Human microbiota from drug-naive patients with obsessive-compulsive disorder drives behavioral symptoms and neuroinflammation via succinic acid in mice.

Emerging evidence suggests that the gut microbiota is closely related to psychiatric disorders. However, little is known about the role of the gut microbiota in the development of obsessive-compulsive disorder (OCD). Here, to investigate the contribution of gut microbiota to the pathogenesis of OCD, we transplanted fecal microbiota from first-episode, drug-naive OCD patients or demographically matched healthy individuals into antibiotic-treated specific pathogen-free (SPF) mice and showed that colonization with OCD microbiota is sufficient to induce core behavioral deficits, including abnormal anxiety-like and compulsive-like behaviors. The fecal microbiota was analyzed using 16 S rRNA full-length sequencing, and the results demonstrated a clear separation of the fecal microbiota of mice colonized with OCD and control microbiota. Notably, microbiota from OCD-colonized mice resulted in injured neuronal morphology and function in the mPFC, with inflammation in the mPFC and colon. Unbiased metabolomic analyses of the serum and mPFC region revealed the accumulation of succinic acid (SA) in OCD-colonized mice. SA impeded neuronal activity and induced an inflammatory response in both the colon and mPFC, impacting intestinal permeability and brain function, which act as vital signal mediators in gut microbiota-brain-immune crosstalk. Manipulations of dimethyl malonate (DM) have been reported to exert neuroprotective effects by suppressing the oxidation of accumulated succinic acid, attenuating the downstream inflammatory response and neuronal damage, and can help to partly improve abnormal behavior and reduce neuroinflammation and intestinal inflammation in OCD-colonized mice. We propose that the gut microbiota likely regulates brain function and behaviors in mice via succinic acid signaling, which contributes to the pathophysiology of OCD through gut-brain crosstalk and may provide new insights into the treatment of this disorder.

The gap between statistical and clinical significance: time to pay attention to clinical relevance in patient-reported outcome measures of insomnia.

BACKGROUND: Appropriately defining and using the minimal important change (MIC) and the minimal clinically important difference (MCID) are crucial for determining whether the results are clinically significant. The aim of this study is to survey the status of randomized controlled trials (RCTs) for insomnia interventions to assess the inclusion and interpretation of MIC/MCID values. METHODS: We conducted a cross-sectional study to survey the status of RCTs for insomnia interventions to assess the inclusion and appropriate interpretation of MIC/MCID values. A literature search was conducted by searching the main sleep medicine journals indexed in PubMed, the Excerpta Medica Database (EMBASE), and the Cochrane Central Register of Controlled Trials (CENTRAL) to identify a broad range of search terms. We included RCTs with no restriction on the intervention. The included studies used the Insomnia Severity Index (ISI) or the Pittsburgh Sleep Quality Index (PSQI) questionnaire as the outcome measures. RESULTS: 81 eligible studies were identified, and more than one-third of the included studies used MIC/MCID (n = 31, 38.3%). Among them, 21 studies with ISI as the outcome used MIC defined as a relative decrease ranging from 3 to 8 points. The most frequently used MIC value was a 6-point decrease (n = 7), followed by 8-point (n = 6) and 7-point decrease (n = 4), a 4 to 5-points decrease (n = 3), and a 30% reduction from baseline; 6 studies used MCID values, ranging from 2.8 to 4 points. The most frequently used MCID value was a 4-point decrease in the ISI (n = 4). 4 studies with PSQI as the outcome used a 3-point change as the MIC (n = 2) and a 2.5 to 2.7-point difference as MCID (n = 2). 4 non-inferiority design studies considered interval estimation when drawing clinically significant conclusions in their MCID usage. CONCLUSIONS: The lack of consistent MIC/MCID interpretation and usage in outcome measures for insomnia highlights the urgent need for further efforts to address this issue and improve reporting practices.

Improved Shi-Tomasi sub-pixel corner detection based on super-wide field of view infrared images.

In this work, we propose a new, to the best of our knowledge, corner point detection method for a super-wide field of view infrared imaging system. First, the edge of the checkerboard calibration board is detected at the pixel level by morphological operation. Second, the interpolation technique is used to refine the edge so that the edge has sub-pixel accuracy. We obtain the four checkerboard unit corners near the real corner point and average the coordinates of the four corners to indirectly obtain the coordinates of the real corner point. Meanwhile, we take pictures of the same calibration board at different angles for repeatability verification. It is proved that the improvement of our algorithm for the detection of corners of super-wide field of view infrared images is more feasible compared to the traditional algorithms.

Factors predicting depressive symptoms in parents of children with autism spectrum disorder in eastern China.

BACKGROUND: Parents of children with autism spectrum disorder (ASD) are at a higher risk of depression than parents of typically developing children and those of children with other developmental disorders. Depression affects the well-being and quality of life of parents of children with ASD and has serious consequences for the long-term health outcomes of children with ASD. Therefore, this study explored the current status of depressive symptoms in parents of children with ASD in eastern China and further analyzed multiple aspects of the predictors of depressive symptoms. METHODS: A multicenter cross-sectional survey was conducted among parents of children with ASD in the rehabilitation department of a large specialized hospital and 10 rehabilitation centers for children with special needs in Lianyungang, Jiangsu Province, Eastern China. A structured questionnaire that focused on child-related factors, parent-related factors, depressive symptoms, courtesy stigma, and social support was used to obtain data. Binary logistic regression was used to identify the independent predictors of depressive symptoms in parents of children with ASD. RESULTS: A total of 409 parents of children with ASD were recruited, of whom 18.8% had depressive symptoms. Parents of children with ASD who raised a child who spoke few to no words (odds ratio [OR]: 2.747, 95% confidence interval [CI]: 1.026-7.357), claimed a high economic burden (OR: 3.215, 95% CI: 1.234-8.379), reported no change or increased severity of ASD in their children (OR: 2.518, 95% CI: 1.108-5.720), and those with a higher courtesy stigma score (OR: 1.189, 95% CI: 1.093-1.294) were more likely to have depressive symptoms. Conversely, parents of children with ASD who were employed (OR: 0.427, 95% CI: 0.201-0.907), satisfied with their current marital status (OR: 0.429, 95% CI: 0.221-0.834), and those with a higher social support score (OR: 0.973, 95% CI: 0.950-0.996) were less likely to have depressive symptoms. CONCLUSIONS: Depressive symptoms are common in parents of children with ASD in eastern China. Therefore, screening and intervention for depressive symptoms in parents of children with ASD is necessary, especially for those with high-risk factors.

Exosome-transmitted miR-29a induces colorectal cancer metastasis by destroying the vascular endothelial barrier.

Metastasis is the leading cause of colorectal cancer treatment failure and mortality. Communication between endothelium and tumor cells in the tumor microenvironment is required for cancer metastasis. Tumor-derived exosomes have been shown to increase vascular permeability by delivering microRNA (miRNA) to vascular endothelial cells, facilitating cancer metastasis. The mechanism by which Epithelial-mesenchymal transition (EMT) tumor cell-derived exosomes influence vascular permeability remains unknown. MicroRNA-29a (miR-29a) expression is up-regulated in colorectal cancer (CRC) tissues, which is clinically significant in metastasis. Exosomal miR-29a secreted by EMT-CRC cells has been found to decrease the expression of Zonula occlusion 1 (ZO-1), Claudin-5, and Occludin via targeting Kruppel-like factor 4 (KLF4). In vitro co-culture investigations further revealed that EMT-cancer cells release exosomal miR-29a, which alters vascular endothelial permeability. Furthermore, exosomal miR-29a promoted liver metastases in CRC mice. Our findings demonstrate that EMT-CRC cells may transport exosomal miR-29a to endothelial cells in the tumor microenvironment (TME). As a result, increased vascular permeability promotes the development and metastasis of CRC. Exosomal miR-29a has the potential to be a predictive marker for tumor metastasis as well as a viable therapeutic target for CRC.

Berberine ameliorates depression-like behaviors in mice via inhibiting NLRP3 inflammasome-mediated neuroinflammation and preventing neuroplasticity disruption.

OBJECTIVES: Neuroinflammation has been suggested that affects the processing of depression. There is renewed interest in berberine owing to its anti-inflammatory effects. Herein, we investigated whether berberine attenuate depressive-like behaviors via inhibiting NLRP3 inflammasome activation in mice model of depression. METHODS: Adult male C57BL/6N mice were administrated corticosterone (CORT, 20 mg/kg/day) for 35 days. Two doses (100 mg/kg/day and 200 mg/kg/day) of berberine were orally administrated from day 7 until day 35. Behavioral tests were performed to measure the depression-like behaviors alterations. Differentially expressed gene analysis was performed for RNA-sequencing data in the prefrontal cortex. NLRP3 inflammasome was measured by quantitative reverse transcription polymerase chain reaction, western blotting, and immunofluorescence labeling. The neuroplasticity and synaptic function were measured by immunofluorescence labeling, Golgi-Cox staining, transmission electron microscope, and whole-cell patch-clamp recordings. RESULTS: The results of behavioral tests demonstrated that berberine attenuated the depression-like behaviors induced by CORT. RNA-sequencing identified that NLRP3 was markedly upregulated after long-term CORT exposure. Berberine reversed the concentrations of peripheral and brain cytokines, NLRP3 inflammasome elicited by CORT in the prefrontal cortex and hippocampus were decreased by berberine. In addition, the lower frequency of neuronal excitation as well as the dendritic spine reduction were reversed by berberine treatment. Together, berberine increases hippocampal adult neurogenesis and synaptic plasticity induced by CORT. CONCLUSION: The anti-depressants effects of berberine were accompanied by reduced the neuroinflammatory response via inhibiting the activation of NLRP3 inflammasome and rescued the neuronal deterioration via suppression of impairments in synaptic plasticity and neurogenesis.

Sex-specific transcriptional signatures in the medial prefrontal cortex underlying sexually dimorphic behavioural responses to stress in rats.

BACKGROUND: Converging evidence suggests that stress alters behavioural responses in a sex-specific manner; however, the underlying molecular mechanisms of stress remain largely unknown. METHODS: We adapted unpredictable maternal separation (UMS) and adult restraint stress (RS) paradigms to mimic stress in rats in early life or adulthood, respectively. The sexual dimorphism of the prefrontal cortex was noted, and we performed RNA sequencing (RNA-Seq) to identify specific genes or pathways responsible for sexually dimorphic responses to stress. We then performed quantitative reverse transcription polymerase chain reaction (qRT-PCR) to verify the results of RNA-Seq. RESULTS: Female rats exposed to either UMS or RS showed no negative effects on anxiety-like behaviours, whereas the emotional functions of the PFC were impaired markedly in stressed male rats. Leveraging differentially expressed genes (DEG) analyses, we identified sex-specific transcriptional profiles associated with stress. There were many overlapping DEGs between UMS and RS transcriptional data sets, where 1406 DEGs were associated with both biological sex and stress, while only 117 DEGs were related to stress. Notably, Uba52 and Rpl34-ps1 were the first-ranked hub gene in 1406 and 117 DEGs respectively, and Uba52 was higher than Rp134-ps1, suggesting that stress may have led to a more pronounced effect on the set of 1406 DEGs. Pathway analysis revealed that 1406 DEGs were primarily enriched in ribosomal pathway. These results were confirmed by qRT-PCR. LIMITATIONS: Sex-specific transcriptional profiles associated with stress were identified in this study, but more in-depth experiments, such as single-cell sequencing and manipulation of male and female gene networks in vivo, are needed to verify our findings. CONCLUSION: Our findings show sex-specific behavioural responses to stress and highlight sexual dimorphism at the transcriptional level, shedding light on developing sex-specific therapeutic strategies for stress-related psychiatric disorders.

Association between Triglycerides to High-Density Lipoprotein Cholesterol Ratio and Death Risk in Diabetic Patients with New-Onset Acute Coronary Syndrome: A Retrospective Cohort Study in the Han Chinese Population.

Background and Aims: The incidence of diabetes mellitus has reached an alarming level. Cardiovascular disease (CVD) is the leading cause of mortality in diabetic patients. However, the association between ratio and survival outcomes in patients with diabetes mellitus (DM) and new-onset acute coronary syndrome (ACS) remains unknown. This study aimed to assess the association between the TG/HDLC ratio and the risk of death in diabetic patients with new-onset acute coronary syndrome in the Han Chinese population. Methods: Data in this study were retrospectively collected from January 2016 to December 2016 from patients with type 2 diabetes mellitus (T2DM) and new-onset ACS in Tianjin Chest Hospital. Patients were classified according to the baseline TG/HDLC ratio. Kaplan-Meier survival curves were used to demonstrate survival outcomes. Univariate and multivariate Cox proportional risk regression analyses were used to evaluate the hazard ratios and 95% confidence intervals (CIs) for the risk of death. Subgroup analysis was used to determine the presence of any interaction. Results: In total, 152 patients died, 98 of them from heart disease. The Kaplan-Meier survival curve showed that there were no significant differences for both all-cause and cardiac mortality between Median 1 and Median 2 in log-rank test. Multivariate Cox regression analyses revealed that the adjusted hazard ratio increased significantly (p < 0.05) with increasing median TG/HDLC for not only all-cause mortality and cardiac death, but also nonfatal stroke, fatal stroke and fatal MI. The association between the TG/HDLC ratio and the risks of all-cause mortality and cardiac death in diabetic patients with new-onset ACS was similar among subgroups (p > 0.05). Conclusions: An elevated TG/HDLC ratio (TG/HDLC > 1.522) is associated with an increased risk of all-cause and cardiac death risks in diabetic patients with new-onset ACS. Therefore, TG/HDLC ratio may be a beneficial parameter to evaluate the prognosis of this high-risk population.

Predictable maternal separation confers adult stress resilience via the medial prefrontal cortex oxytocin signaling pathway in rats.

Early-life stress is normally thought of as a major risk for psychiatric disorders, but many researchers have revealed that adversity early in life may enhance stress resilience later in life. Few studies have been performed in rodents to address the possibility that exposure to early-life stress may enhance stress resilience, and the underlying neural mechanisms are far from being understood. Here, we established a "two-hit" stress model in rats by applying two different early-life stress paradigms: predictable and unpredictable maternal separation (MS). Predictable MS during the postnatal period promotes resilience to adult restraint stress, while unpredictable MS increases stress susceptibility. We demonstrate that structural and functional impairments occur in glutamatergic synapses in pyramidal neurons of the medial prefrontal cortex (mPFC) in rats with unpredictable MS but not in rats with predictable MS. Then, we used differentially expressed gene (DEG) analysis of RNA sequencing data from the adult male PFC to identify a hub gene that is responsible for stress resilience. Oxytocin, a peptide hormone, was the highest ranked differentially expressed gene of these altered genes. Predictable MS increases the expression of oxytocin in the mPFC compared to normal raised and unpredictable MS rats. Conditional knockout of the oxytocin receptor in the mPFC was sufficient to generate excitatory synaptic dysfunction and anxiety behavior in rats with predictable MS, whereas restoration of oxytocin receptor expression in the mPFC modified excitatory synaptic function and anxiety behavior in rats subjected to unpredictable MS. These findings were further supported by the demonstration that blocking oxytocinergic projections from the paraventricular nucleus of the hypothalamus (PVN) to the mPFC was sufficient to exacerbate anxiety behavior in rats exposed to predictable MS. Our findings provide direct evidence for the notion that predictable MS promotes stress resilience, while unpredictable MS increases stress susceptibility via mPFC oxytocin signaling in rats.

Tumor-derived exosomal microRNA-106b-5p activates EMT-cancer cell and M2-subtype TAM interaction to facilitate CRC metastasis.

Epithelial-mesenchymal transition (EMT) is reported to involve in the crosstalk between tumor cells and tumor-associated macrophages (TAMs). Exosomes are considered as important mediators of orchestrating intercellular communication. However, the underlying mechanisms by which EMT-colorectal cancer (CRC) cells promote the M2 polarization of TAMs remain less understood. In this study, we found that EMT-CRC cells promoted the M2-like polarization of macrophages by directly transferring exosomes to macrophages, leading to a significant increase of the microRNA-106b-5p (miR-106b) level in macrophages. Mechanically, an increased level of miR-106b activated the phosphatidylinositol 3-kinase (PI3K)γ/AKT/mammalian target of rapamycin (mTOR) signaling cascade by directly suppressing programmed cell death 4 (PDCD4) in a post-transcription level, contributing to the M2 polarization of macrophages. Activated M2 macrophages, in a positive-feedback manner, promote EMT-mediated migration, invasion, and metastasis of CRC cells. Clinically, miR-106b was significantly elevated in CRC tissues and negatively correlated with the levels of PDCD4 in CRC specimens, and high expression of exosomal miR-106b in plasma was significantly associated with the malignant progression of CRC. Taken together, our results indicate that exosomal miR-106b derived from EMT-CRC cells has an important role in intercellular communication for inducing M2 macrophage polarization, illuminating a novel mechanism underlying CRC progression and offering potential targets for prevention of CRC metastasis.

Wnt5a-induced M2 polarization of tumor-associated macrophages via IL-10 promotes colorectal cancer progression.

BACKGROUND: Tumor-associated macrophages (TAMs) in the tumor microenvironment influence tumor initiation, invasion and metastasis. Several studies have shown that Wnt5a is mainly expressed in the tumor stroma, especially in TAMs. However, whether Wnt5a regulates the polarization and biological function of TAMs in colorectal cancer (CRC) is incompletely understood. METHODS: Immunofluorescence staining was performed to detect CD68 and Wnt5a expression in colorectal tissues from patients (63 CRC specimens VS 20 normal tissues). RT-qPCR, flow cytometry, ELISA and inhibitors were carried out to explore the role of Wnt5a in the polarization of TAMs. Clone formation and transwell assays were performed to determine the effects of Wnt5a-treated macrophages on tumor proliferation, migration and invasion in vitro. Finally, a xenograft model was applied to confirm the effects of Wnt5a+ TAMs on CRC tumorigenesis. RESULTS: We found that high Wnt5a+CD68+/CD68+ TAMs ratio was significantly associated with poor prognosis in CRC patients and Wnt5a+ TAM was an M2-like TAM subtype. Subsequently, we found that Wnt5a induced macrophages to secrete IL-10, which then acted as an autocrine cytokine to induce M2 polarization of these macrophages. IL-10 neutralizing antibody completely reversed the pro-M2 effect of Wnt5a. Mechanistically, the CaKMII-ERK1/2-STAT3 pathway was required for Wnt5a-mediated IL-10 expression in macrophages. Furthermore, Wnt5a-induced M2 macrophages promoted CRC cells proliferation, migration and invasion; knockdown of Wnt5a in TAMs significantly impaired the pro-tumor functions of TAMs. CONCLUSIONS: Our data indicate that Wnt5a could induce M2 polarization of TAMs by regulating CaKMII-ERK1/2-STAT3 pathway-mediated IL-10 secretion, ultimately promoting tumor growth and metastasis of CRC.

Crosstalk between cancer cells and tumor associated macrophages is required for mesenchymal circulating tumor cell-mediated colorectal cancer metastasis.

BACKGROUND: Tumor-associated macrophages (TAMs) are major components of tumor microenvironment that frequently associated with tumor metastasis in human cancers. Circulating tumor cell (CTC), originating from primary tumor sites, is considered to be the precursors of tumor metastasis. However, the regulatory mechanism of TAMs in CTC-mediated tumor metastasis still remains unclear. METHODS: Immunohistochemical staining was used to detect the macrophages infiltration (CD68 and CD163), epithelial-mesenchymal transition (EMT) markers (E-cadherin and Vimentin) expression in serial sections of human colorectal cancer (CRC) specimens. Then, the correlations between macrophages infiltration and clinicopathologic features, mesenchymal CTC ratio, and patients' prognosis were analyzed. A co-culture assay in vitro was used to evaluate the role of TAMs on CRC EMT, migration and invasion, and ELISA, luciferase reporter assay and CHIP were performed to uncover the underlying mechanism. Furthermore, an in vivo model was carried out to confirm the effect of TAMs on mesenchymal CTC-mediated metastasis. RESULTS: Clinically, CD163+ TAMs infiltrated in invasive front was associated with EMT, mesenchymal CTC ratio, and poor prognosis in patients with CRC. CRC-conditioned macrophages regulated EMT program to enhance CRC cells migration and invasion by secreting IL6. TAMs-derived IL6 activated the JAK2/STAT3 pathway, and activated STAT3 transcriptionally inhibited the tumor suppressor miR-506-3p in CRC cells. miR-506-3p, a key miRNA regulating FoxQ1, was downregulated in CRC cells, resulting in increased FoxQ1 expression, which in turn led to the production of CCL2 that promoted macrophage recruitment. Inhibition of CCL2 or IL6 broke this loop and reduced macrophage migration and mesenchymal CTC-mediated metastasis, respectively. CONCLUSIONS: Our data indicates that TAMs induce EMT program to enhance CRC migration, invasion, and CTC-mediated metastasis by regulating the JAK2/STAT3/miR-506-3p/FoxQ1 axis, which in turn leads to the production of CCL2 that promote macrophage recruitment, revealing a new cross-talk between immune cells and tumor cells in CRC microenvironment.

Effect of quality control on the proliferation of the extract from Taraxacum mongolicum Hand.-Mazz. in Lactobacillus plantarum.

In recent years, the fingerprint of high-performance liquid chromatography has been extensively applied in the identification and quality control of traditional Chinese medicine. It can be a potential protocol for assessing the authenticity, stability and consistency of traditional Chinese medicine and guaranteeing the expected biological activity. In this paper, a method using high-performance liquid chromatography to identify and control the quality of the extract of Taraxacum mongolicum Hand.-Mazz. (TME) was established. With this method, the correlation coefficients of the similarity of 10 batches were ≥0.994. The TME displayed a steady proliferative effect in Lactobacillus plantarum. In brief, this study successfully built a reliable, simple and efficient method to control and confirm the quality and the stability of biological activity of the TME.

Resveratrol, a natural polyphenol, prevents chemotherapy-induced cognitive impairment: Involvement of cytokine modulation and neuroprotection.

Chemotherapy-induced cognitive impairment, also known as "chemobrain," is a common side effect. The purpose of this study was to examine whether resveratrol, a natural polyphenol that has nootropic effects, could prevent chemobrain and its underlying mechanisms. Mice received three injections of docetaxel, adriamycin, and cyclophosphamide (DAC) in combination, a common chemotherapy regimen, at two-day intervals within one week. Resveratrol (50 and 100 mg/kg per day) was orally administered for three weeks, beginning one week before the DAC treatment. Water maze test and manganese-enhanced magnetic resonance imaging were used to evaluate animals' cognitive performance and brain neuronal activity, respectively. Blood and brain tissues were collected for measurement of cytokines, cytokine regulators, and biomarkers for neuroplasticity. DAC treatment produced a striking cognitive impairment. Cotreatment with 100 mg/kg resveratrol ameliorated DAC-induced cognitive impairment and decreases in prefrontal and hippocampal neuronal activity. Mice co-treated with both doses of resveratrol displayed significantly lower levels of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), but markedly higher levels of the anti-inflammatory cytokines IL-4 and IL-10 in several sera and brain tissues than those co-treated with vehicle. Resveratrol modulated the cytokine-regulating pathway peroxisome proliferator activated receptor (PPAR)-γ/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and protected against DAC-induced decreases in the expression of the neuroplasticity biomarkers, brain-derived neurotrophic factor (BDNF), tropomyosin receptor kinase B (TrkB), amino acid neurotransmitter receptors, and calmodulin-dependent protein kinase II (CaMKII). These results demonstrate the efficacy of resveratrol in preventing chemobrain and its association with cytokine modulation and neuroprotection.

Wedge-shaped microfluidic chip for circulating tumor cells isolation and its clinical significance in gastric cancer.

BACKGROUND: Circulating tumor cells (CTCs) have great potential in both basic research and clinical application for the managements of cancer. However, the complicated fabrication processes and expensive materials of the existing CTCs isolation devices, to a large extent, limit their clinical translation and CTCs' clinical value. Therefore, it remains to be urgently needed to develop a new platform for achieving CTCs detection with low-cost, mass-producible but high performance. METHODS: In the present study, we introduced a novel wedge-shaped microfluidic chip (named CTC-ΔChip) fabricated by two pieces of glass through wet etching and thermal bonding technique for CTCs isolation, which achieved CTCs enrichment by different size without cell surface expression markers and CTCs identification with three-color immunocytochemistry method (CK+/CD45-/Nucleus+). We validated the feasibility of CTC-ΔChip for detecting CTCs from different types of solid tumor. Furthermore, we applied the newly-developed platform to investigate the clinical significance of CTCs in gastric cancer (GC). RESULTS: Based on "label-free" characteristic, the capture efficiency of CTC-ΔChip can be as high as 93.7 ± 3.2% in DMEM and 91.0 ± 3.0% in whole blood sample under optimized conditions. Clinically, CTC-ΔChip exhibited the feasibility of detecting CTCs from different types of solid tumor, and it identified 7.30 ± 7.29 CTCs from 2 mL peripheral blood with a positive rate of 75% (30/40) in GC patients. Interestingly, we found that GC CTCs count was significantly correlated with multiple systemic inflammation indexes, including the lymphocyte count, platelet count, the level of neutrophil to lymphocyte ratio and platelet to lymphocyte ratio. In addition, we also found that both the positivity rate and CTCs count were significantly associated with multiple clinicopathology parameters. CONCLUSIONS: Our novel CTC-ΔChip shows high performance for detecting CTCs from less volume of blood samples of cancer patients and important clinical significance in GC. Owing to the advantages of low-cost and mass-producible, CTC-ΔChip holds great potential of clinical application for cancer therapeutic guidance and prognostic monitoring in the future.

Neurobiology of Obsessive-Compulsive Disorder from Genes to Circuits: Insights from Animal Models.

Obsessive-compulsive disorder (OCD) is a chronic, severe psychiatric disorder that has been ranked by the World Health Organization as one of the leading causes of illness-related disability, and first-line interventions are limited in efficacy and have side-effect issues. However, the exact pathophysiology underlying this complex, heterogeneous disorder remains unknown. This scenario is now rapidly changing due to the advancement of powerful technologies that can be used to verify the function of the specific gene and dissect the neural circuits underlying the neurobiology of OCD in rodents. Genetic and circuit-specific manipulation in rodents has provided important insights into the neurobiology of OCD by identifying the molecular, cellular, and circuit events that induce OCD-like behaviors. This review will highlight recent progress specifically toward classic genetic animal models and advanced neural circuit findings, which provide theoretical evidence for targeted intervention on specific molecular, cellular, and neural circuit events.

Unilateral percutaneous vertebroplasty in osteoporotic vertebral compression fractures: A clinical efficacy evaluation.

Osteoporotic vertebral compression fractures, often resulting from low-energy trauma, markedly impair the quality of life of elderly individuals. The present retrospective study focused on the clinical efficacy of unilateral percutaneous vertebroplasty (PVP) in the treatment of osteoporotic compression fractures. A total of 68 patients, representing 92 vertebral bodies, who underwent the unilateral PVP technique from March 2020 to January 2023 were evaluated. Key parameters such as visual analogue scale (VAS) values, Oswestry disability index (ODI) scores, Cobb angle measurements, and anterior vertebral height (AVH) were documented pre- and post-surgery. The mean follow-up period was 15.41±3.74 months. The mean pre-operative VAS score was 8.08±0.79, which was significantly reduced to 2.25±0.71 by 24 h post-surgery and stabilized at 1.58±0.51 by the final follow-up. The ODI showed a significant improvement from a pre-operative average of 67.75±7.91 to 19.74±2.90 post-surgery, and was maintained at a low level of 28.00±4.89 at the last assessment. Radiological evaluations revealed significant alterations in Cobb angle and AVH post-operation. Notably, during the follow-up, eight patients developed new compression fractures in different vertebral segments. In conclusion, the unilateral PVP method is safe and efficient for the management of osteoporotic vertebral compression fractures.

Effects of Designed Herbal Formula on Growth Performance, Blood Indices, Organ Traits, and Cecum Microbiology in Broilers.

The objective of this study was to investigate the effect of the designed herbal formula (DHF) on growth performance, blood indices, organ traits, and cecum microbiology in broilers. A total of 96 male broilers of 1 d were selected and randomly assigned to two groups with six replicates of eight broilers each. The control (CON) and the basal diet containing 1.0% DHF (Astragali radix, Atractylodes macrocephala Koidz., Isatis tinctoria Linnaeus, and Citri reticulatae pericarpium, 2:1:1:2) were fed separately. The experiment was conducted for 35 days. The results showed that the DHF diet increased body weight and decreased the feed conversion ratio (FCR) (p < 0.05). At 21 days, the spleen, thymus, lymphocytes, and thrombocytes were increased (p < 0.05), and pancreas, duodenum, heterophils, and mean corpuscular hemoglobin (MCH) were decreased (p < 0.05). At 35 days, the heart, pancreas, white blood cell, heterophils, hemoglobin, MCH and mean corpuscular hemoglobin concentration (MCHC) were decreased, while lymphocytes and middle cells were increased (p < 0.05). The results of microbial diversity analysis showed that the DHF diet decreased the microbial diversity of the cecum. Firmicutes and Bacteroidetes were the dominant phyla, where the DHF diet increased the relative abundances of Bacteroides uniformis, Bacteroides vulgatus, and Faecalibacterium prausnitzii, and then decreased the relative abundance of Shigella sonnei. In conclusion, DHF played a positive role in improving the growth performance, immune performance, and relative abundance of Bacteroides uniformis, Bacteroides vulgatus, and Faecalibacterium prausnitzii in cecum microbiology in broilers, and has the potential to be used as a novel feed additive.

Tele-rehabilitation for Type II diabetics with heart failure with preserved ejection fraction.

Objective: This study aims to determine whether tele-rehabilitation has similar effects to conventional face-to-face physical rehabilitation for diabetic patients with heart failure with preserved ejection fraction (HFpEF). Materials and methods: Demographic, laboratory, diagnostic and rehabilitation information for patients with type 2 diabetes with HFpEF were extracted from disease-specific databases. Outcome measures, including the Short Physical Performance Battery (SPPB), 6-minute walk distance, frailty status, European Quality of Life 5-Dimension 5-Level questionnaire (EQ-5D-5L) and reduction in HbA1c from admission, patients who received tele-rehabilitation therapy were compared to those received face-to-face rehabilitation. Results: In this study, 90 patients with type 2 diabetes and HFpEF using tele-rehabilitation were matched with 90 patients with type 2 diabetes and HFpEF using face-to-face physical rehabilitation. Improvements in the results of the SPPB scores, 6-min walk distance and gait speed and EQ-5D-5L were noted from the follow-up time point 3 months to 6 months in both two groups. There were no significant differences in functional tests and quality of life between the two groups. Conclusion: Our study proved that mobile-based tele-rehabilitation programs are non-inferior to face-to-face physical rehabilitation for diabetes patients after HFpEF. In addition, adherence to the telerehabilitation program showed that the novel technology was accepted well and could be an alternative to the conventional face-to-face rehabilitation program.

iTRAQ-Based Serum Proteomic Analysis Reveals Multifactorial Cellular Function Impairment and Aggravated Systematic Inflammation in Drug-free Obsessive-Compulsive Disorders.

Obsessive-compulsive disorder (OCD) is a debilitating mental disorder with obvious difficulties in treatment. Its pathogenesis has not been fully elucidated. Further understanding of etiology and mechanism needs to be explored further. We employed the isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomic analysis to compare serum proteome profile between OCD patients and healthy controls, in order to find out the possible mechanism of OCD in the downstream biological process. Eighty-one drug-free OCD patients and 78 healthy controls were enrolled. A total of 475 proteins were identified. Totally, 80 proteins with p < 0.05 were selected for gene set enrichment analysis (GSEA), and only those with a fold change ≥1.2 and q value <0.2 between groups were accepted as differentially expressed proteins (DEPs). We observed a significant enrichment of immuno-inflammation-related pathways, along with intriguing expression trends that immuno-inflammation-related proteins were upregulated in GSEA. After that, 2 up-regulated proteins and 13 down-regulated ones were accepted as DEP. According to the available literature, most of the DEPs have not been reported in OCD. These DEPs were enriched in 121 gene ontology (GO) terms, including hepatocyte growth factor receptor activity, angiogenin-PRI complex, and so on. DEPs were enriched in pathways including adherens junction in the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Alterations in DEPs including STXBP5L, GRN, and ANG were validated in OCD animal models. Our study suggested that OCD patients manifested multifactorial impairment in neuronal or non-neuronal cellular function under the inflammatory background. Further research employing larger sample sizes, longitudinal design, stratified analysis, and multiomics methodology will be needed. Experiments in laboratories were essential in illuminating the mechanism.