genes, aiming to enhance comprehension of the potential role of these differentially expressed genes (DEGs). A total of 22 hub genes (highly connected genes) were identified among the DEGs using Cytoscape software. Of these, ERBB2 and VEGFA were upregulated, while the remaining 20 genes (CCNB1, CCNA2, DICER1, NOTCH1, UBE2B, UBE2N, PRMT5, UBE2D1, MAPK3, SOX9, UBE2C, UB2D2, EGF, ACTB, UBA52, SHH, KRAS, UBE2E1, ADAM17 and BRCA2) were downregulated. These hub genes are associated with crucial biological processes such as ubiquitination, cellular senescence, cell proliferation and differentiation, and cell cycle. Among these hub genes, CCNA2 and CCNB1 may be involved in controlling cell cycle, which are critical process in early embryonic development.

Higher High-Mobility Group Box-1 Levels are Associated with White Matter Lesions in Ischemic Stroke Patients.

Background and Purpose: High-mobility group box-1 (HMGB1) is a useful biomarker for disease severity stratification and prognosis prediction. We aim to explore whether the circulating HMGB1 concentrations are associated with the white matter lesions (WMLs) burden in stroke patients. Methods: Between 2022 June and December 2022, patients with acute ischemic stroke were prospectively enrolled. HMGB1 levels were measured by an enzyme-linked immunosorbent assay after admission for all patients. The WMLs severity was assessed by the Fazekas scale. We dichotomized patients into those with moderate-severe WMLs (Fazekas score 3-6) versus those with none-mild WMLs (Fazekas score 0-2). Furthermore, based on the severity of periventricular WMLs (PWMLs) and deep WMLs (DWMLs), patients were categorized as none-mild (Fazekas score 0-1) or moderate-severe (Fazekas score 2-3). Results: A total of 287 participants (mean age: 64.9 years; 157 male) were analyzed. The median serum HMGB1 levels were 7.3 ng/mL (interquartile, 4.3 ng/mL-12.3 ng/mL). After adjustment for potential confounders, elevated HMGB1 levels were associated with the presence of moderate-severe WMLs (first quartile vs fourth quartile, odds ratio [OR], 4.101; 95% confidence interval [CI], 1.948-8.633; P = 0.001) and moderate-severe PWMLs (first quartile vs fourth quartile, OR, 9.181; 95% CI, 4.078-20.671; P = 0.001). Similar results were found when the HMGB1 levels were analyzed as a continuous variable. Conclusion: This study demonstrated that increased HMGB1 levels were associated with the severity of WMLs, mainly in the periventricular region.

JNK regulates the Nrf2/NQO1-ARE pathway against Microcystins-Induced oxidative stress in freshwater mussel Cristaria plicata.

In response to stress, cells can utilize several processes, such as the activation of the Nrf2/Keap1 pathway as a critical regulator of oxidative stress to protect against oxidative damage. C-Jun N-terminal kinase (JNK), a member of the mitogen-activated protein kinase (MAPK) family, is involved in regulating the NF-E2-related nuclear factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway. NAD(P)H quinone redox enzyme-1 (NQO1), a downstream target gene of the Nrf2 pathway, plays a vital role in removing peroxide and providing resistance to oxidative injury. We found that microcystins (MCs) stimulated CpNrf2 to express and increase anti-oxidative enzyme activities in a previous experiment. In our current study, the full-length cDNAs of JNK and NQO1 from Cristaria plicata (designated CpJNK and CpNQO1) were cloned. The relative levels of CpJNK and CpNQO1 were high in hepatopancreas. Upon MCs induction, the relative level of CpNQO1 was increased, whereas that of CpJNK was decreased significantly. In contrast, CpNrf2 knockdown upregulated the expression of CpJNK mRNA and phosphorylation of CpJNK protein (Cpp-JNK), but inhibited CpNQO1 expression. Additionally, we found that JNK inhibitor SP600125 stimulated expression of CpNQO1 and CpNrf2 upon exposure to MCs, and we further confirmed that CpNrf2 protein combined with the ARE element in CpNQO1 gene promoter in vitro, and increased CpNQO1-ARE-luciferase activity in a CpNrf2-dependent manner. These findings indicated C. plicata effectively alleviated MC-induced oxidative injury through JNK participated in regulating the Nrf2/NQO1-ARE pathway.

Activation of the adenosine A1 receptor in the lumbosacral spinal cord improves bladder overactivity in rats with cystitis induced by cyclophosphamide.

PURPOSE: To investigate the effect of intrathecal administration of CCPA, an adenosine A1 receptor agonist, on voiding function in rats with cystitis induced by cyclophosphamide (CYP). METHODS: Thirty 8-week-old Sprague Dawley rats were randomly divided into a control group (n = 15) and a cystitis group (n = 15). Cystitis was induced by a single intraperitoneal injection of CYP (200 mg/kg, dissolved in physiological saline) in rats. Control rats were injected intraperitoneally with physiological saline. The PE10 catheter reached the level of L6-S1 spinal cord through L3-4 intervertebral space for intrathecal injection. Forty-eight hours after intraperitoneal injection, urodynamic tests were conducted to observe the effect of intrathecal administration of 10% dimethylsulfoxide (vehicle) and 1 nmol CCPA on micturition parameters, including basal pressure (BP), threshold pressure (TP), maximal voiding pressure (MVP), intercontraction interval (ICI), voided volume (VV), residual volume (RV), bladder capacity (BC), and voiding efficiency (VE). Histological changes of the bladder of cystitis rats were studied through hematoxylin-eosin staining (HE staining). Moreover, Western blot and immunofluorescence were used to study the expression of adenosine A1 receptor in the L6-S1 dorsal spinal cord in both groups of rats. RESULTS: HE staining revealed submucosal hemorrhage, edema, and inflammatory cell infiltration in the bladder wall of cystitis rats. The urodynamic test showed significant increase in BP, TP, MVP and RV in cystitis rats, while ICI, VV, BC and VE decreased significantly, indicating bladder overactivity. CCPA inhibited the micturition reflex in both control and cystitis rats, and significantly increased TP, ICI, VV, BC, and VE, but had no significant effect on BP, MVP and RV. Western blot and immunofluorescence showed that there was no significant difference in the expression of adenosine A1 receptor in the L6-S1 dorsal spinal cord between the control and cystitis rats. CONCLUSION: The findings of this study suggest that intrathecal administration of the adenosine A1 receptor agonist CCPA alleviates CYP-induced bladder overactivity. Furthermore, our results indicate that the adenosine A1 receptor in the lumbosacral spinal cord may be a promising target for treatment of bladder overactivity.

Recommendation of mHAP and ABCR scoring systems for the decision-making of the first and subsequent TACE session in HCC patients.

BACKGROUND: Due to the high heterogeneity among hepatocellular carcinoma (HCC) patients receiving transarterial chemoembolization (TACE), the prognosis of patients varies significantly. Various predictive scoring systems have been developed to identify the patients who could benefit from TACE. However, there is no consensus on which is better. This study aims to validate and compare the predictive capabilities of scoring systems for first and subsequent TACE. MATERIALS: A total of 524 HCC patients were treated with TACE, and 222 patients who met the inclusion criteria were included. Log-rank test was used to verify the predictive value of six scoring systems for the first TACE and four TACE retreatment scoring systems. Harrell's concordance (C)-index, likelihood ratio and integrated Brier score (IBS) were used to compare the predictive performance. RESULTS: For the scoring systems of TACE, the overall survival (OS) of candidates screened by Hepatoma Arterial-embolization Prognostic (HAP), modified HAP (mHAP), mHAP3, alpha-fetoprotein, Barcelona Clinic Liver Cancer, Child-Pugh and Response (ABCR), albumin-bilirubin grade (ALBI), tumor size, alpha-fetoprotein, first TACE response and pre-/post-TACE was significantly longer than that of the noncandidates (all P < 0.05), whereas the mHAP2 and assessment for retreatment with TACE did not distinguish the candidates from noncandidates (P = 0.206, 0.115, respectively). The predictive and calibration performances of mHAP and ABCR were the highest for the first TACE and TACE retreatment, respectively. CONCLUSION: mHAP identifies the patients who could benefit from the first TACE, whereas ABCR distinguishes patients who could benefit from subsequent TACE sessions.

The potential involvement of MRP5 pump in urethral dysfunction in streptozotocin-induced diabetic rats.

PURPOSE: To examine the effects of i.v. administration of MK-571, a MRP4/5 pump inhibitor, on urethral function in the urethane-anesthetized rat, and the changes of urethral multidrug resistance protein 5 (MRP5) pump in streptozotocin (STZ)-induced diabetes mellitus (DM) rats. METHODS: Isovolumetric cystometry and urethral perfusion pressure (UPP) measurements were carried out in normal control (NC) group and 8week DM groups under urethane anesthesia. When stable rhythmic bladder contractions were showed, UPP parameters were recorded after successive administration of various dose of MK-571. Additionally, urethral cyclic guanosine monophosphate (cGMP) protein level was evaluated by ELISA, and changes of MRP5 pump and neurogenic nitric oxide synthase (nNOs) in the urethra were examined with immunohistochemical staining and Western blot analysis. RESULTS: In NC group, UPPnadir was significantly decreased but UPP change increased after administration of MK-571, while no significant differences in UPP parameters were observed in 8-week DM group. Furthermore, urethral MRP5 protein level was up-regulated, whereas urethral cGMP and nNOS protein levels were down-regulated in 8-week DM group. CONCLUSIONS: MK-571 could not restore NO-mediated urethral relaxation dysfunction in DM rats, which may be attributed to the up-regulation of urethral MRP5 pump, and thus decrease of intracellular cGMP concentration in the urethra. These novel results would be useful for a better understanding of DM-related lower urinary tract dysfunction LUT (LUTD). Also, they could be helpful to study the importance of MRP pumps in the control of urethral relaxation mechanisms under physiological and pathological states.

A review of spatial profiling technologies for characterizing the tumor microenvironment in immuno-oncology.

Interpreting the mechanisms and principles that govern gene activity and how these genes work according to -their cellular distribution in organisms has profound implications for cancer research. The latest technological advancements, such as imaging-based approaches and next-generation single-cell sequencing technologies, have established a platform for spatial transcriptomics to systematically quantify the expression of all or most genes in the entire tumor microenvironment and explore an array of disease milieus, particularly in tumors. Spatial profiling technologies permit the study of transcriptional activity at the spatial or single-cell level. This multidimensional classification of the transcriptomic and proteomic signatures of tumors, especially the associated immune and stromal cells, facilitates evaluation of tumor heterogeneity, details of the evolutionary trajectory of each tumor, and multifaceted interactions between each tumor cell and its microenvironment. Therefore, spatial profiling technologies may provide abundant and high-resolution information required for the description of clinical-related features in immuno-oncology. From this perspective, the present review will highlight the importance of spatial transcriptomic and spatial proteomics analysis along with the joint use of other sequencing technologies and their implications in cancers and immune-oncology. In the near future, advances in spatial profiling technologies will undoubtedly expand our understanding of tumor biology and highlight possible precision therapeutic targets for cancer patients.

Clinical significance and prospective molecular mechanism of NUF2 in gastric cancer exploration: A comprehensive study based on the GeneChip, GEO, Oncomine, and TCGA databases.

Nuf2 is a combination of silica and spindle microtubules during the cells in the cells, participating in regulatory cell proliferation and apoptosis. Previous studies have shown that the growth of gastric cancer (GC) cells is significantly inhibited after siRNA-mediated Nuf2 gene knockout. However, the expression, survival and molecular mechanism of nuf2 in patients with GC are still unclear. This study revealed the prognostic role of Nuf2 in GC and its relationship with immune cells. The expression of Nuf2 in GC by TIMER database and Oncomine database, and evaluated the relationship between the expression of Nuf2 and the survival and prognosis of patients with GC by Kaplan-Meier Plotter database and gene expression profiling interactive analysis database. Here, we revealed that Nuf2 is highly expressed in GC and is related to the prognosis of patients with GC. And there is a significant negative correlation between the Nuf2 transcription level and high immune cell infiltration. Notably, the expression of Nuf2 in GC patients with Her2 negative rather than positive is related to poor OS, FP and PPS, indicating the potential to target Nuf2 gene in GC patients with Her2 negative. We suggested that Nuf2 could be used as a diagnostic gene as a biomarker of the occurrence and prognosis of GC.

Improvement of urethral dysfunction by 5-HT1A receptor agonist NLX-112 in diabetic rats.

OBJECTIVE: To examine the effects of the selective 5-HT1A receptor agonist, NLX-112, on urethral function in streptozotocin-induced diabetic rats. MATERIALS AND METHODS: Female Sprague-Dawley rats (n = 32) were divided into two groups: rats with type 1 diabetes mellitus (T1DM) and age-matched normal control rats (NC). T1DM was induced by intraperitoneal injection of streptozotocin (65 mg/kg). Isovolumetric cystometry and urethral perfusion pressure (UPP) were evaluated 10 weeks postinjection in rats (n = 9 per group). The selective 5-HT1A receptor antagonist, WAY-100635 maleate salt, was administered after NLX-112 hydrochloride dose-response curve was generated (intravenously). The remaining rats were used for immunofluorescence and Western blot assays. RESULTS: Compared to controls, type 1 diabetic rats (T1D rats) had lower maximal intravesical pressure (IP max) and UPP changes. In T1D rats, NLX-112 hydrochloride (0.003-1.0 mg/kg) induced dose-dependent decreases in UPP nadir, IP max, high-frequency oscillations (HFOs) rate; and increases in UPP change and HFOs amplitude. WAY-100635 maleate salt (0.3 mg/kg) partially or completely reversed the NLX-112-induced changes. Immunofluorescence revealed that 5-HT1A receptors were found in the L6-S1 spinal cord dorsolateral nucleus, but the expression was significantly higher in the T1D rats. Additionally, Western blot showed there were significantly more 5-HT1A receptors in the ventral L6-S1 spinal cord of T1D rats. CONCLUSIONS: Urethral dysfunction in T1D rats was improved by NLX-112. 5-HT1A receptors were upregulated in the dorsolateral nucleus of L6-S1 spinal cord in T1D rats. These findings suggest that NLX-112 may constitute a novel therapeutic strategy to treat diabetic urethral dysfunction.

Cross-Sectional and Longitudinal Associations Between the Serum G\lobulin Level, and Renal Impairment and All-Cause Deaths in Chinese Patients With Newly Diagnosed Multiple Myeloma.

Background: A large number of studies have shown that serum globulin plays an important role in a variety of cancers; However, few studies have identified the association between serum globulin levels and end-stage renal disease (ESRD) and all-cause death in Chinese patients with multiple myeloma (MM). Methods: A generalized additive model and smooth curve fitting were fitted to assess the cross-sectional relationship between the serum globulin levels and renal impairment (RI) at baseline. Multivariate-adjusted Cox regression models were performed to determine the associations between the baseline serum globulin levels and the onset of all-cause death and ESRD in patients with MM. Results: 288 participants who were followed for > 3 months were eligible for the retrospective study. The median serum globulin level was 5.1 ± 2.6 mg/dL. The average follow-up time was 23.3 months. Thirty-two patients (11.5%) had ESRD and 24 patients (8.33%) died after diagnosis. In patients with a serum globulin level < 6.1 mg/dL, the serum globulin level had an independent, negative correlation with the occurrence of MM-related RI. Patients were divided into three groups on the basis of serum globulin tertiles: low (L group), 3.3 mg/dL; middle (M group), 3.3-6.0 mg/dL; and high (H group), 6.0 mg/dL. Cox regression analysis showed that low serum globulin levels may be independent risk factors for all-cause death and the occurrence of ESRD in patients with MM; however, an elevated baseline serum globulin can predict all-cause deaths in patients with MM, but cannot predict the onset of ESRD. Conclusions: This observational study suggested that there was a non-linear relationship between the serum globulin level and the occurrence of RI in patients with MM. This finding showed that the serum globulin level had a U-shaped association with all-cause death and an L-shaped association with ESRD in patients with MM.

Application of Muscle Thickness and Quality Measured by Ultrasound in Frailty Assessment in China.

To explore the correlation between Fried Frailty Phenotype (FFP) and the muscle thickness and quality of local muscle, and to provide a reasonable basis for the application of ultrasound measurement in the frailty assessment. A total of 150 people (age ≥ 65 years, 58 women, 92 men) were included from the First Hospital Affiliated to Nanjing Medical University. They were divided into Normal group (40 cases), Prefrailty group (69 cases) and Frailty group (41 cases). The thickness and the quality of local muscle were detected by ultrasound. Participants in the prefrailty group had a higher grayscale value of the vastus lateralis muscle, indicating the deterioration of muscle quality. At the frailty stage, the muscle thickness and quality of the vastus lateralis muscle and the anterior tibialis muscle decreased significantly compared with the normal and the prefrailty group. Pearson's correlation analysis also showed FFP was negatively correlated with muscle thickness and quality of the lower limbs. In multiple regression model, FFP was positively associated with gray value (Vastus lateralis muscle:ß =0.457, p < 0.001; Anterior tibialis muscle: ß = 0.220, p = 0.037) and inversely associated with muscle thickness (Vastus lateralis muscle:ß = -0.973, p = 0.031; Anterior tibialis muscle: ß = -4.551, p = 0.004) in the frailty stage. Together, FFP was closely related to muscle thickness and quality, especially vastus lateralis muscle. Moreover, Muscle quality has deteriorated in the prefrailty stage, which is earlier than muscle thickness.

Acute kidney injury in traumatic brain injury intensive care unit patients.

BACKGROUND: The exact definition of Acute kidney injury (AKI) for patients with traumatic brain injury (TBI) is unknown. AIM: To compare the power of the "Risk, Injury, Failure, Loss of kidney function, and End-stage kidney disease" (RIFLE), Acute Kidney Injury Network (AKIN), Creatinine kinetics (CK), and Kidney Disease Improving Global Outcomes (KDIGO) to determine AKI incidence/stage and their association with the in-hospital mortality rate of patients with TBI. METHODS: This retrospective study collected the data of patients admitted to the intensive care unit for neurotrauma from 2001 to 2012, and 1648 patients were included. The subjects in this study were assessed for the presence and stage of AKI using RIFLE, AKIN, CK, and KDIGO. In addition, the propensity score matching method was used. RESULTS: Among the 1648 patients, 291 (17.7%) had AKI, according to KDIGO. The highest incidence of AKI was found by KDIGO (17.7%), followed by AKIN (17.1%), RIFLE (12.7%), and CK (11.5%) (P = 0.97). Concordance between KDIGO and RIFLE/AKIN/CK was 99.3%/99.1%/99.3% for stage 0, 36.0%/91.5%/44.5% for stage 1, 35.9%/90.6%/11.3% for stage 2, and 47.4%/89.5%/36.8% for stage 3. The in-hospital mortality rates increased with the AKI stage in all four definitions. The severity of AKI by all definitions and stages was not associated with in-hospital mortality in the multivariable analyses (all P > 0.05). CONCLUSION: Differences are seen in AKI diagnosis and in-hospital mortality among the four AKI definitions or stages. This study revealed that KDIGO is the best method to define AKI in patients with TBI.

Weighted Gene Coexpression Network Analysis Identifies TBC1D10C as a New Prognostic Biomarker for Breast Cancer.

Background: Immune checkpoint inhibitors are a promising therapeutic strategy for breast cancer (BRCA) patients. The tumor microenvironment (TME) can downregulate the immune response to cancer therapy. Our study is aimed at finding a TME-related biomarker to identify patients who might respond to immunotherapy. Method: We downloaded raw data from several databases including TCGA and MDACC to identify TME hub genes associated with overall survival (OS) and the progression-free interval (PFI) by WGCNA. Correlations between hub genes and either tumor-infiltrating immune cells or immune checkpoints were conducted by ssGSEA. Result: TME-related green and black modules were selected by WGCNA to further screen hub genes. Random forest and univariate and multivariate Cox regressions were applied to screen hub genes (MYO1G, TBC1D10C, SELPLG, and LRRC15) and construct a nomogram to predict the survival of BRCA patients. The C-index for the nomogram was 0.713. A DCA of the predictive model revealed that the net benefit of the nomogram was significantly higher than others and the calibration curve demonstrated a good performance by the nomogram. Only TBC1D10C was correlated with both OS and the PFI (both p values < 0.05). TBC1D10C also had a high positive association with tumor-infiltrating immune cells and common immune checkpoints (PD-1, CTLA-4, and TIGIT). Conclusion: We constructed a TME-related gene signature model to predict the survival probability of BRCA patients. We also identified a hub gene, TBC1D10C, which was correlated with both OS and the PFI and had a high positive association with tumor-infiltrating immune cells and common immune checkpoints. TBC1D10C may be a new biomarker to select patients who may benefit from immunotherapy.

Metabolic syndrome and its association with components of sarcopenia in older community-dwelling Chinese.

Aging and obesity contribute to muscle dysfunction. This study aimed to determine the cross-sectional associations between components of metabolic syndrome (MetS) and sarcopenia in 251 older community-dwelling Chinese. The total fat-free mass was measured by dual-energy X-ray absorptiometry, muscle strength (handgrip strength) by a handheld dynamometer, physical performance by 4-meter walk, 5-time chair stand test, and the short physical performance battery (SPPB). MetS was defined using the International Diabetes Federation (IDF) criteria. The participants with MetS had a higher appendicular skeletal muscle mass (ASM) and relative ASM (RASM). The males with MetS had higher handgrip strength, and the females with MetS had higher SPPB scores. After adjusting for age and body mass index, the participants with an increased waist circumference had a higher ASM, and those with increased diastolic blood pressure (DBP) also had higher handgrip strength. The males with elevated fasting blood glucose (FBG) levels had a lower gait speed. Components of MetS, such as DPB and FBG, were associated with muscle strength and physical performance in older adults. These results suggest that muscle strength and function should be considered in treating older adults with MetS.

Image quality enhancement of CT hepatic portal venography using dual energy blending with computer determined parameters.

BACKGROUND: Previous studies have shown that using some post-processing methods, such as nonlinear-blending and linear blending techniques, has potential to improve dual-energy computed (DECT) image quality. OBJECTIVE: To improve DECT image quality of hepatic portal venography (CTPV) using a new non-linear blending method with computer-determined parameters, and to compare the results to additional linear and non-linear blending techniques. METHODS: DECT images of 60 patients who were clinically diagnosed with liver cirrhosis were selected and studied. Dual-energy scanning (80 kVp and Sn140 kVp) of CTPV was utilized in the portal venous phase through a dual-source CT scanner. For image processing, four protocols were utilized including linear blending with a weighing factor of 0.3 (protocol A) and 1.0 (protocol B), non-linear blending with fixed blending width of 200 HU and set blending center of 150HU (protocol C), and computer-based blending (protocol D). Several image quality indicators, including signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR) and contrast of hepatic portal vein and hepatic parenchyma, were evaluated using the paired-sample t-test. A 5-grade scale scoring system was also utilized for subjective analysis. RESULTS: SNR of protocols A-D were 9.1±2.1, 12.1±3.0, 11.6±2.8 and 14.4±3.2, respectively. CNR of protocols A-D were 4.6±1.3, 8.0±2.3, 7.0±2.0 and 9.8±2.4, respectively. The contrast of protocols A-D were 37.7±11.6, 91.9±21.0, 66.2±19.0 and 107.7±21.3, respectively. The differences between protocol D and other three protocols were significant (P < 0.01). In subjective evaluation, the modes of protocols A, B, C, and D were rated poor, good, generally acceptable, and excellent, respectively. CONCLUSION: The non-linear blending technique of protocol D with computer-determined blending parameters can help improve imaging quality of CTPV and contribute to a diagnosis of liver disease.

Pelvic Fracture Urethral Distraction Defects in Preschool Boys: How to Recognize and Manage?

OBJECTIVE: To share the cases of pelvic fracture urethral distraction defect (PFUDD) in preschool boys and evaluate the transperineal anastomotic urethroplasty strategy for the treatment of these cases. MATERIALS AND METHODS: Between January 2010 and May 2021, 8 preschool boys (<6 years) with PFUDD underwent the transperineal anastomotic urethroplasty in our center were retrospectively reviewed. Etiology was traumatic pelvic fracture in all boys. The type of trauma included: fall injury in 1 and vehicle crush injury in 7. Urethroplasty was performed at least 3 months after initial trauma or the last failed intervention. One of them suffered from PFUDD associated with urethrorectal fistula received urethroplasty combined with fistula repair. A successful urethroplasty was defined as restoring the patency and continuity of urethra and no further interventions were needed. RESULTS: Follow-up was obtained in all the 8 preschool boys for 3-135 (median: 65) months. The average age was 4.1 years old (range 1-5). After operation, the final success rate was 100%. Neither stenosis recurrence nor urinary fistulas were reported during follow-up. Of the 8 boys, 1 developed urinary incontinence, only occurring after high-intensity exercise such as running. Potency state could not be evaluated for all boys due to the young age. One boy reported having normal morning erection after a follow-up of 135 months. CONCLUSION: PFUDD in preschool boys is a challenge for both the urologist and parent. Our study preliminarily confirmed that the progressive anastomotic urethroplasty strategy can ensure a high success rate.

Anti-Tumor Activity of Expanded PBMC-Derived NK Cells by Feeder-Free Protocol in Ovarian Cancer.

Natural killer (NK) cells have shown great therapeutic potential against a wide range of cancers due to their pan-specific target recognition. Numerous reports indicate that NK cell immunotherapy is an effective therapeutic approach for treating hematological malignancies, but shows limited effects against solid tumors. In this study, several models of ovarian cancer (OC) were used to test the anti-cancer effects of NK cells derived from human peripheral blood mononuclear cells and expanded using a feeder cell-free expansion system (eNKs). The results show that eNKs exhibit potent inhibitory activity on tumor growth in different ovarian cancer xenograft mice (i.e., solid tumors, abdominal metastatic tumors, and ascites), importantly, in a dose-dependent manner. Moreover, adoptive transfer of eNKs resulted in significant reduction in ascites formation in OC peritoneal tumor models, and especially in reducing intraperitoneal ascites. We found that eNKs could migrate to the tumor site, retain their activity, and proliferate to maintain high cell counts in cutaneous xenograft mice. In addition, when increased the infusion with a high dose of 12 × 107 cells/mouse, Graft-versus-host disease could be induced by eNK. These data show that eNK cell immunotherapy could be a promising treatment strategy for ovarian cancers, including solid tumors and ascites.