Effects of Tannic Acid Supplementation of a High-Carbohydrate Diet on the Growth, Serum Biochemical Parameters, Antioxidant Capacity, Digestive Enzyme Activity, and Liver and Intestinal Health of Largemouth Bass, Micropterus salmoides.

We investigated the effects of dietary tannic acid (TA) supplementation of a high-carbohydrate diet on growth, feed utilization, whole-body proximate composition, serum biochemical indicators, antioxidant capacity, digestive enzyme activity, and liver and intestinal health of juvenile largemouth bass, Micropterus salmoides (initial mean weight: 8.08 ± 0.08 g). Five diets were prepared, including a positive control (dietary carbohydrate level, 16%, LC0), a negative control (dietary carbohydrate level, 21%, HC0), and three TA-supplementation diets based on the negative control diet with TA addition at 200, 400, and 800 mg/kg, respectively. After 8 weeks of feeding, the results showed that compared with the LC0 diet, 400-800 mg/kg dietary TA significantly improved the survival rate of largemouth bass (P < 0.05) while significantly reducing its weight-gain rate and specific growth rate (P < 0.05). Compared with the HC0 diet, 400 mg/kg dietary TA significantly increased serum catalase activity (P < 0.05), and significantly decreased serum malondialdehyde, liver glycogen, lightness (L ∗), and yellowness (b ∗) (P < 0.05). Moreover, compared with the HC0 diet, 200-400 mg/kg dietary TA effectively improved the vacuolation of hepatocytes caused by the high-carbohydrate diet and reduced the occurrence of intestinal epithelial cell vacuolation and necrosis. In turn, 800 mg/kg dietary TA significantly inhibited protease activity in the pyloric caecum and intestine (P < 0.05). In conclusion, dietary supplementation with TA inhibited protease activity, which resulted in decreased growth performance in largemouth bass. However, it was also found that 200-400 mg/kg TA enhanced the antioxidant capacity of largemouth bass in the case of the high-carbohydrate diet, reduced liver glycogen levels, and improved liver and intestinal health. Finally, it should be noted that, when the dietary TA level exceeded 800 mg/kg, TA appeared to play a pro-oxidation role in the liver, which may cause oxidative stress in the liver.

Synthetic High-Density Lipoprotein-Based Nanomedicine to Silence SOCS1 in Tumor Microenvironment and Trigger Antitumor Immunity against Glioma.

Immunotherapies have shed light on the treatment of many cancers, but have not improved the outcomes of glioma (GBM). Here, we demonstrated that suppressor of cytokine signaling 1 (SOCS1) was associated with the GBM-associated immunosuppression and developed a multifunctional nanomedicine, which silenced SOCS1 in the tumor microenvironment (TME) of GBM and triggered strong antitumor immunity against GBM. Synthetic high-density lipoprotein (sHDL) was selected as the nanocarrier and a peptide was used to facilitate the blood-brain-barrier (BBB) penetration. The nanocarrier was loaded with a small interfering RNA (siRNA), a peptide, and an adjuvant to trigger antitumor immunity. The nanomedicine concentrated on the TME in vivo, further promoting dendritic cell maturation and T cell proliferation, triggering strong cytotoxic T lymphocyte responses, and inhibiting tumor growth. Our work provides an alternative strategy to simultaneously target and modulate the TME in GBM patients and points to an avenue for enhancing the efficacy of immunotherapeutics.

Association between cumulative exposure periods of flupentixol or any antipsychotics and risk of lung cancer.

BACKGROUND: Preclinical evidence suggests that certain antipsychotic medications may inhibit the development of lung cancer. This study aims to investigate the association between incident lung cancer and different cumulative exposure periods of flupentixol or any antipsychotics. METHODS: Using electronic health records from the Hospital Authority in Hong Kong, this nested case-control study included case participants aged 18 years or older with newly diagnosed lung cancer after initiating antipsychotics between January 1, 2003, and August 31, 2022. Each case was matched to up to ten controls of the same sex and age, who were also antipsychotic users. Multivariable conditional logistic regression models were conducted to quantify the association between lung cancer and different cumulative exposure times of flupentixol (0-365 days [ref]; 366-1825 days; 1826+ days) and any antipsychotics (1-365 days [ref]; 366-1825 days; 1826+ days), separately. RESULTS: Here we show that among 6435 cases and 64,348 matched controls, 64.06% are males, and 52.98% are aged 65-84 years. Compared to patients with less than 365 days of exposure, those with 366-1825 days of exposure to flupentixol (OR = 0.65 [95% CI, 0.47-0.91]) and any antipsychotics (0.42 [0.38-0.45]) have a lower risk of lung cancer. A decreased risk is observed in patients who have 1826+ days of cumulative use of any antipsychotics (0.54 [0.47-0.60]). CONCLUSIONS: A reduced risk of lung cancer is observed in patients with more than one year of exposure to flupentixol or any antipsychotics. Further research on the association between lung cancer and other antipsychotic agents is warranted.

Antipsychotic drugs are mainly used to treat mental illnesses. Certain antipsychotic medications, such as flupentixol, may help protect patients against lung cancer. Here, we investigated whether prolonged use of flupentixol or other antipsychotics could reduce the occurrence of lung cancer among antipsychotic users. We demonstrated that a smaller proportion of patients with one to five years and more than five years of exposure to any antipsychotics develop lung cancer compared to those with less than one year of exposure. Specifically, for flupentixol, we observed a smaller proportion of patients with one to five years of exposure develop lung cancer compared to those with less than one year. To substantiate our current findings, further studies examining other populations and specific antipsychotic agents are necessary for developing effective lung cancer prevention strategies among this high-risk population.

Targeted genome mining for microbial antitumor agents acting through DNA intercalation.

Microbial natural products have been one of the most important sources for drug development. In the current postgenomic era, sequence-driven approaches for natural product discovery are becoming increasingly popular. Here, we develop an effective genome mining strategy for the targeted discovery of microbial metabolites with antitumor activities. Our method employs uvrA-like genes as genetic markers, which have been identified in the biosynthetic gene clusters (BGCs) of several chemotherapeutic drugs of microbial origin and confer self-resistance to the corresponding producers. Through systematic genomic analysis of gifted actinobacteria genera, identification of uvrA-like gene-containing BGCs, and targeted isolation of products from a BGC prioritized for metabolic analysis, we identified a new tetracycline-type DNA intercalator timmycins. Our results thus provide a new genome mining strategy for the efficient discovery of antitumor agents acting through DNA intercalation.

Identifying a prognostic model and screening of potential natural compounds for acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is one of the most common hematologic malignancies with a poor prognosis and high recurrence rate. The discovery of new predictive models and therapeutic agents plays a crucial role. Methods: The differentially expressed gene that was explicitly highly expressed in The Cancer Genome Atlas (TCGA) and GSE9476 transcriptome databases were screened and included in the least absolute shrinkage and selection operator (LASSO) regression model to derive risk coefficients and build a risk score model. Functional enrichment analysis was conducted on the screened hub genes to explore the potential mechanisms. Subsequently, critical genes were incorporated into a nomogram model based on risk scores to analyze prognostic value. Finally, this study combined network pharmacology to find potential natural compounds for hub genes and used molecular docking to verify the binding ability of molecular structures to natural compounds to explore drug development for possible efficacy in AML. Results: A total of 33 highly expressed genes may be associated with poor prognosis of AML patients. After LASSO and multivariate Cox regression analysis of 33 critical genes, Rho-related BTB domain containing 2 (RHOBTB2), phospholipase A2 (PLA2G4A), interleukin-2 receptor-α (IL2RA), cysteine and glycine-rich protein 1 (CSRP1), and olfactomedin-like 2A (OLFML2A) were found to played a significant role in the prognosis of AML patients. CSRP1 and OLFML2A were independent prognostic factors of AML. The predictive power of these 5 hub genes in combination with clinical features was better than clinical data alone in predicting AML in the column line graphs and had better predictive value at 1, 3, and 5 years. Finally, through network pharmacology and molecular docking, this study found that diosgenin in Guadi docked well with PLA2G4A, beta-sitosterol in Fangji docked well with IL2RA, and OLFML2A docked well with 3,4-di-O-caffeoylquinic acid in Beiliujinu. Conclusions: The predictive model of RHOBTB2, PLA2G4A, IL2RA, CSRP1, and OLFML2A combined with clinical features can better guide the prognosis of AML. In addition, the stable docking of PLA2G4A, IL2RA, and OLFML2A with natural compounds may provide new options for treating AML.

Dynamic de novo heterochromatin assembly and disassembly at replication forks ensures fork stability.

Chromatin is dynamically reorganized when DNA replication forks are challenged. However, the process of epigenetic reorganization and its implication for fork stability is poorly understood. Here we discover a checkpoint-regulated cascade of chromatin signalling that activates the histone methyltransferase EHMT2/G9a to catalyse heterochromatin assembly at stressed replication forks. Using biochemical and single molecule chromatin fibre approaches, we show that G9a together with SUV39h1 induces chromatin compaction by accumulating the repressive modifications, H3K9me1/me2/me3, in the vicinity of stressed replication forks. This closed conformation is also favoured by the G9a-dependent exclusion of the H3K9-demethylase JMJD1A/KDM3A, which facilitates heterochromatin disassembly upon fork restart. Untimely heterochromatin disassembly from stressed forks by KDM3A enables PRIMPOL access, triggering single-stranded DNA gap formation and sensitizing cells towards chemotherapeutic drugs. These findings may help in explaining chemotherapy resistance and poor prognosis observed in patients with cancer displaying elevated levels of G9a/H3K9me3.

Mechanism of Procyanidin B2 in the Treatment of Chronic Myeloid Leukemia Based on Integrating Network Pharmacology and Molecular Docking.

OBJECTIVE: To study the pharmacological mechanism of procyanidin B2 (PCB2) on chronic myeloid leukemia (CML) by integrating network pharmacological methods systematically. METHODS: Firstly, the potential target genes of PCB2 were predicted by the pharmacological database and analysis platform (TCMSP and Pharmmapper). Meanwhile, the relevant target genes of CML were collected from GeneCards and DisGene. Pooled data were collected to screen for common target genes. Furthermore, the above intersection genes were imported into the String website to construct a protein-protein interaction (PPI) network, and the Gene Ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were further analyzed. Besides, molecular docking was performed to verify the possible binding conformation between PCB2 and candidate targets. Finally, MTT and RT-PCR experiments of K562 cells were performed to verify the above results of network pharmacology. RESULTS: A total of 229 PCB2 target genes were retrieved, among which 186 target genes had interaction with CML. The pharmacological effects of PCB2 on CML were related to some important oncogenes and signaling pathways. The top ten core targets predicted by Network Analysis were as follows: AKT1, EGFR, ESR1, CASP3, SRC, VEGFA, HIF1A, ERBB2, MTOR, and IGF1. Molecular docking studies confirmed that hydrogen bonding was the main interaction force of PCB2 binding targets. According to the molecular docking score, the following three target proteins were most likely to bind to PCB2: VEGFA (-5.5 kcal/mol), SRC (-5.1 kcal/mol), and EGFR (-4.6 kcal/mol). After treatment of PCB2 for 24h, mRNA expression levels of VEGFA and HIF1A decreased significantly in K562 cells. CONCLUSION: Through integrating network pharmacology combined with molecular docking, the study revealed the potential mechanism of PCB2 anti-chronic myeloid leukemia.

Safety and Efficacy of Combined Imbrication Axle Reconstruction and Z-Type Titanium Plate Fixation for Hinge Fracture Displacement During Open-Door Laminoplasty.

BACKGROUND: Open-door laminoplasty is a classical decompression method used to treat cervical spondylotic myelopathy. However, hinge fracture displacement (HFD) is a common occurrence during this procedure. The current study aimed to investigate the safety and efficacy of a combined imbrication axle reconstruction and Z-type titanium plate fixation method for HFD during open-door laminoplasty. METHODS: In total, 617 patients with cervical spondylotic myelopathy who underwent C3-C7 open-door laminoplasty from March 2015 to October 2018 were included in this retrospective study. Overall, 73 patients developed HFD during surgery. Of these, 43 underwent combined imbrication axle reconstruction and Z-type titanium plate fixation (IRZF group) and 30 underwent traditional titanium plate fixation (TF group). Data such as the operative time, intraoperative blood loss volume, and distribution of fractured hinges were recorded. Both groups were compared in terms of improvement in neurologic function, cervical curvature index, hinge fusion rate, incidence of C5 palsy, severity of axial symptoms, and development of complications. RESULTS: The operative time and intraoperative blood loss were slightly higher in the IRZF group than in the TF group; however, the differences were not significant (p > 0.05). Furthermore, there was no significant difference between the groups in terms of the number of fractured segments and the distribution of fractured hinges (p > 0.05). The cervical curvature index did not decline in the two groups (p > 0.05). The IRZF group had a higher hinge fusion rate than the TF group at 3 (79.6 vs. 57.1%) and 12 (93.9 vs. 74.3%) months postoperatively (p < 0.05). There was no significant difference in the incidence of C5 palsy between the two groups (9.3 vs. 6.7%; p > 0.05). However, the TF group had more severe axial symptoms than the IRZF group (p < 0.05). The neurologic function of the two groups increased postoperatively as per the Japanese Orthopaedic Association scoring system (p < 0.05). Nevertheless, there was no significant difference in terms of neurologic function at any observational time point (p > 0.05). One patient in the TF group with hinge nonunion underwent laminectomy due to lamina displacement into the spinal canal and nerve root compression. CONCLUSION: In patients with HFD, IRZF facilitates a more intimate contact between the lamina and the lateral mass and, therefore, achieves fractured hinge fusion without additional surgical trauma. This technical improvement can significantly promote neurologic recovery, decrease the severity of axial symptoms, and prevent the development of spinal cord or nerve root recompression.

Influence of fixed titanium plate position on the effectiveness of open-door laminoplasty for cervical spondylotic myelopathy.

BACKGROUND: During open-door laminoplasty, the position of the bone gutter is not fixed, and when the gutter migrates inward, the outer end of the titanium plate must be fixed on the lamina edge. It is unclear whether this will affect the clinical efficacy. This study aimed to observe the influence of the titanium plate fixation position on the effectiveness of open-door laminoplasty for cervical spondylotic myelopathy (CSM). METHODS: A total of 98 patients with CSM who underwent open-door laminoplasty from August 2016 to October 2019 were included in this retrospective study. Fifty-five patients had the titanium plate fixed on the lateral mass (lateral mass group), and 43 patients had the titanium plate fixed on the lamina edge (lamina group). The opening angle, opening width, occurrence of hinge fracture, spinal cord drift distance, cervical curvature index (CCI), neurological function recovery (JOA score), neck function (NDI), C5 palsy and severity of axial symptoms were observed and compared between the two groups. RESULTS: The opening angle in the lamina group was significantly larger than that in the lateral mass group, while the opening width and the spinal cord drift distance were significantly smaller than those in the lateral mass group (P < 0.05). The occurrence of hinge fracture in the lamina group was significantly higher than that in the lateral group (25.6% and 9.1%, respectively) (P < 0.05). The CCI was maintained well in both groups (P > 0.05), and there was no significant difference between the groups (P > 0.05). After surgery, the JOA score significantly increased in both groups (P < 0.05), and the neurological recovery rates were similar between the two groups (62.6% vs. 64.5%). The NDI score significantly decreased in both groups (P < 0.05), but the lateral mass group recovered to a greater degree than the lamina group (P < 0.05). The occurrence of C5 palsy was 2.3% in the lamina group and 14.5% in the lateral mass group, and there was a significant difference between the groups (P < 0.05). Postoperative axial symptom severity was significantly worse in the lamina group than in the lateral mass group (P < 0.05). CONCLUSIONS: In open-door laminoplasty, it is feasible to fix the titanium plate on the lateral mass or to the lamina due to the same neurological function recovery. However, fixing it to the lamina will increase the opening angle and decrease the opening width, making the hinge prone to fracture and increasing the severity of postoperative axial symptoms.

Change of Optical Coherence Tomography Morphology and Associated Structural Outcome in Diabetic Macular Edema after Ranibizumab Treatment.

(1) Background: To investigate the correlation between therapeutic outcome and morphologic changes for diabetic macular edema (DME) after intravitreal injection of ranibizumab (IVIR). (2) Methods: This retrospective study included 228 eyes received IVIR for DME. Each participant was traced for two years after the initial IVIR, while the data of ophthalmic examination, optical coherence tomography (OCT) image, and systemic diseases were collected. The study population was categorized into different subgroups according to the existence of OCT morphologic change and the initial OCT morphologic pattern, including diffuse retinal thickening (DRT), cystoid macular edema (CME), serous retinal detachment (SRD), and vitreomacular interface abnormalities (VMIAs). The primary outcomes were the baseline best-corrected visual acuity (BCVA) and central macular thickness (CMT) during a two-year study period. The distribution of OCT morphologic change and its relation to primary outcome were analyzed. (3) Results: Comparing the 42 eyes (18.4%) with OCT morphological changes to another 186 eyes (81.6%) without such alteration, the former showed a poorer baseline BCVA (0.84 ± 0.39 vs. 0.71 ± 0.36, p = 0.035), worse final BCVA (0.99 ± 0.44 vs. 0.67 ± 0.30, p = 0.001), and thicker final CMT (354.21 ± 89.02 vs. 305.33 ± 83.05, p = 0.001). Moreover, the VMIA developed in 14.9% of all DME patients presenting the most common morphologic change among DRT, CME, and SRD. Besides, the presence of stroke was independently correlated to the morphologic change (adjusted odds ratio [aOR]: 6.381, 95% confidence interval (CI): 1.112-36.623, p = 0.038). (4) Conclusions: The change of OCT morphology in DME patients receiving IVIR was correlated to worse structural and visual outcome while the formation of VMIA most commonly occurred after initial treatment.

[The Factors Affecting Relapse in Pediatric B-cell Acute Lymphoblastic Leukemia Patients without Prognostic Fusion Genes Following Up for 10 years].

OBJECTIVE: To analyze the efficacy of children with B-cell acute lymphoblastic leukemia (B-ALL) without prognostic fusion genes treated by CCLG-ALL 2008, and investigate the related factors affecting the recurrence of the patients. METHODS: B-ALL patients without prognostic fusion genes treated by the protocol of CCLG-ALL 2008 in our hospital from March 2008 to December 2012 were retrospectively analyzed. Follow-up time was ended in August 31, 2019. The median follow-up time was 92 months (range 0-136 months). Kaplan-Meier was used to detect the RFS, and COX multivariate regression analysis was employed to identify the independent factors affecting the recurrence of the patients. RESULTS: There were 140 males and 99 females enrolled in this study. The ratio of male to female was 1.41∶1. The median age was 4.4 years old and the median number of WBC at initial stage was 4.98×109/L. There were 77 cases relapsed during the observation while 162 without relapsed, 16 cases lost to follow-up and 72 cases died. The recurrence and mortality rate was 32.22% and 30.1%, respectively, in which 45 cases died of recurrence (62.5% of the total deaths). Univariate analysis showed that the age≥6 years old, WBC >100×109/L, the bone marrow blasts on day 15≥25%, the bone marrow minimal residual disease (MRD) at week 12 >10-4, and the higher risk were the main factors affecting the recurrence of the patients (P<0.05). Multivariate COX regression analysis showed that age≥6 years old, WBC >100×109/L, bone marrow MRD >10-4 at the 12th week were the independent risk factors affecting recurrence of the patients. CONCLUSION: Age, initial WBC, and bone marrow MRD at the 12th week were correlated with recurrence in children with B-ALL without prognostic fusion genes, which can be used as prognostic indices of recurrence risk in clinical.

Predictive factors of nonfatal self-harm among community-dwelling older adults assessed for support services.

BACKGROUND: Older adults receiving support services are a population at risk for self-harm due to physical illness and functional impairment, which are known risk factors. This study aims to investigate the relative importance of predictive factors of nonfatal self-harm among older adults assessed for support services in New Zealand. METHODS: interRAI-Home Care (HC) national data of older adults (aged ≥ 60) were linked to mortality and hospital discharge data between January 1, 2012 and December 31, 2016. We calculated the crude incidence of self-harm per 100,000 person-years, and gender and age-adjusted standardized incidence ratios (SIRs). The Fine and Gray competing risk regression model was fitted to estimate the hazard ratio (HR; 95% CIs) of self-harm associated with various demographic, psychosocial, clinical factors, and summary scales. RESULTS: A total of 93,501 older adults were included. At the end of the follow-up period, 251 (0.27%) people had at least one episode of nonfatal self-harm and 36,333 (38.86%) people died. The overall incidence of nonfatal self-harm was 160.39 (95% CI, 141.36-181.06) per 100,000 person-years and SIR was 5.12 (95% CI, 4.51-5.78), with the highest incidence in the first year of follow-up. Depression diagnosis (HR, 3.02, 2.26-4.03), at-risk alcohol use (2.38, 1.30-4.35), and bipolar disorder (2.18, 1.25-3.80) were the most significant risk factors. Protective effects were found with cancer (0.57, 0.36-0.89) and severe level of functional impairment measured by Activities of Daily Living (ADL) Hierarchy Scale (0.56, 0.35-0.89). CONCLUSION: Psychiatric factors are the most significant predictors for nonfatal self-harm among older adults receiving support services. Our results can be used to inform healthcare professionals for timely identification of people at high risk of self-harm and the development of more efficient and targeted prevention strategies, with specific attention to individuals with depression or depressive symptoms, particularly in the first year of follow-up.

N klA Case Report on a IV-degree Thermal Crush Injury of Right Upper Arm: The Application of Functional Prosthesis Implantation Technology.

Severe IV-degree thermal crush injury of limbs involved the subcutaneous fascia, muscle and bone, which may lead to amputation and has a great impact on the patient's quality of life. We can repair wounds with pedicle flaps or even free flaps, However, there are still huge challenges in bone defect of extremities and functional reconstruction. In recent years, with the development of functional prostheses, we have reconstructed limb functions in many patients helping them to complete their daily lives. We report a case where the right upper arm was injured by thermal crush, leading severe burns to the skin, fascia, muscle and bone. We applied a pedicled latissimus dorsi flap and a free anterolateral thigh flap to repair the wound, and realized the function of limb salvage and movement of the right upper arm by implanting 3D printed scapula, upper arm, and elbow joint prostheses. This case illustrates that IV-degree burns involving bones have new technologies to repair and achieve mobility now.

Correlation of AIF-1 Expression with Immune and Clinical Features in 1270 Glioma Samples.

AIF-1 gene is surrounded by the genes involved in the inflammatory response and located in the major histocompatibility complex (MHC) class III genomic region. It has been found that microglial cells expressed the AIF-1 gene during all stages of mice brain development. However, the role of AIF-1 remains unclear in glioma. A total of 1270 glioma patients from three independent data sets were enrolled in the study. TIMER platform was used for comprehensive molecular characterization of tumor immune infiltrates. Sangerbox was used to analyze AIF-1 RNA sequencing expression data of tumors and normal samples, and to evaluate the association between AIF-1 expression and 29 sub-populations of immune cells. The R language 3.63 was used to identify differentially expressed genes for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Kaplan-Meier survival analysis and univariate/multivariate Cox analysis were used to examine survival distributions. We found that AIF-1 gene was prominently up-regulated, especially in brain glioma including LGG and GBM. A strong correlation was observed between AIF-1 expression and the majority of immune cells, particularly in macrophage, myeloid-derived suppressor cells. Moreover, AIF-1 expression was correlated with immune infiltration level. We found that AIF-1 expression was strongly correlated with the specific immune and prognostic cell markers of monocytes, microglia and macrophages, M1 macrophages, and M2 macrophages after normalization through tumor purity in TCGA-LGG and TCGA-GBM. Higher expression level of AIF-1 was found to be significantly correlated with poor prognosis. GO analysis and KEGG pathways indicated that AIF-1 could affect glioma-related immune activities. Our study suggests that AIF-1 can be treated as a prognostic biomarker for glioma patients. AIF-1 was involved in pro-tumor processes and the regulation of immune status and correlates with poor prognosis.

Obstructive sleep apnea and the incidence and mortality of gastrointestinal cancers: a systematic review and meta-analysis of 5,120,837 participants.

Background: Emerging evidence has shown higher overall cancer incidence in patients with obstructive sleep apnea. Gastrointestinal cancers, including esophageal, stomach, liver, pancreas, and colorectal cancers account for 26% of incident cancers. However, the link between gastrointestinal cancers and obstructive sleep apnea is still unclear. We performed a systematic review and meta-analysis (registered PROSPERO CRD42021220836) to investigate the association between obstructive sleep apnea and incidence of gastrointestinal cancer. Methods: We searched four electronic databases (PubMed, Embase, Cochrane Library, Scopus) and included studies published from inception till 15th November 2020 reporting the association of obstructive sleep apnea with gastrointestinal cancer incidence. Extracted data was meta-analyzed in a random-effects model. Results: A total of seven studies were included, forming a combined cohort of 5,120,837 patients. Studies which adjusted for demographics and comorbidities were included in meta-analysis. Among four studies with 7-11 years of median follow-up, patients with obstructive sleep apnea experienced increased incidence of colorectal cancer (HR 1.70, 95% CI: 1.48-1.96, I2=22%). Pancreatic cancer incidence was nominally increased in three studies (HR 1.36, 95% CI: 0.88-2.09, I2=96), though this was not statistically significant. There was no association between obstructive sleep apnea and liver cancer incidence among three studies (HR 0.99, 95% CI: 0.81-1.22, I2=84). However, the lack of a statistically significant relationship between obstructive sleep apnea and pancreatic cancer in our meta-analysis does not necessarily imply the true absence of an association. Conclusions: An increased risk of colorectal cancer was seen in patients with obstructive sleep apnea among studies with long-term follow-up. Further research is required to explore the utility of incorporating obstructive sleep apnea screening into colorectal cancer screening guidelines to identify high-risk individuals and to confirm a possible association of obstructive sleep apnea with pancreatic cancer. PROSPERO Registration: CRD42021220836.

Zuogui Wan improves trabecular bone microarchitecture in ovariectomy-induced osteoporosis rats by regulating orexin-A and orexin receptor.

OBJECTIVE: To investigate the protective effects of Zuogui Wan (ZGW) on bone loss induced by ovariectomy (OVX) and its mechanism via orexin-A and orexin receptors in the osteoporosis rat model. METHODS: Fifty Sprague-Dawley female rats were randomly divided into sham-operated (sham) group and four OVX subgroups. Rats subjected to sham and OVX were treated with the vehicle (OVX, 1 mL/100 g weight, n = 10), 17ß-estradiol (E2, 50 µg*kg-1*d-1), and ZGW at the doses of 2.3 (ZGW-L) and 4.6 (ZGW-H) g/kg/day lyophilized powder daily for 3 months, respectively. The serum biochemical parameters of 17ß-estrogen (17ß-E2), tartrate-resistant acid phosphatase (TRACP-5b) and bone alkaline phosphatase (BALP) were measured by enzyme-linked immunosorbent assay. Hematoxylin-eosin staining was used to detect the changes in the morphological structure in bones. Microcomputed tomography was used to evaluate the bone mineral density and microarchitecture of the distal femur. The gene or protein expression of orexin-A, orexin receptor 1 (OX1R), orexin receptor 2 (OX2R), osteoprotegerin (OPG) and receptor activator of nuclear factor-κB ligand (RANKL) were assayed by either quantitative polymerase chain reaction or Western blot analysis. RESULTS: Compared with the OVX group, ZGW could reduce the serum level of TRACP-5b and increased the serum levels of BALP and17ß-E2 (P < 0.01). Meanwhile, ZGW could prevent bone loss and improved bone trabecular microarchitecture by increasing the trabeculae structure thickness and trabecular number, and arranging the trabeculae structure properly. Compared with the OVX group, it was upregulated for the orexin-A and OX2R mRNA or protein expression from the hypothalamus and tibiae, and OPG in the tibiae of ZGW groups (P < 0.01, < 0.05), while downregulated for the OX1R mRNA and protein expression in the tibiae and hypothalamus and RANKL from the tibiae (P < 0.01). CONCLUSION: ZGW exhibited a protective effect for PMOP that may be mediated via orexin-A and orexin receptors regulation.

Role of Oil Palm Empty Fruit Bunch-Derived Cellulose in Improving the Sonocatalytic Activity of Silver-Doped Titanium Dioxide.

In this study, a novel cellulose/Ag/TiO2 nanocomposite was successfully synthesized via the hydrothermal method. The cellulose extracted from oil palm empty fruit bunch (OPEFB) could address the disposal issue created by OPEFB biomass. Characterization studies such as FESEM, EDX, HRTEM, XRD, FTIR, UV-Vis DRS, PL, XPS, and surface analysis were conducted. It was observed that the incorporation of cellulose could hinder the agglomeration, reduce the band gap energy to 3 eV, increase the specific surface area to 150.22 m3/g, and lower the recombination rate of the generated electron-hole pairs compared to Ag/TiO2 nanoparticles. The excellent properties enhance the sonocatalytic degradation efficiency of 10 mg/L Congo red (up to 81.3% after 10 min ultrasonic irradiation) in the presence of 0.5 g/L cellulose/Ag/TiO2 at 24 kHz and 280 W. The improvement of catalytic activity was due to the surface plasmon resonance effect of Ag and numerous hydroxyl groups on cellulose that capture the holes, which delay the recombination rate of the charge carriers in TiO2. This study demonstrated an alternative approach in the development of an efficient sonocatalyst for the sonocatalytic degradation of Congo red.

Identifying PIF1 as a Potential Target of Wenxia Changfu Formula in Promoting Lung Cancer Cell Apoptosis: Bioinformatics Analysis and Biological Evidence.

Lung cancer remains the leading cause of cancer-related deaths worldwide. Traditional Chinese medicine (TCM) is a valuable resource of active natural products and plays an important role in cancer treatment with the advantages of high efficiency and safety. Wenxia Changfu formula (WCF) is modified from Dahuang Fuzi decoction from Han Dynasty and has been used for treating lung cancer in China. Our previous research showed that WCF had an antitumor effect in vivo and in vitro, while the mechanism has not been well illustrated. In this study, the effect of WCF on the proliferative ability in three lung cancer cells and one noncancerous human cell line was evaluated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. WCF suppressed A549, H460, and PC-9 cell viability in a dose-dependent manner, with no inhibition of noncancerous MRC-5 cells after 48 h treatment with WCF (0-50 mg/mL). Furthermore, we screened for genes in A549 cells using four WCF-treated samples and four control samples on a gene expression profile microarray. 21 genes were significantly downregulated by WCF, which may potentially play an important role in the proliferation of A549 cells. High-content screening evaluated whether silencing the 21 genes affected A549 cell growth. The results showed that PIF1 knockdown exhibited the most potent inhibition of cell proliferation compared with the other genes. Downregulation of PIF1 increased A549 cell apoptosis and the activity of caspase 3/7. Besides, RT-PCR showed that the expression levels of PIF1 mRNA decreased significantly in A549, H460, and PC-9 cells after WCF treatment. In conclusion, the present observations indicate that WCF may inhibit lung cancer cell proliferation by promoting apoptosis via regulating the expression of PIF1.