Comprehensive pan-cancer investigation of carnosine dipeptidase 1 and its prospective prognostic significance in hepatocellular carcinoma.

Carnosine dipeptidase 1 (CNDP1), an enzyme integral to the hydrolysis of dipeptides containing histidine, plays an indispensable role in myriad physiological processes, including hydrolysis of proteins, maturation of specific biochemical functionalities within proteins, tissue regeneration, and regulation of cell cycle. However, the implications of CNDP1 in oncogenesis and its prognostic value are not yet fully elucidated. Initially, we procured the GSE40367 dataset from the Gene Expression Omnibus and established a protein-protein interaction network. Thereafter, we conducted functional and pathway enrichment analyses utilizing GO, KEGG, and GSEA. Moreover, we undertook an association analysis concerning the expression of CNDP1 with immune infiltration, along with survival analysis across various cancers and specifically in hepatocellular carcinoma (HCC). Our study uncovered a total of 2,248 differentially expressed genes, with a down-regulation of CNDP1 in HCC and other cancers. Our explorations into the relationship between CNDP1 and immune infiltration disclosed a negative correlation between CNDP1 expression and the presence of immune cells in HCC. Survival analyses revealed that diminished expression of CNDP1 correlates with an adverse prognosis in HCC and several other types of cancer. These observations intimate that CNDP1 holds promise as a novel prognostic biomarker for both pan-cancer and HCC.

Nomogram for preoperative estimation of microvascular invasion risk in hepatocellular carcinoma.

Microvascular invasion (MVI) is an adverse prognostic indicator of tumor recurrence after surgery for hepatocellular carcinoma (HCC). Therefore, developing a nomogram for estimating the presence of MVI before liver resection is necessary. We retrospectively included 260 patients with pathologically confirmed HCC at the Fifth Medical Center of Chinese PLA General Hospital between January 2021 and April 2024. The patients were randomly divided into a training cohort (n = 182) for nomogram development, and a validation cohort (n = 78) to confirm the performance of the model (7:3 ratio). Significant clinical variables associated with MVI were then incorporated into the predictive nomogram using both univariate and multivariate logistic analyses. The predictive performance of the nomogram was assessed based on its discrimination, calibration, and clinical utility. Serum carnosine dipeptidase 1 ([CNDP1] OR 2.973; 95 % CI 1.167-7.575; p = 0.022), cirrhosis (OR 8.911; 95 % CI 1.922-41.318; p = 0.005), multiple tumors (OR 4.095; 95 % CI 1.374-12.205; p = 0.011), and tumor diameter ≥3 cm (OR 4.408; 95 % CI 1.780-10.919; p = 0.001) were independent predictors of MVI. Performance of the nomogram based on serum CNDP1, cirrhosis, number of tumors and tumor diameter was achieved with a concordance index of 0.833 (95 % CI 0.771-0.894) and 0.821 (95 % CI 0.720-0.922) in the training and validation cohorts, respectively. It fitted well in the calibration curves, and the decision curve analysis further confirmed its clinical usefulness. The nomogram, incorporating significant clinical variables and imaging features, successfully predicted the personalized risk of MVI in HCC preoperatively.

A comparison of the impact on neuronal transcriptome and cognition of rAAV5 transduction with three different doses in the mouse hippocampus.

Introduction: Recombinant adeno-associated viruses (rAAVs) are widely used in genetic therapeutics. AAV5 has shown superior transduction efficiency, targeting neurons and glial cells in primate brains. Nonetheless, the comprehensive impact of AAV5 transduction on molecular and behavioral alterations remains unexplored. This study focuses on evaluating the effects of AAV5 transduction in the hippocampus, a critical region for memory formation and emotional processes. Methods: In this experiment, fluorescence-activated cell sorting (FACS) was utilized to isolate the mCherry-labeled pyramidal neurons in the hippocampus of CaMkIIα-cre mice following three different doses rAAV5-mCherry infusion after 3 weeks, which were then subjected to RNA sequencing (RNA-seq) to assess gene expression profiles. The cytokines concentration, mRNA expression, and glial response in hippocampi were confirmed by ELASA, digital droplet PCR and immunohistochemistry respectively. Locomotion and anxiety-like behaviors were elevated by Open Field Test and Elevated Plus Maze Test, while the Y-Maze were used to assessed spatial working memory. Recognition memory and fear responses were examined by the Novel Object Recognition Test and Fear Conditioning Test, respectively. Results: We found that 2.88 × 1010 v.g rAAV5 transduction significantly upregulated genes related to the immune response and apoptosis, and downregulated genes associated with mitochondrial function and synaptic plasticity in hippocampal pyramidal neurons, while did not induce neuronal loss and gliosis compared with 2.88 × 109 v.g and 2.88 × 108 v.g. Furthermore, the same doses impaired working memory and contextual fear memory, without effects on locomotion and anxiety-related behaviors. Discussion: Our findings highlight the detrimental impact of high-dose administration compared to median-dose or low-dose, resulting in increased neural vulnerability and impaired memory. Therefore, when considering the expression effectiveness of exogenous genes, it is crucial to also take potential side effects into account in clinical settings. However, the precise molecular mechanisms underlying these drawbacks of high-dose rAAV5-mCherry still require further investigation in future studies.

TEAD4 predicts poor prognosis and transcriptionally targets PLAGL2 in serous ovarian cancer.

The oncogenic function of TEA domain transcription factor 4 (TEAD4) has been confirmed in multiple human malignancies, while its potential role and regulatory mechanism in serous ovarian cancer progression are left unknown. By the gene expression analyses from Gene Expression Profiling Interactive Analysis (GEPIA) database, TEAD4 expression is shown to be up-regulated in serous ovarian cancer samples. Here, we confirmed the high expression of TEAD4 in clinical serous ovarian cancer specimens. In the following functional experiments, we found that TEAD4 overexpression promoted serous ovarian cancer malignant phenotypes, including proliferation, migration and invasion in serous ovarian cancer SK-OV-3 and OVCAR-3 cells, while TEAD4 knockout exerted the opposite function. The tumor growth inhibition of TEAD4 depletion was also affirmed by a Xenograft model in mice. In addition, this phenotypic deterioration induced by TEAD4 overexpression was diminished by PLAG1 like zinc finger 2 (PLAGL2) silencing. More importantly, combined with the results of the dual-luciferase assay, the transcriptional regulation of TEAD4 on PLAGL2 promoter was evidenced. Our results showed that the cancer-promoting gene TEAD4 was involved in serous ovarian cancer progression via targeting PLAGL2 at the transcriptional level.

Controversy on Positive Peritoneal Cytology of Endometrial Carcinoma.

Endometrial carcinoma (EC) is one of the most common gynecological malignancies. Its incidence rate has been increasing year by year. The prognostic factors and treatment strategies of EC have aroused wide concern. The effects of peritoneal cytology on the prognosis and treatment of EC remain controversial. Some factors, such as differentiation degree, muscle invasion, and tumor size, are related to positive peritoneal cytology. Hysteroscopy is commonly used in the diagnosis and treatment of endometrial cancer, but hysteroscopic surgery may cause the tumor to spread into the abdominal cavity, resulting in positive peritoneal cytology. In this review, we discuss the factors related to positive peritoneal cytology and the influence of positive peritoneal cytology on the prognosis of endometrial cancer. Suspicious positive peritoneal cytology may be an independent risk factor for endometrial cancer. The positive rate of peritoneal tumor cells in type II endometrial cancer is higher than other cells and is an independent risk factor for type II endometrial cancer. We also discuss the effects of peritoneal cytology on treatment decisions. Aggressive treatments seem to be more beneficial for patients with positive ascites cytology, but there is a lack of large-scale prospective clinical studies on their effectiveness and safety. The application of peritoneal cytology for endometrial cancer has been decreased in recent years. We believe that peritoneal cytology is necessary for this type of cancer. However, more studies on peritoneal cytology in endometrial cancer should be carried out.

NFAT Overexpression Correlates with CA72-4 and Poor Prognosis of Ovarian Clear-Cell Carcinoma Subtype.

Current biomarkers did not overcome the limitations of clinical application due to the heterogeneity of ovarian tumors. The role of nuclear factor of activated T cells (NFAT) in the prognosis of different histological subtypes of ovarian cancer remains unclear. NFAT expression was analyzed in 302 ovarian tumors from The Cancer Genome Atlas (TCGA) dataset and was further confirmed by 88 ovarian tumor specimens, including 30 clear-cell carcinoma, 34 serous carcinoma, and 24 papillary serous cystadenocarcinoma. The correlations between NFAT expression, cancer biomarkers, and clinical characteristics in different subtypes of ovarian tumors were analyzed. ALGGEN PROMO, reporter assay, and NFAT overexpression and knockdown were used to identify chondroadherin (CHAD) as the downstream target of NFAT. NFAT was significantly upregulated only in late-stage clear-cell carcinoma, but not in other two subtypes. NFAT levels were correlated with CA72-4 levels and poor overall survival and disease-free survival (P < 0.05), suggesting that NFAT together with CA72-4 were specific prognostic markers for clear-cell carcinoma. Pathological stage and lymph node metastasis were the prognostic factors affecting serous carcinoma (P < 0.05), while CA-125 was the prognostic factor affecting papillary serous cystadenocarcinoma (P < 0.05). PROMO and reporter assay indicated that CHAD was the downstream target of NFAT. In addition, NFAT overexpression and silencing increased and reduced CHAD expression, respectively. NFAT together with CA72-4 were specific tumor markers for risk assessment of unique clear-cell subtype of ovarian tumors. CHAD was identified as the downstream target gene of NAFT and was associated with poor survival of ovarian cancer.

[Experience in the treatment of chronic gastritis with HE's tube acupuncture technique].

HE 's tube acupuncture technique is developed on the base of the theories of zangfu, meridian and collateral by HE Hui-wu, the eminent master of traditional Chinese medicine in 1920s. It is a set of acupuncture technique, in which, the function of the traditional pressing hand is replaced by the needle tube and the seven skills and five manipulations are specially included. In this paper, the experience in the treatment of chronic gastritis with HE 's tube acupuncture technique was introduced. "Regulating the spleen function for the deficiency syndrome" and "taking the liver into the great consideration for the excess syndrome" are the basic principles of treatment. The specific manipulations are predominant, e.g. the conducting-qi manipulation, the sparrow-pecking manipulation, the rotating manipulation, the lifting-thrusting manipulation and the circling manipulation. Moreover, the unique needling techniques are adopted at Zhongwan (CV 12), Weishu (BL 21) and Yanglingquan (GB 34), etc.

Astrocytic GABAB Receptors in Mouse Hippocampus Control Responses to Behavioral Challenges through Astrocytic BDNF.

Major depressive disorder (MDD) is a common mood disorder that affects almost 20% of the global population. In addition, much evidence has implicated altered function of the gamma-aminobutyric acid (GABAergic) system in the pathophysiology of depression. Recent research has indicated that GABAB receptors (GABABRs) are an emerging therapeutic target in the treatment of stress-related disorders such as MDD. However, which cell types with GABABRs are involved in this process is unknown. As hippocampal dysfunction is implicated in MDD, we knocked down GABABRs in the hippocampus and found that knocking down these receptors in astrocytes, but not in GABAergic or pyramidal neurons, caused a decrease in immobility in the forced swimming test (FST) without affecting other anxiety- and depression-related behaviors. We also generated astrocyte-specific GABABR-knockout mice and found decreased immobility in the FST in these mice. Furthermore, the conditional knockout of GABABRs in astrocytes selectively increased the levels of brain-derived neurotrophic factor protein in hippocampal astrocytes, which controlled the decrease in immobility in the FST. Taken together, our findings contribute to the current understanding of which cell types expressing GABABRs modulate antidepressant activity in the FST, and they may provide new insights into the pathological mechanisms and potential targets for the treatment of depression.

Expression Patterns of Inducible Cre Recombinase Driven by Differential Astrocyte-Specific Promoters in Transgenic Mouse Lines.

Astrocytes are the most abundant cell type in the central nervous system (CNS). They provide trophic support for neurons, modulate synaptic transmission and plasticity, and contribute to neuronal dysfunction. Many transgenic mouse lines have been generated to obtain astrocyte-specific expression of inducible Cre recombinase for functional studies; however, the expression patterns of inducible Cre recombinase in these lines have not been systematically characterized. We generated a new astrocyte-specific Aldh1l1-CreERT2 knock-in mouse line and compared the expression pattern of Cre recombinase between this and five widely-used transgenic lines (hGfap-CreERT2 from The Jackson Laboratory and The Mutant Mouse Resource and Research Center, Glast-CreERT2, Cx30-CreERT2, and Fgfr3-iCreERT2) by crossing with Ai14 mice, which express tdTomato fluorescence following Cre-mediated recombination. In adult Aldh1l1-CreERT2:Ai14 transgenic mice, tdTomato was detected throughout the CNS, and five novel morphologically-defined types of astrocyte were described. Among the six evaluated lines, the specificity of Cre-mediated recombination was highest when driven by Aldh1l1 and lowest when driven by hGfap; in the latter mice, co-staining between tdTomato and NeuN was observed in the hippocampus and cortex. Notably, evident leakage was noted in Fgfr3-iCreERT2 mice, and the expression level of tdTomato was low in the thalamus when Cre recombinase expression was driven by Glast and in the capsular part of the central amygdaloid nucleus when driven by Cx30. Furthermore, tdTomato was clearly expressed in peripheral organs in four of the lines. Our results emphasize that the astrocyte-specific CreERT2 transgenic lines used in functional studies should be carefully selected.

Higher expression of calcineurin predicts poor prognosis in unique subtype of ovarian cancer.

BACKGROUND: The role of calcineurin/NFAT signaling in ovarian cancer has been unknown. NFAT was significantly overexpressed in ovarian cancer tissues and that overexpression of NFAT was significantly associated with metastasis and poor prognosis on clinical tissue level. To investigate whether NFAT upstream protein, calcineurin (CN), affects the prognosis in various histological subtype of ovarian cancer (OC). METHODS: The association between CN and clinical features was analyzed in 50 OC patients treated from 2007 to 2012. CN expression was examined using immunohistochemistry. We observed the association of CN expression with the prognosis in these patients. RESULTS: CN expression was significantly increased in later-stage tumor tissue of serous carcinoma compared with those with early-stage. The expression of CN positively correlated with the serum cancer antigen 125 (CA125) level in ovarian clear-cell carcinoma and the serum alpha-fetoprotein (AFP) level in papillary serous cystadenocarcinoma. Particularly, higher CN expression in tumor tissues significantly correlated with reduced overall survival among patients with serous carcinoma. In addition, the serum cancer antigen 72-4 (CA72-4) level, serum carcinoembryonic antigen (CEA) levels, pathological stage, lymph node metastasis, and chemotherapeutic resistance were identified as significant prognostic factors in ovarian clear-cell carcinoma, serous carcinoma, or papillary serous cystadenocarcinoma. CONCLUSIONS: CN is upregulated in ovarian cancer tissues with later-stage and that the expression of CN, CA72-4, and CEA was remarkably associated with poor prognosis in unique subtype of ovarian cancer. CN levels may be investigated for use as a prognostic biomarker for risk assessment in unique subtype of OC patients.

erbb4 Deficits in Chandelier Cells of the Medial Prefrontal Cortex Confer Cognitive Dysfunctions: Implications for Schizophrenia.

erbb4 is a known susceptibility gene for schizophrenia. Chandelier cells (ChCs, also known as axo-axonic cells) are a distinct GABAergic interneuron subtype that exclusively target the axonal initial segment, which is the site of pyramidal neuron action potential initiation. ChCs are a source of ErbB4 expression and alterations in ChC-pyramidal neuron connectivity occur in the medial prefrontal cortex (mPFC) of schizophrenic patients and animal models of schizophrenia. However, the contribution of ErbB4 in mPFC ChCs to the pathogenesis of schizophrenia remains unknown. By conditional deletion or knockdown of ErbB4 from mPFC ChCs, we demonstrated that ErbB4 deficits led to impaired ChC-pyramidal neuron connections and cognitive dysfunctions. Furthermore, the cognitive dysfunctions were normalized by L-838417, an agonist of GABAAα2 receptors enriched in the axonal initial segment. Given that cognitive dysfunctions are a core symptom of schizophrenia, our results may provide a new perspective for understanding the etiology of schizophrenia and suggest that GABAAα2 receptors may be potential pharmacological targets for its treatment.

The effects of a catheter clamping protocol on bladder function in neurosurgical patients: a controlled trial.

There is scant evidence-based literature on the best strategies for short-term urinary catheter removal. This clinical trial explored the effects of an early urinary catheter clamping protocol on bladder function in neurosurgical patients. Eligible patients were divided into observation and control groups. Those in the observation group had their catheter clamped postoperatively on return to the ward and unclamped at dedicated intervals. The control group received standard care; the catheter was on free drainage during the entire time in situ. The mean catheter indwelling time was 2.6 days. Compared with the control group, the observation group experienced shorter time to first postoperative urination, less residual urine volume and better subjective perception during their first postoperative urination. For patients undergoing neurosurgery and associated short-term indwelling urinary catheterization, an early catheter clamping protocol is effective in facilitating bladder function, reducing the rate of dysuria and making patients feel more comfortable after catheter removal.

[Treatment of autism children: observation on efficacy of behavior training with retention of needles on head].

OBJECTIVE: To observe the effect difference of behavior training with head needling retention and behavior training after acupuncture for autism children. METHODS: Sixty qualified autism children were divided randomly into simultaneous head needling retention and behavior training group (trial group) and behavior training after acupuncture treatment group (control group) with 30 case in each group. Retention needles on the head with simultaneous behavior training was applied for the trial group. The main acupoints included Sishen Xue, Dingshen Sanxue (3 points for mental tranquilization), Nao Sanxue (3 points for the function of brain), Shou Zhisanxue (3 points for mental activities on hand) and Zozhi Sonxue (3 points for mental activities on foot). Other points were combined according to conditions of patients. Needles on the 4 extremities were withdrawn first after 30 minutes, needles on head were remained during behavior training. While behavior training was applied to the control group when acupuncture treatment was completely accomplished. Treatments were applied once a day to both groups. And 3 months was taken as one observation cycle. Estimation was made on therapeutic effect and developing level of autism children with CARS and PEP. RESULTS: The total effective rate of the trial group was 83.3% (25/30), better than 66.7% (20/30) of the control group (P < 0.05). The CARS scores of both groups declined after the treatment. And the score of trail group was lower than the control group (all P < 0.05). While the PEP scores of both groups increased, and the score of trail group was higher than the control group (all P < 0.05). The increasing level of scores of cognitive understanding and cognitive expression were all better than the control group (all P < 0.05). CONCLUSION: The effect of behavior training with head needle retention on autism children is better than behavior training after acupuncture treatment, especially in enhancing cognition understanding and cognition expression.

A core competency model for Chinese baccalaureate nursing graduates: a descriptive correlational study in Beijing.

BACKGROUND: A review of the literature showed that the core competencies needed by newly graduated Chinese nurses were not as of yet undocumented. OBJECTIVE: To develop a psychometrically sound instrument for identifying and measuring the core competencies needed by Chinese nursing baccalaureate graduates. DESIGN: Descriptive correlational and multicentre study. SETTING: Seven major tertiary teaching hospitals and three major medical universities in Beijing. PARTICIPANTS: 790 subjects, including patients, nursing faculty members, doctors and nurses. METHOD: A reliable and valid self-report instrument, consisting of 58 items, was developed using multiple methods. It was then distributed to 790 subjects to measure nursing competency in a broader Chinese context. The psychometric characteristics of reliability and validity were supported by descriptive and inferential analyses. RESULTS: The final instrument consists of six dimensions with 47 items. The content validity index was 0.90. The overall scale reliability was 0.97 with dimensions range from 0.87 to 0.94. Six domains of core competencies were identified: professionalism; direct care; support and communication; application of professional knowledge; personal traits; and critical thinking and innovation. CONCLUSION: The findings of this study provide valuable evidence for a psychometrically sound measurement tool, as well as for competency-based nursing curriculum reform.