Detailed role of Let-7e in human diseases.

As part of the epigenetic machinery, microRNAs (miRNAs) are extensively utilized by eukaryotes. By modulating gene expression in a variety of ways, these short RNAs mediate crucial physiological processes. This suggests that abnormalities in miRNA biogenesis and expression can be traced back to a variety of diseases. In addition, miRNAs are promising clinical candidates, especially for preclinical diagnosis. The Let family of miRNAs was one of the first to be discovered. As a prominent member of this category, extensive research has been conducted on Let-7e. The vast majority of evidence indicates an association between let-7e dysregulation and the onset and progression of disease, including malignancies. Because their effect depends on the genetic profile of disease and the affected tissue, different miRNAs play diverse roles in various diseases. However, what counts in miRNA studies is that just one miRNA may target numerous mRNAs in a cell at the exact time, therefore summarizing the effect of a single miRNA in human diseases can provide better insights into disease detection and treatment. The goal of this study is to gain a deeper understanding of how let-7e functions in human cells so that it can be utilized more effectively in clinical settings for diagnosis, prognosis, and treatment. We have reviewed the research on let-7e, focusing on the molecular underpinnings of biological processes controlled by this miRNA that contribute to the development and etiology of numerous disorders.

Estrogen-immuno-neuromodulation disorders in menopausal depression.

A significant decrease in estrogen levels puts menopausal women at high risk for major depression, which remains difficult to cure despite its relatively clear etiology. With the discovery of abnormally elevated inflammation in menopausal depressed women, immune imbalance has become a novel focus in the study of menopausal depression. In this paper, we examined the characteristics and possible mechanisms of immune imbalance caused by decreased estrogen levels during menopause and found that estrogen deficiency disrupted immune homeostasis, especially the levels of inflammatory cytokines through the ERα/ERß/GPER-associated NLRP3/NF-κB signaling pathways. We also analyzed the destruction of the blood-brain barrier, dysfunction of neurotransmitters, blockade of BDNF synthesis, and attenuation of neuroplasticity caused by inflammatory cytokine activity, and investigated estrogen-immuno-neuromodulation disorders in menopausal depression. Current research suggests that drugs targeting inflammatory cytokines and NLRP3/NF-κB signaling molecules are promising for restoring homeostasis of the estrogen-immuno-neuromodulation system and may play a positive role in the intervention and treatment of menopausal depression.

MiRNA polymorphisms affect the prognosis of gastric cancer: insights from Xianyou, Fujian.

Introduction: Gastric cancer, characterized by high incidence and substantial disease burden, has drawn continuous attention regarding its occurrence and prognosis. Genetics plays a crucial role in influencing the prognosis of gastric cancer, and single nucleotide polymorphisms are closely associated with the occurrence, development, and prognosis of this malignant tumor. Our study aims to conduct survival analysis on patients carrying different single nucleotide polymorphisms, exploring the relationship between miRNA single nucleotide polymorphisms and the prognosis of gastric cancer. Methods: Genetic data from 344 patients in Xianyou, Fujian, formed the basis of our study. We delineated the survival rate and median survival time, utilizing the log-rank test and COX regression analysis as statistical tools. Results: Upon stratifying the data by sex or operation, it was discerned that the GG genotype at MSH2 rs17502941 independently posed a heightened risk for gastric cancer. Other stratification analyses suggested that the subsequent single nucleotide polymorphisms were correlated with patient prognosis: rs17502941, rs884225, rs1468063, rs7143252, and rs2271738. Discussion: The outcomes of this study strongly suggest that miRNA polymorphisms significantly influence the survival time of gastric cancer patients and can serve as effective predictors for the prognosis of gastric cancer.

A mitochondrion-targeted cyanine agent for NIR-II fluorescence-guided surgery combined with intraoperative photothermal therapy to reduce prostate cancer recurrence.

Poorly identified tumor boundaries and nontargeted therapies lead to the high recurrence rates and poor quality of life of prostate cancer patients. Near-infrared-II (NIR-II) fluorescence imaging provides certain advantages, including high resolution and the sensitive detection of tumor boundaries. Herein, a cyanine agent (CY7-4) with significantly greater tumor affinity and blood circulation time than indocyanine green was screened. By binding albumin, the absorbance of CY7-4 in an aqueous solution showed no effects from aggregation, with a peak absorbance at 830 nm and a strong fluorescence emission tail beyond 1000 nm. Due to its extended circulation time (half-life of 2.5 h) and high affinity for tumor cells, this fluorophore was used for primary and metastatic tumor diagnosis and continuous monitoring. Moreover, a high tumor signal-to-noise ratio (up to ~ 10) and excellent preferential mitochondrial accumulation ensured the efficacy of this molecule for photothermal therapy. Therefore, we integrated NIR-II fluorescence-guided surgery and intraoperative photothermal therapy to overcome the shortcomings of a single treatment modality. A significant reduction in recurrence and an improved survival rate were observed, indicating that the concept of intraoperative combination therapy has potential for the precise clinical treatment of prostate cancer.

The CXCR4 might be a potential biomarker for esophageal squamous cell carcinoma: A meta-analysis.

OBJECTIVE: To evaluate the relationship between CXCL12/CXCR4 and the progress, prognosis of esophageal squamous cell carcinoma (ESCC), providing evidence for potential early diagnosis, clinical treatment, prognosis evaluation, and therapeutic target of ESCC. METHODS: Databases of PubMed, the Cochrane Library, Embase, and Web of Science were searched for the relationship between CXCL12/CXCR4 and clinicopathological characteristics and survival time of ESCC. Stata16.0 software was used to conduct meta-analysis. RESULTS: A total of 10 studies involving 1216 cases of patients with ESCC were included in our study. The results indicated that high-level expression of CXCR4 was significantly correlated with tumor differentiation [OR = 0.69, 95% confidence interval (CI): (0.50, 0.97)], tumor infiltration [OR = 0.39, 95% CI: (0.25, 0.61)], lymph node metastasis [OR = 0.36, 95% CI: (0.21, 0.61)], clinical stage [OR = 0.33, 95% CI: (0.24, 0.45)] of ESCC. The expression of CXCR4 was also significantly correlated with OS [HR = 2.00, 95% CI: (1.63, 2.45)] and disease-free survival [HR = 1.76, 95% CI: (1.44, 2.15)] in patients of ESCC after surgical resection. No significant relationship was observed between the expression of CXCL12 and the clinicopathological characteristics of ESCC. CONCLUSION: CXCR4 might be a potential biomarker for the progress and prognosis evaluation, and therapeutic target for ESCC.

Clinical application of two types of Hook-Wire needle localization procedures for pulmonary small nodule biopsy.

BACKGROUND: With the widespread use of low-dose spiral computed tomography (LDCT) and increasing awareness of personal health, the detection rate of pulmonary nodules is steadily rising. OBJECTIVE: To evaluate the success rate and safety of two different models of Hook-Wire needle localization procedures for pulmonary small nodule biopsy. METHODS: Ninety-four cases with a total of 97 pulmonary small nodules undergoing needle localization biopsy were retrospectively analyzed. The cases were divided into two groups: Group A, using breast localization needle steel wire (Bard Healthcare Science Co., Ltd.); Group B, using disposable pulmonary nodule puncture needle (SensCure Biotechnology Co., Ltd.). All patients underwent video-assisted thoracoscopic surgery (VATS) for nodule removal on the same day after localization and biopsy. The puncture localization operation time, success rate, complications such as pulmonary hemorrhage, pneumothorax, hemoptysis, and postoperative comfort were observed and compared. RESULTS: In Group A, the average localization operation time for 97 nodules was 15.47 ± 5.31 minutes, with a success rate of 94.34%. The complication rate was 71.69% (12 cases of pneumothorax, 35 cases of pulmonary hemorrhage, 2 cases of hemoptysis), and 40 cases of post-localization discomfort were reported. In Group B, the average localization operation time was 25.32 ± 7.83 minutes, with a 100% success rate. The complication rate was 29.55% (3 cases of pneumothorax, 15 cases of pulmonary hemorrhage, 0 cases of hemoptysis), and 3 cases reported postoperative discomfort. According to the data analysis in this study, Group B had a lower incidence of puncture-related complications than Group A, along with a higher success rate and significantly greater postoperative comfort. CONCLUSIONS: The disposable pulmonary nodule puncture needle is safer and more effective in pulmonary small nodule localization biopsy, exhibiting increased comfort compared to the breast localization needle. Additionally, the incidence of complications is significantly lower.

FOXA1-Driven pathways exacerbate Radiotherapy-Induced kidney injury in colorectal cancer.

OBJECTIVE: This study aimed to investigate the role of FOXA1 in acute kidney injury (AKI) induced by radiotherapy in colorectal cancer. Although FOXA1 is known to be aberrantly expressed in malignant tumors, its contribution to AKI remains unclear. This study aimed to explore the involvement of FOXA1 in AKI induced by radiotherapy in colorectal cancer and its influence on the regulation of downstream target genes. METHODS: Firstly, a transcriptome analysis was performed on mice to establish a radiation-induced AKI model, and qPCR was used to determine the expression of FOXA1 in renal cell injury models induced by X-ray irradiation. Additionally, FOXA1 was silenced using lentiviral vectors to investigate its effects on the apoptosis of mice with radiation-induced AKI and HK-2 cells. Next, bioinformatics analysis and various experimental validation methods such as ChIP assays, co-immunoprecipitation, and dual-luciferase reporter assays were employed to explore the relationship between FOXA1 and the downstream regulatory factors ITCH promoter and the ubiquitin ligase-degradable TXNIP. Finally, lentiviral overexpression or knockout techniques were used to investigate the impact of the FOXA1/ITCH/TXNIP axis on oxidative stress and the activation of inflammatory body NLRP3. RESULTS: This study revealed that FOXA1 was significantly upregulated in the renal tissues of mice with radiation-induced AKI and in the injured HK-2 cells. Furthermore, in vitro cell experiments and animal experiments demonstrated that FOXA1 suppressed the transcription of the E3 ubiquitin ligase ITCH, thereby promoting apoptosis of renal tubular cells and causing renal tissue damage. Further in vivo animal experiments confirmed that TXNIP, a protein degraded by ITCH ubiquitination, could inhibit oxidative stress and the activation of NLRP3 inflammasome in the AKI mouse model. CONCLUSION: FOXA1 enhances oxidative stress, cell apoptosis, and NLRP3 inflammasome activation by regulating the ITCH/TXNIP axis, thereby exacerbating radiotherapy-induced AKI.

Characterization of preclinical Alzheimer's disease model: spontaneous type 2 diabetic cynomolgus monkeys with systemic pro-inflammation, positive biomarkers and developing AD-like pathology.

BACKGROUND: The key to the prevention and treatment of Alzheimer's disease (AD) is to be able to predict and diagnose AD at the preclinical or early stage, but the lack of a preclinical model of AD is the critical factor that causes this problem to remain unresolved. METHODS: We assessed 18 monkeys in vivo evaluation of pro-inflammatory cytokines and AD pathological biomarkers (n = 9 / type 2 diabetic mellitus (T2DM) group, age 20, fasting plasma glucose (FPG) ≥ 100 mg/dL, and n = 9 / negative control (NC) group, age 17, FPG < 100 mg/dL). Levels of pro-inflammatory cytokines and AD pathological biomarkers was measured by ELISA and Simoa Technology, respectively. 9 monkeys evaluated ex vivo for AD-like pathology (n = 6 / T2DM group, age 22.17, FPG ≥ 126 mg/dL, and n = 3 / NC group, age 14.67, FPG < 100 mg/dL). To evaluate the pathological features of AD in the brains of T2DM monkeys, we assessed the levels of Aß, phospho-tau, and neuroinflammation using immunohistochemistry, which further confirmed the deposition of Aß plaques by Bielschowsky's silver, Congo red, and Thioflavin S staining. Synaptic damage and neurodegeneration were assessed by immunofluorescence. RESULTS: We found not only increased levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) in peripheral blood (PB) and brain of T2DM monkeys but also changes in PB of AD pathological biomarkers such as decreased ß-amyloid (Aß) 42 and Aß40 levels. Most notably, we observed AD-like pathological features in the brain of T2DM monkeys, including Aß plaque deposition, p-tau from neuropil thread to pre-neurofibrillary tangles (NFTs), and even the appearance of extracellular NFT. Microglia were activated from a resting state to an amoeboid. Astrocytes showed marked hypertrophy and an increased number of cell bodies and protrusions. Finally, we observed impairment of the postsynaptic membrane but no neurodegeneration or neuronal death. CONCLUSIONS: Overall, T2DM monkeys showed elevated levels of peripheral and intracerebral inflammation, positive AD biomarkers in body fluids, and developing AD-like pathology in the brain, including Aß and tau pathology, glial cell activation, and partial synaptic damage, but no neuronal degeneration or death as compared to the healthy normal group. Hereby, we consider the T2DM monkeys with elevation of the peripheral pro-inflammatory factors and positive AD biomarkers can be potentially regarded as a preclinical AD model.

Letermovir Effectively Prevents Cytomegalovirus Infection in Patients with Aplastic Anemia After Hematopoietic Stem Cell Transplantation: A Real-World Retrospective Cohort Study.

INTRODUCTION: In this single-center retrospective cohort study, we investigated the efficacy of letermovir in preventing Cytomegalovirus (CMV) infection in patients with aplastic anemia (AA) who have undergone allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Based on whether or not letermovir was used for preventing CMV infection, the patients were categorized into two groups: letermovir and control groups. The overall survival (OS) rate and cumulative incidence of CMV infection during the first 100 days after allo-HSCT were evaluated. The study included 21 matched pairs of patients, identified through propensity score matching analysis, to compare CMV infection rates, treatment efficacy, and regression. RESULTS: The incidence of CMV infection within 100 days after transplantation was significantly lower in the letermovir group than in the control group (26.5 vs. 77.4%, respectively; P < 0.001), among a total of 87 patients who underwent the transplant. In the matched cohort of 21 patients with AA, the letermovir group also showed a significantly reduced cumulative incidence of CMV infection (14.3 vs. 90.5% in the control group; P < 0.001). Compared to the control group, patients with CMV infection in the letermovir group had lower CMV-DNA load and a shorter clearance time. However, there was no significant difference in OS between both groups (P = 0.34). CONCLUSIONS: Letermovir effectively prevents CMV infection in allo-HSCT recipients with AA and demonstrates a high safety profile.

Pterostilbene upregulates MICA/B via the PI3K/AKT signaling pathway to enhance the capability of natural killer cells to kill cervical cancer cells.

Natural killer (NK) cells are triggered by the innate immune response in the tumor microenvironment. The extensive set of stimulating and inhibiting receptors mediates the target recognition of NK cells, and controls the strength of the effector reaction countering specific targeted cells. Yet, lacking major MHC (histocompatibility complex) MICA/B class I chain-related proteins on the membrane of tumor cells results in the failure of NK cell recognition and ability to resist NK cell destruction. Searching databases and molecular docking suggested that in cervical cancer, pterostilbene (3,5-dimethoxy-40-hydroxystilbene; PTS) in Vaccinium corymbosum extract could constrain PI3K/AKT signaling and improving the MICA/B expression. In flow cytometry, MTT assay, viability/cytotoxicity assay, and colony development assays, PTS reduced the development of cervical cancer cells and increased apoptosis. The quantitative real-time PCR (qRT-PCR) and a Western blot indicate that PTS controlled the cytolytic action of NK cells in tumor cells via increasing the MICA/B expression, thus modifying the anti-tumor immune response in cervical cancer.

Utility of dexmedetomidine on surgical site wound pain undergoing thoracoscopic surgery: A meta-analysis.

We conducted this study aimed to evaluate the analgesic effect of dexmedetomidine in thoracoscopic surgery on postoperative wound pain, and to provide a reference for clinical use of the drug. We searched PubMed, Embase, Cochrane Library, Web of Science, Wanfang, Chinese Biomedical Literature Database and China National Knowledge Infrastructure databases, and supplemented with manual searching. We searched from database inception to October 2023, to collect the randomised controlled trials (RCTs) on dexmedetomidine application in thoracoscopic surgery. Two researchers screened all the literature according to the inclusion and exclusion criteria and the literature included in the study was evaluated for quality, extracted information and required data. Stata 17.0 software was employed for data analysis and the outcomes were 2 6, 12, 24 and 48 h postoperative wound visual analog scores (VAS). Twenty-four RCTs totalling 2246 patients undergoing thoracoscopic surgery were finally included. The analysis revealed dexmedetomidine applied to thoracoscopic surgery significantly reduced the postoperative wound VAS scores at 2 h (SMD: -0.96, 95% CI: -1.57 to -0.36, p = 0.002), 6 h (SMD: -0.98, 95% CI: -1.27 to -0.69, p < 0.001), 12 h (SMD: -1.19, 95% CI: -1.44 to -0.94, p < 0.001), 24 h (SMD: -0.91, 95% CI: -1.16 to -0.66, p < 0.001) and 48 h (SMD: -0.75, 95% CI: -1.02 to -0.48, p < 0.001). Our results suggest dexmedetomidine applied to thoracoscopic surgery can significantly reduce postoperative wound pain, which is worthy of clinical application.

Characterization of Epidermal Function in Individuals with Primary Cutaneous Amyloidosis.

Purpose: To compare epidermal biophysical properties, indicators of epidermal function, in individuals with and without primary cutaneous amyloidosis (PCA). Patients and Methods: This study incorporated 189 patients with PCA and 166 healthy individuals. The GPSkin Barrier was employed to measure transepidermal water loss (TEWL) rates and hydration levels of the stratum corneum. The Sebumeter and the Skin pH Meter were utilized to determine the skin surface's sebum content and pH, respectively. The severity of pruritus in participants was evaluated using the visual analog scale (VAS). Results: Compared to the control group without PCA, individuals with PCA displayed a notable increase in skin surface pH and TEWL and a decrease in the hydration levels of the stratum corneum (p<0.0001 for all parameters). Additionally, the sebum content was markedly lower in those with PCA than in the controls (p<0.0001). Of particular note, both TEWL and skin surface pH at the lesion sites on the back and the shin were more elevated in lichenoid amyloidosis (LA) and in macular amyloidosis (MA), whereas hydration levels of the stratum corneum and sebum levels were diminished in LA compared to MA (p<0.05). In conclusion, both hydration levels of the stratum corneum and sebum content exhibited an inverse relationship with pruritus severity, whereas TEWL and skin surface pH demonstrated a positive correlation with pruritus intensity. Conclusion: The function of the epidermis is compromised in individuals diagnosed with PCA. However, the mechanisms underlying these changes await further investigation.

Relationship between esophageal squamous cell carcinoma risk and alcohol-related ALDH2 and ADH1B polymorphisms: Evidence from a meta-analysis and Mendelian randomization analysis.

BACKGROUND: Previous studies have shown that ALDH2 and ADH1B genes may be associated with alcohol metabolism and the risk of esophageal squamous cell carcinoma (ESCC), with inconsistent results. This meta-analysis aimed at comprehensively assessing the associations between ALDH2 and ADH1B polymorphisms and the risk of ESCC to synthesize and clarify the evidence. METHODS: We calculated summary estimates of the associations between four genetic variants (rs671 and rs674 in ALDH2, and rs1229984 and rs1042026 in ADH1B) and the ESCC risk across 23 publications in the additive model and allelic model. Venice criteria, Bayesian false discovery probability (BFDP), and false-positive reporting probability (FPRP) were used to assess the strength of epidemiological evidence. Heterogeneity among studies was evaluated by using the Higgin's I2 statistic, and publication bias was assessed by using funnel plots and Begg's test. A Mendelian randomization (MR) analysis was performed to determine the causal association between alcohol intake and esophageal cancer risk. Data from the HaploReg v4.1 and PolyPhen-2 were analyzed for functional annotations. RESULTS: Of the four genetic variants, rs671 of ALDH2 was associated with a significantly reduced risk of ESCC (OR: 0.60, 95% CI: 0.50-0.73), whereas rs1229984 of ADH1B was associated with a significantly increased risk (2.50, 95% CI: 1.70-3.69) in the additive model. In the allelic model, the variant rs1229984 of ADH1B also increased the risk of ESCC (OR: 1.50; 95% CI: 1.21-1.87). The result for the variant rs671 was considered as strong epidemiological evidence. Functional annotations identified that the four variants were related to the enhancer histone marks and motif changes. The other two variants were not associated with the ESCC risk (rs674 of ALDH2 OR: 1.22, 95% CI: 0.71-2.12; rs1042026 of ADH1B OR: 1.28, 95% CI: 0.52-3.14) in the additive model. The MR analysis did not find a causal effect of alcohol on the esophageal cancer risk. CONCLUSIONS: The results showed that ADH1B rs1229984 was significantly associated with an increased the risk of ESCC.

Exploring the Prognosis-Related Genetic Variation in Gastric Cancer Based on mGWAS.

The use of metabolome genome-wide association studies (mGWAS) has been shown to be effective in identifying functional genes in complex diseases. While mGWAS has been applied to biomedical and pharmaceutical studies, its potential in predicting gastric cancer prognosis has yet to be explored. This study aims to address this gap and provide insights into the genetic basis of GC survival, as well as identify vital regulatory pathways in GC cell progression. Genome-wide association analysis of plasma metabolites related to gastric cancer prognosis was performed based on the Generalized Linear Model (GLM). We used a log-rank test, LASSO regression, multivariate Cox regression, GO enrichment analysis, and the Cytoscape software to visualize the complex regulatory network of genes and metabolites and explored in-depth genetic variation in gastric cancer prognosis based on mGWAS. We found 32 genetic variation loci significantly associated with GC survival-related metabolites, corresponding to seven genes, VENTX, PCDH 7, JAKMIP1, MIR202HG, MIR378D1, LINC02472, and LINC02310. Furthermore, this study identified 722 Single nucleotide polymorphism (SNP) sites, suggesting an association with GC prognosis-related metabolites, corresponding to 206 genes. These 206 possible functional genes for gastric cancer prognosis were mainly involved in cellular signaling molecules related to cellular components, which are mainly involved in the growth and development of the body and neurological regulatory functions related to the body. The expression of 23 of these genes was shown to be associated with survival outcome in gastric cancer patients in The Cancer Genome Atlas (TCGA) database. Based on the genome-wide association analysis of prognosis-related metabolites in gastric cancer, we suggest that gastric cancer survival-related genes may influence the proliferation and infiltration of gastric cancer cells, which provides a new idea to resolve the complex regulatory network of gastric cancer prognosis.

Structural characterization of an isocytosine-specific deaminase VCZ reveals its application potential in the anti-cancer therapy.

Non-natural nucleobase isocytosine (IC) is the isomer of cytosine; its chemical derivate 5-fluoroisocytosine (5-FIC) together with the isocytosine-specific deaminase (ICD) VCZ was suggested to be potential practical enzyme/prodrug pair for cancer therapy through gene-directed enzyme-prodrug therapy (GDEPT) method. In this study, we have determined the crystal structures of apo-VCZ and its complex with 5-FU. We identified the critical residues for substrate binding and catalytic reaction. We also captured the substrate-induced conformational changes of VCZ, then proposed the conjectural reaction procedures of VCZ for converting the IC into the uracil. Moreover, we evaluated the therapeutic effect of wildtype or the mutated VCZ protein in the colorectal cancer cell lines. Our studies will shed light on optimizing the ICD/5-FIC pairs by modifying either the enzyme or the prodrug based on the structural observations, thereby improving the possibility of applying the ICD/5-FIC pair in clinical trials.

Prognostic Implication of Plasma Metabolites in Gastric Cancer.

Gastric cancer (GC) typically carries a poor prognosis as it is often diagnosed at a late stage. Altered metabolism has been found to impact cancer outcomes and affect patients' quality of life, and the role of metabolites in gastric cancer prognosis has not been sufficiently understood. We aimed to establish a prognostic prediction model for GC patients based on a metabolism-associated signature and identify the unique role of metabolites in the prognosis of GC. Thus, we conducted untargeted metabolomics to detect the plasma metabolites of 218 patients with gastric adenocarcinoma and explored the metabolites related to the survival of patients with gastric cancer. Firstly, we divided patients into two groups based on the cutoff value of the abundance of each of the 60 metabolites and compared the differences using Kaplan-Meier (K-M) survival analysis. As a result, 23 metabolites associated with gastric cancer survival were identified. To establish a risk score model, we performed LASSO regression and Cox regression analysis on the 60 metabolites and identified 8 metabolites as an independent prognostic factor. Furthermore, a nomogram incorporating clinical parameters and the metabolic signature was constructed to help individualize outcome predictions. The results of the ROC curve and nomogram plot showed good predictive performance of metabolic risk features. Finally, we performed pathway analysis on the 24 metabolites identified in the two parts, and the results indicated that purine metabolism and arachidonic acid metabolism play important roles in gastric cancer prognosis. Our study highlights the important role of metabolites in the progression of gastric cancer and newly identified metabolites could be potential biomarkers or therapeutic targets for gastric cancer patients.

Prognostic significance of the novel nutrition-inflammation marker of lymphocyte-C-reactive protein ratio in patients with nasopharyngeal carcinoma receiving concurrent chemoradiotherapy.

Background: Recent studies indicate that the novel lymphocyte-C-reactive protein ratio (LCR) is strongly associated with the survival of various tumors, but its prognostic value in nasopharyngeal carcinoma (NPC) is understudied. This study aimed to explore the relationship between LCR and overall survival (OS) in NPC and develop a predictive model. Methods: A total of 841 NPC patients who received concurrent chemoradiotherapy (CCRT) between January 2010 and December 2014 were retrospectively enrolled and randomly divided into a training cohort (n = 589) and a validation cohort (n = 252), and 122 patients between January 2015 and March 2015 were included as an additional validation cohort. Univariate and multivariate Cox analyses were performed to identify variables associated with OS and construct a predictive nomogram. The predictive accuracy of the nomogram was evaluated and independently validated. Results: The LCR score differentiated NPC patients into two groups with distinct prognoses (HR = 0.53; 95% CI: 0.32-0.89, P = 0.014). Multivariate analysis showed that age, T stage, N stage, EBV-DNA status, and LCR score were independently associated with OS, and a predictive nomogram was developed. The nomogram had a good performance for the prediction of OS [C-index = 0.770 (95% CI: 0.675-0.864)]. and outperformed the traditional staging system [C-index = 0.589 (95% CI: 0.385-0.792)]. The results were internally and additionally validated using independent cohorts. Conclusion: The pretreatment LCR could independently predict the overall survival in NPC patients. A novel LCR-based prognostic model of an easy-to-use nomogram was established, and it outperformed the conventional staging system in terms of predictive power. Further external verification remains necessary.

Ziwuliuzhu Acupuncture Modulates Clock mRNA, Bmal1 mRNA and Melatonin in Insomnia Rats.

Background: In clinics, Ziwuliuzhu acupuncture is widely considered an effective method of treating insomnia; however, there is currently limited information available regarding its possible mechanisms. Although the method of Ziwuliuzhu acupuncture possesses a unique rhythmic pattern. Objectives: In this study, we have creatively combined the traditional Chinese medicine of Ziwuliuzhu with a modern biological rhythm to investigate the internal mechanism of insomnia. Methods: Pathological tissue from the hypothalamus was analyzed using hematoxylin-eosin staining. The level of TNF (tumor necrosis factor)-α in the SCN (suprachiasmatic nucleus) area of the hypothalamus was detected in situ using the TUNEL fluorescence staining assay. The concentration of hypothalamic melatonin was detected using the enzyme-linked immunosorbent assay (ELISA). The mRNA expression of Clock and Bmal1 was measured using RT-qPCR. Results: In the Ziwuliuzhu acupuncture groups, the structural damage in the hypothalamic neurons was alleviated compared to the model group and the expression of inflammatory factors was reduced. The mRNA expression levels of Clock and Bmal1 were significantly increased (p < 0.05). The concentration of melatonin was significantly increased (p < 0.001). Although there were no significant differences between the treatment groups (diazepam group, Nazi group, Najia group, and routine group) (p > 0.05). Conclusion: Ziwuliuzhu acupuncture alleviated neuronal damage and modulated the inflammatory reaction in the hypothalamus of rats with insomnia. Moreover, Ziwuliuzhu acupuncture increased the expression levels of Clock and Bmal1 mRNA, and MT content. This study has potentially highlighted one of the mechanisms through which Ziwuliuzhu acupuncture can be used to treat insomnia.

Barrier function and ultrastructure characteristics of epidermis in patients with primary cutaneous amyloidosis.

Previous studies on primary cutaneous amyloidosis (PCA) have mainly focused on exploring genetic mutation and components of amyloid in patients with PCA. However, studies on skin barrier function in PCA patients are scarce. Here, we detected the skin barrier function in PCA patients and healthy people by using noninvasive techniques and characterized ultrastructural features of PCA lesions compared with healthy people using transmission electron microscopy (TEM). The expression of proteins related to skin barrier function was examined by immunohistochemistry staining. A total of 191 patients with clinically diagnosed PCA and 168 healthy individuals were enrolled in the study. Our analysis revealed that all investigated lesion areas displayed higher transepidermal water loss and pH values, and lower Sebum levels and stratum corneum hydration levels in PCA patients compared with the same site area in healthy individuals. The TEM results showed that the intercellular spaces between the basal cells were enlarged and the number of hemidesmosomes decreased in PCA lesions. Immunohistochemical staining showed that the expression of integrin α6 and E-cadherin in PCA patients was less than that in healthy controls, while no differences in the expression of loricrin and filaggrin were observed. Our study revealed that individuals with PCA displayed skin barrier dysfunction, which may be related to alterations in epidermal ultrastructure and a decrease in the skin barrier-related protein E-cadherin. However, the molecular mechanisms underlying skin barrier dysfunction in PCA remain to be elucidated.