Effects of enzyme supplementation on growth performance, digestibility of phosphorus, femur parameters and fecal microbiota in growing pigs fed different types of diets.

A 42-days study was conducted to evaluate the effects of different dietary types (corn-or wheat-soybean meal-based diet) and phytase (Phy) or a multi-carbohydrase and phytase complex (MCPC) supplementation on growth performance, digestibility of phosphorus (P), intestinal transporter gene expression, plasma indexes, bone parameters, and fecal microbiota in growing pigs. Seventy-two barrows (average initial body weight of 24.70 ± 0.09 kg) with a 2 × 3 factorial arrangement of treatments and main effects of diet type (corn-or wheat-soybean meal-based-diets) and enzyme supplementation (without, with Phy or with MCPC). Each group was designed with 6 replicate pens. The MCPC increased (p < 0.05) average daily gain (ADG) and final body weight (BW). A significant interaction (p = 0.01) was observed between diet type and enzyme supplementation on apparent total tract digestibility (ATTD) of P. The ATTD of P was higher (p < 0.05) in wheat soybean meal-based diets compared to corn-soybean meal-based diets. Compared with the corn-soybean meal-based diet, the relative expression of SLC34A2 and VDR genes in the ileum and SLC34A3 in jejunum of growing pigs fed the wheat-soybean meal based diet was lower (p < 0.05). The MCPC significantly reduced (p < 0.05) the relative expression of TRPV5 and CALB1 genes in the ileum and increased the expression of CALB1 in the duodenum compared to control diet. The phytase increased (p < 0.05) the relative expression of SLC34A1 gene in the duodenum in comparison to control diet and MCPC-supplemented diet. The Ca and P contents in plasma from pigs fed corn-soybean meal-based diet were higher (p < 0.05) than those from pigs fed wheat-soybean meal-based diet, and the parathyroid hormone (PTH) and calcitonin (CT) concentrations were lower (p < 0.05) than those fed wheat-soybean meal-based diet. The content of Ca and P in the femur and the bone strength of pigs in the corn-soybean meal group were significantly higher (p < 0.05) than those in the wheat-soybean meal groups. The phytase increased (p < 0.05) the Ca and P content and bone strength of the femur. Additionally, diet type and both enzymes significantly improved fecal microbial diversity and composition. Taken together, diet type and exogenous enzymes supplementation could differently influence the growth performance, utilization of phosphorus, intestinal transporter gene expression, bone mineralization and microbial diversity and composition in growing pigs.

Risk factors and predictive models for frozen shoulder.

This study aims to explore the risk factors associated with frozen shoulder (FS) and develop a predictive model for diagnosing FS, in order to facilitate early detection of the condition. A total of 103 patients diagnosed with FS and admitted to the Department of Joint Surgery at Suining Central Hospital between October 2021 and October 2023 were consecutively included in the study. Additionally, 309 individuals without shoulder joint diseases, matched for age and gender, who visited the department during the same time, were included as the control group.The complete recording of clinical data for all patients was followed by the utilization of statistical tests such as the Mann-Whitney U test, sample t test, and chi-square test to compare different groups. Additionally, multivariate binary logistic regression analysis was employed to identify risk factors associated with the occurrence of FS in patients, leading to the establishment of a prediction model and derivation of a simplified equation. The diagnostic effectiveness of individual indicators and prediction models was assessed through the use of receiver operating characteristic (ROC) curve analysis. In the sample of 103 individuals, 35 were identified as male and 68 as female, with an average age range of 40-70 years (mean age: 54.20 ± 6.82 years). The analysis conducted between different groups revealed that individuals with a low body mass index (BMI), in conjunction with other factors such as diabetes, cervical spondylosis, atherosclerosis, and hyperlipidemia, were more susceptible to developing FS. Logistic regression analysis further indicated that low BMI, diabetes, cervical spondylosis, and hyperlipidemia were significant risk factors for the occurrence of FS. These variables were subsequently incorporated into a predictive model, resulting in the creation of a simplified equation.The ROC curve demonstrated that the combined indicators in the predictive model exhibited superior diagnostic efficacy compared to single indicators, as evidenced by an area under the curve of 0.787, sensitivity of 62.1%, and specificity of 82.2%. Low BMI, diabetes, cervical spondylosis, and hyperlipidemia are significant risk factors associated with the occurrence of FS. Moreover, the utilization of a prediction model has demonstrated superior capability in forecasting the likelihood of FS compared to relying solely on individual indicators. This finding holds potential in offering valuable insights for the early diagnosis of FS.

OCIAD2 promotes pancreatic cancer progression through the AKT signaling pathway.

BACKGROUND: OCIAD2（Ovarian carcinoma immunoreactive antigen-like protein 2） is a protein reported in various cancers. However, the role of OCIAD2 has not been explored in pan-cancer datasets. The purpose of this research lies in analyzing the expression level and prognostic-related value of OCIAD2 in different human cancers, as well as revealing the underlying mechanism in specific cancer type (pancreatic adenocarcinoma, PAAD). METHODS: The correlation between OCIAD2 expression level and clinical relevance in different human cancers was investigated from bioinformatical perspective (GTEx and TCGA). The OCIAD2 expression level and clinical significance in PAAD were explored in GEO datasets and tissue microarray. Functional experiments were used to determine the OCIAD2 cell functions in vitro and in vivo. GSEA, western blot and immunohistochemistry were used to uncover the potential mechanism. RESULTS: OCIAD2 expression level was closely correlated with clinical relevance in many cancer types through pan-cancer analysis, and we found OCIAD2 was highly expressed in PAAD and associated with poorer prognosis. OCIAD2 acted as the promotor of Warburg effect and influenced PAAD cells proliferation, migration and apoptosis. Mechanistically, OCIAD2 upregulation may boost glycolysis in PAAD via activating the AKT signaling pathway in PAAD. CONCLUSIONS: In PAAD, OCIAD2 promotes Warburg effect via AKT signaling pathway and targeting cancer cells metabolic reprogramming could be a potential treatment.

Neuroendoscopic Parafascicular Evacuation of Spontaneous Intracerebral Hemorrhage (NESICH Technique): A Multicenter Technical Experience with Preliminary Findings.

INTRODUCTION: Intracerebral hemorrhage (ICH) is a severe manifestation of stroke, demonstrating notably elevated global mortality and morbidity. Thus far, effective therapeutic strategies for ICH have proven elusive. Currently, minimally invasive techniques are widely employed for ICH management, particularly using endoscopic hematoma evacuation in cases of deep ICH. Exploration of strategies to achieve meticulous surgery and diminish iatrogenic harm, especially to the corticospinal tract, with the objective of enhancing the neurological prognosis of patients, needs further efforts. METHODS: We comprehensively collected detailed demographic, clinical, radiographic, surgical, and postoperative treatment and recovery data for patients who underwent endoscopic hematoma removal. This thorough inclusion of data intends to offer a comprehensive overview of our technical experience in this study. RESULTS: One hundred fifty-four eligible patients with deep supratentorial intracerebral hemorrhage who underwent endoscopic hematoma removal were included in this study. The mean hematoma volume was 42 ml, with 74 instances of left-sided hematoma and 80 cases of right-sided hematoma. The median Glasgow Coma Scale (GCS) score at admission was 10 (range from 4 to 15), and the median time from symptom onset to surgery was 18 (range 2 to 96) h. The mean hematoma clearance rate was 89%. The rebleeding and mortality rates within 1 month after surgery were 3.2% and 7.8%, respectively. At the 6-month mark, the proportion of patients with modified Rankin Scale (mRS) scores of 0-3 was 58.4%. CONCLUSION: Both the reduction of surgery-related injury and the protection of the residual corticospinal tract through endoscopic hematoma removal may potentially enhance neurological functional outcomes in patients with deep ICH, warranting validation in a forthcoming multicenter clinical study.

History of suicidal behavior and clozapine prescribing among people with schizophrenia in China: a cohort study.

BACKGROUND: Clozapine is an off-label drug used in most countries to prevent suicide in individuals with schizophrenia. However, few studies have reported real-world prescription practices. This study aimed to explore the association between a history of suicidal behavior and clozapine prescribing during eight weeks of hospitalization for individuals with early-stage schizophrenia. METHODS: This observational cohort study used routine health data collected from a mental health hospital in Beijing, China. The study included 1057 inpatients who had schizophrenia onset within 3 years. History of suicidal behavior was coded from reviewing medical notes according to the Columbia Suicide Severity Rating Scale. Information on antipsychotic use during hospitalization was extracted from the prescription records. Time to clozapine use was analyzed using Cox regression models adjusted for sociodemographic and clinical covariates. RESULTS: The prevalence rates of self-harm, suicidal behavior, and suicide attempt were 12.3%, 7.5%, and 5.4%, respectively. A history of self-harm history was positively associated with clozapine uses upon admission (4.1% vs. 0.8%, exact p = 0.009). Among those who had not used clozapine and had no clozapine contraindication, A history of suicidal behavior increased the possibility of switch to clozapine within 56 days after admission (Hazard Ratio[95% CI], 6.09[2.08-17.83]) or during hospitalization (4.18[1.62-10.78]). CONCLUSION: The use of clozapine for early-stage schizophrenia was more frequent among those with suicidal behavior than among those without suicidal behavior in China, although the drug instructions do not label its use for suicide risk.

Identification and evolution of PDK-1-like involving lamprey innate immunity.

3-phosphoinositide-dependent protein kinase-1 (PDK-1) is a key kinase regulating the activity of the PI3K/AKT pathway and a major regulator of the AGC protein kinase family. It is essential in the physiological activities of cells, embryonic development, individual development and immune response. In this study, we have identified for the first time an analogue of PDK-1 in the most primitive vertebrate, lamprey, and named it PDK-1-like. The protein sequence similarity of lamprey PDK-1-like to human, mouse, chicken, African xenopus and zebrafish PDK-1 were 64.4 %, 64.5 %, 65.0 %, 61.3 % and 63.2 %, respectively. The phylogenetic tree showed that PDK-1-like of lamprey were located at the base of the vertebrate branch, in line with the trend of biological evolution. Meanwhile, homology analysis showed that PDK-1 proteins across species shared a conserved kinase structural domain and a Pleckstrin Homology (PH) domain. Genomic synteny analysis revealed that the large-scale duplication blocks were not found in lamprey genome and neighbor genes of lamprey PDK-1-like presented dramatic differences compared with jawed vertebrates. More importantly, qPCR analysis showed that PDK-1-like was widely expressed in lamprey. Its mRNA expression levels varied in response to different pathogenic stimuli, and its expression was generally up-regulated under Polyinosinic-Polycytidylic acid (Poly(I:C)) stimulation. Pearson's correlation analysis showed that PDK-1-like was involved in co-expressed with MyD88-independent TLR-3 pathway during the immune response of lamprey, instead of MyD88-dependent TLR-3 pathway. In summary, our composite results offer valuable clues to the origin and evolution of PDK-1, and imply that PDK-1 s are among the most ancestral immune regulators in vertebrates.

Unveiling the heightened susceptibility: Exploring early hypophosphatemia in critically ill trauma patients.

BACKGROUND: Phosphorus is a vital mineral crucial for various physiological functions. Critically ill trauma patients frequently experience hypophosphatemia during the immediate post-traumatic phase, potentially impacting outcomes. This study aims to investigate the incidence of early hypophosphatemia in critically major trauma patients. METHODS: In this prospective observational study, trauma patients admitted to the intensive care unit (ICU) within one day were enrolled. These patients were categorized into Hypo-P groups and Non-hypo groups based on the development of new-onset hypophosphatemia within 72 h after feeding. The primary outcome assessed was the incidence of new-onset hypophosphatemia. The secondary outcomes included ICU and hospital stay, ventilation duration, and mortality. RESULTS: 76.1% of patients developed a new onset of hypophosphatemia within 72 h after feeding. The Hypo-P group had significantly longer ICU stays (8.1 days ± 5.5 vs. 4.4 days ± 3.1; p = 0.0251) and trends towards extended hospital stay, ventilation duration, and higher mortality. Additionally, they demonstrated significantly higher urine fractional excretion of phosphate (FEPO4) on the first ICU day (29.2% ± 14.23 vs. 19.5% ± 8.39; p = 0.0242). CONCLUSION: Critically ill trauma patients exhibited a significantly higher incidence of early hypophosphatemia than typical ICU rates, indicating their heightened vulnerability. The significantly high urine FEPO4 underscores the crucial role of renal loss in disrupting phosphate metabolism in this early acute phase after trauma. A significant correlation was observed between hypophosphatemia and longer ICU stays. Monitoring and managing phosphate levels may influence outcomes, warranting further investigation.

Hypotension prediction index for prevention of intraoperative hypotension in patients undergoing general anesthesia: a randomized controlled trial.

BACKGROUND: Intraoperative hypotension is a common side effect of general anesthesia. Here we examined whether the Hypotension Prediction Index (HPI), a novel warning system, reduces the severity and duration of intraoperative hypotension during general anesthesia. METHODS: This randomized controlled trial was conducted in a tertiary referral hospital. We enrolled patients undergoing general anesthesia with invasive arterial monitoring. Patients were randomized 1:1 either to receive hemodynamic management with HPI guidance (intervention) or standard of care (control) treatment. Intraoperative hypotension treatment was initiated at HPI > 85 (intervention) or mean arterial pressure (MAP) < 65 mmHg (control). The primary outcome was hypotension severity, defined as a time-weighted average (TWA) MAP < 65 mmHg. Secondary outcomes were TWA MAP < 60 and < 55 mmHg. RESULTS: Of the 60 patients who completed the study, 30 were in the intervention group and 30 in the control group. The patients' median age was 62 years, and 48 of them were male. The median duration of surgery was 490 min. The median MAP before surgery presented no significant difference between the two groups. The intervention group showed significantly lower median TWA MAP < 65 mmHg than the control group (0.02 [0.003, 0.08] vs. 0.37 [0.20, 0.58], P < 0.001). Findings were similar for TWA MAP < 60 mmHg and < 55 mmHg. The median MAP during surgery was significantly higher in the intervention group than that in the control group (87.54 mmHg vs. 77.92 mmHg, P < 0.001). CONCLUSIONS: HPI guidance appears to be effective in preventing intraoperative hypotension during general anesthesia. Further investigation is needed to assess the impact of HPI on patient outcomes. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04966364); 202105065RINA; Date of registration: July 19, 2021; The recruitment date of the first patient: July 22, 2021.

Spatiotemporal heterogeneity of LMOD1 expression summarizes two modes of cell communication in colorectal cancer.

Cellular communication (CC) influences tumor development by mediating intercellular junctions between cells. However, the role and underlying mechanisms of CC in malignant transformation remain unknown. Here, we investigated the spatiotemporal heterogeneity of CC molecular expression during malignant transformation. It was found that although both tight junctions (TJs) and gap junctions (GJs) were involved in maintaining the tumor microenvironment (TME), they exhibited opposite characteristics. Mechanistically, for epithelial cells (parenchymal component), the expression of TJ molecules consistently decreased during normal-cancer transformation and is a potential oncogenic factor. For fibroblasts (mesenchymal component), the expression of GJs consistently increased during normal-cancer transformation and is a potential oncogenic factor. In addition, the molecular profiles of TJs and GJs were used to stratify colorectal cancer (CRC) patients, where subtypes characterized by high GJ levels and low TJ levels exhibited enhanced mesenchymal signals. Importantly, we propose that leiomodin 1 (LMOD1) is biphasic, with features of both TJs and GJs. LMOD1 not only promotes the activation of cancer-associated fibroblasts (CAFs) but also inhibits the Epithelial-mesenchymal transition (EMT) program in cancer cells. In conclusion, these findings demonstrate the molecular heterogeneity of CC and provide new insights into further understanding of TME heterogeneity.

Risk factors for subsequent suicidal acts among 12-25-year-old high-risk callers to a suicide prevention hotline in China: a longitudinal study.

BACKGROUND: A few previous cross-sectional studies investigated correlated factors of suicidal ideation or suicide attempts among suicide prevention hotline callers; however, scarcely any evidence was from a longitudinal study. In addition, it is still unclear whether improvements in some suicide risk factors could reduce the occurrence of subsequent suicidal acts. This longitudinal study focusing on the risk factors for subsequent suicidal acts among adolescent and young adult callers with high suicide risk aims to fill this gap. METHODS: This study recruited 12-25-year-old high-risk callers to a China nationwide suicide prevention hotline. Potential risk factors, including hopefulness, psychological distress, depression, history of suicide attempts, alcohol or substance misuse, and acute life events, were examined during the index calls, and improvements in hopefulness, psychological distress, and suicide intent were assessed before ending the index calls. The recruited callers were followed up 12 months after their index calls. The primary outcome was the occurrence of suicidal acts (suicide attempts or suicide death) during follow-up. Kaplan-Meier survival curves, log-rank tests, and Cox proportional hazards model were used. RESULTS: During the follow-up period, 271 of 1656 high-risk adolescent and young adult callers attempted suicide, and seven callers died by suicide. After adjusting for demographic variables, low hopefulness (Hazard Ratio [HR] = 2.03, 95% Confidence Interval [CI]=[1.47, 2.80]) at the beginning of the index call was associated with a higher risk for subsequent suicidal acts, whereas improvements in psychological distress (HR = 0.61, 95%CI [0.41, 0.89]) and suicidal intent (HR = 0.56, 95%CI [0.38, 0.84]) during the index call reduced the risk of subsequent suicidal acts. In addition, alcohol or substance misuse (Model 2, HR = 1.65, 95%CI [1.11, 2.46]) and suicide attempt history(Model 1: one episode, HR = 1.96, 95%CI=[1.05, 3.66]; two or more episodes, HR = 2.81, 95%CI [1.59, 4.96]. Model 2: one episode, HR = 2.26, 95%CI [1.06, 4.82]; two or more episodes: HR = 3.28, 95%CI [1.63, 6.60]) were risk factors for subsequent suicidal acts. CONCLUSIONS: While suicide prevention hotline operators deliver brief psychological interventions to high-risk adolescent and young adult callers, priority should be given to callers with low hopefulness and to the alleviation of callers' high psychological distress and suicide intent.

Occurrence and spatiotemporal distribution of arsenic biotransformation genes in urban dust.

Microbially-mediated arsenic biotransformation plays a pivotal role in the biogeochemical cycling of arsenic; however, the presence of arsenic biotransformation genes (ABGs) in urban dust remains unclear. To investigate the occurrence and spatiotemporal distributions of ABGs, a total of one hundred and eighteen urban dust samples were collected from different districts of Xiamen city, China in summer and winter. Although inorganic arsenic species, including arsenate [As(V)] and arsenite [As(III)], were found to be predominant, the methylated arsenicals, particularly trimethylarsine oxide [TMAs(V)O] and dimethylarsenate [DMAs(V)], were detected in urban dust. Abundant ABGs were identified in urban dust via AsChip analysis (a high-throughput qPCR chip for ABGs), of which As(III) S-adenosylmethionine methyltransferase genes (arsM), As(V) reductase genes (arsC), As(III) oxidase genes (aioA), As(III) transporter genes (arsB), and arsenic-sensing regulator genes (arsR) were the most prevalent, collectively constituting more than 90 % of ABGs in urban dust. Microbes involved in arsenic methylation were assigned to bacteria (e.g., Actinomycetes and Alphaproteobacteria), archaea (e.g., Halobacteria), and eukaryotes (e.g., Chlamydomonadaceae) in urban dust via the arsM amplicon sequencing. Temperature, a season-dependent environmental factor, profoundly affected the abundance of ABGs and the composition of microbes involved in arsenic methylation. This study provides new insights into the presence of ARGs within the urban dust.

Association between ambient temperature and influenza prevalence: A nationwide time-series analysis in 201 Chinese cities from 2013 to 2018.

BACKGROUND: Temperature affects influenza transmission; however, currently, limited evidence exists about its effect in China at the national and city levels as well as how temperature can be integrated into influenza interventions. METHODS: Meteorological, pollutant, and influenza data from 201 cities in mainland China between 2013 and 2018 were analyzed at both the city and national levels to investigate the relationship between temperature and influenza prevalence. We examined the impact of temperature on the time-varying reproduction number (Rt) using generalized additive quasi-Poisson regression models combined with the distributed lag nonlinear model. Threshold temperatures were determined for seven regions based on the early warning threshold of serious influenza outbreaks, set at Rt = 1.2. A multivariate random-effects meta-analysis was employed to assess region-specific associations. The excess risk (ER) index was defined to investigate the correlation between Rt and temperature, modified based on seasonal and regional characteristics. RESULTS: At the national level and in the central, northern, northwestern, and southern regions, temperature was found to be negatively correlated with relative risk, whereas the shapes of the data curves for the eastern, southwestern, and northeastern regions were not well defined. Low temperatures had an observable effect on influenza prevalence; however, the effects of high temperatures were not obvious. At an Rt of 1.2, the threshold temperatures for reaching a warning for serious influenza outbreaks were - 24.3 °C in the northeastern region, 16.6 °C in the northwestern region, and between 1℃ and 10 °C in other regions. CONCLUSION: The study findings revealed that temperature had a varying effect on influenza transmission trends (Rt) across different regions in China. By identifying region-specific temperature thresholds at Rt = 1.2, more effective early warning systems for influenza outbreaks could be tailored. These findings emphasize the significance of the region-specific adaptation of influenza prevention and control measures.

Roles and challenges encountered by midwives in the management of postpartum haemorrhage following normal vaginal delivery: A scoping review.

AIMS: To establish a comprehensive understanding of the roles of midwives and the challenges they encounter in the prevention, diagnosis and management of postpartum haemorrhage (PPH) following normal vaginal delivery. DESIGN: We conducted a scoping review following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis for Scoping Reviews (PRISMA-ScR) recommendations. METHODS: We considered studies related to the roles of midwives and the challenges they encounter in the prevention, diagnosis and management of PPH during vaginal delivery. We excluded guidelines, consensuses, abstracts of meetings and non-English language studies. Databases, including the Cochrane Library, PubMed, Web of Science, Ovid, Medline, Embase, JBI EBP and BIOSIS Previews, were searched on January 1, 2023, with no time limitations. RESULTS: We included 28 publications. Midwives play important roles in the prevention, diagnosis and management of postpartum haemorrhage during vaginal delivery. In the prevention of PPH, midwives' roles include identifying and managing high-risk factors, managing labour and implementing skin-to-skin contact. In the diagnosis of PPH, midwives' roles include early recognition and blood loss estimation. In the management of PPH, midwives are involved in mobilizing other professional team members, emergency management, investigating causes, enhancing uterine contractions, the repair of perineal tears, arranging transfers and preparation for surgical intervention. However, midwives face substantial challenges, including insufficient knowledge and skills, poor teamwork skills, insufficient resources and the need to deal with their negative emotions. Midwives must improve their knowledge, skills and teamwork abilities. Health care system managers and the government should give full support to midwives. Future research should focus on developing clinical practice guidelines for midwives for preventing, diagnosing and managing postpartum haemorrhage.

Plasmodium vivax serological exposure markers: PvMSP1-42-induced humoral and memory B-cell response generates long-lived antibodies.

Plasmodium vivax serological exposure markers (SEMs) have emerged as promising tools for the actionable surveillance and implementation of targeted interventions to accelerate malaria elimination. To determine the dynamic profiles of SEMs in current and past P. vivax infections, we screened and selected 11 P. vivax proteins from 210 putative proteins using protein arrays, with a set of serum samples obtained from patients with acute P. vivax and documented past P. vivax infections. Then we used a murine protein immune model to initially investigate the humoral and memory B cell response involved in the generation of long-lived antibodies. We show that of the 11 proteins, especially C-terminal 42-kDa region of P. vivax merozoite surface protein 1 (PvMSP1-42) induced longer-lasting long-lived antibodies, as these antibodies were detected in individuals infected with P. vivax in the 1960-1970s who were not re-infected until 2012. In addition, we provide a potential mechanism for the maintenance of long-lived antibodies after the induction of PvMSP1-42. The results indicate that PvMSP1-42 induces more CD73+CD80+ memory B cells (MBCs) compared to P. vivax GPI-anchored micronemal antigen (PvGAMA), allowing IgG anti-PvMSP1-42 antibodies to be maintained for a long time.

Changes in Serum Interleukin-8 Levels Predict Response to Immune Checkpoint Inhibitors Immunotherapy in Unresectable Hepatocellular Carcinoma Patients.

Background: Effective biomarkers are needed to predict the efficacy of immune checkpoint inhibitors (ICIs) therapy in hepatocellular carcinoma (HCC). We evaluated the early changes in serum interleukin-8 (IL-8) levels as a biomarker of response to ICIs in patients with unresectable HCC. Methods: Eighty patients who received ICIs therapy alone or in combination with other treatments for unresectable HCC were included. Serum was collected at baseline and 2-4 weeks after the first dose. Serum IL-8 levels were measured using by ELISA. Results: In the progressive disease (PD) group, serum IL-8 levels increased significantly before the second dose of ICIs therapy compared with baseline levels (P < 0.001). Early changes in serum IL-8 levels were significantly associated with the response to ICIs therapy (P < 0.001). A cutoff value of 8.1% increase over the baseline most effectively predicted the response to ICIs. Increases in serum IL-8 levels > 8.1% indicated the uselessness of ICIs immunotherapy in patients with unresectable HCC. Patients with increases in serum IL-8 levels > 8.1% had significantly shorter overall survival (OS) and progression-free survival (PFS) than those with increases in serum IL-8 levels ≤ 8.1% (P < 0.001). Increases in serum IL-8 levels > 8.1% were independent prognosticators of worse OS (P = 0.003) and PFS (P < 0.001). Conclusion: Early changes in serum IL-8 levels, measured only 2-4 weeks after starting therapy, could predict the response to ICIs therapy, as well as OS and PFS of patients with unresectable HCC. Increases in serum IL-8 levels > 8.1% indicated the uselessness of ICIs immunotherapy and predicted worse OS and PFS.

Tetrahydrofolate Attenuates Cognitive Impairment after Hemorrhagic Stroke by Promoting Hippocampal Neurogenesis via PTEN Signaling.

Intracerebral hemorrhage (ICH), the most common subtype of hemorrhagic stroke, leads to cognitive impairment and imposes significant psychological burdens on patients. Hippocampal neurogenesis has been shown to play an essential role in cognitive function. Our previous study has shown that tetrahydrofolate (THF) promotes the proliferation of neural stem cells (NSCs). However, the effect of THF on cognition after ICH and the underlying mechanisms remain unclear. Here, we demonstrated that administration of THF could restore cognition after ICH. Using Nestin-GFP mice, we further revealed that THF enhanced the proliferation of hippocampal NSCs and neurogenesis after ICH. Mechanistically, we found that THF could prevent ICH-induced elevated level of PTEN and decreased expressions of phosphorylated AKT and mTOR. Furthermore, conditional deletion of PTEN in NSCs of the hippocampus attenuated the inhibitory effect of ICH on the proliferation of NSCs and abnormal neurogenesis. Taken together, these results provide molecular insights into ICH-induced cognitive impairment and suggest translational clinical therapeutic strategy for hemorrhagic stroke.

Prediction and classification of chemical composition of ancient glass objects based on generalized Shapley functions.

Ancient glass products have suffered from the baptism of time and experienced changes in the burial environment and weathering, resulting in a change in the proportions of their chemical composition and interfering with their accurate identification by later generations. In this paper, the chemical composition of ancient glass products is predicted and identified. First, the multivariate statistical ANOVA test is applied to explore the relationship between whether the cultural relics samples are weathered or not and the glass type, decoration, and color to derive a law of chemical composition of the cultural relics and to analyze the correlation and difference among the four factors. Second, compared with the relevant data of the existing glass products, the missing values are processed by using the method of filling in the plurality. The weathering condition of the sampling points of the samples whose surfaces are not weathered is judged by the "distance discrimination method." Combined with the characteristics of the lead-barium glass and the high-potassium glass, the law of the chemical composition content on the surface of the samples, weathered or not, is explored. The modeling of the gray prediction method was applied again to predict the chemical composition content before weathering. Finally, the generalized Shapley function of fuzzy measurement was used to analyze the correlation between indicators and the chemical compositions and their differences. The scheme proposed in this paper can solve the difficult problem of category judgment in archeology, which is of great significance in promoting the smooth progress of archaeological work.

Efficacy and safety of enteral supplementation with high-dose vitamin D in critically ill patients with vitamin D deficiency.

BACKGROUND: Vitamin D deficiency is associated with mortality and morbidity in critically ill patients. This study investigated the safety and effectiveness of enteral high-dose vitamin D supplementation in intensive care unit (ICU) patients in Asia. METHODS: This was a multicenter, prospective, randomized-controlled study. Eligible participants with vitamin D deficiency were randomly assigned to the control or vitamin D supplementation group. In the vitamin D supplementation group, the patients received 569,600 IU vitamin D. The primary outcome was the serum 25(OH)D level on day 7. RESULTS: 41 and 20 patients were included in the vitamin D supplementation and control groups, respectively. On day 7, the serum 25(OH)D level was significantly higher in the vitamin D supplementation group compared to the control group (28.5 [IQR: 20.2-52.6] ng/mL and 13.9 [IQR: 11.6-18.8] ng/mL, p < 0.001). Only 41.5% of the patients achieved serum 25(OH)D levels higher than 30 ng/mL in the supplementation group. This increased level was sustained in the supplementation group on both day 14 and day 28. There were no significant adverse effects noted in the supplementation group. Patients who reached a serum 25(OH)D level of >30 ng/mL on day 7 had a significantly lower 30-day mortality rate than did those who did not (5.9% vs 37.5%, p < 0.05). CONCLUSIONS: In our study, less than half of the patients reached adequate vitamin D levels after the enteral administration of high-dose vitamin D. A reduction in 30-day mortality was noted in the patients who achieved adequate vitamin D levels. TRIAL REGISTRATION CLINICALTRIALS. GOV ID: NCT04292873, Registered, March 1, 2020.