INSM1 expression in primary and metastatic neuroendocrine neoplasms at distinct locations.

BACKGROUND: Insulinoma-associated protein 1 (INSM1) has been reported as a valuable marker for neuroendocrine neoplasms (NENs). The aims of this study were to evaluate any change in INSM1 expression between primary and metastatic NENs in distinct locations, as well as the expression of INSM1 at different differentiation levels. Furthermore, we would also investigate the significance of INSM1 expression in non-neuroendocrine neoplasms (non-NENs). METHODS: We collected 78 cases with primary NENs and 16 cases with metastatic NENs. An addition 7 cases of non-NENs with neuroendocrine (NE) differentiation and 84 cases of other non-NENs, respectively, were included as controls. RESULTS: In our cohort, 82% of primary NENs and 88% of metastatic NENs expressed INSM1 with no difference between them. There was no difference in the expression of INSM1 in the lung and digestive system, and its staining pattern was independent of tumor differentiation or location. The proportion of INSM1 -positive in non-NENs with NE differentiation was significantly higher than that in other non-NENs. INSM1 sensitivity for primary NENs (82%) was comparable to Chromogranin A (82%), less than that of Synaptophysin (96%) and CD56 (94%); specificity was higher (96% vs 94%, 82%, and 89%, respectively). The sensitivity of INSM1 for well differentiated NENs was significantly higher than that of poorly differentiated NENs (100% vs 79%). CONCLUSIONS: INSM1 is a useful neuroendocrine marker in primary and metastatic NENs, helping to identify primary NENs with different degrees of differentiation. The expression of INSM1 was independent of tumor location. It should be with caution to interpret the expression of INSM1 in non-NENs that morphologically resemble NENs.

Construction and application of nasopharyngeal carcinoma-specific big data platform based on electronic health records.

OBJECTIVE: To establish a nasopharyngeal carcinoma-specific big data platform based on electronic health records (EHRs) to provide data support for real-world study of nasopharyngeal carcinoma. METHODS: A multidisciplinary expert team was established for this project. Based on industry standards and practical feasibility, the team designed the nasopharyngeal carcinoma data element standards including 14 modules and 640 fields. Data from patients diagnosed with nasopharyngeal carcinoma who visited Southern Hospital after 1999 were extracted from 15 EHRs systems and were cleaned, structured, and standardized using information technologies such as machine learning and natural language processing. In addition, a series of measures such as quality control and data encryption were taken to ensure data quality and patient privacy. At the platform application level, 10 functional modules were designed according to the needs of nasopharyngeal carcinoma research. RESULTS: As of 1 October 2022, the Big Data platform has included 11,617patients, of whom 8228 (70.83 %) were male and 3389 (29.17 %) were female, with a median age of 48 years (interquartile range, 40 years). The data in the platform were validated to have a high level of completeness and accuracy, especially for key variables such as social demographics, laboratory tests and vital signs. Currently, six projects involving risk factors, early diagnosis, treatment efficacy and prevention of treatment-related toxic reactions have been conducted on the platform. CONCLUSIONS: We have established a high-quality NPC-specific big data platform by integrating heterogeneous data from multiple sources in the EHR. The platform provides an effective tool and strong data support for real-world studies of nasopharyngeal carcinoma, which helps to improve research efficiency, reduce costs, and improve the quality of research results. We expect to promote multicenter nasopharyngeal carcinoma data sharing in the future to facilitate the generation of high-quality real-world evidence in nasopharyngeal carcinoma. This article may provide some reference value for other comprehensive hospitals to establish a big data platform for nasopharyngeal carcinoma.

The Proton of Alcohols as Hydrogen Source in Diboron-Mediated Nickel-Catalyzed Asymmetric Transfer Hydrogenation of Cyclic N-Sulfonyl Imines.

The proton of alcohols as the sole hydrogen source in diboron-mediated nickel-catalyzed asymmetric transfer hydrogenation of cyclic N-sulfonyl imines has been developed, providing the chiral cyclic sulfamidates in excellent enantioselectivities. The mechanistic investigations suggested that the proton of alcohols could be activated by tetrahydroxydiboron to form active nickel hydride species.

Comparative efficacy of different reconstruction methods after wide local excision of the nail unit: A retrospective study.

BACKGROUND: Wide local excision (WLE) of the nail unit is widely used in treating in situ and minimally invasive malignant subungual tumours. After WLE, diverse reconstruction methods have been reported. However, the best repair method has yet to be determined. OBJECTIVE: To compare the repair effects and postoperative morbidity of secondary intention healing (SIH), artificial dermis grafting combined with secondary intention healing (ADGSIH) and full-thickness skin grafting (FSG) after WLE of the nail unit. METHODS: We retrospectively reviewed 21 patients who underwent WLE of the nail unit. The re-epithelializing time, functional and cosmetic outcomes, postoperative complications and patients' satisfaction were assessed from the follow-up records. RESULTS: The FSG group showed more rapid healing and better functional and cosmetic outcomes than the SIH and ADGSIH groups. The ADGSIH and FSG groups showed significant pain relief compared to the SIH group. No serious early and late postoperative complications were reported. The median follow-up period was 26 months, and no recurrence was observed. All patients were satisfied with the treatment. CONCLUSIONS: FSG after the WLE of the nail unit is a therapeutic option with convenient application, significant pain relief, rapid recovery and satisfying functional and cosmetic outcomes.

Quantitation of macropinocytosis in glioblastoma based on high-content analysis.

BACKGROUND: Macropinocytosis is a pathway utilized for the internalization of extracellular fluid, albumin and dissolved molecules. Assessing macropinocytosis has been challenging in the past because the combination of manual acquisition and visual evaluation of images is laborious, making this type of assessment difficult for high-throughput applications. Therefore, there is a need to develop sensitive and specific macropinocytosis evaluation methods. METHODS: This paper proposed a quantitative and time-saving method for macropinocytosis detection based on high-content analysis (HCA). Additionally, cell proliferation was evaluated using CCK8 test. RESULTS: The term "macropinosome index" was defined to estimate macropinocytosis and allow comparisons between different cell lines and treatments. Furthermore, we demonstrated that macropinocytosis can promote glioblastoma (GBM) cell survival under L-glutamine (L-Gln)-deficient conditions that resemble the tumour microenvironment. CONCLUSIONS: HCA represents a novel, nonsubjective and high-throughput assay for macropinocytosis assessment. In addition, L-Gln deprivation increased the macropinosome index in GBM cells, suggesting that this process may be used to design GBM therapies. AVAILABILITY OF DATA AND MATERIALS: The datasets supporting the conclusions of this article are included within the article and its supplementary materials.

Efficacy and safety of moxibustion on cancer-related fatigue: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: The goal of this research was to review the literature from randomized controlled trials (RCTs) on the impacts of moxibustion on cancer-related fatigue (CRF) as well as provide credible evidence to guide clinical practice. METHODS: Three English electronic medical databases (PubMed, Embase, and the Cochrane Library) and two Chinese databases (China National Knowledge Infrastructure and Wanfang) were searched. Only randomized controlled trials on the effect of moxibustion on CRF were included in this systematic review. Study selection, data extraction, and validation were all carried out independently by two reviewers. The revised Cochrane Risk of Bias tool was used to assess the quality of the RCTs (RoB 2.0). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was applied to assess effect sizes in individual RCTs and pooled effect sizes in meta-analyses. Data were meta-analyzed using Stata (version 14.0). RESULTS: In a random-effects meta-analysis of 24 RCTs with 1894 participants, the aggregated standardized mean difference (SMD) revealed a statistically significant association between moxibustion and alleviation from cancer-related fatigue (SMD = - 1.66, 95% CI = - 2.05, - 1.28, p = 0.000). Pooled results, however, show significant heterogeneity (I2 = 92.5%), and the evidence is insufficient to determine whether this association varies systematically by measuring tools and moxibustion modalities. Furthermore, evidence ranging from very low to low showed that moxibustion had an immediate positive effect on patients with CRF. CONCLUSION: Moxibustion may have a therapeutic effect on cancer-related fatigue. However, further large-scale, multicenter, high-quality RCTs on moxibustion for fatigue relief and safety are still needed because of the handful of studies included and the low methodological quality.

Single-cell and spatial transcriptome analysis reveals the cellular heterogeneity of liver metastatic colorectal cancer.

In this study, we comprehensively charted the cellular landscape of colorectal cancer (CRC) and well-matched liver metastatic CRC using single-cell and spatial transcriptome RNA sequencing. We generated 41,892 CD45- nonimmune cells and 196,473 CD45+ immune cells from 27 samples of six CRC patients, and found that CD8_CXCL13 and CD4_CXCL13 subsets increased significantly in liver metastatic samples that exhibited high proliferation ability and tumor-activating characterization, contributing to better prognosis of patients. Distinct fibroblast profiles were observed in primary and liver metastatic tumors. F3+ fibroblasts enriched in primary tumors contributed to worse overall survival by expressing protumor factors. However, MCAM+ fibroblasts enriched in liver metastatic tumors might promote generation of CD8_CXCL13 cells through Notch signaling. In summary, we extensively analyzed the transcriptional differences of cell atlas between primary and liver metastatic tumors of CRC by single-cell and spatial transcriptome RNA sequencing, providing different dimensions of the development of liver metastasis in CRC.

The impact of hospital-family integrated continuation nursing based on information technology on patients unhealthy mood, family function and sexual function after cervical cancer surgery.

The objective of this study was to explore the impact on hospital-family integrated continuation care based on information technology on the negative emotions, family function, and sexual function of patients after cervical cancer surgery. The clinical case data onto 114 postoperative cervical cancer patients who were nursing in our hospital from July 2019 to July 2021 were selected and were divided into a control group and an observation group. The control group used routine nursing care, and on this basis, the observation group used information technology as the basis for hospital-family integrated continuation care, and we observed and compared the differences in the 2 groups of patients bad mood, family function, and sexual function. The score of anxiety (P = .017), depression (P = .009), fatigue rating (P = .012), and anger (P < .001) in the observation group after care were significantly lower than those in the control group. Problem solving, role, emotional response, emotional involvement, and family function total score in the observation group after care was significantly lower than those in the control group (P < .05). Sexual desire score, sexual arousal score, vaginal lubrication score, orgasm score, sexual satisfaction score, dyspareunia score, and Female Sexual Function Inventory total scores in the observation and control groups after care were significantly higher than those before care (P < .05). The sexual function scores in the observation group after care was significantly higher than those in the control group (P < .05). The hospital-family integrated continuation care based on information technology is more effective than conventional nursing care for patients after cervical cancer surgery.

Noval ceRNA axis-mediated high expression of TOP2A correlates with poor prognosis and tumor immune infiltration of hepatocellular carcinoma.

Background: Hepatocellular carcinoma (HCC) is a highly malignant tumor with limited treatment options, suboptimal efficacy, and poor prognosis, resulting in an economic burden to countries worldwide. TOP2A is a mammalian protein that plays a vital role in DNA replication. Previous studies have shown that upregulation of TOP2A expression is associated with tumorigenesis and progression in various cancers, but the exact mechanism of upregulation remains unclear. Methods: We first conducted a pan-cancer analysis using The Cancer Genome Atlas (TCGA) and Genotype-Tissue Expression (GTEx) databases to study the oncogenicity of TOP2A through the cBioPortal database. Next, using The Encyclopedia of RNA Interactomes (ENCORI) database, we identified microRNAs (miRNAs) that are associated with the downregulation of TOP2A and investigated potential long non-coding RNAs (lncRNAs) that may act as competing endogenous RNAs (ceRNAs) by binding to candidate miRNAs. We then analyzed immune cell infiltration and immune checkpoints using the TIMER database. Finally, we performed a multivariate regression analysis using lncRNAs and clinical pathological characteristics, constructed a nomogram to predict the prognosis of HCC based on the analysis results, and evaluated its diagnostic efficiency. Results: TOP2A was highly expressed in HCC and was associated with poor patient prognosis. TOP2A was subject to post-transcriptional regulation in HCC, with the ceRNA mechanism being a significant pathway. miR-139-5p was an important miRNA that suppressed the upregulation of TOP2A in HCC, and patients with low expression of miR-139-5p had worse overall survival (OS). After screening and analysis, three lncRNAs, AC078846.1, AC124798.1 and SNHG3, were found to inhibit the activity of miR-139-5p through the ceRNA mechanism, and patients with high expression of these three lncRNAs had worse prognosis. In addition, TOP2A was found to be closely related to tumor-infiltrating immune cells (TIICs) and immune checkpoints. A nomogram constructed using the three lncRNAs and selected clinicopathological features showed good predictive value for the prognosis of liver cancer. Conclusions: The TOP2A-miR-139-5p-AC078846.1/AC124798.1/SNHG3 axis plays a significant role in the progression of HCC and leads to poor patient outcomes. Additionally, TOP2A influences the development of HCC by affecting TIICs and immune checkpoints. A nomogram constructed using the three lncRNAs and clinicopathological features has good clinical utility.

Value Of Anteroposterior-To-Transverse Ratio in Ultrasonic Diagnosis of Thyroid Nodule in Different Locations.

PURPOSE: To investigate the value of anteroposterior-to-transverse ratio (ATR) and the effect on features of nodules in ultrasound (US) diagnosis of thyroid nodules in different locations.  Methods: The nodules were divided into three groups according to the different nodule location: isthmus group; upper and lower poles of bilobed thyroid group; and the middle of the bilobed thyroid group. The diameters of the nodules were recorded, and ATR of the nodule was calculated on the transverse and longitudinal sections. The transverse and the longitudinal sections of ATR of thyroid nodules in different groups were compared.  Result: The transverse section of ATR was significantly different among the three groups (p = 0.001). In addition, there are significant differences in many US features among three groups, including nodule composition, thyroid parenchyma, morphology, echogenicity, shape, calcifications, vascularity, nodule ACR TI-RADS and histopathologic (all p < 0.05). In the group of upper and lower poles of bilobed thyroid, significant difference was found between the transverse and the longitudinal section of ATR (p = 0.019). The cut-off values of transverse section and longitudinal section of ATR were 0.967 and 0.750, respectively.  Conclusion: The transverse section of ATR at different location of thyroid may be a predictor for malignancy with clinical diagnostic significance.

The effect of dermoscopy in assisting on defining surgical margins of basal cell carcinoma.

To investigate the diagnostic value of dermoscopy in defining the tumor margin of basal cell carcinoma (BCC) for the appropriate surgical margin. A total of 107 BCC patients were enrolled for this study. The tumor boundaries were observed by naked eye and dermoscope respectively, and 5 mm outward was used as surgical margin according to the dermoscopy-defined margin. Pathological examinations were performed at 2 mm intervals in the direction previously marked and the effect was assessed accordingly. There were still 16.8% of patients whose visual margin was insufficient to the dermoscopy-detected margin. With 2 mm excision margin from the dermoscopy-guided tumor margin, excision range in 12 patients (11.2%) proved to be inadequate, but only 18 surgical margins (4.2%) in the whole 428 excision margin specimens proved to be tumor-positive. While with 4 mm margin, residual lesion was observed in 2 (0.5%) of 107 BCC patients, and positive margin was found in 2 (0.3%) of 428 margin specimen. There has been no recurrence in our study so far. Dermoscopy is superior to visual inspection for defining BCC tumor margin. Under preoperative dermoscopy detection, a 4 mm excision margin of BCC can achieve a radical resection rate of 98.1%, and 92.3% for a 2 mm excision margin of pigmented BCC.

Surgical repair for deformities of the nail unit.

The nail apparatus is the largest and most complex skin appendage. Defects in this unit can result in significant functional insufficiency and cosmetic disfigurement. Common nail deformities include split nail, short nail, onycholysis, nail malalignment, hooked nail, and absent nail. Currently, surgical repair is the primary treatment for such deformities. Based on the etiological and anatomical classifications, one or more appropriate operations can be selected to repair nail unit deformities. These include autologous fat grafting, longitudinal cicatrectomy, Z-plasties, nail bed elongation, split-thickness sterile matrix grafting, volar V-Y advanced flap reconstruction, sterile matrix particle grafting, germinal matrix flaps, and germinal matrix grafting. This review discusses the fundamental classification of nail unit deformities, common reconstructive surgical techniques, and their features.

The feasibility and efficacy of perioperative auricular acupuncture technique via intradermal needle buried for postoperative movement-evoked pain after open radical gastrectomy: A randomized controlled pilot trial.

INTRODUCTION: Auricular acupuncture is widely used in the treatment of pain. Recently, the most commonly used method of auricular acupuncture is to embed an intradermal needle into the skin to enhance analgesia through continuous stimulation. We aimed to explore the efficacy and feasibility of this form of auricular acupuncture in the treatment of postoperative movement-evoked pain. METHODS: This single-blind randomized controlled pilot trial was conducted between 23/8/2019 and 10/1/2020. Forty patients were recruited and randomised to either the control group (n = 20) or the experimental group (n = 20). Patients in the control group received sham auricular acupuncture, while patients in the experimental group received auricular acupuncture. A standard routine analgesia was performed in both groups. The patients with NRS score≥4 were given rescue analgesia. Postoperative pain, use of opioids and other analgesics, postoperative recovery and patient's satisfaction were recorded. RESULTS: The credibility and feasibility of auricular acupuncture for postoperative pain were high in both groups. After auricular acupuncture, the scores of the postoperative movement-evoked pain had a tendency to decrease, but no significant difference was observed between two groups at any time point (P = 0.234∼0.888). The data on postoperative pain at rest confirmed that no significant difference was observed between two groups within 48 h of surgery (P = 0.134∼0.520), and the postoperative pain at rest scores decreased over time; however, from the third day, the pain at rest scores of the experimental group were decreased, and significant differences were observed between the two groups (P = 0.039∼0.047). As for use of rescue analgesic, total opioid consumption and the incidence of postoperative nausea and vomiting, there were no significant differences between the two groups (P = 0.311, P = 0.101, P = 0.661) . In terms of patients' satisfaction, the score of the experimental group was higher than that of the control group, and a significant difference was observed between the two groups (P = 0.000). As for adverse events, two participants reported pain and one patient reported discomfort at the insertion sites during the process of auricular acupuncture intervention, but they both were minor and tolerable. CONCLUSION: Auricular acupuncture may have a relief effect on mild postoperative pain at rest with pain score below 3, suggesting that it may be a feasible adjuvant method to relieve mild pain at rest. However, more multi-centre and large-sample studies are needed to verify this result.

[Sexual experience of male bladder cancer patients after transurethral resection of bladder tumor: A qualitative study].

OBJECTIVE: To investigate the efficiency and complications of modified urethral reconstruction with lingual mucosa in the treatment of complicated anterior urethral stricture (CAUS). OBJECTIVE: To investigate the sexual experience and feelings of male patients with bladder cancer after transurethral resection of bladder tumor (TURBT), and provide some evidence for doctors and nurses in giving advice about the sexual problems of the patients. METHODS: This study included 32 male patients with bladder cancer after treated by TURBT from March 2020 to March 2021. The patients were aged 33－63 (51.91 ± 6.75) years, with a disease course of 13－38 (20.56 ± 7.49) month, and the interviews lasting 31－63 (39.06 ± 8.04) minutes. Among them, 10 (31.25%) lived in the rural area, 22 (68.75%) lived in the urban area, 12 (37.5%) had college education or above, 7 (21.88%) had senior high school education, 10 (31.25%) had junior high school education, and 3 (9.37%) had primary school education. Using the semi-structured method, we conducted interviews with the patients about their sexual experience and needs for sexual function rehabilitation and subjected the results of interviews to Colaizzi analysis. RESULTS: The interviews with the patients covered five topics, which showed intentional refraining from sexual life in 6 (18.75%) of the cases, worrying about hurting the partner by sexual contact in 8 (25%), neglecting sexual troubles in 8 (25%), negative emotions in 5 (15.63%), and expecting medical support in 17 (53.13%). CONCLUSIONS: Male patients with bladder cancer have poor sexual experience after TURBT. Doctors and nurses should inform the patients of potential sexual troubles during the treatment and follow-up, and provide relevant active intervention.

Prognostic value of different lymph node staging methods for node-positive cardia gastric cancer: a register-based retrospective cohort study.

OBJECTIVE: To investigate the prognostic efficacy of lymph node ratio (LNR) and log odds of positive lymph nodes (LODDS) in node-positive cardia gastric adenocarcinoma (CGA). DESIGN: A registry-based retrospective cohort study. SETTING: Patients diagnosed with node-positive CGA in the Surveillance, Epidemiology, and End Results database from 2010 to 2015. PARTICIPANTS: A total of 1038 patients were enrolled and randomly assigned (7:3) to the training set (n=723) or validating set (n=315). PRIMARY OUTCOME MEASURE: Cancer-specific survival (CSS). RESULTS: The baseline characteristics of the training and validation sets were similar. Based on the optimal cut-off values, LNR was classified into low (<0.09), medium (0.09~0.33) and high (>0.33) groups; LODDS was also classified into low (<-2.09), medium (-2.09~-0.65) and high (>-0.65) groups. CSS was significantly different across LNR and LODDS subgroups. The Harrell concordance index of the N stage was lower than that of the LNR or LODDS. The Akaike information criterion of the N stage was higher than that of the LNR or LODDS. Independent predictors included race, T stage, M stage and LNR (or LODDS), and they were incorporated into nomograms for 1-year, 2-year and 5-year CSS prediction. Calibration plots showed satisfactory results for internal and external validity of the nomogram. CONCLUSIONS: LNR and LODDS staging methods have better prognostic efficacy than the traditional N staging method in CGA with node metastasis. Moreover, the two values are promising substitutes for N staging in nomogram development when other independent prognostic factors are incorporated.

Qigong Exercise for Patients with Gastrointestinal Cancer Undergoing Chemotherapy and at High Risk for Depression: A Randomized Clinical Trial.

Aims and objectives: This study evaluated the effects of a Chinese traditional qigong exercise-monkey frolic in Wuqinxi on depression and quality of life in patients with gastrointestinal cancer undergoing chemotherapy and at high risk for depression. Methods: In this prospective, randomized-controlled clinical trial, 80 patients with gastrointestinal cancer undergoing chemotherapy and at high risk for depression were randomized to an intervention group or a control group. Participants in the intervention group participated in qigong exercise five sessions each week and also received conventional treatment for 4 weeks; whereas participants in the control group received conventional treatment only. The primary outcome was the change in depressive symptoms as obtained through the Self-Rating Depression Scale. Automatic negative thoughts and quality of life were measured by the Automatic Thoughts Questionnaire and the European Organization for Research and Treatment of Cancer Core Quality of Life Questionnaire-core30, respectively. Analyses were based on analysis of covariance (ANCOVA) with the "intention-to-treat" population, defined as all randomized patients by imputing mean of the column in place of missing data. Results: Seventy-nine participants (98.8%) completed the study, 40 in the intervention group and 39 in the control group. Results of ANCOVA revealed that, compared with the control group, the intervention group reported significantly lower depression scores, fewer negative thoughts, and showed significant improvement in global health status and physical, role, emotional, cognitive, and social functions (p < 0.05) following the intervention. Post-treatment scores for all symptoms in the intervention group were significantly lower than those in the control group (p < 0.05), except for financial difficulties. No significant differences between the two groups were present in the adverse events (all p > 0.05). Conclusions: Qigong exercise may be useful for relieving depression, reducing negative thoughts, and improving the quality of life in patients with gastrointestinal cancer undergoing chemotherapy. Clinical Trial Registry (#ChiCTR2100043417).

PSMA conjugated combinatorial liposomal formulation encapsulating genistein and plumbagin to induce apoptosis in prostate cancer cells.

Although the biomedical sciences have achieved tremendous success in developing novel approaches to managing prostate cancer, this disease remains one of the major health concerns among men worldwide. Liposomal formulations of single drugs have shown promising results in cancer treatment; however, the use of multi drugs has shown a better therapeutic index than individual drugs. The identification of cancer-specific receptors has added value to design targeted drug delivering nanocarriers. We have developed genistein and plumbagin co-encapsulating liposomes (∼120 nm) with PSMA specific antibodies to target prostate cancer cells selectively in this work. These liposomes showed >90 % decrease in PSMA expressing prostate cancer cell proliferation without any appreciable toxicity to healthy cells and human red blood cells. Release of plumbagin and genistein was found to decrease the expression of PI3/AKT3 signaling proteins and Glut-1 receptors (inhibited glucose uptake and metabolism), respectively. The decrease in migration potential of cells and induced apoptosis established the observed anti-proliferative effect in prostate cancer cell lines. The discussed strategy of developing novel, non-toxic, and PSMA specific antibody conjugated liposomes carrying genistein and plumbagin drugs may also be used for encapsulating other drugs and inhibit the growth of different types of cancers.

Gut-Brain Axis: Possible Role of Gut Microbiota in Perioperative Neurocognitive Disorders.

Aging is becoming a severe social phenomenon globally, and the improvements in health care and increased health awareness among the elderly have led to a dramatic increase in the number of surgical procedures. Because of the degenerative changes in the brain structure and function in the elderly, the incidence of perioperative neurocognitive disorders (PND) is much higher in elderly patients than in young people following anesthesia/surgery. PND is attracting more and more attention, though the exact mechanisms remain unknown. A growing body of evidence has shown that the gut microbiota is likely involved. Recent studies have indicated that the gut microbiota may affect postoperative cognitive function via the gut-brain axis. Nonetheless, understanding of the mechanistic associations between the gut microbiota and the brain during PND progression remains very limited. In this review, we begin by providing an overview of the latest progress concerning the gut-brain axis and PND, and then we summarize the influence of perioperative factors on the gut microbiota. Next, we review the literature on the relationship between gut microbiota and PND and discuss how gut microbiota affects cognitive function during the perioperative period. Finally, we explore effective early interventions for PND to provide new ideas for related clinical research.

Flavonoids from Stem and Leaf of Scutellaria Baicalensis Georgi Inhibit the Phosphorylation on Multi-sites of Tau Protein Induced by Okadaic Acid and the Regulative Mechanism of Protein Kinases in Rats.

AIM: The present study aims to investigate the effect of flavonoids from stem and leaf of Scutellaria Baicalensis Georgi (SSF) on multi-sites phosphorylation of tau protein in the cerebral cortex and hippocampus of rats induced by okadaic acid (OA) and the regulative mechanism of the protein kinases. METHODS: The model of AD-like memory impairment and neuronal injuries was established in male SD rats who were microinjected with OA (200 ng/kg) to establish a memory impairment model and screened for successful model rats by Morris water maze on day 21 after surgery. The successful model rats were continuously administered with intragastric infusion (ig) SSF 25, 50 and 100 mg/kg or Ginkgo biloba leaves flavonoids (GLF) 200 mg/kg for 36 d. The relative protein expressed levels of phosphorylated tau protein at sites of Ser199, Ser202, Ser214, Ser404 and Thr231, protein kinases (CDK5, PKA, pTyr216-GSK3ß and pSer9-GSK3ß) were detected by Western blotting. RESULTS: The relative protein expressed levels of p-tau(Ser199), p-tau(Ser202), p-tau(Ser214), p-- tau(Ser404), p-tau(Thr231) and pTyr216-GSK3ß were significantly increased in both cerebral cortex and hippocampus regions of the model rats subjected to intracerebroventricular injection of OA (P<0.01), while the protein expressed levels of CDK5, PKA and pSer9-GSK3ß (P<0.01) were reduced. SSF can dramatically reverse these increments in phosphorylated tau protein levels (P<0.01) and differently regulate the protein expressed levels of CDK5, PKA and GSK3ß (P<0.01) in rats' cerebral cortex and hippocampus induced by OA. GLF also exhibit a similar effect to SSF. CONCLUSION: The results demonstrated that SSF could inhibit the hyperphosphorylation of tau in rats' cerebral cortex and hippocampus induced by microinjection of OA, which may be related to the activities of protein kinase CDK5, PKA and GSK3ß.

Carnosic acid alleviates depression-like behaviors on chronic mild stressed mice via PPAR-γ-dependent regulation of ADPN/FGF9 pathway.

RATIONALE: The pathway of adiponectin (ADPN)/fibroblast growth factor 9 (FGF9) was recently thought as a key role in the development of depression. ADPN is crucially regulated by peroxisome proliferator-activated receptor-gamma (PPAR-γ). Natural material carnosic acid (CA) has been applied for therapeutics of mental disorders. OBJECTIVES: To evaluate the antidepressive effect of CA in stress-treated mice and define whether its effects is involved in the regulation of ADPN/FGF9 pathway. METHODS: In vivo study, the levels of ADPN and FGF9 in both serum and hippocampus tissues, the expressions of ADPN receptor 2 (AdipoR2) in hippocampus and PPAR-γ in abdominal adipose, as well as the pathological changes of hippocampus were determined in 28-day period of chronic unpredictable mild stress (CUMS)-induced depression model of male ICR (Institute of Cancer Research) mice or adipo-/- mice. In vitro study, the level of ADPN and the mRNA expressions of both ADPN and PPAR-γ were determined in mouse 3T3-L1 preadipocytes. RESULTS: In vivo study, treatment with CA (50 or 100 mg/kg per day) for 21 days markedly suppressed depressive-like behaviors, the elevating levels of FGF9 and decreasing levels of ADPN in both serum and hippocampus tissues, the downregulating protein and mRNA expressions of AdipoR2 in hippocampus and PPAR-γ in abdominal adipose, as well as the pathological injury of hippocampus induced by CUMS in male ICR mice. The antidepressive effects of CA were markedly attenuated in male CUMS-treated adipo-/- mice. In vitro study, incubation with CA (3-30 µmol/L) for 24 h could concentration-dependently upregulate the mRNA expressions of both PPAR-γ and ADPN as well as increase the level of ADPN. The experiments using PPAR-γ-specific inhibitor GW9662 and transient transfection with mutated PPAR-γ-binding site promotor constructs showed that the activation of PPAR-γ mediated CA-induced ADPN expression in adipocytes. CONCLUSIONS: CA could significantly improve stress-induced depressive disorder, which may be related to regulating the dysfunction of ADPN-FGF9 pathway via activating PPAR-γ in adipocytes.