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ObjectivesThis study summarizes the epidemiological characteristics, species distribution, and drug sensitivity of clinical nontuberculous mycobacteria (NTM) isolates at the Public Health Clinical Center of Chengdu, China, from January 2017 to December 2022.MethodsWe retrospectively analyzed data from patients with clinically isolated NTM strains. Chi-square analysis assessed the rate of Mycobacterium strain isolation over 6 years.ResultsThe number of samples tested for Mycobacterium tuberculosis (MTB) and/or NTM increased each year, while MTB detection decreased and NTM detection rose significantly each year (P=0.03). The average age of NTM patients was 51 ± 17.53 years, with a 14.1% HIV infection rate. The predominant isolates were Mycobacterium avium-intracellulare (MAC) and M. chelonae/M. abscessus, with 96.4% of cases being of Han ethnicity. Amikacin, moxifloxacin, and clarithromycin were effective against M. avium and M. intracellulare; linezolid, amikacin, and cefoxitin were effective against M. chelonae/M. abscessus. Over 90% of NTM cases originated from the respiratory tract.ConclusionThe NTM isolation rate in Southwest China has risen in recent years, primarily among elderly patients with a high HIV co-infection rate. The main NTM isolates were MAC and M. chelonae/M. abscessus. Amikacin, moxifloxacin, clarithromycin, and linezolid exhibited strong antibacterial activity against SGM, while amikacin and linezolid displayed relatively better antibacterial activity against RGM. The prevalence of NTM infection may be positively associated with regional economic development and health conditions.

When rockfall occurs along dense rock slopes, the rotation direction of rockfall is not always downhill. Specifically, the rockfall may obtain a reverse rotation speed (RRS) after impact under certain conditions, the effect of which on the restitution coefficient (RC) cannot be ignored. According to the statistical results of the reverse rotation (RR) phenomena of blocks obtained from previous experiments, the occurrence of RR is correlated to the block shape, incident angle, and contact attitude. In this study, considering a typically shaped cubic block, the critical condition for the RR is preliminarily deduced. Based on the results, the influence of the RRS on the RC for four typically shaped blocks is examined using a customized device. Results show that the tangential RC (Rt) values of each block are not sensitive to the change in the RRS, the distribution is relatively concentrated and the values are high. Moreover, the normal RC (Rn) values are not sensitive to the RRS, and the distribution is relatively discrete. The RRS influences Rn; however, it is difficult to directly establish the relationship between them. To this end, considering the contact attitude and shape of the block, an integral variable, the impact coefficient (Ic), is proposed to determine the influence of RRS on Rn. Moreover, the impact-bounce behaviours of the block are categorized and analysed. For the block rebound following a single impact, Ic and Rn are positively and negatively correlated when the mass centre of the block (MC) is in front and behind the contact point (CP), respectively. For the block rebound following two successive impacts, with the increase in Ic, the Rn increases. These conclusions help clarify the mechanism of the influence of the RRS on RC and provide vital information and ideas for the development and optimization of a program to accurately predict rockfall trajectories.

BackgroundThe incidence of prostate cancer (PCa) has continued to increase since the US Preventive Services Task Force (USPSTF) recommendations against prostate-specific antigen (PSA)-based screening for all men in 2012, approximately half of additional diagnosed cases are advanced-stage, including regional PCa and metastatic PCa (mPCa). It is very important to investigate the shift in mPCa incidence and mPCa-related mortality risk, as the survival of mPCa remains poor.ObjectiveTo investigate the incidence temporal trend of mPCa stratified by metastatic site, including bone and visceral metastatic involvement, and potential survival improvements.MaterialsBased on the recently released Surveillance, Epidemiology, and End Results (SEER) data (2010-2019), the age-adjusted incidence rates of mPCa with bone and visceral involvement with annual percentage changes (APCs) were assessed by a joinpoint regression model in men aged 45 years and older by age and race groups, and potential recent improvements in overall survival (OS) and cancer-specific survival (CSS) were estimated by the Kaplan−Meier method and Cox regression model.ResultsFrom 2010 to 2019, a total of 19081 (84.8%) and 3413 (15.2%) mPCa patients with bone and visceral involvement, respectively, were recorded in the SEER database. Considering all races and age groups, the incidence rate of mPCa with bone metastasis remained stable during 2017-2019 (APC, 0.9%; p=0.421) after increasing during 2010-2017 (APC, 5.8%; p

As a typical solitary animal, adult giant pandas rely on chemical signals (sex pheromones) to transmit reproductive information during oestrous. Although researchers have confirmed that the gut microbiota is related to the emission and reception of sex pheromones, there is no clear correlation between the gut microbes and the synthesis of sex pheromone of giant pandas, that is, which gut microbes and microbial metabolites are participate in the synthesis of giant panda’s sex pheromone. As a mirror of gut microbiota, fecal microbiota can reflect the composition of gut microbiota and its interaction with host to some extent. The purpose of this study is to explore how the gut microbes affect the synthesis of sex pheromones in captive giant pandas by combining analysis of the fecal microbiome and metabolomics. The results of correlation and microbial function analysis show that intestinal microorganisms such as Veillonellaceae and Lactobacillilaceae are associated with the synthesis of short chain fatty acid (acetic acid) and volatile ester metabolites, such as 1-butanol, 3-methyl, acetate, acetic acid, hexyl ester and 3-hexen-1-ol, acetate, (Z). In summary, based on this study, we believe that volatile metabolites such as fecal acetate participate in the process of mate preference of captive giant pandas and affect their expression of natural mating behavior. The possible mechanism is that the gut microbes can promote the synthesis of key chemical signaling substances in perianal glands through mediated intermediate fecal metabolites, thus affecting the normal information exchange between giant pandas individuals. The results of this study have greatly enriched our understanding of gut microbes regulating the synthesis of sex pheromones in giant pandas.

Major psychiatric disorders create a significant public health burden, and mental disorders such as major depressive disorder, bipolar disorder, and schizophrenia are major contributors to the national disease burden. The search for biomarkers has been a leading endeavor in the field of biological psychiatry in recent decades. And the application of cross-scale and multi-omics approaches combining genes and imaging in major psychiatric studies has facilitated the elucidation of gene-related pathogenesis and the exploration of potential biomarkers. In this article, we summarize the results of using combined transcriptomics and magnetic resonance imaging to understand structural and functional brain changes associated with major psychiatric disorders in the last decade, demonstrating the neurobiological mechanisms of genetically related structural and functional brain alterations in multiple directions, and providing new avenues for the development of quantifiable objective biomarkers, as well as clinical diagnostic and prognostic indicators.

Background and aimsAn increasing number of studies have confirmed that non-textbook outcomes (non-TO) are a risk factor for the long-term outcome of malignant tumors. It is particularly important to identify the predictive factors of non-TO to improve the quality of surgical treatment. We attempted to construct two nomograms for preoperative and postoperative prediction of non-TO after laparoscopic hepatectomy for hepatocellular carcinoma (HCC).MethodsPatients who underwent curative-intent hepatectomy for HCC between 2014 and 2021 at two Chinese hospitals were analyzed. Using univariate and multivariate analyses, the independent predictors of non-TO were identified. The prediction accuracy is accurately measured by the receiver operating characteristic (ROC) curve and calibration curve. ROC curves for the preoperative and postoperative models, Child–Pugh grade, BCLC staging, and 8th TNM staging were compared relative to predictive accuracy for non-TO.ResultsAmong 515 patients, 286 patients (55.5%) did not achieve TO in the entire cohort. Seven and eight independent risk factors were included in the preoperative and postoperative predictive models by multivariate logistic regression analysis, respectively. The areas under the ROC curves for the postoperative and preoperative models, Child–Pugh grade, BCLC staging, and 8th TNM staging in predicting non-TO were 0.762, 0.698, 0.579, 0.569, and 0.567, respectively.ConclusionOur proposed preoperative and postoperative nomogram models were able to identify patients at high risk of non-TO following laparoscopic resection of HCC, which may guide clinicians to make individualized surgical decisions, improve postoperative survival, and plan adjuvant therapy against recurrence.

Goats with diverse economic phenotypic traits play an important role in animal husbandry. However, the genetic mechanisms underlying complex phenotypic traits are unclear in goats. Genomic studies of variations provided a lens to identify functional genes. In this study, we focused on the worldwide goat breeds with outstanding traits and used whole-genome resequencing data in 361 samples from 68 breeds to detect genomic selection sweep regions. We identified 210–531 genomic regions with six phenotypic traits, respectively. Further gene annotation analysis revealed 332, 203, 164, 300, 205, and 145 candidate genes corresponding with dairy, wool, high prolificacy, poll, big ear, and white coat color traits. Some of these genes have been reported previously (e.g., KIT, KITLG, NBEA, RELL1, AHCY, and EDNRA), while we also discovered novel genes, such as STIM1, NRXN1, LEP, that may be associated with agronomic traits like poll and big ear morphology. Our study found a set of new genetic markers for genetic improvement in goats and provided novel insights into the genetic mechanisms of complex traits.

BackgroundDelirium detection is challenging due to the fluctuating nature and frequent hypoactive presentation. This study aimed to determine an optimal strategy that detects delirium with higher sensitivity but lower effort in older patients admitted to the intensive care unit (ICU) after surgery.MethodsThis was a secondary analysis of the database from a randomized trial. Seven hundred older patients (aged ≥65 years) who were admitted to the ICU after elective noncardiac surgery were enrolled. Delirium was assessed with the Confusion Assessment Method for the ICU (CAM-ICU) twice daily during the first 7 days postoperatively. The sensitivity of different strategies in detecting delirium were analyzed and compared.ResultsOf all enrolled patients, 111 (15.9%; 95% CI: 13.3% to 18.8%) developed at least one episode of delirium during the first 7 postoperative days. Among patients who developed delirium, 60.4% (67/111) had their first delirium onset on postoperative day 1, 84.7% (94/111) by the end of day 2, 91.9% (102/111) by the end of day 3, and 99.1% (110/111) by the end of day 4. Compared with delirium assessment twice daily for 7 days, twice-daily measurements for 5 days detected 100% of delirium patients with 71% efforts; twice-daily measurements for 4 days detected 99% (95% CI: 94% to 100%) of delirium patients with 57% efforts; twice-daily assessment for 3 days detected 92% (95% CI: 85% to 96%) of delirium patients with only 43% efforts.ConclusionsFor older patients admitted to the ICU after elective noncardiac surgery, it is reasonable to detect delirium with the CAM-ICU twice daily for no more than 5 days, and if the personnel and funds are insufficient, 4 days could be sufficient.

BackgroundOsteoarticular tuberculosis (TB) is an uncommon form of extrapulmonary TB. In this study, we analyzed the epidemiological characteristics, common sites, and drug resistance profiles of osteoarticular TB infections occurring in southwest China.MethodsA total of 3,254 cases of patients clinically diagnosed with osteoarticular TB infections between 2013 and 2021 were retrospectively analyzed. Patients' demographic and clinical characteristics were collected. Drug sensitivity testing was performed using the microporous plate ratio method. Chi-squared analysis was used to analyze the rates of and trends in mycobacterial isolates.ResultsOf the 3,254 patients, 1,968 (60.5%) were men and boys, and 1,286 (39.5%) were women and girls; patients' ages ranged from 1 to 91 years, with an average of 42 ± 19.3 years. In terms of disease, 2,261 (69.5%) had spinal TB, mainly thoracic (815, 36%) or lumbar (1,080, 48%); joint TB was found in 874 cases (26.9%), mainly occurring in the knee (263, 30%) or hip (227, 26%); and both spinal and joint TB were observed in 119 cases (3.7%). Drug susceptibility tests were performed on 241 isolated strains of MTB; 70 strains (29.0%) were resistant to at least one drug, and MDR-TB and XDR-TB were observed in 7.1 and 1.2% of strains, respectively.ConclusionsIn southwest China over this period, osteoarticular TB mainly affected middle-aged and young men with poor nutritional status. Patients from ethnic minority areas also accounted for a large proportion of cases. Spinal TB is prone to occur in the lumbar and thoracic vertebrae, and joint TB is prone to occur in the lower limb joints. Additionally, there has been an increasing trend in the number of TB cases over the past 9 years, and drug resistance has also increased.

Background: Intracellular copper homeostasis requires a complex system. It has shown considerable prospects for intervening in the tumor microenvironment (TME) by regulating copper homeostasis and provoking cuproptosis. Their relationship with hepatocellular carcinoma (HCC) remains elusive.Methods: In TCGA and ICGC datasets, LASSO and multivariate Cox regression were applied to obtain the signature on the basis of genes associated with copper homeostasis and cuproptosis. Bioinformatic tools were utilized to reveal if the signature was correlated with HCC characteristics. Single-cell RNA sequencing data analysis identified differences in tumor and T cells’ pathway activity and intercellular communication of immune-related cells. Real-time qPCR analysis was conducted to measure the genes’ expression in HCC and adjacent normal tissue from 21 patients. CCK8 assay, scratch assay, transwell, and colony formation were conducted to reveal the effect of genes on in vitro cell proliferation, invasion, migration, and colony formation.Results: We constructed a five-gene scoring system in relation to copper homeostasis and cuproptosis. The high-risk score indicated poor clinical prognosis, enhanced tumor malignancy, and immune-suppressive tumor microenvironment. The T cell activity was markedly reduced in high-risk single-cell samples. The high-risk HCC patients had a better expectation of ICB response and reactivity to anti-PD-1 therapy. A total of 156 drugs were identified as potential signature-related drugs for HCC treatment, and most were sensitive to high-risk patients. Novel ligand-receptor pairs such as FASLG, CCL, CD40, IL2, and IFN-Ⅱ signaling pathways were revealed as cellular communication bridges, which may cause differences in TME and immune function. All crucial genes were differentially expressed between HCC and paired adjacent normal tissue. Model-constructed genes affected the phosphorylation of mTOR and AKT in both Huh7 and Hep3B cells. Knockdown of ZCRB1 impaired the proliferation, invasion, migration, and colony formation in HCC cell lines.Conclusion: We obtained a prognostic scoring system to forecast the TME changes and assist in choosing therapy strategies for HCC patients. In this study, we combined copper homeostasis and cuproptosis to show the overall potential risk of copper-related biological processes in HCC for the first time.

Dapagliflozin has been used to treat patients with type 1 diabetes mellitus; however, the actual drug efficacy of dapagliflozin on glycated hemoglobin (HbA1c) and whether there is a rebound from dapagliflozin efficacy on HbA1c remain unknown. The present study aimed to explore the actual therapeutic effect and rebound situation of dapagliflozin on HbA1c in type 1 diabetes mellitus patients. A total of 1,594 type 1 diabetes mellitus patients were enrolled for analysis using a non-linear mixed effect model from randomized controlled trials from published literature works including two 5 mg/day dapagliflozin dosage groups and three 10 mg/day dapagliflozin dosage groups. The change rate of HbA1c from a baseline value was chosen as a dapagliflozin pharmacodynamic evaluation index. After deducting control group effects, the therapeutic effect of 5 and 10 mg/day dapagliflozin on HbA1c in type 1 diabetes mellitus patients had no significant difference. In addition, the actual maximal efficacy (AEmax) of dapagliflozin on HbA1c was -6.24% at week 9. When it reached the AEmax, the dapagliflozin pharmacodynamic rebound on HbA1c occurred, and when the treatment was continued for 0.5 and 1 year, the actual efficacies were -4.70% (75% AEmax) and -3.27% (52% AEmax), respectively. This was the first time to clarify the actual therapeutic effect and rebound situation of dapagliflozin on HbA1c in type 1 diabetes mellitus patients, providing a reference value for clinical practices.

BackgroundThe sivelestat is a neutrophil elastase inhibitor thought to have an effect against acute lung injury (ALI) in patients after scheduled cardiac surgery. However, the beneficial effect of sivelestat in patients undergoing emergent cardiovascular surgery remains unclear. We aim to evaluate the effect of sivelestat on pulmonary protection in patients with ALI after emergent cardiovascular surgery.MethodsFirstly, a case-control study in 665 patients undergoing emergent cardiovascular surgery from January 1st, 2020 to October 26th, 2022 was performed. 52 patients who received sivelestat (0.2mg/kg/h for 3 days) and 613 age- and sex-matched controls. Secondly, a propensity-score matched cohort (sivelestat vs control: 50 vs 50) was performed in these 665 patients. The primary outcome was a composite of adverse outcomes, including 30-day mortality, ECMO, continuous renal replacement therapy (CRRT) and IABP, etc. The secondary outcome included pneumonia, ventricular arrhythmias and mechanical ventilation time, etc.ResultsIn propensity-matched patients, the 30-day mortality (16% vs 24%, P=0.32), stroke (2% vs 8%, P=0.17), ECMO(6% vs 10%, P=0.46), IABP(4% vs 8%, P=0.40) and CRRT(8% vs 20%, P=0.08) had no differences between sivelestat and control group; sivelestat could significantly decrease pneumonia (40% vs 62%, P=0.03), mechanical ventilation time (median: 96hours, IQR:72-120hours vs median:148hours, IQR:110-186hours, P

BackgroundKetamine is approved for antidepressant therapy, but evidence regarding its use in women with perinatal depression is lacking. Herein, we investigated the effects of low-dose ketamine in women with prenatal depressive symptoms and tested the feasibility of a future large randomized trial.MethodsThis was a randomized, double-blind, placebo-controlled pilot trial. Sixty-six women with prenatal depressive symptoms who were scheduled for elective cesarean delivery were randomized to receive either low-dose ketamine (0.5 mg/kg) or placebo (normal saline). The study drugs were intravenously infused over a 40-minute period after clamping the umbilical cord. The primary outcome was depression score assessed with the Edinburgh Postnatal Depression Scale at 48 h postpartum. Among other and safety outcomes, occurrence of nausea or vomiting was observed, pain intensity was assessed with the numeric rating scale. The feasibility of implementing the protocol was also evaluated.ResultsA total of 64 parturients were included in the intention-to-treat analysis. The depression score at 48 h did not differ between groups: median 9 (interquartile range 6 to 13) with ketamine vs. 8 (6 to 10) with placebo; median difference 1, 95% CI −1 to 3; P = 0.608. The pain intensity at 4 h postpartum was less severe in the ketamine group (median difference −1, 95% CI −1 to 0, P = 0.002). Among safety outcomes, intraoperative nausea or vomiting was less common in patients given ketamine (0.0% [0/33] with ketamine vs. 21.2% [7/33] with placebo, P = 0.011). Recruitment was satisfactory and the protocol was acceptable to participants and clinicians.ConclusionsA single low-dose ketamine infusion did not decrease the depression score at 2 days, but reduced intraoperative nausea and vomiting and lowered pain intensity at 4 h after cesarean delivery among women with prenatal depressive symptoms. The study protocol is feasible for a large randomized trial.Clinical Trial RegistrationThe study was registered with ClinicalTrials.gov (identifier: NCT03336541; 08/11/2017).

Thoracic surgery has increased drastically in recent years, especially in light of the severe outbreak of the 2019 novel coronavirus disease (COVID-19). Routine “passive” chest computed tomography (CT) screening of inpatients detects some pulmonary diseases requiring thoracic surgeries timely. As an essential device for thoracic anesthesia, the double-lumen tube (DLT) is particularly important for anesthesia and surgery. With the continuous upgrading of the DLTs and the widespread use of fiberoptic bronchoscopy (FOB), the position of DLT in thoracic surgery is gradually becoming more stable and easier to observe or adjust. However, DLT malposition still occurs during transferring patients from a supine to the lateral position in thoracic surgery, which leads to lung isolation failure and hypoxemia during one-lung ventilation (OLV). Recently, some innovative DLTs or improved intervention methods have shown good results in reducing the incidence of DLT malposition. This review aims to summarize the recent studies of the incidence of left-sided DLT malposition, the reasons and effects of malposition, and summarize current methods for reducing DLT malposition and prospects for possible approaches. Meanwhile, we use bibliometric analysis to summarize the research trends and hot spots of the DLT research.

ObjectiveHyperglycemia is common in critically ill patients after surgery and is associated with worse perioperative outcomes. Yet, the impact of postoperative hyperglycemia on long-term outcomes remains unclear. We therefore analyzed the association between early postoperative hyperglycemia and 3-year overall survival in older patients who were admitted to the intensive care unit after surgery.MethodsThis was a post hoc analysis of database obtained from a previous randomized trial and 3-year follow-up. The underlying trial enrolled 700 patients aged 65 years or older who were admitted to the intensive care unit after elective non-cardiac surgery. Early postoperative time-weighted average blood glucose was calculated and was divided into three levels, i.e., 10.0 mmol/L. The primary outcome was 3-year overall survival. The association between time-weighted average blood glucose level and 3-year overall survival was analyzed with Cox proportional hazard regression models. Subgroup analyses were also performed in patients with or without diabetes, and in patients following cancer or non-cancer surgery.ResultsA total of 677 patients (mean age 74 years, 60% male sex) were included in the final analysis. Within 3 years after surgery, deaths occurred in 22.1% (30/136) of patients with time-weighted average blood glucose 10.0 mmol/L (unadjusted hazard ratio 1.91, 95% CI 1.28 to 2.85, P = 0.002). After adjustment for confounding factors, the risk of 3-year mortality remained higher in patients with time-weighted average blood glucose from 8.0 to 10.0 mmol/L (adjusted hazard ratio 2.28, 95% CI 1.47 to 3.54, P < 0.001) and in those >10.0 mmol/L (adjusted hazard ratio 2.00, 95% CI 1.29 to 3.10, P = 0.002). Similar results were obtained in the subgroups of patients without diabetes and patients following cancer surgery.ConclusionFor older patients admitted to the intensive care unit after elective non-cardiac surgery, high early blood glucose (time-weighted average blood glucose ≥ 8.0 mmol/L) was associated with poor 3-year overall survival. The impact of moderate glycemic control on long-term survival deserves further investigation.

Traditional pavement materials used in the orthotropic steel bridge deck suffer from various pavement distresses and thus reduce the service life of the steel bridge. Therefore, this study proposed a novel engineered material named polyester polyurethane concrete (PPUC) for the steel bridge deck pavement. Indoor laboratory experiments and numerical comparison analysis were conducted to comprehensively assess the feasibility of PPUC as the steel bridge deck pavement and ordinary Portland cement (OPC), guss asphalt concrete (GAC), asphalt mastic concrete (SMAC) and epoxy asphalt concrete (EAC) were used as references compared with PPUC. After the specimens of PPUC were prepared by mixing polyester polyurethane binder (PPUB) and aggregate with the binder-aggregate ratio of 15%, the specimens were subjected to compressive test, splitting tensile test, flexural tensile strength test, wheel tracking test, low-temperature cracking test, freeze-thaw splitting test, shear test and pull-out test. The mechanical performance comparison of different pavement structures with different materials was also analyzed using finite element analysis method. Results show that PPUC presents higher mechanical properties (compressive, tensile and flexural strength) compared to OPC, and it has good durability properties compared to SMAC, GAC, and EAC, such as high temperature stability, low temperature cracking resistance and water stability. In addition, PPUC has strong adhesive property with steel deck and does not change significantly with temperature changes. The finite element simulation results show that the maximum tensile strength and maximum compressive strength of PPUC in the single-layer structure are 0.51 MPa and 3.52 MPa respectively, which are much smaller than the experimental values and those of other materials. The maximum tensile strength and maximum shear strength of PPUC in the PPUC + SMAC composite structure are 0.232 MPa and 0.148 MPa respectively, which are also much smaller than the experimental values and those of other structures. The mechanical performance comparison results indicate that PPUC pavement structure can improve the overall stiffness of the steel bridge deck and protect the wear layer. These results support that the PPUC has a promising application for the steel bridge deck pavement.

Background: Esophageal Squamous Cell Cancer (ESCC) is an aggressive disease associated with a poor prognosis. As a newly defined form of regulated cell death, ferroptosis plays a crucial role in cancer development and treatment and might be a promising therapeutic target. However, the expression patterns of ferroptosis-related genes (FRGs) in ESCC remain to be systematically analyzed.Methods: First, we retrieved the transcriptional profile of ESCC from TCGA and GEO datasets (GSE47404, GSE23400, and GSE53625) and performed unsupervised clustering to identify different ferroptosis patterns. Then, we used the ssGSEA algorithm to estimate the immune cell infiltration of these patterns and explored the differences in immune cell abundance. Common genes among patterns were finally identified as signature genes of ferroptosis patterns.Results: Herein, we depicted the multi-omics landscape of FRGs through integrated bioinformatics analysis and identified three ESCC subtypes with distinct immune characteristics: clusters A-C. Cluster C was abundant in CD8+ T cells and other immune cell infiltration, while cluster A was immune-barren. By comparing the differently expressed genes between clusters of diverse datasets, we defined a gene signature for each cluster and successfully validated it in the TCGA-ESCC dataset.Conclusion: We provided a comprehensive insight into the expression pattern of ferroptosis genes and their interaction with immune cell infiltration. Additionally, we established a gene signature to define the ferroptosis patterns, which might be used to predict the response to immunotherapy.

The aim of the present study is to investigate the quantitative effects of sodium–glucose cotransporter-2 (SGLT-2) inhibitors on the quality of life in heart failure (HF) patients. A total of 14,674 HF patients from two dapagliflozin and three empagliflozin studies is included for analysis via the nonlinear mixed-effect modeling (NONMEM) software, among which the change rate of the Kansas City Cardiomyopathy Questionnaire (KCCQ) score is used as the evaluation index. There is no significant difference in the pharmacodynamics influencing the quality of life in HF patients between the SGLT-2 inhibitors: 10 mg/day dapagliflozin and 10 mg/day empagliflozin. For the clinical summary score (CSS), total symptom score (TSS), and overall summary score (OSS), the Emax of the SGLT-2 inhibitors on the quality of life in HF patients is 3.74%, 4.43%, and 4.84%, respectively, and ET50 is 2.23, 4.37, and 7.15 weeks, respectively. In addition, the time duration of achieving 25%, 50%, 75%, and 80% Emax is 0.75, 2.23, 6.69, and 8.92 weeks for the CSS; 1.46, 4.37, 13.11, and 17.48 weeks for the TSS; and 2.39, 7.15, 21.45, and 28.6 weeks for the OSS, respectively. Therefore, to reach the plateau period (80% of Emax) of SGLT-2 inhibitors on the CSS, TSS, and OSS, 10 mg/day dapagliflozin (or 10 mg/day empagliflozin) is required to be taken for 8.92 weeks, 17.48 weeks, and 28.6 weeks, respectively. This is the first time that the quantitative effects of SGLT-2 inhibitors on the quality of life in HF patients are being explored.

Background & aimsThe long-term prognosis of patients with metabolic syndrome (MS) and hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) after radical hepatectomy remains unclear. The purpose of this study was to elucidate the effect of MS on long-term survival for patients with HBV-related HCC after hepatectomy.MethodsPatients with HBV-HCC after hepatectomy were included. Patients were stratified into MS-HBV-HCC and HBV-HCC groups. Clinical features and surgical outcomes were compared between the two groups, and COX regression analysis was used to determine independent risk factors associated with overall survival (OS) and recurrence-free survival (RFS).Result389 patients (MS-HBV-HCC group: n=50, HBV-HCC group: n=339) were enrolled for further analysis. Baseline characteristics showed that patients with MS-HBV-HCC were associated with a high rate of elderly patients, ASA score, and co-morbid illness, but a lower rate of anatomy hepatectomy. There were no significant differences in perioperative complications. After excluding patients who relapsed or died within 90 days after surgery, multivariate Cox regression analysis showed MS was an independent risk factor of OS (HR 1.68, 95% CI 1.05-2.70, P = 0.032) and RFS (HR 1.78, 95% CI 1.24-2.57, P = 0.002).ConclusionMS is an independent risk factor for poor OS and RFS in HBV-infected HCC patients after radical hepatectomy. This suggests that we need to strengthen postoperative follow-up of the relevant population and encourage patients to develop a healthy lifestyle.

PurposeTo investigate the influence of changes in T1 slope (T1S) and cervical sagittal vertical axis (CSVA) on cervical laminoplasty outcomes.MethodsEighty-one patients with cervical spondylotic myelopathy (CSM) treated with cervical laminoplasty were enrolled in this study. Demographic parameters included age and follow-up time. Imaging data included occiput-C2 lordosis (OC2), C2–C7 Cobb angle (CL), T1S, CSVA. Outcome assessment indicators included the Japanese Orthopedic Association (JOA) score, JOA recovery rate, and neck disability index (NDI). All patients were grouped based on preoperative T1S and variation in CL after surgery, respectively. Patients with decreased CL postoperatively were further grouped according to whether they were combined with T1S reduction.ResultsThere were no significant differences in the final JOA score, JOA recovery rate, or NDI between patients with different T1S. Patients with loss of CL postoperatively had lower JOA score and JOA recovery rate, but higher NDI than patients with sustained CL. Furthermore, patients with CL loss but compensate for it with reduction in T1S had lower CSVA, higher JOA score and JOA recovery rate than those with CL loss alone.ConclusionsDecreased T1S postoperatively prevents the tendency of the cervical spine to tilt forward by regulating CSVA and facilitates recovery of neurological function after cervical laminoplasty.

Knowledge of adequate diets can improve an individual's health status. Although previous studies have identified the main resources from which Chinese people acquire dietary knowledge, it is still unclear whether information sources regarding diets (ISRDs) can increase individuals' knowledge of adequate diets (KAD) and which ISRDs are most effective in conveying KAD to the Chinese population. In this study, we interviewed 4,710 residents in Eastern China regarding their ISRDs and KAD. Descriptive statistics, ANOVA, and multivariate linear regression were used to analyze the effectiveness of different ISRDs in transmitting KAD to Chinese individuals and to determine the relationship between ISRDs and KAD. Results showed that the KAD scores of the respondents were low overall in Eastern China. Providing dietary information through expert lectures, books, newspapers, magazines, and social media could significantly improve the average KAD score of Chinese individuals. Respondents with a greater number of ISRDs were more likely to have higher KAD scores. These findings suggest that the number of ISRDs should be increased. In particular, emphasis should be placed on the role of expert lectures, books, newspapers, magazines, and social media.

ObjectiveThis study investigated the effects of 12 weeks of specifically designed physical activity intervention on working memory and motor competence in preschool children and explored the correlation between working memory changes and motor competence changes by the intervention.MethodsFour classes of preschool children were grouped into an intervention group and a control group. Children in the intervention group received a 12-week physical activity intervention, while children in the control group followed their daily routine as usual. Before and after the intervention period, children were assessed with the 1-back task and Movement Assessment Battery for Children, second edition (MABC-2) to measure their working memory and motor competence, respectively.ResultsRegarding working memory, the accuracy on the 1-back task increased significantly in the intervention group relative to the control group. The intervention group demonstrated a greater decrease in response time from pre- to posttest than the control group, but the difference was not statistically significant. Regarding motor competence, children's manual dexterity, aiming and catching and total score increased significantly in the intervention group relative to the control group, while no significant difference in static and dynamic balance was observed between the two groups. Furthermore, the correlation results showed that changes in the efficacy and efficiency of working memory were positively related to changes in static and dynamic balance and the total score on the MABC-2.ConclusionThese findings demonstrated that 12 weeks of specifically designed physical activity intervention could improve preschool children's efficacy of working memory as well as manual dexterity, aiming and catching and global motor competence. The improvement in the efficacy and efficiency of working memory was positively related to the improvement in static and dynamic balance and global motor competence.

The decline in natural mating behavior is the primary reason underlying in the poor population growth of captive giant pandas. However, the influencing factors and underlying mechanisms remain unclear to data. It is speculated that the decline in natural mating behavior could be related to the psychological stress caused by captivity, which restricts their free choice of mates. In order to test this hypothesis, we performed urinary metabolomics analysis using Ultra-High-Performance Liquid Chromatography-Mass Spectrometry (UHPLC/-MS) combined with 16S rDNA sequencing for exploring the physiological mechanism underlying the decline in the natural mating behavior of captive giant panda. The results demonstrated that the decline in mating ability could be related to abnormalities in arginine biosynthesis and neurotransmitter synthesis. Additionally, the relative abundance of bacteria from the Firmicutes, Proteobacteria, and Actinobacteria phyla and the Acinetobacter, Weissella, and Pseudomonas genus was significantly reduced in the group with low natural mating behavior. These findings imply that the inhibition of arginine synthesis induced by environmental changes could be related to the poor libido and failure of mate selection in captive giant pandas during the breeding period. The results also demonstrate the relationship between the altered urinary microbes and metabolites related to arginine and neurotransmitter synthesis. These findings may aid in understanding the mechanism underlying environment-induced mate selection in captive giant pandas and propose a novel strategy for determining the sexual desire of giant pandas based on urinary microbes. The method would be of great significance in improving the natural reproductive success rate of captive giant pandas.

Cancer is one of the most serious diseases threatening human health, so it is particularly important to develop effective tumor-targeting drugs. As the first CDK4/6 inhibitor, palbociclib effectively inhibits tumor proliferation by blocking the cell cycle to the G1 phase. 10-HCPT is a Topo I inhibitor; however, its clinical application has been greatly limited due to its high toxicity. Based on the successful development of double target inhibitors, three novel palbociclib derivatives (HP-1, HP-2, and HP-3) were designed and synthesized from Palbociclib and 10-HCPT, and their biological activities were investigated. At first, the possible binding sites of the three compounds to Topo I and CDK4/6 were predicted by molecular docking. Then, we evaluated the anti-proliferative effects of the three palbociclib derivatives. In general, human lung cancer cells were more sensitive to HP-1, HP-2, and HP-3, especially NCI-H460. In addition, cell cycle arrest and apoptosis induction were investigated by flow cytometry. The three palbociclib derivatives, especially HP-1, had obvious cell cycle arrest phenomenon on NCI-H460 cells and induced apoptosis of NCI-H460 cells significantly. In the end, it was proved that these three drugs had obvious cyclin-dependent kinase inhibitory activities. In short, all the data showed that HP-1, HP-2, and HP-3 could play anti-cancer roles by acting on dual targets and had the characteristics of high efficiencies and low toxicities, which opened up a new idea for the study of palbociclib derivatives.

BackgroundSleep disturbances are prevalent in patients requiring invasive mechanical ventilation in the intensive care unit (ICU) and are associated with worse outcomes. Sedative-dose dexmedetomidine may improve sleep quality in this patient population but is associated with adverse events. Herein, we tested the effect of low-dose dexmedetomidine infusion on nighttime sleep quality in postoperative ICU patients with invasive ventilation.MethodsIn this pilot randomized trial, 80 adult patients who were admitted to the ICU after non-cardiac surgery and required invasive mechanical ventilation were randomized to receive either low-dose dexmedetomidine (0.1 to 0.2 μg/kg/h, n = 40) or placebo (n = 40) for up to 72 h. The primary endpoint was overall subjective sleep quality measured using the Richards–Campbell Sleep Questionnaire (score ranges from 0 to 100, with a higher score indicating better quality) in the night of surgery. Secondary outcomes included sleep structure parameters monitored with polysomnography from 9:00 PM on the day of surgery to the next 6:00 AM.ResultsAll 80 patients were included in the intention-to-treat analysis. The overall subjective sleep quality was median 52 (interquartile 20, 66) with placebo vs. 61 (27, 79) with dexmedetomidine, and the difference was not statistically significant (median difference 8; 95% CI: −2, 22; P = 0.120). Among 68 patients included in sleep structure analysis, those in the dexmedetomidine group tended to have longer total sleep time [median difference 54 min (95% CI: −4, 120); P = 0.061], higher sleep efficiency [median difference 10.0% (95% CI: −0.8%, 22.3%); P = 0.060], lower percentage of stage N1 sleep [median difference −3.9% (95% CI: −11.8%, 0.5%); P = 0.090], higher percentage of stage N3 sleep [median difference 0.0% (95% CI: 0.0%, 0.4%); P = 0.057], and lower arousal index [median difference −0.9 (95% CI −2.2, 0.1); P = 0.091] but not statistically significant. There were no differences between the two groups regarding the incidence of adverse events.ConclusionAmong patients admitted to the ICU after surgery with intubation and mechanical ventilation, low-dose dexmedetomidine infusion did not significantly improve the sleep quality pattern, although there were trends of improvement. Our findings support the conduct of a large randomized trial to investigate the effect of low-dose dexmedetomidine in this patient population.Clinical trial registrationClinicalTrial.gov, identifier: NCT03335527.

BackgroundEarly identification of patients who will benefit from immune checkpoint inhibitors (ICIs) has recently become a hot issue in cancer immunotherapy. Peripheral cytokines are key regulators in the immune system that can induce the expression of immune checkpoint molecules; however, the association between peripheral cytokines and the efficiency of ICIs remains unclear.MethodsA systematic review was conducted in several public databases from inception through 3 February 2022 to identify studies investigating the association between peripheral cytokines (i.e., IL-1β, IL-2, IL-2RA, IL-2R, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12, IL-15, IL-17, TNF-α, IFN-γ, and TGF-β) and ICI treatment. Survival data, including overall survival (OS) and/or progression-free survival (PFS), were extracted, and meta-analyses were performed.ResultsTwenty-four studies were included in this analysis. The pooled results demonstrated that the pretreatment peripheral levels of IL-6 (univariate analysis: HR = 2.53, 95% CI = 2.21–2.89, p < 0.00001; multivariate analysis: HR = 2.21, 95% CI = 1.67–2.93, p < 0.00001) and IL-8 (univariate analysis: HR = 2.17, 95% CI = 1.98–2.38, p < 0.00001; multivariate analysis: HR = 1.88, 95% CI= 1.70–2.07, p < 0.00001) were significantly associated with worse OS of cancer patients receiving ICI treatment in both univariate and multivariate analysis. However, high heterogeneity was found for IL-6, which might be attributed to region, cancer type, treatment method, sample source, and detection method.ConclusionThe peripheral level of IL-8 may be used as a prognostic marker to identify patients with inferior response to ICIs. More high-quality prospective studies are warranted to assess the predictive value of peripheral cytokines for ICI treatment.

The present study aimed to explore the effect of carnitine supplementation on body weight in patients with polycystic ovary syndrome (PCOS) and predict an appropriate dosage schedule using a machine-learning approach. Data were obtained from literature mining and the rates of body weight change from the initial values were selected as the therapeutic index. The maximal effect (Emax) model was built up as the machine-learning model. A total of 242 patients with PCOS were included for analysis. In the machine-learning model, the Emax of carnitine supplementation on body weight was −3.92%, the ET50 was 3.6 weeks, and the treatment times to realize 25%, 50%, 75%, and 80% (plateau) Emax of carnitine supplementation on body weight were 1.2, 3.6, 10.8, and 14.4 weeks, respectively. In addition, no significant relationship of dose-response was found in the dosage range of carnitine supplementation used in the present study, indicating the lower limit of carnitine supplementation dosage, 250 mg/day, could be used as a suitable dosage. The present study first explored the effect of carnitine supplementation on body weight in patients with PCOS, and in order to realize the optimal therapeutic effect, carnitine supplementation needs 250 mg/day for at least 14.4 weeks.

ObjectiveCervical sagittal parameters have been widely used to predict clinical outcomes in patients with cervical spondylotic myelopathy (CSM). This study aims to coin a novel cervical sagittal parameter defined as the ratio of cervical sagittal vertical axis to T1 slope (CSVA/T1S) and to investigate the correlation between CSVA/T1S and postoperative HRQOL after laminoplasty.MethodsA total of 102 CSM patients treated with cervical laminoplasty from our database were retrospectively reviewed. All patients were followed up for >12 months. Radiological parameters were measured using lateral cervical radiographs, including occiput-C2 lordosis (OC2), cervical lordosis (CL), CSVA, and T1S. Clinical parameters included the Japanese Orthopedic Association (JOA) score, neck disability index (NDI), and JOA recovery rate. Patients were grouped by preoperative T1S, T1S-CL, and CSVA/T1S value, respectively. Clinical and radiological outcomes were compared between the groups.ResultsPatients with high CSVA/T1S had greater OC2 and CSVA but lower CL than those in the low CSVA/T1S group pre-and postoperatively. With respect to HRQOL results, the final NDI was 12.46 ± 9.11% in the low CSVA/T1S group, which was significantly lower than that in the high CSVA/T1S group (17.68 ± 8.81%, P = 0.040). Moreover, only CSVA/T1S was detected to be significantly correlated with final NDI (r = 0.310, P = 0.027). No significant correlation was found between clinical results and other cervical sagittal parameters, including T1S, CSVA, and T1S-CL.ConclusionsPreoperative CSVA/T1S was correlated with postoperative NDI in patients with CSM after cervical laminoplasty. Patients with low preoperative CSVA/T1S achieved better neurological function improvement after cervical laminoplasty. Cervical laminoplasty could be an appropriate choice for patients with lower preoperative CSVA/T1S.

Background: Obstructive sleep apnea (OSA) is common in surgical patients and associated with worse perioperative outcomes. Objectives: To investigate the effect of mini-dose dexmedetomidine supplemented analgesia on postoperative sleep quality pattern in patients at high risk of OSA. Design: A pilot randomized, double-blind, placebo-controlled trial. Setting: A tertiary university hospital in Beijing, China. Patients: One hundred and fifty-two adult patients who had a STOP-Bang score ≥3 and a serum bicarbonate level ≥28  mmol/L and were scheduled for major noncardiac surgery between 29 January 2021 and 20 September 2022. Intervention: After surgery, patients were provided with high-flow nasal cannula and randomized in a 1:1 ratio to receive self-controlled opioid analgesia supplemented with either mini-dose dexmedetomidine (median 0.02  μg/kg/h) or placebo. We monitored polysomnogram from 9:00  pm to 6:00  am during the first night. Main outcome measures: Our primary outcome was the percentage of stage 2 non-rapid eye movement (N2) sleep. Secondary and exploratory outcomes included other postoperative sleep structure parameters, sleep-respiratory parameters, and subjective sleep quality (Richards-Campbell Sleep Questionnaire; 0–100 score range, higher score better). Results: All 152 patients were included in intention-to-treat analysis; 123 patients were included in sleep structure analysis. Mini-dose dexmedetomidine supplemented analgesia increased the percentage of stage N2 sleep (median difference, 10%; 95% CI, 1 to 21%; p  =  0.029); it also decreased the percentage of stage N1 sleep (median difference, −10%; 95% CI, −20% to −1%; p  =  0.042). Other sleep structure and sleep-respiratory parameters did not differ significantly between the two groups. Subjective sleep quality was slightly improved with dexmedetomidine on the night of surgery, but not statistically significant (median difference, 6; 95% CI, 0 to 13; p  =  0.060). Adverse events were similar between groups. Conclusion: Among patients at high risk of OSA who underwent noncardiac surgery, mini-dose dexmedetomidine supplemented analgesia may improve sleep quality without increasing adverse events. [ABSTRACT FROM AUTHOR]

Objectives: Olanzapine is used for treating bipolar disorder (BPD); however, the optimal initial dosing regimen is unclear. The present study aimed to investigate the optimal olanzapine initial dosage in patients with BPD via model-informed precision dosing (MIPD) based on a real-world study. Methods: Thirty-nine patients with BPD from the real-world study were collected to construct the MIPD model. Results: Weight, combined used quetiapine influenced olanzapine clearances in patients with BPD, where the clearance rates were 0.152:1 in patients with or without quetiapine under the same weight. We simulated olanzapine doses once a day or twice a day, of which twice a day was optimal. Without quetiapine, for twice-a-day olanzapine doses, 0.80, 0.70, and 0.60 mg/kg/day were suitable for 40- to 56-kg BPD patients, 56- to 74-kg BPD patients, and 74- to 100-kg BPD patients, respectively. With quetiapine, for twice-a-day olanzapine doses, 0.05 mg/kg/day was suitable for 40- to 100-kg BPD patients. Conclusion: This study was the first to investigate the optimal olanzapine initial dosage in patients with BPD via MIPD based on a real-world study, providing clinical reference for the precision medication of olanzapine in BPD patients. [ABSTRACT FROM AUTHOR]

Introduction: Human cytomegalovirus (HCMV) is the most common viral infection seen in newborns. The major route of transmission for acquired human cytomegalovirus infection is breast milk from mothers who are HCMV seropositive to the infants. Thus, a rapid, economical, and simple method to perform HCMV test in breast milk is crucial and necessary for preventing acquired HCMV infection, especially in underdeveloped regions with limited laboratory resources. Methods: In this study, an effective technique for the detection of HCMV was constructed by combining multienzyme isothermal rapid amplification (MIRA) and lateral flow chromatography strip (LFD). Primers for the conserved HCMV sequence UL83 were utilized for MIRA-LFD testing. Results: Our results showed that the entire MIRA reaction could be completed in 12 minutes at 37°C, and LFD outcomes could be observed visibly after 10 minutes. The detection sensitivity of this method reached 50 copy/ml. Samples of breast milk were examined to compare MIRA-LFD and conventional qPCR. The accuracy of MIRA-LFD was 100%. Discussion: The straightforward, rapid, economic features of the test can provide the significant advantages for the prevention of breast milk-acquired cytomegalovirus infection, particularly in resource-limited locations with high seroprevalence of cytomegalovirus. [ABSTRACT FROM AUTHOR]

Background and aimsRecently, the effectiveness of “textbook outcomes (TO)” in the evaluation of surgical quality has been recognized by more and more scholars. This study tended to examine the association between preoperative albumin–bilirubin (ALBI) grades and the incidence of achieving or not achieving TO (non-TO) in patients with hepatocellular carcinoma (HCC) undergoing laparoscopic hepatectomy.MethodsThe patients were stratified into two groups: ALBI grade 1 (ALBI ≤ -2.60) and ALBI grade 2/3 (ALBI > -2.60). The characteristics of patients and the incidence of non-TO were compared. Multivariate analyses were performed to determine whether ALBI grade was independently associated with TO.ResultsIn total, 378 patients were enrolled, including 194 patients (51.3%) in the ALBI grade 1 group and 184 patients (48.7%) in the ALBI grade 2/3 group. In the whole cohort, 198 patients (52.4%) did not achieve TO, and the incidence of non-TO in the ALBI grade 2/3 group was obviously higher than that in the ALBI grade 1 group (n = 112, 60.9% vs. n = 86, 44.3%, P = 0.001). The multivariate analyses showed that ALBI grade 2/3 was an independent risk factor for non-TO (OR: 1.95, 95%CI: 1.30–2.94, P = 0.023).ConclusionsMore than half (52.4%) of the patients with hepatocellular carcinoma did not achieve TO after laparoscopic hepatectomy, and preoperative ALBI grade 2/3 was significantly associated with non-TO. Improving the liver function reserve of patients before operation, thereby reducing the ALBI grade, may increase the probability for patients to reach TO and enable patients to benefit more from surgery.

BackgroundHigh serum uric acid (SUA) levels increase the risk of overall cancer morbidity and mortality, particularly for digestive malignancies. Nevertheless, the correlation between SUA level and clinical outcomes of the postoperative patients with colorectal cancer (CRC) treated by chemotherapy is unclear. This study aimed at exploring the relationship between baseline SUA level and progression-free survival (PFS), disease control rate (DCR), and safety in postoperative CRC patients receiving chemotherapy.Patients and MethodsWe conducted a retrospective study to evaluate the relationship between baseline SUA level and PFS, DCR, and incidence of serious adverse events of 736 postoperative CRC patients treated with FOLFOX, FOLFIRI or XELOX at our center.ResultsData from our center suggested that high baseline SUA level is linked to poor PFS in non-metastatic CRC patients using FOLFOX (HR=2.59, 95%CI: 1.29-11.31, p=0.018) and in male patients using FOLFIRI (HR=3.77, 95%CI: 1.57-39.49, p=0.012). In patients treated by FOLFIRI, a high SUA is also linked to a low DCR (p=0.035). In patients using FOLFOX, high baseline SUA level is also linked to a high incidence of neutropenia (p=0.0037). For patients using XELOX, there is no significant correlation between SUA level and PFS, effectiveness, or safety.ConclusionsThese findings imply that a high SUA level is a promising biomarker associated with poor PFS, DCR and safety of postoperative CRC patients when treated with FOLFOX or FOLFIRI.

BackgroundNeuraxial analgesia is widely used to relieve labor pain; its effects on long-term neurodevelopment of offspring remain unclear. This study was designed to investigate the influence of maternal neuraxial labor analgesia on offspring mental development.MethodsThis was a predefined secondary analysis of a 2-year prospective longitudinal study. Nulliparous women with single-term cephalic pregnancy preparing for vaginal delivery self-selected neuraxial analgesia or not during labor. Mothers and their offspring were followed up 2 years later. children's mental development was assessed with the bayley scales of infant development. A multivariable logistic model was used to identify factors associated with below-average mental development (Mental Development Index

The papillary thyroid carcinoma (PTC) metastasizes through lymphatic spread, but the follicular thyroid cancer (FTC) metastasis occurs by following hematogenous spread. To date, the molecular mechanism underlying different metastatic routes between PTC and FTC is still unclear. Here, we showed that specifically androgen-regulated gene (SARG) was significantly up-regulated in PTC, while obviously down-regulated in FTC through analyzing the Gene Expression Omnibus (GEO) database. Immunohistochemistry assay verified that the PTC lymph node metastasis was associated with higher levels of SARG protein in clinical PTC patient samples. SARG-knockdown decreased TPC-1 and CGTH-W3 cells viability and migration significantly. On the contrary, SARG-overexpressed PTC cells possessed more aggressive migratory ability and viability. In vivo, SARG overexpression dramatically promoted popliteal lymph node metastasis of xenografts from TPC-1 cells mouse footpad transplanting. Mechanistically, SARG overexpression and knockdown significantly increased and decreased the expression of vascular endothelial growth factor C (VEGF-C) and VEGF receptor 3 (VEGFR-3), respectively, thereby facilitating or inhibiting the tube formation in HUVECs. The tube formation experiment showed that SARG overexpression and knockdown promoted or inhibited the number of tube formations in HUVEC cells, respectively. Taken together, we showed for the first time the differential expression profile of SARG between PTC and FTC, and SARG promotes PTC lymphatic metastasis via VEGF-C/VEGFR-3 signal. It indicates that SARG may represent a target for clinical intervention in lymphatic metastasis of PTC.

BackgroundNatural killer (NK) cells play major roles in eliminating tumor cells. Preliminary studies have shown that NK cells and their receptors/ligands have prognostic value in malignant tumors. However, the relevance of NK cells and their receptors/ligands level to the prognosis of hepatocellular carcinoma (HCC) remains unclear.MethodsSeveral electronic databases were searched from database inception to November 8, 2021. Random effects were introduced to this meta-analysis. The relevance of NK cells and their receptors/ligands level to the prognosis of HCC was evaluated using hazard ratios (HRs) with 95% confidence interval (95%CI).Results26 studies were included in the analysis. The pooled results showed that high NK cells levels were associated with better overall survival (HR=0.70, 95%CI 0.57–0.86, P=0.001) and disease-free survival (HR=0.61, 95%CI 0.40-0.93, P=0.022) of HCC patients. In subgroup analysis for overall survival, CD57+ NK cells (HR=0.70, 95%CI 0.55-0.89, P=0.004) had better prognostic value over CD56+ NK cells (HR=0.69, 95%CI 0.38-1.25, P=0.224), and intratumor NK cells had better prognostic value (HR=0.71, 95%CI 0.55-0.90, P=0.005) over peripheral NK cells (HR=0.66, 95%CI 0.41-1.06, P=0.088). In addition, high level of NK cell inhibitory receptors predicted increased recurrence of HCC, while the prognostic role of NK cell activating receptors remained unclear.ConclusionNK cells and their inhibitory receptors have prognostic value for HCC. The prognostic role of NK cell activating receptors is unclear and more high-quality prospective studies are essential to evaluate the prognostic value of NK cells and their receptors/ligands for HCC.

Several studies have reported a link between lipid disorders and suicidality. However, few studies have investigated the relationship between suicidal behavior and blood lipid profiles in patients with first-episode and drug-naive (FEDN) major depressive disorder (MDD). The main purpose of this study was to examine the relationship between plasma lipid profiles and suicide attempts in a large sample of FEDN MDD patients in the Chinese Han population, which has not been reported. A total of 1,718 MDD outpatients were recruited. Their clinical and demographic data as well as plasma lipid parameters were collected. We obtained suicide attempt data through interviews with patients and their family members. We rated the Hamilton Depression Scale (HAMD) and Hamilton Anxiety Scale (HAMA) for all patients. The suicide attempt rate of MDD patients was 20.14%, of which 13.68% in the last month and 6.46% in the past. Further, compared with non-attempters, suicide attempters had significantly higher total levels of cholesterol (TC) and low-density lipoprotein cholesterol (LDL-c), higher HAMA and HAMD scores, but significantly lower high-density lipoprotein cholesterol (HDL-c) levels. Logistic regression analysis showed that suicide attempts were correlated with higher TC, lower HDL-c, and higher HAMA and HAMD scores with the adjusted odds ratio (OR) of 1.35, 0.52,1.28, and 1.08, respectively (all p < 0.05). Our findings suggest that FEDN patients with MDD have a high rate of attempted suicide. In the early stage of MDD patients, certain blood lipid parameters and more severe symptoms of anxiety and depression are correlated with suicide attempts. However, due to the cross-sectional design of this study, it is impossible to draw a causal relationship between lipid profiles and suicide attempts. Moreover, an inverse correlation can also be considered, that is, high cholesterol may be the consequence of suicide attempts and depression.

Background: The present study aimed to investigate the drug-drug interaction and initial dosage optimization of aripiprazole in patients with schizophrenia based on population pharmacokinetics. Research design and methods: A total of 119 patients with schizophrenia treated with aripiprazole were included to build an aripiprazole population pharmacokinetic model using nonlinear mixed effects. Results: The weight and concomitant medication of fluoxetine influenced aripiprazole clearance. Under the same weight, the aripiprazole clearance rates were 0.714:1 in patients with or without fluoxetine, respectively. In addition, without fluoxetine, for the once-daily aripiprazole regimen, dosages of 0.3 and 0.2 mg kg-1 day-1 were recommended for patients with schizophrenia weighing 40-95 and 95-120 kg, respectively, while for the twice-daily aripiprazole regimen, 0.3 mg kg-1 day-1 was recommended for those weighing 40-120 kg. With fluoxetine, for the once-daily aripiprazole regimen, a dosage of 0.2 mg kg-1 day-1 was recommended for patients with schizophrenia weighing 40-120 kg, while for the twice-daily aripiprazole regimen, 0.3 and 0.2 mg kg-1 day-1 were recommended for those weighing 40-60 and 60-120 kg, respectively. Conclusion: This is the first investigation of the effects of fluoxetine on aripiprazole via drug-drug interaction. The optimal aripiprazole initial dosage is recommended in patients with schizophrenia. [ABSTRACT FROM AUTHOR]

In the face of the unprecedented public health crisis caused by the novel coronavirus pneumonia epidemic, front-line health workers are under enormous mental pressure. This paper aims to explore the mental health challenges faced by front-line health workers in the early stages of a public health emergency, such as stress, anxiety, and depression. At the same time, the factors that increase their mental stress are analyzed, and practical measures are put forward to prevent and manage mental health problems, aiming at improving the quality of medical treatment during public health emergencies. This paper has some reference value for people engaged in mental health prevention. [ABSTRACT FROM AUTHOR]

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor β superfamily that alleviates cardiac hypertrophy, myocardial infarction, and vascular injury by regulating oxidative stress, inflammation, and cell survival. However, the roles and underlying mechanisms of GDF11 in diabetic cardiomyopathy (DCM) remain largely unknown. In this study, we sought to determine whether GDF11 could prevent DCM. After establishing a mouse model of diabetes by administering a high-fat diet and streptozotocin, intramyocardial injection of an adeno-associated virus was used to achieve myocardium-specific GDF11 overexpression. GDF11 remarkably improved cardiac dysfunction and interstitial fibrosis by reducing the levels of reactive oxygen species and protecting against cardiomyocyte loss. Mechanistically, decreased sirtuin 1 (SIRT1) expression and activity were observed in diabetic mice, which was significantly increased after GDF11 overexpression. To further explore how SIRT1 mediates the role of GDF11, the selective inhibitor EX527 was used to block SIRT1 signaling pathway, which abolished the protective effects of GDF11 against DCM. In vitro studies confirmed that GDF11 protected against H9c2 cell injury in high glucose and palmitate by attenuating oxidative injury and apoptosis, and these effects were eliminated by SIRT1 depletion. Our results demonstrate for the first time that GDF11 protects against DCM by regulating SIRT1 signaling pathway.

Sirolimus is already used in the treatment of tuberous sclerosis complex (TSC), however, with narrow therapeutic range and considerable inter- and intra-individual pharmacokinetic variability, making it hard to develop an appropriate sirolimus initial dosage regimen, especially in children with TSC. The aim of this study was to recommend the optimal sirolimus initial dosing regimen in pediatric patients with TSC. Underlying physiological and genetic factors were collected to explore the effects on clinical sirolimus concentrations by establishing a nonlinear mixed effect (NONMEM) model, and to further simulate the optimal sirolimus initial dosing regimen using Monte Carlo method in pediatric patients with TSC. The once-daily regimen and the twice-daily regimen were recommended, respectively. For once-daily regimen, the dosages of 0.10, 0.07, 0.05, 0.04, 0.03 mg/kg/day were recommended for children with weights of 5–10, 10–20, 20–30, 30–50, and 50–60 kg, respectively. For twice-daily regimen, the dosages of 0.04, 0.03, 0.02 mg/kg/day (the daily dose was divided evenly into two doses) were recommended for children with weights of 5–20, 20–40, 40–60 kg, respectively. The initial dosages of sirolimus in children with TSC were recommended for the first time.

Exercise can induce brain plasticity. Functional near-infrared spectroscopy (fNIRS) is a functional neuroimaging technique that exploits cerebral hemodynamics and has been widely used in the field of sports psychology to reveal the neural mechanisms underlying the effects of exercise. However, most existing fNIRS studies are cross-sectional and do not include exercise interventions. In addition, attributed to differences in experimental designs, the causal relationship between exercise and brain functions remains elusive. Hence, this systematic review aimed to determine the effects of exercise interventions on alterations in brain functional activity in healthy individuals using fNIRS and to determine the applicability of fNIRS in the research design of the effects of various exercise interventions on brain function. Scopus, Web of Science, PubMed, CNKI, Wanfang, and Weipu databases were searched for studies published up to June 15, 2021. This study was performed in accordance with the PRISMA guidelines. Two investigators independently selected articles and extracted relevant information. Disagreements were resolved by discussion with another author. Quality was assessed using the Cochrane risk-of-bias method. Data were pooled using random-effects models. A total of 29 studies were included in the analysis. Our results indicated that exercise interventions alter oxygenated hemoglobin levels in the prefrontal cortex and motor cortex, which are associated with improvements in higher cognitive functions (e.g., inhibitory control and working memory). The frontal cortex and motor cortex may be key regions for exercise-induced promotion of brain health. Future research is warranted on fluctuations in cerebral blood flow during exercise to elucidate the neural mechanism underlying the effects of exercise. Moreover, given that fNIRS is insensitive to motion, this technique is ideally suited for research during exercise interventions. Important factors include the study design, fNIRS device parameters, and exercise protocol. The examination of cerebral blood flow during exercise intervention is a future research direction that has the potential to identify cortical hemodynamic changes and elucidate the relationship between exercise and cognition. Future studies can combine multiple study designs to measure blood flow prior to and after exercise and during exercise in a more in-depth and comprehensive manner. [ABSTRACT FROM AUTHOR]

Objective: Currently, sentinel lymph node biopsy (SLNB) is increasingly used in endometrial cancer, but the rate of missed metastatic lymph nodes compared to systemic lymph node dissection has been a concern. We conducted a systematic review and meta-analysis to evaluate the false negative rate (FNR) of SLNB in patients with endometrial cancer and to explore the risk factors associated with this FNR. Data sources: Three databases (PubMed, Embase, Web of Science) were searched from initial database build to January 2023 by two independent reviewers. Research eligibility criteria: Studies were included if they included 10 or more women diagnosed with International Federation of Gynecology and Obstetrics (FIGO) stage I or higher endometrial cancer, the study technique used sentinel lymph node localization biopsy, and the reported outcome metrics included false negative and/or FNR. Study appraisal and synthesis methods: Two authors independently reviewed the abstracts and full articles. The FNR and factors associated with FNR were synthesized through random-effects meta-analyses and meta-regression. The results: We identified 62 eligible studies. The overall FNR for the 62 articles was 4% (95% CL 3-5).There was no significant difference in the FNR in patients with high-risk endometrial cancer compared to patients with low-risk endometrial cancer. There was no difference in the FNR for whether frozen sections were used intraoperatively. The type of dye used intraoperatively (indocyanine green/blue dye) were not significantly associated with the false negative rate. Cervical injection reduced the FNR compared with alternative injection techniques. Indocyanine green reduced the FNR compared with alternative Tc-99m. Postoperative pathologic ultrastaging reduced the FNR. Conclusions: Alternative injection techniques (other than the cervix), Tc-99m dye tracer, and the absence of postoperative pathologic ultrastaging are risk factors for a high FNR in endometrial cancer patients who undergo SLNB; therefore, we should be vigilant for missed diagnosis of metastatic lymph nodes after SLNB in such populations. [ABSTRACT FROM AUTHOR]

Introduction: Postmenopausal osteoporosis (PMOP) is a common chronic disease, and the loss of bone density and bone strength after menopause are its main symptoms. Effective treatments for PMOP are still uncertain, but Chinese medicine has some advantages in slowing down bone loss. Shengu granules are often used clinically to treat PMOP. It has been shown to be an effective prescription for the treatment of PMOP, and there is evidence that gut flora may play an important role. However, whether Shengu granules attenuate PMOP by modulating gut flora and related mechanisms remains unclear. Methods: In this study, we mainly examined the bone strength of the femur, the structure of the intestinal microbiota, SCFAs in the feces and the level of FOXP3 cells in the colon. To further learn about the inflammation response, the condition of the mucosa and the level of cytokines in the serum also included in the testing. In addition, to get the information of the protein expression, the protein expression of OPG and RANKL in the femur and the protein expression of ZO-1 and Occludin in the colon were taken into account. Results: The osteoporosis was significantly improved in the SG group compared with the OVX group, and the diversity of intestinal flora, the secretion level of SCFAs and the expression level of FOXP3 were significantly increased compared with the OVX group. In terms of inflammatory indicators, the intestinal inflammation scores of the SG group was significantly lower than those in the OVX group. Additionally, the serum expression levels of IL-10 and TGF-ß in the SG group were significantly increased compared with the OVX group, and the expression levels of IL-17 and TNF-a were significantly decreased compared with the OVX group. In terms of protein expression, the expression levels of ZO-1, Occluding and OPG were significantly increased in the SG group compared with the OVX group, and the expression level of RANKL was significantly decreased compared with the OVX group. Discussion: Shengu granules treatment can improve the imbalance of intestinal flora, increase the secretion of SCFAs and the expression of FOXP3, which reduces the inflammatory response and repairs the intestinal barrier, as well as regulates the expression of OPG/RANKL signaling axis. Overall, Shengu granules ameliorate ovariectomy-induced osteoporosis by the gut-bone-immune axis. [ABSTRACT FROM AUTHOR]

Objective: To systematically review and analyze the effects of exercise interventions on health behavior among middle-aged and older adults. Methods: A Meta-analysis was performed using NoteExpress software to screen randomized controlled trials (RCTs) published between January 1, 2000, and March 31, 2023, which were identified through databases including CNKI, Web of Science, Pubmed, and 6 more sources, based on predefined literature inclusion criteria. Following the quality assessment, we conducted both the overall and subgroup Meta-analyses of the exercise intervention moderator variables using Review Manager 5.4.1 software, encompassing data among the 18 RCTs. The effect size was measured as the standardized mean difference within its corresponding 95% confidence interval. Heterogeneity was assessed using the I2 metrics. Results: (1) The overall results indicate a significant impact of exercise intervention on health behaviors, characterized by a large effect size [SMD = 1.02 > 0.8, 95% CI (0.73, 1.32), P < 0.001]. (2) The highest degree of heterogeneity in the relationship between exercise interventions and health behaviors was associated with the duration of one exercise session (I² = 71.2%), which was the most influential moderator variable. (3) The aerobic and resistance intervention in group exercise lasting 30-60 min per time a day, 6-7 times per week over a period of 8-12 weeks demonstrated the most substantial effect size. Conclusion: (1) The exercise intervention significantly promotes the health behavior in middle-aged and older adults, emphasizing the importance of carefully considering the duration of individual exercise sessions when designing and implementing exercise intervention. (2) Considering the accessibility for middle-aged and older adults, the optimal exercise intervention should include the means of group practice, the types of aerobic and resistance exercise, with a duration of 30-60 min per time a day, beginning with a lower weekly frequency and gradually increase to 6-7 times per week, and lasting for 8 to 12 weeks. [ABSTRACT FROM AUTHOR]