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IntroductionThis study aims to explore the incidence of different metastatic patterns in paraaortic lymph nodes and their corresponding survival outcomes in patients with endometrial cancer, as well as to identify the associated risk factors of such metastasis.Material and methodsPubMed, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, and Clinical Trials.gov were searched from inception to February 10, 2024.The analysis was conducted using R version 4.2.3.ResultsA total of 47 studies involving 33,425 endometrial cancer patients were analyzed. Meta-analysis results revealed that the rate of isolated paraaortic lymph node metastasis, where pelvic lymph nodes were negative but paraaortic lymph nodes were positive (PLN-PAN+), was found to be 2.58% (95% CI 0.0195-0.0329). The rates for PLN+PAN- and PLN+PAN+ were notably higher at 8.54% (95% CI 0.0642-0.1092) and 8.37% (95% CI 0.0613-0.1090), respectively. For clinical stage I EC, the occurrence rate was 5.92% for PLN+PAN- (95% CI 0.0258-0.1032), 1.00% for PLN-PAN+ (95% CI 0.0081-0.0120), and 2.99% for PLN+PAN+ (95% CI 0.0188-0.0431). The survival outcomes indicate a decreasing trend from the PLN-PAN+ and PLN+PAN- groups to the PLN+PAN+ group. Additionally, the survival outcomes of patients with isolated paraaortic lymph node metastasis appear to be comparable to, or not inferior to, those of the PLN+PAN- group. The analysis indicated that pelvic lymph node metastasis (OR 16.72, 95% CI 10.03-27.86), myometrial invasion ≥50% (OR 5.18, 95% CI 3.09-8.69), lymph-vascular space invasion (LVSI) (OR 3.46, 95% CI 2.49-4.81), cervical invasion (OR 4.00, 95% CI 2.09-7.66), and non-endometrioid cancer (OR 2.39, 95% CI 1.17-4.86) were risk factors for paraaortic lymph node metastasis.ConclusionsIsolated paraaortic lymph node metastasis, though relatively rare, can still occur even in clinical stage I endometrial cancer. The survival outcomes of patients with isolated paraaortic lymph node metastasis appear to be comparable to, or not inferior to, those of the PLN+PAN- group. Even in patients with negative pelvic lymph nodes, careful consideration should be given to the possibility of paraaortic lymph node metastasis, especially in those with high-risk factors.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42024503959.

ObjectiveTo summarize stage migration and survival outcomes in patients with cervical cancer at Stage IIIC according to the 2018 FIGO staging system, and to investigate prognostic factors influencing Stage IIIC1.MethodsPubMed, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), International Clinical Trials Registry Platform (ICTRP), and Clinical Trials.gov were searched from inception to February 6, 2024. The analysis was conducted using STATA 16.0.ResultsA total of 25 studies with 82954 cervical cancer patients were included in the analysis. The migration rates to FIGO 2018 Stage IIIC ranged from 18% to 37% for early-stage tumors (Stage IB to IIA) in FIGO 2009, and from 32% to 52% for advanced stage tumors (Stage IIB to IIIB). The overall survival (OS) for Stage IIIC1 is poorer compared to Stage IB1 (HR 0.53, 95% CI 0.35-0.80, p=0.003) and Stage IB2 (HR 0.61, 95% CI 0.43-0.85, p=0.004). It is comparable to Stage IB3, yet it shows better survival outcomes than Stages IIB (HR 2.91, 95% CI 1.01-8.39, p=0.047), IIIA (HR 1.96, 95% CI 1.78-2.17, p=0.000), and IIIB (HR 1.56, 95% CI 1.04-2.35, p=0.031). Tumors size ≥4cm (HR 1.45, 95% CI 1.10-1.92, p=0.00), metastatic lymph node ≥ 3 (HR 2.21, 95% CI 1.56-3.15, p=0.000) and T stage are prognostic factors for OS of Stage IIIC1.ConclusionsThe migration rates to FIGO 2018 Stage IIIC varied between 18% and 52% for patients initially classified under FIGO 2009 Stages IB1 to IIIB. The FIGO 2018 staging system underscores the pivotal role of lymph node metastasis in predicting prognosis and provides valuable insights into the distinct prognostic implications associated with different stages, particularly for early stages. For advanced stages, incorporation of tumor-related factors such as T stage might better elucidate survival differences and guide clinical treatment decisions.Protocol registrationCRD 42023451793.

Pancreatic tumors are small in size, diverse in shape, and have low contrast and high texture similarity with surrounding tissue. As a result, the segmentation model is easily confused by complex and changeable background information, leading to inaccurate positioning of small targets and false positives and false negatives. Therefore, we design a cascaded pancreatic tumor segmentation algorithm. In the first stage, we use a general multi-scale U-Net to segment the pancreas, and we exploit a multi-scale segmentation network based on non-local localization and focusing modules to segment pancreatic tumors in the second stage. The non-local localization module learns channel and spatial position information, searches for the approximate area where the pancreatic tumor is located from a global perspective, and obtains the initial segmentation results. The focusing module conducts context exploration based on foreground features (or background features), detects and removes false positive (or false negative) interference, and obtains more accurate segmentation results based on the initial segmentation. In addition, we design a new loss function to alleviate the insensitivity to small targets. Experimental results show that the proposed algorithm can more accurately locate pancreatic tumors of different sizes, and the Dice coefficient outperforms the existing state-of-the-art segmentation model. The code will be available at https://github.com/HeyJGJu/Pancreatic-Tumor-SEG.

We describe a technique to reattach the detached Descemet’s membrane, following cataract surgery. From the main clear corneal cataract incision, aqueous humor is ejected completely by apposition of the cornea to the iris for approximately 3 s. This ensures the fluid in the space between the stroma and Descemet’s membrane is ejected and the detached Descemet’s membrane returns to its original position. Sterile air is injected through a paracentesis 180 degrees away from the Descemet’s membrane detachment, to maintain a complete air-filled chamber. Full air tamponade is maintained for 20 min, following which one-third of the air is ejected from the chamber to prevent an increase of postoperative intraocular pressure.

BackgroundCurrently, disease-modifying therapies (DMTs) for progressive multiple sclerosis (PMS) are widely used in clinical practice. At the same time, there are a variety of drug options for DMTs, but the effect of the drugs that can better relieve symptoms and improve the prognosis are still inconclusive.ObjectivesThis systematic review aimed to evaluate the efficacy and safety of DMTs for PMS and to identify the best among these drugs.MethodsMEDLINE, EMBASE, the Cochrane Library, and clinicaltrials.gov were systematically searched to identify relevant studies published before 30 January, 2023. We assessed the certainty of the evidence using the confidence in the network meta-analysis (CINeMA) framework. We estimated the summary risk ratio (RR) for dichotomous outcomes and mean differences (MD) for continuous outcomes with 95% credible intervals (CrIs).ResultsWe included 18 randomized controlled trials (RCTs) involving 9,234 patients in the study. DMT can effectively control the disease progression of MS. Among them, mitoxantrone, siponimod, and ocrelizumab are superior to other drug options in delaying disease progression (high certainty). Mitoxantrone was the best (with high certainty) for mitigating deterioration (progression of disability). Ocrelizumab performed best on the pre- and post-treatment Timed 25-Foot Walk test (T25FW; low certainty), as did all other agents (RR range: 1.12–1.05). In the 9-Hole Peg Test (9HPT), natalizumab performed the best (high certainty), as did all other agents (RR range: 1.59–1.09). In terms of imaging, IFN-beta-1b performed better on the new T2 hypointense lesion on contrast, before and after treatment (high certainty), while siponimod performed best on the change from baseline in the total volume of lesions on T2-weighted image contrast before and after treatment (high certainty), and sWASO had the highest area under the curve (SUCRA) value (100%). In terms of adverse events (AEs), rituximab (RR 1.01), and laquinimod (RR 1.02) were more effective than the placebo (high certainty). In terms of serious adverse events (SAEs), natalizumab (RR 1.09), and ocrelizumab (RR 1.07) were safer than placebo (high certainty).ConclusionDMTs can effectively control disease progression and reduce disease deterioration during the treatment of PMS.Systematic review registrationhttps://inplasy.com/?s=202320071, identifier: 202320071.

During the COVID-19 pandemic, elderly patients with underlying condition, such as tumors, had poor prognoses after progressing to severe pneumonia and often had poor response to standard treatment. Mesenchymal stem cells (MSCs) may be a promising treatment for patients with severe pneumonia, but MSCs are rarely used for patients with carcinoma. Here, we reported a 67-year-old female patient with lung adenocarcinoma who underwent osimertinib and radiotherapy and suffered from radiation pneumonitis. Unfortunately, she contracted COVID-19 and that rapidly progressed to severe pneumonia. She responded poorly to frontline treatment and was in danger. Subsequently, she received a salvage treatment with four doses of MSCs, and her symptoms surprisingly improved quickly. After a lung CT scan that presented with a significantly improved infection, she was discharged eventually. Her primary disease was stable after 6 months of follow-up, and no tumor recurrence or progression was observed. MSCs may be an effective treatment for hyperactive inflammation due to their ability related to immunomodulation and tissue repair. Our case suggests a potential value of MSCs for severe pneumonia that is unresponsive to conventional therapy after a COVID-19 infection. However, unless the situation is urgent, it needs to be considered with caution for patients with tumors. The safety in tumor patients still needs to be observed.

BackgroundThere are many similarities in the clinical manifestations of human norovirus and SARS-CoV-2 infections, and nucleic acid detection is the gold standard for diagnosing both diseases. In order to expedite the identification of norovirus and SARS-CoV-2, a quantitative one-step triplex reverse transcription PCR (RT-qPCR) method was designed in this paper.MethodsA one-step triplex RT-qPCR assay was developed for simultaneous detection and differentiation of human norovirus GI (NoV-GI), GII (NoV-GII) and SARS-CoV-2 from fecal specimens.ResultsThe triplex RT-qPCR assay had high detection reproducibility (CV

ObjectiveTo explore the factors influencing the successful implementation of same-day discharge in patients undergoing minimally invasive hysterectomy for malignant and non-malignant gynecological diseases.MethodWe searched PubMed, Embase, Cochrane Central Register of Controlled Trials, International Clinical Trials Registry Platform, and Clinical Trials.gov from inception to May 23, 2023. We included case-control and cohort studies published in English reporting same-day discharge factors in patients undergoing minimally invasive hysterectomy for malignant and non-malignant gynecological diseases. STATA 16.0 was used for the meta-analysis. Risk factors were assessed using odds ratios (OR) (relative risk (RR)/hazard ratios (HR)) with 95% confidence intervals (CI), and logistic regression determined the same-day discharge rate (%).ResultsWe analyzed 29 studies with 218192 patients scheduled for or meeting same-day discharge criteria. The pooled rates were 50% (95% CI 0.46-0.55), and were similar for malignant and non-malignant gynecological diseases (48% and 47%, respectively). In terms of basic characteristics, an increase in age (OR: 1.03; 95% CI: 1.01–1.05), BMI (OR: 1.02; 95% CI: 1.01–1.03), and comorbidities including diabetes and lung disease were risk factors affecting SDD, while previous abdominal surgery history (OR: 1.54; 95% CI: 0.93–2.55) and hypertension (OR: 1.53; 95% CI: 0.80–2.93) appeared not to affect SDD. In terms of surgical characteristics, radical hysterectomy (OR: 3.46; 95% CI: 1.90–6.29), surgery starting after 14:00 (OR: 4.07; 95% CI: 1.36–12.17), longer surgical time (OR: 1.03; 95% CI: 1.01–1.06), intraoperative complications (OR: 4.68; 95% CI: 1.78–12.27), postoperative complications (OR: 3.97; 95% CI: 1.68–9.39), and surgeon preference (OR: 4.47; 95% CI: 2.08–9.60) were identified as risk factors. However, robotic surgery (OR: 0.44; 95% CI: 0.14–1.42) and intraoperative blood loss (OR: 1.16; 95% CI: 0.98–1.38) did not affect same-day discharge.ConclusionsAn increase in age, body mass index, and distance to home; certain comorbidities (e.g., diabetes, lung disease), radical hysterectomy, surgery starting after 14:00, longer surgical time, operative complications, and surgeon preference were risk factors preventing same-day discharge. Same-day discharge rates were similar between malignant and non-malignant gynecological diseases. The surgery start time and body mass index have a greater impact on same-day discharge for malignant diseases than non-malignant diseases.

BackgroundEndovascular thrombectomy (EVT) is an important treatment for patients with acute ischemic stroke (AIS). A number of studies have suggested that anesthesia type (conscious sedation vs. general anesthesia) during intra-arterial treatment for acute ischemic stroke has implications for patient outcomes.MethodsPubMed, EMBASE, Cochrane Library and clinicaltrials.gov were searched for randomized controlled trials (RCTs) that were performed to evaluate general anesthesia (GA) and conscious sedation (CS) up to May 30, 2023. Review Manager 5.3 software was used to assess the data. The risk ratio (RR) and mean difference (MD) were analyzed and calculated with a fixed effect model.ResultsWe pooled 930 patients from seven RCTs. We conducted a meta-analysis comparing the outcomes of GA and CS in the included trials. The rate of functional independence in the GA group was higher than that in the CS group (RR: 1.17, 95% CI: 1.00–1.35; P = 0.04; I2 = 16%). The GA group had a higher successful recanalization rate than the CS group (RR: 1.15, 95% CI: 1.08–1.22; P < 0.0001; I2 = 26%). The GA group had a higher pneumonia rate than the CS group (RR: 1.69, 95% CI: 1.22–2.34; P = 0.002; I2 = 26%). In addition, there was no significant difference between GA and CS with respect to the National Institutes of Health Stroke Scale (NIHSS) score at 24 h (P = 0.62), Modified Rankin Scale (mRS) score at 90 days (P = 0.25), intracerebral hemorrhage (P = 0.54), and mortality at 3 months (P = 0.61).ConclusionGA demonstrated superiority over CS in achieving successful recanalization and functional independence at 3 months when performing EVT in AIS patients. However, it was also associated with a higher risk of pneumonia. Further studies, particularly those with long-term follow-ups, are necessary to identify precise strategies for selecting the appropriate anesthetic modality in EVT patients.Systematic review registrationINPLASY202370116.

BackgroundThis meta-analysis evaluates the efficacy and safety of amyloid-β (Aβ) targeted therapies for delaying cognitive deterioration in Alzheimer’s disease (AD).MethodsPubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were systematically searched to identify relevant studies published before January 18, 2023.ResultsWe pooled 33,689 participants from 42 studies. The meta-analysis showed no difference between anti-Aβ drugs and placebo in the Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog), and anti-Aβ drugs were associated with a high risk of adverse events [ADAS-Cog: MDs = −0.08 (−0.32 to 0.15), p = 0.4785; AEs: RR = 1.07 (1.02 to 1.11), p = 0.0014]. Monoclonal antibodies outperformed the placebo in delaying cognitive deterioration as measured by ADAS-Cog, Clinical Dementia Rating–Sum of Boxes (CDR-SB), Mini-Mental State Examination (MMSE) and Alzheimer’s Disease Cooperative Study–Activities of Daily Living (ADCS-ADL), without increasing the risk of adverse events [ADAS-Cog: MDs = −0.55 (−0.89 to 0.21), p = 0.001; CDR-SB: MDs = −0.19 (−0.29 to −0.10), p

Hyperspectral imaging (HSI) is a promising technology that can provide valuable support for the advancement of the medical field. Bibliometrics can analyze a vast number of publications on both macroscopic and microscopic levels, providing scholars with essential foundations to shape future directions. The purpose of this study is to comprehensively review the existing literature on medical hyperspectral imaging (MHSI). Based on the Web of Science (WOS) database, this study systematically combs through literature using bibliometric methods and visualization software such as VOSviewer and CiteSpace to draw scientific conclusions. The analysis yielded 2,274 articles from 73 countries/regions, involving 7,401 authors, 2,037 institutions, 1,038 journals/conferences, and a total of 7,522 keywords. The field of MHSI is currently in a positive stage of development and has conducted extensive research worldwide. This research encompasses not only HSI technology but also its application to diverse medical research subjects, such as skin, cancer, tumors, etc., covering a wide range of hardware constructions and software algorithms. In addition to advancements in hardware, the future should focus on the development of algorithm standards for specific medical research targets and cultivate medical professionals of managing vast amounts of technical information.

Introduction: Quasi-public water conservancy PPP (Public-private participation) projects are closely related to people’s livelihoods and involve multiple participating stakeholders. Previous research on risk sharing in such projects has primarily focused on qualitative analysis of risk factors. Due to self-interest considerations, the collaborating parties tend to deflect and transfer risks to each other as much as possible in the risk sharing process. Additionally, some quantitative analysis methods have been predominantly based on a unilateral perspective.Methods: Therefore, the present study proposed a new model, which is based on the Shapley Value and the Utility Theory, encompassing a comprehensive analysis of multiple factors such as the proportion of capital contribution, bargaining position, risk management capabilities, and risk-taking willingness of heterogeneous subjects. Firstly, the relationship between the risk losses of different stakeholders and their corresponding value scales and utility attributes is comprehensively analysed, and the transformation characteristics and links of their risk preferences on spatial and temporal scales are summarised. Secondly, The utility values of heterogeneous subjects are employed as quantitative indicators to evaluate utility, leading to the construction of a comprehensive utility objective function for these subjects. Finally, The Shapley Value is then applied to modify the risk-sharing ratio based on the Utility Theory.Results: The research results show that the risk sharing ratio obtained by single use of shapley value theory or utility theory will be biased toward one side, while the result calculated by using the combination of the two methods is 57.35% for the government to share the risk ratio, and 42.65% for the social capital side, which is a more balanced result.Discussion: The proposed model enriches the risk management method and theory of quasi public welfare water conservancy PPP projects.

BackgroundLong-term impact of sepsis on whole body systems is not well investigated. The aim of the study was to explore the potential association of neonatal/adult sepsis with several inflammation-related diseases in multiple physiological systems.MethodsInstrumental variables for neonatal and adult sepsis were collected from the public genome-wide association studies, which must satisfy the correlation, exclusivity and independence assumptions. Mendelian randomization methods (including random-effect inverse-variance weighted, MR-PRESSO, weighted median and MR-Egger) were used to determine the genetic association of neonatal/adult sepsis with asthma, allergy, rheumatoid arthritis, body mass index/obesity, type 1/type 2 diabetes and intelligence/dementia. Sensitivity analyses were conducted to assess heterogeneity and horizontal pleiotropy. The study was performed by TwoSampleMR in R software.ResultsThe inverse-variance weighted method reported that neonatal sepsis was related to the decreased level of body mass index (OR = 0.988, 95%CI = 0.980 ~ 0.997, P = 0.007), and adult sepsis was related to the decreased risk of obesity (OR = 0.785, 95%CI = 0.655 ~ 0.940, P = 0.009). These results were supported by the other Mendelian randomization methods. In addition, the study did not find any association of neonatal/adult sepsis with the other inflammation-related diseases. No heterogeneity and horizontal pleiotropy were found using sensitivity analyses.ConclusionSepsis had the potential to reduce the risk of obesity or body mass index level at a genetic level, both in neonates and in adults.

BackgroundWorsening heart failure (WHF) is a heterogeneous clinical syndrome with poor prognosis. More effective risk stratification tools are required to identify high-risk patients. Evidence suggest that aberrant ceramide accumulation can be affected by heart failure risk factors and as a driver of tissue damage. We hypothesized that specific ceramide lengths and ratios serve as biomarkers for risk stratification in WHF patients by reflecting pathological changes of distinct organ dysfunctions.MedthodsWe measured seven plasma ceramides using liquid chromatography-mass spectrometry (LC-MS) in 1,558 patients, including 1,262 participants in retrospective discovery set and 296 WHF patients in prospective validation set in BIOMS-HF study (Registry Study of Biomarkers in Heart Failure). Univariable and multivariable logistic regression models were constructed to identify associations of ceramides with organ dysfunctions.ResultsWe constructed three ceramide-based scores linked independently to heart, liver, and kidney dysfunction, with ceramides and ratios included in each score specifying systemic inflammation, chronic metabolic disorder, and water-sodium retention. The combined ceramide heart failure score (CHFS) was independently associated with adverse outcomes [Hazard Ratio, 2.80 (95% CI: 1.78–4.40; P

Endometriosis is one of the most common benign gynecological disorders in reproductive-aged women. The major symptoms are chronic pelvic pain and infertility. Despite its profound impact on women’s health and quality of life, its pathogenesis has not been fully elucidated, it cannot be cured and the long-term use of drugs yields severe side effects and hinders fertility. This review aims to present the advances in pathogenesis and the newly reported lead compounds and drugs managing endometriosis. This paper investigated Genetic changes, estrogen-dependent inflammation induction, progesterone resistance, imbalance in proliferation and apoptosis, angiogenesis, lymphangiogenesis and neurogenesis, and tissue remodeling in its pathogenesis; and explored the pharmacological mechanisms, constitutive relationships, and application prospects of each compound in the text. To date, Resveratrol, Bay1316957, and bardoxifene were effective against lesions and pain in controlled animal studies. In clinical trials, Quinagolide showed no statistical difference with the placebo group; the results of phase II clinical trial of the IL-33 antibody have not been announced yet; clinical trial stage III of vilaprisan was suspended due to drug toxicity. Elagolix was approved for the treatment of endometriosis-related pain, but clinical studies of Elagolix for the pretreatment of patients with endometriosis to before In vitro fertilization treatment have not been fulfilled. The results of a clinical study of Linzagolix in patients with moderate to severe endometriosis-related pain have not been disclosed yet. Letrozole improved the fertility of patients with mild endometriosis. For endometriosis patients with infertility, oral GnRH antagonists and aromatase inhibitors are promising drugs, especially Elagolix and Letrozole.

Prostate cancer is currently the most common malignancy among men. Given the limitations of current conventional anticancer therapies, new high-risk treatments are urgently needed. Previous studies have shown that embryonic stem cells (ESCs) can reverse the tumorigenic phenotype of tumor cells. However, there are still challenges in using human ESCs (hESCs) directly in cancer treatment. To facilitate the practical application of hESCs, we established a co-culture system consisting of prostate cancer cell lines and hESCs and investigated the antitumor activity of the supernatant of the co-culture system (Co-Sp) in vitro and in vivo, as well as the underlying mechanisms involved. The Co-Sp decreased the viability of prostate cancer cells in a concentration-dependent manner, significantly inhibited colony formation, and induced cell cycle arrest at the G0/G1 phase of the cell cycle. In addition, Co-Sp promoted apoptosis of prostate cancer cells and inhibited cell migration and invasion. In vivo studies also revealed that Co-Sp inhibited tumor growth in the xenograft model. Mechanistic studies showed that Co-Sp reduced the expression of cyclin D1, cyclin E, CDK4, CDK2, MMP-9, MMP-1, and Bcl-2, and increased the expression of p21, cleaved caspase-9, cleaved caspase-3, cleaved PARP, and Bax in prostate cancer cells. Furthermore, the Co-Sp decreased the phosphorylation of PI3K, AKT, and mTOR in cells and tumor tissues. Taken together, our results indicated that the Co-Sp has potent antitumor activity and could directly inhibit tumor growth. Our findings provide a new and effective way for the application of hESCs in cancer therapy and contribute to a new strategy for clinical stem cell therapy.

IntroductionUlcerative colitis (UC) is an inflammatory bowel disease characterized by recurrent and remitting inflammation of the mucosa of the colon and rectum, the incidence of which is on the rise. Glucagon-like peptide-2 (GLP-2) is a newly discovered neurotrophic factor, but its efficacy and mechanism of action in UC remain unclear. In this study, we investigated the protective effects and potential targets of GLP-2 on dextran sodium sulfate (DSS)-induced UC in mice through integrative analysis.MethodsThe effects of GLP-2 on UC were assessed by calculating the disease activity index, colonic mucosal damage index, and pathological histological scores. Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry were used to detect the expression of GLP-2, nuclear factor kappa-B (NF-κB), interleukin-6 (IL-6), and signal transducer and activator of transcription-3 (STAT3). The 16SrRNA gene was used to detect changes in gut microbiota in mouse colonic tissues, and oral glucose tolerance test (OGTT) blood glucose levels were used to analyze the differences in flora.ResultsThe results showed that GLP-2 could reduce the inflammation of UC mice, which may be achieved by inhibiting the potential targets of NF-κB, and Janus kinase (JAK)/STAT3 inflammatory pathways, regulating sugar metabolism, increasing dominant species, and improving microbial diversity.DiscussionThis study provides new insight into the potential of GLP-2 for achieving more ideal UC treatment goals in future.

Background: Systematic comparisons of the doses of the Food and Drug Administration (FDA)-approved dual orexin receptor antagonists (DORAs) for people with insomnia are limited.Methods: PubMed, Embase, Cochrane Library, and Clinicaltrials. gov were systematically searched to identify relevant studies published before 31 October 2022. We assessed the certainty of evidence using the confidence in network meta-analysis (CINeMA) framework.Results: We pooled 7257 participants from 9 randomized controlled trials (RCTs). Moderate to high certainty evidence demonstrated suvorexant (20 and 40 mg) and daridorexant (10 and 50 mg) as the most effective in latency to persistent sleep (LPS) reduction. Lemborexant at 5 and 10 mg was the most effective in subjective sleep onset time (sTSO) reduction. For wake time after sleep onset (WASO), all drugs except daridorexant 5 mg were more effective than placebo. Lemborexant 5 mg was among the best in subjective WASO (sWASO) (moderate to high certainty) and had the highest surface under the curve ranking area (SUCRA) values for sWASO (100%). For total sleep time (TST), suvorexant and daridorexant, except the respective minimum doses, were more effective than placebo, while suvorexant 40 mg and lemborexant 10 mg may have been the most effective for subjective TST (sTST) (low to very low certainty). Suvorexant 40 mg (RR 1.09), suvorexant 80 mg (RR 1.65), and daridorexant 25 mg (RR 1.16) showed a higher safety risk than placebo.Conclusion: Suvorexant 20 mg, lemborexant 5 mg, lemborexant 10 mg, and daridorexant 50 mg represent suitable approaches for insomnia.Clinical Trial Registration:clinicaltrials.gov, PROSPERO (CRD42022362655).

BackgroundST-segment elevation myocardial infarction (STEMI) patients are at a high residual risk of major adverse cardiovascular events (MACEs) after revascularization. Risk factors modify prognostic risk in distinct ways in different STEMI subpopulations. We developed a MACEs prediction model in patients with STEMI and examined its performance across subgroups.MethodsMachine-learning models based on 63 clinical features were trained in patients with STEMI who underwent PCI. The best-performing model (the iPROMPT score) was further validated in an external cohort. Its predictive value and variable contribution were studied in the entire population and subgroups.ResultsOver 2.56 and 2.84 years, 5.0% and 8.33% of patients experienced MACEs in the derivation and external validation cohorts, respectively. The iPROMPT score predictors were ST-segment deviation, brain natriuretic peptide (BNP), low-density lipoprotein cholesterol (LDL-C), estimated glomerular filtration rate (eGFR), age, hemoglobin, and white blood cell (WBC) count. The iPROMPT score improved the predictive value of the existing risk score, with an increase in the area under the curve to 0.837 [95% confidence interval (CI): 0.784–0.889] in the derivation cohort and 0.730 (95% CI: 0.293–1.162) in the external validation cohort. Comparable performance was observed between subgroups. The ST-segment deviation was the most important predictor, followed by LDL-C in hypertensive patients, BNP in males, WBC count in females with diabetes mellitus, and eGFR in patients without diabetes mellitus. Hemoglobin was the top predictor in non-hypertensive patients.ConclusionThe iPROMPT score predicts long-term MACEs following STEMI and provides insights into the pathophysiological mechanisms for subgroup differences.

PurposeThis study aimed to investigate potential biological mechanisms underlying cognitive function alterations in Type 2 diabetes mellitus (T2DM) patients by integrating cortical morphology with peripheral cytokine levels and brain-derived neurotrophic factor (BDNF) levels, and to offer potential insights for the early detection of T2DM-related cognitive impairment.MethodsThis study included 16 T2DM patients with a Montreal Cognitive Assessment (MoCA) score of at least 26 points, as well as 16 healthy controls with normal cognitive function. The participants also completed the digit span test and digit symbol substitution test. Participants’ serum levels of Interleukin 4 (IL-4), IL-6, IL-10, tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and BDNF were also examined. Each subject underwent a high-resolution 3T structural brain MRI scan. Based on the aparc. a2009s atlas, we calculated the cortical thickness, sulcus depth, gyrification index, and fractal dimension for each participant using surface-based morphometry (SBM). Correlation analysis between cognitive measures, serum levels of cytokines and BDNF, and SBM indices were further performed.ResultsThe levels of IL-4 and BDNF showed significant group differences. In the T2DM group, the sulcus depth exhibited a significant decrease in the left transverse frontopolar gyri and sulci, as well as in the right pole-occipital; the fractal dimension showed a significant increase in the right posterior-dorsal part of the cingulate gyrus; and the gyrification index significantly increased in the left inferior part of the precentral sulcus and right triangular part of the inferior frontal gyrus. Correlation analysis revealed a significant positive correlation between IL-10 levels and the sulcus depth of left transverse frontopolar gyri and sulci; a significant positive correlation between the sulcus depth of the right pole-occipital and the digit span test-forward scores, and a significant negative correlation between the gyrification index of the left inferior part of the precentral sulcus and the digit span test-backward scores among T2DM participants.ConclusionT2DM patients without cognitive impairment displayed reductions in IL 4 and BDNF levels, as well as significant alterations in their SBM indices, indicating that prior to the emergence of cognitive impairment, the SBM indices, peripheral cytokines, and BDNF may have altered in T2DM patients. IL-10 may lessen inflammation-related brain edema and preserve sulcus depth in T2DM patients through its anti-inflammatory activity.

The recalcitrant structure of raw poplar limited the production of fermentable sugars when applied as the material in the pretreatment of biochemical conversions. Phosphoric acid pretreatment is an efficient method to destroy the compact lignocellulose matrix presence in the poplar. In this study, phosphoric acid pretreatment of poplar was optimised by an orthogonal experimental design [L9(33)] to improve enzymatic digestibility through investigating the effects of reaction temperature, time duration, and phosphoric acid concentration. The optimal conditions were selected based on the variance of chemical compositions, hemicellulose removal ratio, and delignification of the woody material after pretreatment. The optimum enzymatic hydrolysis yield of up to 73.44% was obtained when the phosphoric acid pretreatment performed at 190°C for 150 min under 1.5% of v/v phosphoric acid concentration.

IntroductionType 2 diabetes mellitus (T2DM) can accelerate cognitive decline and even dementia so that the underlying mechanism deserves further exploration. In the resting state, brain function is still changing dynamically. At present, it is still unknown whether the dynamic functional connectivity (dFC) between various brain regions is in a stable state. It is necessary to interpret brain changes from a new perspective, that is, the stability of brain architecture.MethodsIn this study, we used a fixed dynamic time scale to explore the stability of dynamic functional architecture in T2DM, then the dynamic effective connectivity (dEC) was used to further explain how information flows through dynamically fluctuating brain architecture in T2DM.ResultTwo brain regions with decreased stability were found including the right supra-marginal gyrus (SMG) and the right median cingulate gyrus (MCG) in T2DM subjects. The dEC variation has increased between the left inferior frontal gyrus (IFG) and the right MCG. The direction of causal flow is from the right MCG to the left IFG.ConclusionThe combination of stability and dEC can not only show the stability of dynamic functional architecture in brain but also reflect the fluidity of brain information, which is an innovative and interesting attempt in the field of neuroimaging. The changes of dynamic architecture in T2DM patients may present an innovative perspective and explanation for their cognitive decline.

ObjectiveThis study aims to explore the changes in the structure, perfusion, and function of the bilateral hippocampus in type 2 diabetes mellitus (T2DM) applying multimodal MRI methods, hoping to provide reliable neuroimaging evidence for the diagnosis of hippocampus-related brain injury in T2DM.MethodsWe recruited 30 T2DM patients and 45 healthy controls (HCs), on which we performed 3D T1-weighted images, resting-state functional MRI (rs-fMRI), arterial spin labeling (ASL) sequences, and a series of cognitive tests. Then, we compared the differences of two groups in the cerebral blood flow (CBF) value, amplitude of low-frequency fluctuation (ALFF) value, fractional ALFF (fALFF) value, coherence-based regional homogeneity (Cohe-ReHo) value, and degree centrality (DC) values of the bilateral hippocampus.ResultsIn the T2DM group, the bilateral hippocampal volumes and the CBF value of the right hippocampus were lower than those in the HCs, while the ALFF value, fALFF value, and Cohe-ReHo value of the bilateral hippocampus were higher than those in the HCs. Correlation analysis showed that fasting blood glucose (FBG) was negatively correlated with the residuals of left hippocampal volume (r = −0.407, P = 0.025) and right hippocampal volume (r = −0.420, P = 0.021). The residual of the auditory-verbal learning test (AVLT) (immediate) score was positively correlated with the residual of right hippocampal volume (r = 0.369, P = 0.045).ConclusionThis study indicated that the volume and perfusion of the hippocampus are decreased in T2DM patients that related to chronic hyperglycemia. Local spontaneous neural activity and coordination are increased in the hippocampus of T2DM patients, possibly as an adaptive compensation for cognitive decline.

Radiotherapy is applied in about 70% patients with tumors, yet radioresistance of tumor cells remains a challenge that limits the efficacy of radiotherapy. Ferroptosis, an iron-dependent lipid peroxidation regulated cell death, is involved in the development of a variety of tumors. Interestingly, there is evidence that ferroptosis inducers in tumor treatment can significantly improve radiotherapy sensitivity. In addition, related studies show that Glutathione S-transferase P1 (GSTP1) is closely related to the development of ferroptosis. The potential mechanism of targeting GSTP1 to inhibit tumor cells from evading ferroptosis leading to radioresistance has been proposed in this review, which implies that GSTP1 may play a key role in radiosensitization of lung cancer via ferroptosis pathway.

ObjectiveThis meta-analysis evaluated the diagnostic value of intraoperative brainstem auditory evoked potential (BAEP) for predicting post-operative hearing loss.MethodsResearch articles in MEDLINE, Embase, and Cochrane Library databases were searched and selected up to 20 January 2022, and data were extracted following a standard procedure. A diagnostic accuracy test meta-analysis was performed using a mixed-effect binary regression model.ResultsA total of 693 patients from 15 studies were extracted. The change in intraoperative BAEP showed high sensitivity (0.95) but low specificity (0.37), with an area under the curve of 0.83. Diagnostic accuracy of the loss of potentials showed high sensitivity (0.82) and specificity (0.79). The area under the curve was 0.88. No factor was found to account for the heterogeneity of the results according to the meta-regression and subgroup analyses (all P-values > 0.05).ConclusionsOur results showed that the loss of BAEP has meaningful value for predicting hearing loss after vestibular schwannoma surgery. The change in BAEP is also important for its high sensitivity during hearing preservation surgery.

PurposeThis study aimed to investigate the changes in brain structure and function in middle-aged patients with type 2 diabetes mellitus (T2DM) using morphometry and blood oxygen level-dependent functional magnetic resonance imaging (BOLD-fMRI).MethodsA total of 44 middle-aged patients with T2DM and 45 matched healthy controls (HCs) were recruited. Surface-based morphometry (SBM) was used to evaluate the changes in brain morphology. Degree centrality (DC) and functional connectivity (FC) were used to evaluate the changes in brain function.ResultsCompared with HCs, middle-aged patients with T2DM exhibited cortical thickness reductions in the left pars opercularis, left transverse temporal, and right superior temporal gyri. Decreased DC values were observed in the cuneus and precuneus in T2DM. Hub-based FC analysis of these regions revealed lower connectivity in the bilateral hippocampus and parahippocampal gyrus, left precuneus, as well as left frontal sup.ConclusionCortical thickness, degree centrality, as well as functional connectivity were found to have significant changes in middle-aged patients with T2DM. Our observations provide potential evidence from neuroimaging for analysis to examine diabetes-related brain damage.

Osteosarcoma (OS), the most common malignant tumor in the musculoskeletal system, mainly occurs in adolescents. OS results in high mortality and disability rates due to a fatal metastatic tendency and subsequent iatrogenic damage caused by surgery, radiotherapy and chemotherapy. Recently, immunotherapies have resulted in promising prognoses with reduced side effects compared with traditional therapies. Immune checkpoint inhibitors (ICIs), which are a representative immunotherapy for OS, enhance the antitumor effects of immune cells. ICIs have shown satisfactory outcomes in other kinds of malignant tumors, especially hemopoietic tumors. However, there is still a high percentage of failures or severe side effects associated with the use of ICIs to treat OS, leading to far worse outcomes. To reveal the underlying mechanisms of drug resistance and side effects, recent studies elucidated several possible reasons, including the activation of other inhibitory immune cells, low immune cell infiltration in the tumor microenvironment, different immune properties of OS subtypes, and the involvement of osteogenesis and osteolysis. According to these mechanisms, researchers have developed new methods to overcome the shortcomings of ICIs. This review summarizes the recent breakthroughs in the use of ICIs to treat OS. Although numerous issues have not been solved yet, ICIs are still the most promising treatment options to cure OS in the long run.

ObjectiveGeneral hospitals admit lower gestational age neonates than maternal and child health care centers, therefore associated with a higher morbidity and mortality. This study aimed to assess the etiology and clinical characteristics of neonatal sepsis in different medical setting models.MethodsNeonates admitted to 5 tertiary medical centers, including one national general hospital, two maternal and child health care hospitals and two regional general hospitals, in central-south China with culture-proven sepsis between January 2010 and December 2019 were included in the study. We compared maternal and neonatal characteristics, pathogen distribution, treatment and neonatal outcomes among 3 different medical setting models in this retrospective cohort.ResultsWe identified 757 episodes of culture-proven sepsis in 757 neonates. The predominant pathogens were coagulase-negative staphylococci, Klebsiella pneumoniae, Escherichia coli and Group B streptococci. A total of 683 neonates with detailed information were involved in further comparison; 54.6% were from the national general hospital, 35.9% were from the maternal and child health care hospital, and 9.5% were from the regional general hospital. Neonates in national and regional general hospitals had significantly lower gestational age and birthweight (P

PurposeTo identify and compare the value of functional MRI (fMRI) in predicting the early response of metastatic cervical lymph nodes (LNs) to induction chemotherapy (IC) in nasopharyngeal carcinoma (NPC) patients.MethodsThis prospective study collected 94 metastatic LNs from 40 consecutive NPC patients treated with IC from January 2021 to May 2021. Conventional diffusion-weighted imaging, diffusion kurtosis imaging, intravoxel incoherent motion, and dynamic contrast-enhanced magnetic resonance imaging were performed before and after IC. The parameter maps apparent diffusion coefficient (ADC), mean diffusion coefficient (MD), mean kurtosis (MK), Dslow, Dfast, perfusion fraction (PF), Ktrans, Ve, and Kep) of the metastatic nodes were calculated by the Functool postprocessing software. All LNs were classified as the responding group (RG) and non-responding group (NRG) according to Response Evaluation Criteria in Solid Tumors 1.1. The fMRI parameters were compared before and after IC and between the RG and the NRG. The significant parameters are fitted by logistic regression analysis to produce new predictive factor (PRE)–predicted probabilities. Logistic regression analysis and receiver operating characteristic (ROC) curves were performed to further identify and compare the efficacy of the parameters.ResultsAfter IC, the mean values of ADC, MD, and Dslow significantly increased, while MK, Dfast, and Ktrans values decreased dramatically, while no significant difference was detected in Ve and Kep. Compared with NRG, PF-pre and Ktrans-pre values in the RG were higher statistically. The areas under the ROC for the pretreatment PF, Ktrans, and PRE were 0.736, 0.722, and 0.810, respectively, with the optimal cutoff value of 222 × 10-4, 934 × 10-3/min, and 0.6624, respectively.ConclusionsThe pretreatment fMRI parameters PF and Ktrans showed promising potential in predicting the response of the metastatic LNs to IC in NPC patients.Clinical Trial RegistrationThis study was approved by the ethics board of the Chinese PLA General Hospital, and registered on 30 January 2021, in the Chinese Clinical Trial Registry; http://www.chictr.org.cn/showproj.aspx?proj=121198, identifier (ChiCTR2100042863).

PurposeCognitive impairment is generally found in individuals with type 2 diabetes mellitus (T2DM). Although they may not have visible symptoms of cognitive impairment in the early stages of the disorder, they are considered to be at high risk. Therefore, the classification of these patients is important for preventing the progression of cognitive impairment.MethodsIn this study, a convolutional neural network was used to construct a model for classifying 107 T2DM patients with and without cognitive impairment based on T1-weighted structural MRI. The Montreal cognitive assessment score served as an index of the cognitive status of the patients.ResultsThe classifier could identify T2DM-related cognitive decline with a classification accuracy of 84.85% and achieved an area under the curve of 92.65%.ConclusionsThe model can help clinicians analyze and predict cognitive impairment in patients and enable early treatment.

BackgroundThe COVID-19 pandemic has profoundly influenced the world. In wave after wave, many countries suffered from the pandemic, which caused social instability, hindered global growth, and harmed mental health. Although research has been published on various mental health issues during the pandemic, some profound effects on mental health are difficult to observe and study thoroughly in the short term. The impact of the pandemic on mental health is still at a nascent stage of research. Based on the existing literature, we used bibliometric tools to conduct an overall analysis of mental health research during the COVID-19 pandemic.MethodResearchers from universities, hospitals, communities, and medical institutions around the world used questionnaire surveys, telephone-based surveys, online surveys, cross-sectional surveys, systematic reviews and meta-analyses, and systematic umbrella reviews as their research methods. Papers from the three academic databases, Web of Science (WOS), ProQuest Academic Database (ProQuest), and China National Knowledge Infrastructure (CNKI), were included. Their previous research results were systematically collected, sorted, and translated and CiteSpace 5.1 and VOSviewers 1.6.13 were used to conduct a bibliometric analysis of them.ResultAuthors with papers in this field are generally from the USA, the People's Republic of China, the UK, South Korea, Singapore, and Australia. Huazhong University of Science and Technology, Hong Kong Polytechnic University, and Shanghai Jiao Tong University are the top three institutions in terms of the production of research papers on the subject. The University of Toronto, Columbia University, and the University of Melbourne played an important role in the research of mental health problems during the COVID-19 pandemic. The numbers of related research papers in the USA and China are significantly larger than those in the other countries, while co-occurrence centrality indexes in Germany, Italy, England, and Canada may be higher.ConclusionWe found that the most mentioned keywords in the study of mental health research during the COVID-19 pandemic can be divided into three categories: keywords that represent specific groups of people, that describe influences and symptoms, and that are related to public health policies. The most-cited issues were about medical staff, isolation, psychological symptoms, telehealth, social media, and loneliness. Protection of the youth and health workers and telemedicine research are expected to gain importance in the future.

In epidemiological studies, type 2 diabetes mellitus (T2DM) has been associated with cognitive impairment and dementia, but studies about functional network connectivity in T2DM without cognitive impairment are limited. This study aimed to explore network connectivity alterations that may help enhance our understanding of damage-associated processes in T2DM. MRI data were analyzed from 82 patients with T2DM and 66 normal controls. Clinical, biochemical, and neuropsychological assessments were conducted in parallel with resting-state functional magnetic resonance imaging, and the cognitive status of the patients was assessed using the Montreal Cognitive Assessment-B (MoCA-B) score. Independent component analysis revealed a positive correlation between the salience network and the visual network and a negative connection between the left executive control network and the default mode network in patients with T2DM. The differences in dynamic brain network connectivity were observed in the precuneus, visual, and executive control networks. Internal network connectivity was primarily affected in the thalamus, inferior parietal lobe, and left precuneus. Hemoglobin A1c level, body mass index, MoCA-B score, and grooved pegboard (R) assessments indicated significant differences between the two groups (p < 0.05). Our findings show that key changes in functional connectivity in diabetes occur in the precuneus and executive control networks that evolve before patients develop cognitive deficits. In addition, the current study provides useful information about the role of the thalamus, inferior parietal lobe, and precuneus, which might be potential biomarkers for predicting the clinical progression, assessing the cognitive function, and further understanding the neuropathology of T2DM.

Tomatoes (Solanum lycopersicum L. Micro-Tom) were grown in a plastic greenhouse. When plants anthesis, the 100 μmol m–2 s–1 blue light-emitting diode (LED) light (430 ± 10 nm) was supplemented from 6:00 to 18:00. There were 5 treatments, which contained different blue light frequencies with the same intensity: S6 (30 min blue light and 30 min pause), S8 (30 min blue light and 15 min pause), S10 (30 min blue and 8 min pause), S12 (continuous blue light for 12 h), and control (CK) (natural light, without any supplemental light). Agronomic traits and nutritional qualities of tomato fruits were measured at 30, 34, 38, 42, and 46 days after anthesis (DAA), respectively. Different frequencies of supplemental blue light could accelerate flowering of tomato plants and promote fruit ripening about 3–4 days early via promoting ethylene evolution of fruits, which significantly facilitated the processes of color change and maturity in tomato fruits. The contents of lycopene, total phenolic compounds, total flavonoids, vitamin C, and soluble sugar, as well as the overall antioxidant activity of tomato fruits were significantly enhanced by all the supplemental blue light treatments. In all, different frequencies of supplemental blue light prominently reinforced the antioxidant levels and nutritional qualities of tomato fruits, especially lycopene content, and S10 was more optimal for tomato fruits production in a plastic greenhouse.

BackgroundVaccine hesitancy is responsible for low vaccine coverage and increased risk of epidemics. The purpose of this study was to assess whether public knowledge, attitudes, practices, and willingness to vaccinate against COVID-19 have changed over time and at different stages of vaccination.MethodsTwo consecutive surveys were conducted among residents of the Leshan Community in Jinan from May to June, 2021 (n = 423) (basic dose vaccination phase) and from December, 2021 to January, 2022 (n = 470) (booster vaccination phase). Randomly sampling was used in residents to complete an anonymous questionnaire. Chi-square test was used to compare the changes in knowledge, attitudes and practices of the subjects in different survey stages. Multivariable logistic regression analysis was used to explore factors related to vaccination hesitancy.ResultsIn the booster vaccination phase, protective behaviors (89.9%) of residents increased significantly compared with the basic vaccination phase (74.5%). Residents were more hesitant to receive booster doses than basal doses of COVID-19 vaccine (OR: 18.334, 95% CI: 9.021–37.262). Residents with other marital statuses (OR: 2.719, 95% CI: 1.632–4.528), negative attitudes toward government measures were more hesitant to get vaccinated (OR: 2.576, 95% CI: 1.612–4.118). People who thought their physical condition was very good or good were more likely to be vaccinated than those who thought they were in fair or poor health (OR: 0.516, 95% CI: 0.288–0.925; OR: 0.513, 95% CI: 0.295–0.893). Young people inclined to use new media (such as WeChat and microblog) to obtain information, while the elderly inclined to use traditional methods (such as television). Government propaganda, residents' perception of the importance of vaccines and the risk of disease were the main reasons for accelerating residents to vaccinate. The main reasons affecting residents' lack of vaccination were contraindications to the vaccine or inconvenient time for vaccination.ConclusionsVaccine hesitancy increased significantly with change in vaccination stage. Strategies should be adopted to increase vaccination coverage such as improving the convenience of vaccination, promoting through multiple channels.

Objective: We aimed to explore whether the percent amplitude of fluctuation (PerAF) measurement could provide supplementary information for amplitude of low-frequency fluctuation (ALFF) about spontaneous activity alteration in type 2 diabetes mellitus (T2DM) subjects without mild cognitive impairment (MCI). Then we further evaluated the synchronization through the method of functional connectivity (FC) to better demonstrate brain changes in a more comprehensive manner in T2DM.Methods: Thirty T2DM subjects without MCI and thirty well-matched healthy subjects were recruited in this study. Subjects’ clinical data, neuropsychological test results, and resting-state functional magnetic resonance imaging (rs-fMRI) data were acquired. Voxel-based group difference comparisons between PerAF and ALFF were conducted. Then, seed-based FC between the recognized brain regions based on PerAF and ALFF and the rest of the whole brain was performed.Results: Compared with healthy group, T2DM group had significantly decreased PerAF in the bilateral middle occipital gyrus and the right calcarine, increased ALFF in the right orbital inferior frontal gyrus and decreased ALFF in the right calcarine. Seed-based FC analysis showed that the right middle occipital gyrus of T2DM subjects exhibited significantly decreased FC with the right caudate nucleus and right putamen. According to the partial correlation analyses, hemoglobin A1c (HbA1c) and immediate memory scores on the auditory verbal learning test (AVLT) were negatively correlated in the T2DM group. However, we found that total cholesterol was positively correlated with symbol digit test (SDT) scores.Conclusion: PerAF and ALFF may have different sensitivities in detecting the abnormal spontaneous brain activity in T2DM subjects. We suggest PerAF values may add supplementary information and indicate additional potential neuronal spontaneous activity in T2DM subjects without MCI, which may provide new insights into the neuroimaging mechanisms underlying early diabetes-associated cognitive decline.

Objective: Cognitive impairment in type 2 diabetes mellitus (T2DM) patients is related to changes in hippocampal structure and function. However, the alternation of hippocampal subfields volumes and their relationship with cognitive function are unclear. This study explored morphological alterations in the hippocampus and its subfields in T2DM patients and their relationship with cognitive function.Methods: Thirty T2DM patients and 20 healthy controls (HCs) were recruited and underwent 3-dimensional, high-resolution T1-weighted sequence (3D-T1) and a battery of cognitive tests. Freesurfer 6.0 was performed to segment the hippocampus into 12 subregions automatically. Then relationships between hippocampal subfield volumes and neurocognitive scale scores in the T2DM group were evaluated.Results: Immediate memory scores on the auditory verbal learning test (AVLT) and Montreal Cognitive Assessment (MoCA) scores in T2DM patients were lower than in the HCs. T2DM patients showed that volumes of the bilateral hippocampus were significantly reduced, mainly in the bilateral molecular layer, granule cell and molecular layer of the dentate gyrus (GC-ML-DG), cornu ammonis 4 (CA4), fimbria, and left subiculum and the right hippocampus amygdala transition area (HATA) compared to HCs. In addition, T2DM patients showed the FINS was negatively correlated with volume of left GC-ML-DG (r = −0.415, P = 0.035) and left CA4 (r = −0.489, P = 0.011); the FBG was negatively correlated with volume of right fimbria (r = −0.460, P = 0.018); the HOMA-IR was negatively correlated with volume of left GC-ML-DG (r = −0.367, P = 0.046) and left CA4(r = 0.462, P = 0.010). Partial correlation analysis found that the volume of right HATA in T2DM group was positively correlated with AVLT (immediate) scores (r = 0.427, P = 0.03).Conclusion: This study showed the volumes of multiple hippocampal subfields decreased and they were correlated with FINS, FBG and HOMA-IR in T2DM patients. We hypothesized that decreased hippocampal subfields volumes in T2DM patients was related to insulin resistance and impaired vascular function. In addition, we also found that abnormal hippocampal subfields volumes were related to memory function in T2DM patients, suggesting that reduced volumes in specific hippocampal subfields may be the potential mechanism of memory dysfunction in these patients.

The spatial variability of soil properties is inherent. A series of direct shear tests were carried out on strongly weathered slates samples with weak bedding planes, the result of which indicates the existence of variability of shear strength parameters. Based on the testing results, several numerical simulations of slopes were conducted considering such a variability of shear strength. The results had shown that the weak bedding planes affect the shape of sliding arc as well as the factor of safety of slopes. As the dip angle of bedding planes increases, the shape of the sliding surface changes from circular to a mixed form of circular and planner. When incorporating the spatial variability of weak planes’ shear strength into the stability analysis, the safety factors of slopes would reduce, in which the sliding arc exhibited a sliding band comprising multiple sets of sliding arcs.

Diabetes with high blood glucose levels may damage the brain nerves and thus increase the risk of dementia. Previous studies have shown that dementia can be reflected in altered brain structure, facilitating computer-aided diagnosis of brain diseases based on structural magnetic resonance imaging (MRI). However, type 2 diabetes mellitus (T2DM)-mediated changes in the brain structures have not yet been studied, and only a few studies have focused on the use of brain MRI for automated diagnosis of T2DM. Hence, identifying MRI biomarkers is essential to evaluate the association between changes in brain structure and T2DM as well as cognitive impairment (CI). The present study aims to investigate four methods to extract features from MRI, characterize imaging biomarkers, as well as identify subjects with T2DM and CI.

Background: Structural and functional brain alterations that underlie cognitive decline have been observed in elderly adults with type 2 diabetes mellitus (T2DM); however, whether these alterations can be observed in patients with early-onset T2DM remains unclear. Therefore, we aimed to describe the abnormalities in brain volume and functional patterns in patients with early-onset T2DM in the present study.Methods: We enrolled 20 patients with early-onset T2DM and 20 healthy controls (HCs). Changes in brain volume were assessed using voxel-based morphology (VBM), while changes in brain function were assessed using degree centrality (DC) and functional connectivity (FC).Results: Compared to HCs, patients with early-onset T2DM exhibited gray matter reductions in the left orbital superior, middle, and inferior frontal gyri as well as the right superior frontal gyrus. The gray matter reductions in the right superior frontal gyrus were negatively associated with the urine albumin to creatinine ratio. Furthermore, increased DC values were observed in the left superior temporal gyrus, left Heschl gyrus, and left hippocampus in patients with early-onset T2DM. An FC analysis of these regions revealed elevated connectivity in the right precuneus, left inferior parietal gyrus, left Heschl gyrus, bilateral post-central gyrus, bilateral insula, bilateral superior temporal gyrus, and bilateral medial and paracingulate gyrus. Furthermore, the FC of the hubs to the superior temporal gyrus, insula, and Heschl gyrus was increased and positively correlated with trail making test-B.Conclusion: Decreased local gray matter volume and increased DC and FC may represent the neurobiological mechanism underlying cognitive dysfunction in patients with early-onset T2DM.

Objective: Aortic dissection (AD) is characterized by an acute onset, rapid progress, and high mortality. Levels of soluble ST2 (sST2) on presentation are elevated in patients with acute AD, which can be used to discriminate AD patients from patients with chest pain. sST2 concentrations were found to be highly heritable in the general population. The aim of this study was to investigate the associations of variations in ST2-related gene expression with sST2 concentrations and AD risk.Methods: This case-control study involving a total of 2,277 participants were conducted, including 435 AD patients and age- and sex-matched 435 controls in the discovery stage, and 464 patients and 943 controls in the validation stage. Eight ST2-related genes were selected by systematic review. Tag single-nucleotide polymorphisms (SNPs) were screened out from the Chinese population of the 1,000 Genomes Database. Twenty-one ST2-related SNPs were genotyped, and plasma sST2 concentrations were measured.Results: In the discovery stage, rs13019803 located in IL1R1 was significantly associated with AD after Bonferroni correction (p = 0.0009) and was correlated with circulating sST2 levels in patients with type A AD(AAD) [log-sST2 per C allele increased by 0.180 (95%) CI: 0.002 – 0.357] but not in type B. Combining the two stages together, rs13019803C was associated with plasma sST2 level in AAD patients [log-sST2 increased by 0.141 (95% CI: 0.055–0.227) for per C allele]. Odds ratio of rs13019803 on the risk of AAD is 1.67 (95% CI: 1.33–2.09).Conclusions: The IL1R1 SNP rs13019803C is associated with higher sST2 levels and increased risk of AAD.

This paper focuses on image segmentation, image correction and spatial-spectral dimensional denoising of images in hyperspectral image preprocessing to improve the classification accuracy of hyperspectral images. Firstly, the images were filtered and segmented by using spectral angle and principal component analysis, and the segmented results are intersected and then used to mask the hyperspectral images. Hyperspectral images with a excellent segmentation result was obtained. Secondly, the standard reflectance plates with reflectance of 2 and 98% were used as a priori spectral information for image correction of samples with known true spectral information. The mean square error between the corrected and calibrated spectra is less than 0.0001. Comparing with the black-and-white correction method, the classification model constructed based on this method has higher classification accuracy. Finally, the convolution kernel of the one-dimensional Savitzky-Golay (SG) filter was extended into a two-dimensional convolution kernel to perform joint spatial-spectral dimensional filtering (TSG) on the hyperspectral images. The SG filter (m = 7,n = 3) and TSG filter (m = 3,n = 4) were applied to the hyperspectral image of Pavia University and the quality of the hyperspectral image was evaluated. It was found that the TSG filter retained most of the original features while the noise information of the filtered hyperspectral image was less. The hyperspectral images of sample 1–1 and sample 1–2 were processed by the image segmentation and image correction methods proposed in this paper. Then the classification models based on SG filtering and TSG filtering hyperspectral images were constructed, respectively. The results showed that the TSG filter-based model had higher classification accuracy and the classification accuracy is more than 98%.

Overuse of antibiotics in clinical medicine has contributed to the global spread of multidrug-resistant bacterial pathogens, including Acinetobacter baumannii. We present a case of an 88-year-old Chinese man who developed hospital-acquired pneumonia caused by carbapenem-resistant A. baumannii (CRAB). A personalized lytic pathogen-specific single-phage preparation was nebulized to the patient continuously for 16 days in combination with tigecycline and polymyxin E. The treatment was well tolerated and resulted in clearance of the pathogen and clinical improvement of the patient’s lung function.

Background: Type 2 diabetes mellitus (T2DM)-related cognitive decline is associated with neuroimaging changes. However, only a few studies have focused on early functional alteration in T2DM prior to mild cognitive impairment (MCI). This study aimed to investigate the early changes of global connectivity patterns in T2DM by using a resting-state functional magnetic resonance imaging (rs-fMRI) technique.Methods: Thirty-four T2DM subjects and 38 age-, sex-, and education-matched healthy controls (HCs) underwent rs-fMRI in a 3T MRI scanner. Degree centrality (DC) was used to identify the functional hubs of the whole brain in T2DM without MCI. Then the functional connectivity (FC) between hubs and the rest of the brain was assessed by using the hub-based approach.Results: Compared with HCs, T2DM subjects showed increased DC in the right cerebellum lobules III–V. Hub-based FC analysis found that the right cerebellum lobules III–V of T2DM subjects had increased FC with the right cerebellum crus II and lobule VI, the right temporal inferior/middle gyrus, and the right hippocampus.Conclusions: Increased DC in the right cerebellum regions III–V, as well as increased FC within cerebellar regions and ipsilateral cerebrocerebellar regions, may indicate an important pathophysiological mechanism for compensation in T2DM without MCI.

Upregulation of neuronal oxidative stress is involved in the progression of secondary brain injury (SBI) following intracerebral hemorrhage (ICH). In this study, we investigated the potential effects and underlying mechanisms of luteolin on ICH-induced SBI. Autologous blood and oxyhemoglobin (OxyHb) were used to establish in vivo and in vitro models of ICH, respectively. Luteolin treatment effectively alleviated brain edema and ameliorated neurobehavioral dysfunction and memory loss in vivo. Also, in vivo, we found that luteolin promoted the activation of the sequestosome 1 (p62)/kelch‐like enoyl-coenzyme A hydratase (ECH)‐associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway by enhancing autophagy and increasing the translocation of Nrf2 to the nucleus. Meanwhile, luteolin inhibited the ubiquitination of Nrf2 and increased the expression levels of downstream antioxidant proteins, such as heme oxygenase-1 (HO-1) and reduced nicotinamide adenine dinucleotide phosphate (NADPH): quinine oxidoreductase 1 (NQO1). This effect of luteolin was also confirmed in vitro, which was reversed by the autophagy inhibitor, chloroquine (CQ). Additionally, we found that luteolin inhibited the production of neuronal mitochondrial superoxides (MitoSOX) and alleviated neuronal mitochondrial injury in vitro, as indicated via tetrachloro-tetraethylbenzimidazol carbocyanine-iodide (JC-1) staining and MitoSOX staining. Taken together, our findings demonstrate that luteolin enhances autophagy and anti-oxidative processes in both in vivo and in vitro models of ICH, and that activation of the p62-Keap1-Nrf2 pathway, is involved in such luteolin-induced neuroprotection. Hence, luteolin may represent a promising candidate for the treatment of ICH-induced SBI.

Type 2 diabetes mellitus (T2DM) is associated with cognitive dysfunction and may even progress to dementia. However, the underlying mechanism of altered functional topological organization and cognitive impairments remains unclear. This study explored the topological properties of functional whole brain networks in T2DM patients with graph theoretical analysis using a resting-state functional magnetic resonance imaging (rs-fMRI) technique. Thirty T2DM patients (aged 51.77 ± 1.42 years) and 30 sex-, age-, and education-matched healthy controls (HCs) (aged 48.87 ± 0.98 years) underwent resting-state functional imaging in a 3.0 T MR scanner in addition to detailed neuropsychological and laboratory tests. Then, graph theoretical network analysis was performed to explore the global and nodal topological alterations in the functional whole brain networks of the T2DM patients. Finally, correlation analyses were performed to investigate the relationship between the altered topological parameters, cognitive performances and clinical variables. Compared to HCs, we found that T2DM patients displayed worse performances in general cognitive function and several cognitive domains, including episodic memory, attention and executive function. In addition, T2DM patients showed a higher small-worldness (σ), a higher normalized clustering coefficient (γ) and a higher local efficiency (Eloc). Moreover, decreased nodal topological properties were mainly distributed in the occipital lobes, frontal lobes, left median cingulate and paracingulate gyri, and left amygdala, while increased nodal topological properties were mainly distributed in the right gyrus rectus, right anterior cingulate and paracingulate gyri, right posterior cingulate gyrus, bilateral caudate nucleus, bilateral cerebellum 3, bilateral cerebellum crus 1, vermis (1, 2) and vermis 3. Some disrupted nodal topological properties were correlated with cognitive performance and HbA1c levels in T2DM patients. This study shows altered functional topological organization in T2DM patients, mainly suggesting a compensation mechanism of the functional whole brain network in the relatively early stage to counteract cognitive impairments.

Objectives: We aimed to investigate whether an inter-voxel diffusivity metric (local diffusion homogeneity, LDH), can provide supplementary information to traditional intra-voxel metrics (i.e., fractional anisotropy, FA) in white matter (WM) abnormality detection for type 2 diabetes mellitus (T2DM).Methods: Diffusion tensor imaging was acquired from 34 T2DM patients and 32 healthy controls. Voxel-based group-difference comparisons based on LDH and FA, as well as the association between the diffusion metrics and T2DM risk factors [i.e., body mass index (BMI) and systolic blood pressure (SBP)], were conducted, with age, gender and education level controlled.Results: Compared to the controls, T2DM patients had higher LDH in the pons and left temporal pole, as well as lower FA in the left superior corona radiation (p < 0.05, corrected). In T2DM, there were several overlapping WM areas associated with BMI as revealed by both LDH and FA, including right temporal lobe and left inferior parietal lobe; but the unique areas revealed only by using LDH included left inferior temporal lobe, right supramarginal gyrus, left pre- and post-central gyrus (at the semiovale center), and right superior radiation. Overlapping WM areas that associated with SBP were found with both LDH and FA, including right temporal pole, bilateral orbitofrontal area (rectus gyrus), the media cingulum bundle, and the right cerebellum crus I. However, the unique areas revealed only by LDH included right inferior temporal lobe, right inferior occipital lobe, and splenium of corpus callosum.Conclusion: Inter- and intra-voxel diffusivity metrics may have different sensitivity in the detection of T2DM-related WM abnormality. We suggested that LDH could provide supplementary information and reveal additional underlying brain changes due to diabetes.

While the depolymerization of lignin to chemicals catalyzed by ionic liquids has attracted significant attention, the relevant molecular mechanism, especially the cleavage of specific bonds related to efficient depolymerization, still needs to be deeply understood for the complexity of this natural aromatic polymer. This work presents a detailed understanding of the cleavage of the most abundant β-O-4 bond in the model system, guaiacylglycerol β-guaiacyl ether, by a Brønsted acidic IL (1-methyl-3-(propyl-3-sulfonate) imidazolium bisulfate ([C3SO3Hmim][HSO4]) using density functional theory calculation and molecular dynamics simulation. It has been found that [C3SO3Hmim][HSO4] generates zwitterion/H2SO4via proton transfer with an energy barrier of 0.38 kcal/mol, which plays a dominant role in the lignin depolymerization process. Subsequently, the reaction can be carried out via three potential pathways, including (1) the dehydration of α-C-OH, (2) dehydration of γ-C-OH, and (3) the protonation of β-O. The electrophilic attack of H2SO4 and the hydrogen-bonding interaction between GG and zwitterion are the two most important factors to promote the depolymerization reaction. In all steps, the dehydration of α-C-OH route is computed to be favored for the experiment. The relatively higher energy barrier for β-O-4 bond dissociation among these reaction steps is attributed to the hindrance of the self-assembled clusters of GG in the mixed system. Further, the dense distribution of H13([C3SO3Hmim]) surrounding O21(GG), indicated by sharp peaks in RDFs, reveals that -SO3H in cations plays a substantial role in solvating lignin. Hopefully, this work will demonstrate new insights into lignin depolymerization by functionalized ILs in biomass conversion chemistry.

Cronobacter species can cause necrotizing enterocolitis and meningitis in neonates and infants, their infection is closely relevant to their responses to extreme growth conditions. In this study, the response of Cronobacter species to amino acid deficiency has been investigated. Four Cronobacter species formed smooth colonies when grown on the solid LB medium, but formed mucoid colonies when grown on the amino acid deficient M9 medium. When the mucoid colonies were stained with tannin mordant, exopolysaccharide around the cells could be discerned. The exopolysaccharide was isolated, analyzed, and identified as colanic acid. When genes wcaD and wcaE relevant to colanic acid biosynthesis were deleted in Cronobacter sakazakii BAA-894, no exopolysaccharide could be produced, confirming the exopolysaccharide formed in C. sakazakii grown in M9 is colanic acid. On the other hand, when genes rcsA, rcsB, rcsC, rcsD, or rcsF relevant to Rcs phosphorelay system was deleted in C. sakazakii BAA-894, colanic acid could not be produced, suggesting that the production of colanic acid in C. sakazakii is regulated by Rcs phosphorelay system. Furthermore, C. sakazakii BAA-894 grown in M9 supplemented with amino acids could not produce exopolysaccharide. Transcriptomes of C. sakazakii BAA-894 grown in M9 or LB were analyzed. A total of 3956 genes were differentially expressed in M9, of which 2339 were up-regulated and 1617 were down-regulated. When C. sakazakii BAA-894 was grown in M9, the genes relevant to the biosynthesis of exopolysaccharide were significantly up-regulated; on the other hand, the genes relevant to the flagellum formation and chemotaxis were significantly down-regulated; in addition, most genes relevant to various amino acid biosynthesis were also significantly regulated. The results demonstrate that amino acid deficiency has a global impact on C. sakazakii cells.

The Gram-positive human pathogen Staphylococcus aureus is a leading cause of severe bacterial infections. Recent studies have shown that various cell types could readily internalize S. aureus and infected cells have been proposed to serve as vehicle for the systemic dissemination of the pathogen. Here we focused on the intracellular behavior of the Community-Associated Methicillin-Resistant S. aureus strain USA300. Supporting earlier observations, we found that wild-type S. aureus strain USA300 persisted for longer period within endothelial cells than within macrophages and that a mutant displaying the small colony variant phenotype (ΔhemDBL) had increased intracellular persistence. Time-lapse microscopy revealed that initial persistence of wild-type bacteria in endothelial cells corresponded to distinct single cell events, ranging from active intracellular bacterial proliferation, leading to cell lysis, to non-replicating bacterial persistence even 1 week after infection. In sharp contrast, ΔhemDBL mutant bacteria were essentially non-replicating up to 10 days after infection. These findings suggest that internalization of S. aureus in endothelial cells triggers its persistence and support the notion that endothelial cells might constitute an intracellular persistence niche responsible for reported relapse of infection after antibiotic therapy.