Peanut-Colonized Piriformospora indica Enhanced Drought Tolerance by Modulating the Enzymes and Expression of Drought-Related Genes.

Peanut (Arachis hypogaea L.) is an important cash and oil seed crop, mostly distributed in arid and semi-arid areas. In recent years, due to the influence of atmospheric circulation anomalies and other factors, drought has become frequent and increasingly serious in China. This has posed serious challenges to peanut production. The objective of this study was to investigate the potential of the endophytic fungus Piriformospora indica to form a symbiotic relationship with peanut plants and to evaluate the drought tolerance of P. indica-colonized peanut plants subjected to a simulated drought stress treatment using 20% polyethylene glycol 6000 (PEG6000). The endophytic fungus P. indica affected the physiological characteristics of the host plant by colonizing the plant roots, thereby conferring greater resistance to drought stress. This fungus strongly colonized the roots of peanuts and was found to enhance root activity after 24 h of P. indica colonization under PEG6000. Catalase (CAT) and peroxidase (POD) activities were increased at 24 h in peanut leaves colonized with P. indica. Expression of drought-related genes, such as AhNCED1, AhP5CS, and DREB2A was upregulated at 24 h of P. indica colonization. In addition, after PEG6000 treatment, proline, soluble protein, and abscisic acid (ABA) concentrations in plants were increased, while the accumulation of malondialdehyde (MDA), and hydrogen peroxide (H2O2) was decreased in P. indica colonized peanut. In conclusion, P. indica mediated peanut plant protection against the detrimental effects of drought resulted from enhanced antioxidant enzyme activities, and the upregulated expression of drought-related genes for lower membrane damage.

Association between iron content in grey matter nuclei and functional outcome in patients with acute ischaemic stroke: A quantitative susceptibility mapping study.

BACKGROUND AND PURPOSE: This study aimed to investigate the association between iron content in grey matter (GM) nuclei and functional outcome in acute ischaemic stroke (AIS) patients utilizing quantitative susceptibility mapping. METHODS: Forty AIS patients and 40 age-, sex- and education-matched healthy controls underwent quantitative susceptibility mapping to assess susceptibility values, which are positively correlated with iron content, in the caudate nucleus, putamen, globus pallidus, thalamus, red nucleus and substantia nigra. The nuclei on the contralateral side were measured in AIS patients to minimize confounding due to oedema or haemorrhage. Functional outcome was determined by the modified Rankin Scale (mRS) score at 3 months after stroke. Poor outcome was defined as mRS >2, whilst a good outcome was defined as ≤2. RESULTS: Susceptibility values were significantly higher in most contralateral GM nuclei in AIS patients than in the corresponding left or right nuclei in healthy controls. AIS patients with poor outcome showed significantly lower susceptibility value than those with good outcome in the contralateral caudate nucleus, but no significant differences were observed in other GM nuclei. Binary logistic regression analysis revealed a significant association between the susceptibility value of the contralateral caudate nucleus and poor outcome after adjustment for confounders (adjusted odds ratio 0.692, 95% confidence interval 0.486-0.986, p = 0.042). Receiver operating characteristic curve analysis showed an acceptable ability of the susceptibility value of the contralateral caudate nucleus to predict poor outcome (area under the curve 0.740, p = 0.013). CONCLUSIONS: Lower iron content in the contralateral caudate nucleus was associated with poor functional outcome in AIS patients.

Pharmacological Inhibition of Epac1 Protects against Pulmonary Fibrosis by Blocking FoxO3a Neddylation.

Background: Idiopathic Pulmonary fibrosis (IPF) is characterized by progressive scarring and fibrosis within the lungs. There is currently no cure for IPF; therefore, there is an urgent need to identify novel therapeutic targets that can prevent the progression of IPF. Compelling evidence indicates that the second messenger, cyclic adenosine monophosphate (cAMP), inhibits lung fibroblast proliferation and differentiation through the classical PKA pathway. However, the contribution of the e xchange p rotein directly a ctivated by c AMP 1 (Epac1) to IPF pathophysiological processes is yet to be investigated. Objective: To determine the role of the cAMP-binding protein Epac1 in the progression of IPF. Methods: We used lung samples from IPF patients or healthy controls, mouse lung samples, or lung fibroblast isolated from a preclinical mouse model of PF induced by bleomycin intratracheal injection. The effect of bleomycin (BLM) treatment was determined in Epac1 knock-out mice or wild-type littermates. Epac1 expression was modulated in vitro by using lentiviral vectors or adenoviruses. The therapeutic potential of the Epac1-selective pharmacological inhibitor, AM-001, was tested in vivo and in vitro, using a bleomycin mouse model of PF and an ex vivo precision-cut lung slices (PCLs) model of human lung fibrosis. Results: Epac1 expression was increased in the lung tissue of IPF patients, in IPF-diseased fibroblasts and in BLM-challenged mice. Furthermore, Epac1 genetic or pharmacological inhibition with AM-001 decreased normal and IPF fibroblast proliferation and the expression of profibrotic markers, αSMA, TGF-ß/SMAD2/3, and interleukin-6 (IL-6)/STAT3 signaling pathways. Consistently, blocking Epac1 protected against BLM-induced lung injury and fibrosis, suggesting a therapeutic effect of Epac1 inhibition on PF pathogenesis and progression. Global gene expression profiling revealed a decrease in the key components of the profibrotic gene signature and neddylation pathway in Epac1-deficient lung fibroblasts and IPF human-derived PLCs. Mechanistically, the protective effect of Epac1 inhibition against PF development involves the inhibition of FoxO3a neddylation and its subsequent degradation by NEDD8, and in part, by limiting the proliferative capacity of lung-infiltrating monocytes. Conclusions: We demonstrated that Epac1 is an important regulator of the pathological state of fibroblasts in PF and that small molecules targeting Epac1 can serve as novel therapeutic drugs against PF.

Straw degradation enhanced in Thermomyces lanuginosus by transferring AgCMCase from Aspergillus glaucus.

Fungi play a crucial role in straw composting due to the synergistic degradation effects of their secreted lignocellulose hydrolases. An efficient straw-composting system relies on thermophilic fungi and their lignocellulose hydrolases. Thermomyces lanuginosus, a typical thermophilic fungus in compost, lacks cellulase genes. A versatile Thermomyces strain capable of degrading cellulose, T. lanuginosus M85, which grows at 67 °C, was developed and transformed using the AgCMCase of Aspergillus glaucus. The R6 transformant exhibited high-level expression of the AgCMCase. Significant quantities of active cellulase produced by R6 were detected in the cellulose fermentation broth, peaking within 6-8 days. Compost analysis indicated that R6 increased the internal compost temperatures and prolonged high-temperature durations. Correspondingly, more reducing sugars and humus were released, which could promote plants growth. In summary, a cellulase-producing strain of T. lanuginosus capable of efficiently converting straws into organic fertilizers was engineered. This innovation holds considerable promise for sustainable and circular agricultural practices.

Earth-Moon dynamics from cyclostratigraphy reveals possible ocean tide resonance in the Mesoproterozoic era.

Cyclostratigraphy is an important observational window into the history of the Earth-Moon system. However, there is limited information from the Mesoproterozoic era (1.0 to 1.6 billion years ago); accordingly, only weak constraints on Earth-Moon separation and tidal dissipation are available for this time. To close this knowledge gap, we analyze cyclostratigraphy from the Yemahe Formation (~1.2 billion years ago), Wumishan Formation (~1.5 billion years ago), and Chuanlinggou Formation (~1.6 billion years ago) in China. We use a Bayesian inversion method to analyze the three cyclostratigraphic sections. We combine previous results with these three estimates to construct an updated Earth-Moon system evolution and tidal dissipation history after 2.5 billion years ago. The results show a tidal dissipation peak that is consistent with the model predictions within the error range but also that there may be an additional resonance fluctuation in the Mesoproterozoic era.

Ventral posteromedial nucleus of the thalamus gates the spread of trigeminal neuropathic pain.

BACKGROUND: Widespread neuropathic pain usually affects a wide range of body areas and inflicts huge suffering on patients. However, little is known about how it happens and effective therapeutic interventions are lacking. METHODS: Widespread neuropathic pain was induced by partial infraorbital nerve transection (p-IONX) and evaluated by measuring nociceptive thresholds. In vivo/vitro electrophysiology were used to evaluate neuronal activity. Virus tracing strategies, combined with optogenetics and chemogenetics, were used to clarify the role of remodeling circuit in widespread neuropathic pain. RESULTS: We found that in mice receiving p-IONX, along with pain sensitization spreading from the orofacial area to distal body parts, glutamatergic neurons in the ventral posteromedial nucleus of the thalamus (VPMGlu) were hyperactive and more responsive to stimulations applied to the hind paw or tail. Tracing experiments revealed that a remodeling was induced by p-IONX in the afferent circuitry of VPMGlu, notably evidenced by more projections from glutamatergic neurons in the dorsal column nuclei (DCNGlu). Moreover, VPMGlu receiving afferents from the DCN extended projections further to glutamatergic neurons in the posterior insular cortex (pIC). Selective inhibition of the terminals of DCNGlu in the VPM, the soma of VPMGlu or the terminals of VPMGlu in the pIC all alleviated trigeminal and widespread neuropathic pain. CONCLUSION: These results demonstrate that hyperactive VPMGlu recruit new afferents from the DCN and relay the extra-cephalic input to the pIC after p-IONX, thus hold a key position in trigeminal neuropathic pain and its spreading. This study provides novel insights into the circuit mechanism and preclinical evidence for potential therapeutic targets of widespread neuropathic pain.

Association between metabolic syndrome and outcomes of large-artery atherosclerosis stroke treated with reperfusion therapy.

AIM: We aimed to investigate the impact of metabolic syndrome (MetS) on the outcomes of stroke patients with large-artery atherosclerosis who underwent reperfusion therapy. METHODS: A retrospective analysis was carried out on patients receiving reperfusion therapy for atherothrombotic stroke between January 2019 and May 2021. MetS was diagnosed according to the AHA/NHLBI criteria. The primary outcome was the composite outcome of disability (modified Rankin Scale [mRS] score 3-5), death or stroke recurrence within 3 months of stroke onset. Secondary outcomes included disability and death within 3 months as well as hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) within 24 hours after reperfusion treatment. The independent association of MetS with the above outcomes and the highly correlated components of MetS was examined using binary logistic regression analysis. RESULTS: A total of 174 patients were enrolled. MetS patients had a higher proportion of the composite outcome (p = 0.012), disability (p = 0.029) and HT (p = 0.049) than those without MetS, except for death (p = 0.375) and sICH (p = 0.306). Following adjustments, MetS remained independently associated with the composite outcome (adjusted OR, 3.011 [95 %CI 1.372-6.604]; p = 0.006) and disability (adjusted OR, 2.727 [95 %CI 1.220-6.098]; p = 0.015), but not HT (adjusted OR, 1.872 [95 %CI 0.854-4.104]; p = 0.117). Hypertriglyceridemia was remarkedly associated with the composite outcome (adjusted OR, 9.746 [95 % CI 2.402-39.536]; p = 0.001) and disability (adjusted OR, 6.966 [95 % CI 1.889-25.692]; p = 0.004). CONCLUSION: MetS is independently associated with an increased risk of composite outcome and disability in patients with large-artery atherosclerosis stroke receiving reperfusion therapy, and hypertriglyceridemia is the main component that drives the effect of MetS on outcomes.

Performance evaluation and clinical application of the UA-5600 automatic dry chemistry urine analyzer in renal diseases.

Background: Urine testing as a routine screening programme, abnormal test results can be suggestive to clinicians but can sometimes be overlooked, and the establishment of a diagnostic model can better assist clinicians in identifying potential problems. BLD (blood), LEU (leukocyte), PRO (protein) and GLU (glucose) are the four most important parameters in urine testing, and the accuracy of their results is a key concern for clinicians, so it is essential to verify the accuracy of their results. In this study, we evaluated the analytical and clinical performance of Mindray's automatic urine dry chemistry analyzer, the UA-5600 (Hereinafter referred to as the (UA-5600), and the test strips configured with the instrument, and developed a machine-learning (ML) model for kidney disease screening from the results of 11 parameters output from the UA-5600 with the aim of detecting abnormal urine test results. Methods: Urine samples from outpatients and inpatients at The First Affiliated Hospital of Sun Yat-sen University were collected from August to September 2022 to evaluate the performance of the Mindray UA-5600 dry chemistry analyzer and test strips. The evaluation of the UA-5600 and its test strips focused on the agreement of the urine BLD and LEU readings with the RBC (red blood cell) and WBC (white blood cell) counts obtained by the Mindray EH-2090 urine formed element analyzer. We also compared the PRO and GLU readings with the results of the Mindray BS-2800M biochemistry analyzer. Urine samples from outpatients and inpatients were retrospectively analysed and grouped according to LIS diagnosis. Additionally, eight ML models for kidney disease screening were developed using 11 parameters measured by the UA-5600. And the model was validated by the validation set. Results: The UA-5600 had an 89.55% concordance rate for BLD and a 91.04% concordance rate for LEU compared to the EH-2090 analyzer. When benchmarked against the BS-2800M, the concordance rates for PRO and GLU were 94.14% and 95.20%, respectively. A total of 1,691 samples were used for the construction of the ML models, of which 346 patients (135 males and 211 females, age range: 18 to 98 years) diagnosed with renal disease, and 1,345 patients (397 males and 948 females, age range: 18 to 92 years) with non-renal disease diagnosed with other conditions. Notably, the Naïve Bayes (NB) model, which was built from the UA-5600 parameters, demonstrated superior predictive capabilities for renal disease, with an area under the receiver operating characteristic curve of 0.9470, a sensitivity of 0.7767, and a specificity of 0.9457. Conclusions: The Mindray UA-5600 demonstrates robust detection abilities for both BLD and LEU, and its results for PRO and GLU align closely with those obtained from the chemistry analyzer. The NB model has a good screening ability and shows promise as an effective screening tool.

A 52-week follow-up, multi-center, randomized, double-blinded comparison of efficacy and safety of two hyaluronic acid fillers for the treatment of moderate-to-severe nasolabial folds in Chinese population.

INTRODUCTION: To investigate the efficacy and safety of Cutegel® MAX (Cutegel) in the correction of moderate-to-severe nasolabial folds (NLFS) compared to Restylane® (Restylane, control). METHODS: This study was a 52-week, multicenter, randomized, double-blinded, active-controlled clinical trial. Qualified participants with moderate-to-severe NLFs were randomly assigned in a 1:1 ratio to receive Cutegel or Restylane. For the primary efficacy endpoint, the response rate was defined as the percentage of subjects exhibiting an improvement of at least one-point based on blinded evaluation of Wrinkle Severity Rating Scale (WSRS) at 24 weeks after injection. Other secondary efficacy endpoints and treatment-emergent adverse events (TEAEs) were assessed. RESULTS: Of 340 subjects randomized, 317 completed the week 52 visit. In the per protocol set (PPS), the blinded evaluator-assessed response rates at week 24 were 81.17% for Cutegel versus 77.56% for Restylane (p = 0.327). The between-group treatment differences in response rates were 3.60% [95% confidence interval (CI) = (-5.39%, 12.60%)], which demonstrated the noninferiority of Cutegel. Other secondary efficacy endpoints supported this. No significant differences were observed in the occurrence of adverse events between the two groups. CONCLUSION: Similar to Restylane, Cutegel was effective and well tolerated in correcting moderate-to-severe NLFs among the Chinese population.

Nasolabial folds (NLFs) are among the early indicators of facial aging process. In the past, rhytidectomy has been considered a safe procedure, yet it continues to carry risks such as hematoma, skin necrosis, nerve injury, and infection. With the ongoing development of biomaterials including hyaluronic acid (HA), minimally invasive injection procedures for the aesthetic correction of NLFs have become the preferred choice in recent years. The widespread use of HA has resulted in the development of various types of commercial HA fillers, such as Cutegel and Restylane. It is well known that HA filler products produce varying effects, attributable to differences in their components and physical properties. Previous studies have established that Restylane is a safe and effective HA dermal filler for the correction of NLFs. However, there is a lack of studies on both the cosmetic results and safety data for Cutegel in the published literature. Therefore, a randomized, double-blinded, active-controlled clinical trial was conducted at seven Chinese hospitals to evaluate the efficacy and safety of Cutegel for the correction of moderate-to-severe NLFs, compared to the approved Restylane in China. Among the 340 randomized subjects, 170 subjects received Cutegel, and 169 subjects received Restylane. Both groups reported similar improvements in WSRS (the between-group treatment differences in response rates exceeded the prespecified noninferiority margins), and also in other efficacy evaluations. Additionally, the two treatment groups showed similar safety profiles. In summary, Cutegel proved to be well tolerated and effective in this randomized, active-controlled clinical study, demonstrating its noninferiority to Restylane and validating its use as an alternative treatment for Chinese subjects with moderate-to-severe NLFs.

Tumor Regression Following Engineered Polyomavirus-Specific T Cell Therapy in Immune Checkpoint Inhibitor-Refractory Merkel Cell Carcinoma.

Although immune check-point inhibitors (CPIs) revolutionized treatment of Merkel cell carcinoma (MCC), patients with CPI-refractory MCC lack effective therapy. More than 80% of MCC express T-antigens encoded by Merkel cell polyomavirus, which is an ideal target for T-cell receptor (TCR)-based immunotherapy. However, MCC often repress HLA expression, requiring additional strategies to reverse the downregulation for allowing T cells to recognize their targets. We identified TCRMCC1 that recognizes a T-antigen epitope restricted to human leukocyte antigen (HLA)-A*02:01. Seven CPI-refractory metastatic MCC patients received CD4 and CD8 T cells transduced with TCRMCC1 (TTCR-MCC1) preceded either by lymphodepleting chemotherapy or an HLA-upregulating regimen (single-fraction radiation therapy (SFRT) or systemic interferon gamma (IFNγ)) with concurrent avelumab. Two patients who received preceding SFRT and IFNγ respectively experienced tumor regression. One experienced regression of 13/14 subcutaneous lesions with 1 'escape' lesion and the other had delayed tumor regression in all lesions after initial progression. Although TTCR-MCC1 cells with an activated phenotype infiltrated tumors including the 'escape' lesion, all progressing lesions transcriptionally lacked HLA expression. While SFRT/IFNγ did not immediately upregulate tumor HLA expression, a secondary endogenous antigen-specific T cell infiltrate was detected in one of the regressing tumors and associated with HLA upregulation, indicating in situ immune responses have the potential to reverse HLA downregulation. Indeed, supplying a strong co-stimulatory signal via a CD200R-CD28 switch receptor allows TTCR-MCC1 cells to control HLA-downregulated MCC cells in a xenograft mouse model, upregulating HLA expression. Our results demonstrate the potential of TCR gene therapy for metastatic MCC and propose a next strategy for overcoming epigenetic downregulation of HLA in MCC.

A Case of Complex Giant Rhinophyma Treated With Cosmetic Surgery.

ABSTRACT: Rhinophyma leads to severe facial deformities and significant social pressure for patients. Patients often seek medical intervention due to cosmetic defects and functional impairments, such as nasal congestion and airway collapse. Currently, there are numerous treatment modalities for rhinophyma, each with distinct advantages and disadvantages, leading to a lack of consensus in nasal vegetation management. Severe thickening in the nasal area can obstruct breathing through external nasal valve blockage, necessitating appropriate management for relief. This article presents a case study involving severe rhinophyma with respiratory obstruction that was successfully treated using incomplete resection followed by reconstruction to restore normal nasal contour. This not only achieved an upright position for nasal columella but also improved nasal contour to achieve normal appearance levels while completely relieving respiratory tract obstruction and enhancing patients' ventilation function. This method is easily performed without requiring additional expensive equipment, making it economically feasible even in ordinary medical centers while enabling patients to achieve a high quality of life.

Pseudo-NRBC in the Mindray BC-6800Plus analyzer: A clue for diagnostic anticipation of fungemia. Experimental and preliminary clinical reports.

INTRODUCTION: Candidemia can be a significant cause of death in immunosuppressed or debilitated patients particularly. Abnormalities of the instrumental cytograms of some hematological analyzers, such as Mindray BC-6800Plus, can be related to circulating Candida. We studied the possible diagnostic usefulness of this information. METHODS: A fungal bloodstream infection has been simulated by adding aliquots of Candida albicans, Candida parapsilosis, and Candida glabrata to 75 leftovers and anonymized peripheral blood samples. Cytographic abnormalities like those of experimental samples were used to select patients with possible fungemia. The microscopic review of peripheral blood smears constituted the confirmatory method. RESULTS: In all experimental samples, the various Candida types caused pseudo-NRBC and morphological abnormalities of WNB and DIFF cytograms. Circulating blastospores, free or engulfed by neutrophils, were the microscopic findings in the peripheral blood smears. In the clinical verification, 72 patients were recruited based on the presence of an evocative cluster in the WNB and DIFF cytograms. The microscopic review of 39 out of 72 samples was positive for NRBC. According to blood cultures, light microscopy revealed fungal forms of several Candida or non-Candida types in the remaining 33 samples. Nine of these cases were not yet known to suffer from bloodstream infection. CONCLUSIONS: Although further confirmatory clinical studies are required for these diagnostic abilities, the BC 6800Plus cytographic abnormalities related to fungemia have proven helpful in rapidly monitoring persistent fungemia in already diagnosed patients. In unknown or undiagnosed cases, they could be the trigger point for the subsequent diagnostic-therapeutic pathway.

Probiotics for the prevention of gestational diabetes mellitus: A meta-analysis of randomized controlled trials.

Changes of intestinal microbiota have been shown to be involved in the development of gestational diabetes mellitus (GDM). We performed a meta-analysis to systematically evaluate the potential role of probiotics for the prevention of GDM. Systematic literature search was performed in electronic databases including PubMed, Cochrane library, Embase, Web of Science, Wanfang, and China National Knowledge Infrastructure (CNKI) to obtain relevant randomized controlled studies. A random-effects model was used to pool the results by incorporating the impact of the potential heterogeneity. Meta-regression and subgroup analyses were conducted to evaluate the source of heterogeneity. Fourteen studies involving 3527 pregnant women were included. Results showed that probiotics significantly reduced the incidence of GDM as compared to control (risk ratio [RR]: 0.71, 95% confidence interval [CI]: 0.52-0.96, P = 0.03) with significant heterogeneity (I2 = 73%). The meta-regression showed that body mass index (BMI) of women was positively associated with the RR for the effect of probiotics on GDM (coefficient = 0.084, P = 0.01). The results of subgroup analyses also suggested that probiotics significantly reduced the risk of GDM in women with BMI < 26 kg/m2, but not in those with BMI ≥ 26 kg/m2 (P for subgroup difference = 0.001). In addition, the preventative efficacy of probiotics on GDM was remarkable in women < 30 years, but not in those ≥ 30 years (P for subgroup difference < 0.001). In conclusion, probiotics may be effective in reducing the risk of GDM, particularly for women with lower BMI and younger age.

Modelling the Flow Behaviour of Al Alloy Sheets at Elevated Temperatures Using a Modified Zerilli-Armstrong Model and Phenomenological-Based Constitutive Models.

The flow behaviour of AA2060 Al alloy under warm/hot deformation conditions is complicated because of its dependency on strain rates (ε˙), strain (ε), and deformation modes. Thus, it is crucial to reveal and predict the flow behaviours of this alloy at a wide range of temperatures (T) and ε˙ using different constitutive models. Firstly, the isothermal tensile tests were carried out via a Gleeble-3800 thermomechanical simulator at a T range of 100, 200, 300, 400, and 500 °C and ε˙ range of 0.01, 0.1, 1, and 10 s-1 to reveal the warm/hot flow behaviours of AA2060 alloy sheet. Consequently, three phenomenological-based constitutive models (L-MJC, S1-MJC, S2-MJC) and a modified Zerilli-Armstrong (MZA) model representing physically based constitutive models were developed to precisely predict the flow behaviour of AA2060 alloy sheet under a wide range of T and ε˙. The predictability of the developed constitutive models was assessed and compared using various statistical parameters, including the correlation coefficient (R), average absolute relative error (AARE), and root mean square error (RMSE). By comparing the results determined from these models and those obtained from experimentations, and confirmed by R, AARE, and RMSE values, it is concluded that the predicted stresses determined from the S2-MJC model align closely with the experimental stresses, demonstrating a remarkable fit compared to the S1-MJC, L-MJC, and MZA models. This is because of the linking impact between softening, the strain rate, and strain hardening in the S2-MJC model. It is widely known that the dislocation process is affected by softening and strain rates. This is attributed to the interactions that occurred between ε and ε˙ from one side and between ε, ε˙, and T from the other side using an extensive set of constants correlating the constitutive components of dynamic recovery and softening mechanisms.

Serum copeptin in women with gestational diabetes mellitus: A meta-analysis.

Previous studies have reported mixed results regarding the relationship between serum copeptin levels and gestational diabetes mellitus (GDM) risk. To address inconsistencies in prior research, this meta-analysis examines the potential link between serum copeptin levels and the risk of developing GDM. Our objective was to comprehensively evaluate this association. We systematically reviewed observational studies from Medline, Web of Science, Embase, Wanfang, and China National Knowledge Infrastructure (CNKI) databases up to October 15, 2023, employing a random-effects model to integrate the data while considering heterogeneity. This analysis incorporated 10 studies comprising 625 women with GDM and 1212 healthy pregnant controls. Our findings showed no significant difference in serum copeptin levels between women with GDM and those without (standardized mean difference [SMD] 0.01, 95% confidence interval [CI] -0.22 to 0.24, P = 0.92, I2 = 75%). Univariate meta-analysis indicated a positive correlation between the body mass index (BMI) of the participants and the outcomes (coefficient = 0.11, P = 0.002). Further subgroup analysis demonstrated that women with a mean BMI ≥ 26 kg/m2 and GDM had significantly higher serum copeptin levels compared to their non-GDM counterparts (SMD 0.31, 95% CI 0.05 to 0.57, P = 0.02, I2 = 46%). Conversely, no difference was observed in women with a BMI < 26 kg/m2 (SMD -0.23, 95% CI -0.37 to-0.09, P = 0.002, I2 = 0%, P for subgroup difference = 0.003). Variables, such as the country of study, maternal age, the timing of blood sampling, copeptin measurement methods, or GDM diagnostic criteria did not significantly affect the results. In summary, the association between serum copeptin levels and GDM risk is influenced by the BMI of pregnant women, indicating that elevated serum copeptin might be linked to GDM in individuals with a BMI ≥ 26 kg/m2.

Serum heme oxygenase-1 level predicts clinical outcome after acute ischemic stroke.

AIMS: The relationship between heme oxygenase-1 (HO-1) and human ischemic stroke outcome remains unclear, which was investigated in this study. METHODS: Acute ischemic stroke patients admitted within 24 h were enrolled. Serum HO-1 levels at baseline were measured via ELISA. Poor 3-month functional outcome was defined as modified Rankin Scale (mRS) score 3-6. Multivariable-adjusted binary logistic regression and restricted cubic spline models were employed to examine association between serum HO-1 and functional outcome. HO-1's additive prognostic utility was assessed by net reclassification index (NRI) and integrated discrimination improvement (IDI). RESULTS: Of 194 eligible patients, 79 (40.7%) developed poor functional outcomes at 3-month follow-up. The highest quartile of serum HO-1 was independently associated with a lower risk of poor functional outcome (adjusted OR 0.13, 95% CI 0.04-0.45; p = 0.001) compared with the lowest HO-1 category. The relationship between higher HO-1 levels and reduced risk of poor functional outcome was linear and dose responsive (p = 0.002 for linearity). Incorporating HO-1 into the analysis with conventional factors significantly improved reclassification for poor functional outcomes (NRI = 41.2%, p = 0.004; IDI = 5.0%, p = 0.004). CONCLUSIONS: Elevated serum HO-1 levels at baseline were independently associated with improved 3-month functional outcomes post-ischemic stroke. Serum HO-1 measurement may enhance outcome prediction beyond conventional clinical factors.

Performance of the digital cell morphology analyzer MC-100i in a multicenter study in tertiary hospitals in China.

BACKGROUND: This study investigated the performance of the MC-100i, a pre-commercial digital morphology analyzer utilizing a convolutional neural network algorithm, in a multicentric setting involving up to 11 tertiary hospitals in China. METHODS: Blood smears were analyzed by MC-100i, verified by morphologists, and manually differentiated. The classification performance on WBCs and RBCs was evaluated by comparing the classification results using different methods. The PLT and PLT clump counting performance was also assessed. The total assay time including hands-on time was evaluated. RESULTS: The agreements between pre- and post-classification were high for normal WBCs (κ > 0.96) and lower for overall abnormal WBCs (κ = 0.90). The post-classification results correlated well with manual differentials for both normal and abnormal WBCs (r > 0.93), except for basophils (r = 0.8480) and atypical lymphocytes (r = 0.8211). The clinical sensitivity and specificity of each RBC abnormality after verification were above 90 % using microscopy reviews as the reference. The PLTs counted by the MC-100i before and after verification correlated well with those measured by the PLT-O mode (r = 0.98). Moreover, PLT clumps were successfully classified by the analyzer in EDTA-dependent pseudothrombocytopenia blood samples. CONCLUSIONS: The MC-100i is an accurate and reliable digital cell morphology analyzer, offering another intelligent option for hematology laboratories.

A new hematological parameter model for the diagnosis and prognosis of sepsis in emergency department: A single-center retrospective study.

INTRODUCTION: Sepsis, a syndrome of organ dysfunction caused by an unregulated host response to infection. This study aimed to develop a novel sepsis diagnostic model of hematological parameters and evaluate its effectiveness in the early identification and prognosis of sepsis in emergency departments. METHODS: A retrospective study was conducted in Emergency Department. Cell population data parameters related to monocytes and neutrophils were obtained using the Mindary BC-6800 plus hematology analyzer. Receiver operating characteristic (ROC) curve analysis, logistic regression analysis was performed to assess the performance of the parameters and establish a diagnostic and prognostic model of sepsis, which was then verified with a validation cohort. RESULTS: Mon_XW exhibited the best diagnostic performance (area under the ROC curve [AUC] = 0.848, 95% confidence interval [CI]: 0.810-0.885, p < 0.001), followed by Neu_Y and Neu_YW (AUC = 0.777 95% CI: 0.730-0.824, p < 0.001). Logistic regression analysis identified Mon_XW and Neu_Y as independent predictors, which were used to establish a diagnostic model named hematological parameter for sepsis (HPS). HPS demonstrated the best diagnostic performance with an AUC of 0.862 (95% CI: 0.826-0.898, p < 0.001), sensitivity of 70.0%, and specificity of 87.1%, compared to C-reactive protein (CRP) and procalcitonin (PCT). The validation cohort also found that the positive predictive value of HPS was 70.4% and the negative predictive value was 92.2%. CONCLUSION: The developed HPS model showed promising diagnostic efficacy for sepsis in the emergency department, which outperformed CRP and PCT in terms of sensitivity and specificity. By enabling early identification and prognosis of sepsis, that contributes to reducing sepsis-related mortality.

Comparison of Characteristics and Outcomes Between Acute Ischemic Stroke Patients with Different Types of Heart Failure.

Acute ischemic stroke (AIS) can be complicated by heart failure involving preserved ejection fraction (HFpEF) or reduced ejection fraction (HFrEF), and whether or not the prognosis differs between the 2 types of patients remains unclear. We compared the clinical characteristics and outcomes of the 2 types of patients at 3 months after the stroke.We retrospectively analyzed patients who, between 1 January 2018 and 1 January 2021, experienced AIS that was complicated by HFrEF or HFpEF. All patients had been prospectively registered in the Chengdu Stroke Registry. Poor outcome was defined as a modified Rankin Scale (mRS) score of 2-6 at 3 months. Univariate and binary logistic regression was used to assess whether HFpEF was associated with a significantly worse prognosis than HFrEF.Among the final sample of 108 patients (60.2% men; mean age, 73.08 ± 10.82 years), 75 (69.4%) had HFpEF. Compared to HFrEF patients, those with HFpEF were older (P = 0.002), were more likely to have chronic kidney disease (P = 0.033), and were more likely to experience a poor outcome (P = 0.022). After adjustments, HFpEF was associated with significantly greater risk of poor outcome than HFrEF (OR 4.13, 95%CI 1.20-15.79, P = 0.029). However, rates of hemorrhagic transformation or mortality at 3 months after AIS did not differ significantly between the 2 types of heart failure (all P > 0.05).Patients with AIS involving HFpEF experience worse outcomes than those with HFrEF and therefore may require special monitoring and management. Our findings need to be verified in large prospective studies.

Secondary somatosensory cortex glutamatergic innervation of the thalamus facilitates pain.

ABSTRACT: Although the secondary somatosensory cortex (SII) is known to be involved in pain perception, its role in pain modulation and neuropathic pain is yet unknown. In this study, we found that glutamatergic neurons in deep layers of the SII (SII Glu ) responded to bilateral sensory inputs by changing their firing with most being inhibited by contralateral noxious stimulation. Optical inhibition and activation of unilateral SII Glu reduced and enhanced bilateral nociceptive sensitivity, respectively, without affecting mood status. Tracing experiments revealed that SII Glu sent dense monosynaptic projections to the posterolateral nucleus (VPL) and the posterior nucleus (Po) of the thalamus. Optical inhibition and activation of projection terminals of SII Glu in the unilateral VPL and Po inhibited and facilitated pain on the contralateral side, respectively. After partial sciatic nerve ligation, SII Glu became hyperactive as evidenced by higher frequency of spontaneous firing, but the response patterns to peripheral stimulation remained. Optical inhibition of SII Glu alleviated not only bilateral mechanical allodynia and thermal hyperalgesia but also the negative affect associated with spontaneous pain. Inhibition of SII Glu terminals in the VPL and Po also relieved neuropathic pain. This study revealed that SII Glu and the circuits to the VPL and Po constitute a part of the endogenous pain modulatory network. These corticothalamic circuits became hyperactive after peripheral nerve injury, hence contributes to neuropathic pain. These results justify proper inhibition of SII Glu and associated neural circuits as a potential clinical strategy for neuropathic pain treatment.