In Silico Design and Synthesis of Antifungal Peptides Guided by Quantitative Antifungal Activity.

Antifungal peptides (AFPs) are emerging as promising candidates for advanced antifungal therapies because of their broad-spectrum efficacy and reduced resistance development. In silico design of AFPs, however, remains challenging, due to the lack of an efficient and well-validated quantitative assessment of antifungal activity. This study introduced an AFP design approach that leverages an innovative quantitative metric, named the antifungal index (AFI), through a three-step process, i.e., segmentation, single-point mutation, and global multipoint optimization. An exhaustive search of 100 putative AFP sequences indicated that random modifications without guidance only have a 5.97-20.24% chance of enhancing antifungal activity. Analysis of the search results revealed that (1) N-terminus truncation is more effective in enhancing antifungal activity than the modifications at the C-terminus or both ends, (2) introducing the amino acids within the 10-60% sequence region that enhance aromaticity and hydrophobicity are more effective in increasing antifungal efficacy, and (3) incorporating alanine, cysteine, and phenylalanine during multiple point mutations has a synergistic effect on enhancing antifungal activity. Subsequently, 28 designed peptides were synthesized and tested against four typical fungal strains. The success rate for developing promising AFPs, with a minimal inhibitory concentration of ≤5.00 µM, was an impressive 82.14%. The predictive and design tool is accessible at https://antifungipept.chemoinfolab.com.

The Predictive Value of Geriatric Nutritional Risk Index Combined with the GRACE Score in Predicting the Risk of One Year Poor Prognosis in Elderly Patients with Non-ST Segment Elevation Myocardial Infarction After PCI.

Background: As a nutritional indicator, a lower level of geriatric nutritional risk index (GNRI) has been suggested as a predictor for poor prognosis in acute coronary syndrome (ACS). However, whether GNRI could improve the predictive value of the Global Registry of Acute Coronary Events (GRACE) score for the prognosis in elderly patients with non-ST segment elevation myocardial infarction (NSTEMI) after PCI remains unclear. Methods: A total of 446 elderly patients with NSTEMI after percutaneous coronary intervention (PCI) were consecutively enrolled. Patients were divided into major adverse cardiovascular and cerebrovascular events (MACCE) group and control group according to the occurrence of MACCE during one year follow up. The clinical parameters including GNRI were compared to investigate the predictors for MACCE. The performance after the addition of GNRI to the GRACE score for predicting MACCE was determined. Results: A total of 68 patients developed MACCE. In unadjusted analyses, the rate of MACCE was significantly higher in the 93.8

Anti-osteoporotic effects of Yi Mai Jian on bone metabolism of ovariectomized rats.

Yi Mai Jian herbal formula (YMJ) is formulated with Eucommiae Folium, Astragali Radix, Ligustri Lucidi Fructus, and Elaeagnus Fructus to improve bone function in traditional Chinese medicine. The anti-osteoporotic effects of YMJ in bone metabolism were evaluated in ovariectomized (OVX) rats. The skeletal structure of the femur and vertebrae was analyzed after treating OVX rats with YMJ for 114 days. The results showed that YMJ significantly increased the bone mineral density (BMD) and trabecular number (Tb. N) of the femur and 5th lumbar vertebrae and reduced trabecular separation (Tb. Sp). Moreover, trabecular bone volume/total tissue volume (BV/TV), bone stiffness, and maximum femur load were significantly increased. The serum concentrations of NTX1 and PYD were significantly decreased. According to these results, YMJ could ameliorate osteoporosis in ovariectomized rats. Eucommiae Folium and Elaeagnus Fructus inhibited osteoclast differentiation, Ligustri Lucidi Fructus inhibited calcium reabsorption, Astragali Radix stimulated osteoblast proliferation, and Astragali Radix and Eucommiae Folium stimulated mineralization. Therefore, the combination of the four herbs into one formula, YMJ, could alleviate bone remodeling caused by low estrogen levels. We suggest that YMJ could be a healthy food candidate for preventing post-menopausal osteoporosis.

Spatio-temporal variation and drivers of blue carbon sequestration in Hainan Island, China.

Blue carbon ecosystems, such as mangrove, seagrass bed and salt marsh, have attracted increasing attention due to their remarkable capacity for efficient carbon sequestration. However, the current threat posed by human activities to these ecosystems necessitates the characterization of their changes and identification of the primary driving factors in order to facilitate the gradual restoration of blue carbon ecosystems. In this study, we present an analysis of the spatio-temporal characteristics and primary influencing factors governing carbon sequestration in mangrove and seagrass beds located in Hainan Island. The findings revealed a 40% decline in carbon sequestration by mangroves from 1976 to 2017, while seagrass beds exhibited a 13% decrease in carbon sequestering between 2009 and 2016. The decline in carbon sequestration was primarily concentrated in Wenchang city, with aquaculture and population growth identified as the primary driving factors. Despite the implementation of measures aimed at reducing aquaculture in Hainan Island to promote blue carbon sequestration over the past two decades, the resulting recovery remains insufficient in achieving macro-level goals for carbon sequestration. This study emphasizes the necessity of safeguarding blue carbon ecosystems in Hainan Island by effectively mitigating anthropogenic disturbances.

The characteristics of arterial risk factors and ankle-brachial index in patients with lower extremity chronic venous diseases: results from the BEST study.

BACKGROUND: The aim of our study was to explore the characteristics of the arterial risk factors and ankle-brachial index (ABI) in patients with lower extremity chronic venous disease (LECVD). METHODS: A total of 2642 subjects were employed in our study. The lifestyle and clinical data were collected. The history of vascular diseases contained coronary artery disease, stroke, hypertension, and diabetes. ABI low than 0.9 was considered as lower extremity artery disease (LEAD). A series of blood indicators were measured. RESULTS: Patients with ABI low than 0.9 belonged to the group of LEAD. Age, smoking, drinking, hypertension, diabetes mellitus, lipid-lowering drug, antidiabetic, total protein, total protein, triglyceride, low-density lipoprotein cholesterol, glycosylated hemoglobin and homocysteine were the common risk factors shared by LEAD and LECVD (P<0.05). The prevalence of LEAD in patients with LECVD was higher than those without LECVD (P<0.05). In Pearson correlation analysis, LECVD was related to LEAD (P<0.05). Before and after adjusted shared factors, as the performance of the logistic regression models, LEAD was an independent risk factor for the prevalence of LECVD (OR=2.937, 95% CI: [1.956, 4.411], P<0.001). CONCLUSIONS: Our study demonstrated that an ABI lower than 0.9 is an independent risk factor for LECVD.

Perineural invasion in cervical cancer: A multicenter retrospective study.

OBJECTIVE: The study aimed to evaluate the accuracy of perineural invasion (PNI) diagnosis in cervical cancer, and to analyze the impact of PNI on the prognosis and postoperative adjuvant treatment decisions for cervical cancer. METHODS: A retrospective pathological review of PNI in cervical cancer was conducted from 2004 to 2016 in 15 hospitals. RESULTS: This study included a total of 1208 cases, comprising 273 cases with PNI and 935 cases without. The false positive rate and false negative rate of PNI diagnosis were 5.35% (50/935) and 33.33% (91/273), respectively. Adenocarcinoma, deep stromal invasion, lymphovascular space invasion (LVSI) (+), and margin involvement were independent risk factors for PNI. Both 5-year overall survival rate (OS) and 5-year disease-free survival rate (DFS) of PNI group were worse than non-PNI group. PNI was an independent risk factor for 5-year OS and 5-year DFS. In cases receiving standard postoperative adjuvant treatment, among those with two intermediate-risk factors, both 5-year OS and DFS were worse in the PNI group. Among cases with three intermediate-risk factors or at least one high-risk factor, there was no difference in 5-year OS between the two groups, but 5-year DFS was worse in the PNI group. CONCLUSION: The diagnosis of PNI in cervical cancer was not accurate. Adenocarcinoma, deep stromal invasion, LVSI, and margin involvement were independent risk factors for PNI. PNI was an independent risk factor for 5-year OS and DFS. PNI has the potential to serve as a new high-risk factor, thus providing guidance for postoperative adjuvant therapy.

Whole-transcriptome profiling and identification of cold tolerance-related ceRNA networks in japonica rice varieties.

Introduction: Low-temperature stress negatively impacts rice yield, posing a significant risk to food security. While previous studies have explored the physiological and linear gene expression alterations in rice under low-temperature conditions, the changes in competing endogenous RNA (ceRNA) networks remain largely unexamined. Methods: We conducted RNA sequencing on two japonica rice varieties with differing cold-tolerance capabilities to establish ceRNA networks. This enabled us to investigate the transcriptional regulatory network and molecular mechanisms that rice employs in response to low-temperature stress. Results: We identified 364 differentially expressed circular RNAs (circRNAs), 224 differentially expressed microRNAs (miRNAs), and 12,183 differentially expressed messenger RNAs (mRNAs). WRKY family was the most prominent transcription factor family involved in cold tolerance. Based on the expression patterns and targeted relationships of these differentially expressed RNAs, we discerned five potential ceRNA networks related to low-temperature stress in rice: osa-miR166j-5p from the miR166 family was associated with cold tolerance; osa-miR528-3p and osa-miR156j-3p were linked to stress response; and osa-miR156j-3p was involved in the antioxidant system. In addition, Os03g0152000 in the antioxidant system, as well as Os12g0491800 and Os05g0381400, correlated with the corresponding stress response and circRNAs in the network. A gene sequence difference analysis and phenotypic validation of Os11g0685700 (OsWRKY61) within the WRKY family suggested its potential role in regulating cold tolerance in rice. Discussion and conclusion: We identified Os11g0685700 (OsWRKY61) as a promising candidate gene for enhancing cold tolerance in japonica rice. The candidate miRNAs, mRNAs, and circRNAs uncovered in this study are valuable targets for researchers and breeders. Our findings will facilitate the development of cold-tolerant rice varieties from multiple angles and provide critical directions for future research into the functions of cold-tolerance-related miRNAs, mRNAs, and circRNAs in rice.

Diagnostic value of laboratory parameters for complicated appendicitis: A two­center study.

There are two types of treatment for acute appendicitis (AA): surgery and antibiotic therapy. Some patients with complex appendicitis are treated with surgery; however, for uncomplex appendicitis, most could be treated effectively with antibiotics instead. How to distinguish complex appendicitis from uncomplex appendicitis before surgery is currently unknown. The present study aimed to assess the efficacy of the laboratory parameters to diagnose complicated appendicitis. Data from 1,514 cases with acute appendicitis who were admitted to Beijing Tsinghua Changgung Hospital and Beijing Aerospace General Hospital (both Beijing, China) from January 2016 to September 2021 were retrospectively analyzed. All cases were divided into uncomplicated and complicated appendicitis. Independent variables were analyzed by uni- and multivariate logistic regression analyses. Receiver operating characteristic (ROC) curve analysis was used to identify significant parameters in the multivariate logistic regression analysis. Cut-off values, sensitivity, specificity and accuracy with area under the curve (AUC)>0.600 were considered significant parameters. Significant differences were found in age (P<0.001), body temperature (P<0.001), white blood cell (WBC) count (P<0.001), C-reactive protein (CRP; P<0.001), neutrophil count (P<0.001), neutrophil-to-lymphocyte ratio (NLR, P=0.019), platelet-to-lymphocyte ratio (PLR, P<0.001), platelet count (P<0.001), coefficient of variation (CV) and standard deviation (SD) of red blood cell distribution width (RDW); both P<0.001), mean platelet volume (MPV, P<0.001) and total (P<0.001) and direct bilirubin (P<0.001) between the two groups. CRP, neutrophil count, NLR, PLR, platelet count, RDW-CV, RDW-SD, MPV and direct bilirubin levels were found as the independent variables to diagnose complicated appendicitis. In patients with acute appendicitis, CRP >22.95 mg/l, NLR >5.7, serum direct bilirubin >6.1 mmol/l and RDW-SD>17.7 fl were significantly associated with complicated appendicitis.

Methodologic Quality and Pharmacotherapy Recommendations for Patient Blood Management Guidelines for Cardiac Surgery on Cardiopulmonary Bypass.

Patient blood management (PBM) guidelines for patients undergoing cardiac surgery under cardiopulmonary bypass (CPB) have increased during the past decade, and pharmacotherapy plays an important role in PBM. In the face of the undefined consistency in the methodologic quality and pharmacotherapy recommendations across multiple guidelines, this study exclusively evaluated methodologies of the related guideline development process, and compiled medication recommendations of PBM for cardiac surgery patients. PBM guidelines for cardiac surgery under CPB were searched through some mainstream literature and guideline databases from database establishment to May 15, 2023. Nine guidelines meeting inclusion criteria were included in this study. The quality of the guidelines was evaluated using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool. "Stakeholder involvement" received the lowest mean score of 49.38% in the AGREE II scoring among the guidelines. PBM for cardiac surgery patients spans the perioperative phase. Drug therapy strategies of PBM for cardiac surgery patients involve anemia therapy, perioperative administration of antithrombotic drugs, intraoperative anticoagulation, and the use of hemostatic drugs. Unlike for adults, there is less evidence about the management of antithrombotic drugs and hemostatic drugs for pediatric cardiac surgery patients. Recombinant activated factor VII (rFVIIa) and desmopressin (DDAVP) are not recommended after pediatric cardiac surgery, whereas prothrombin complex concentrate could be considered in clinical trials. As for the controversies regarding the administration of rFVIIa and DDAVP after adult cardiac surgery by different societies, clinicians should exercise their clinical judgment based on individual patient features.

Cannabidiol Alleviates Neurological Deficits After Traumatic Brain Injury by Improving Intracranial Lymphatic Drainage.

Traumatic brain injury (TBI) persists as a substantial clinical dilemma, largely because of the absence of effective treatments. This challenge is exacerbated by the hindered clearance of intracranial metabolic byproducts and the continual accrual of deleterious proteins. The glymphatic system (GS) and meningeal lymphatic vessels (MLVs), key elements of the intracranial lymphatic network, play critical roles in the clearance of harmful substances. Cannabidiol (CBD) has shown promise in reducing metabolite overload and bolstering cognitive performance in various neurodegenerative diseases. The precise mechanisms attributing to its beneficial effects in TBI scenarios, however, are yet to be distinctly understood. Utilizing a fluid percussion injury paradigm, our research adopted a multifaceted approach, encompassing behavioral testing, immunofluorescence and immunohistochemical analyses, laser speckle imaging, western blot techniques, and bilateral cervical efferent lymphatic ligation. This methodology aimed to discern the influence of CBD on both neurological outcomes and intracranial lymphatic clearance in a murine TBI model. We observed that CBD administration notably ameliorated motor, memory, and cognitive functions, concurrently with a significant reduction in the concentration of phosphorylated tau protein and amyloid-ß. In addition, CBD expedited the turnover and elimination of intracranial tracers, increased cerebral blood flow, and enhanced the efficacy of fluorescent tracer migration from MLVs to deep cervical lymph nodes (dCLNs). Remarkably, CBD treatment also induced a reversion in aquaporin-4 (AQP-4) polarization and curtailed neuroinflammatory indices. A pivotal discovery was that the surgical interruption of efferent lymphatic conduits in the neck nullified CBD's positive contributions to intracranial waste disposal and cognitive improvement, yet the anti-neuroinflammatory actions remained unaffected. These insights suggest that CBD may enhance intracranial metabolite clearance, potentially via the regulation of the intracranial lymphatic system, thereby offering neurofunctional prognostic improvement in TBI models. Our findings underscore the potential therapeutic applicability of CBD in TBI interventions, necessitating further comprehensive investigations and clinical validations to substantiate these initial conclusions.

Case Report: Technical description and clinical evaluation of three cases of unilateral biportal endoscopic decompression for symptomatic spinal epidural lipomatosis.

Objective: To investigate the clinical characteristics and outcomes of three patients with symptomatic Spinal epidural lipomatosis (SEL) treated using Unilateral Biportal Endoscopic (UBE) surgery. Methods: This report retrospectively analyzed the clinical data of three patients with SEL admitted to our hospital. The analysis covers onset characteristics, clinical manifestations, and the most recent radiologic grading system of neural compression (Manjila classification). Furthermore, it details the decompression accomplished through the application of a minimally invasive UBE surgical technique, specifically targeting the removal of proliferated fat responsible for nerve and spinal cord compression. Results: This technique was performed successfully in 3 patients with SEL. Radiating pain was reduced, and the functional disability and radiologic compression were improved in all three patients. Postoperative spinal instability and surgical complications related to the procedure were not observed. Conclusions: For SEL, timely diagnosis and appropriate intervention can prevent the progression of neurological disability. UBE is a minimally invasive muscle-preserving technique that achieves neural decompression directly by the removal of excessive intraspinal adipose tissue buildup.

A novel pH-sensitive hemi-cyanine containing tetrahydropyridine ring near-infrared fluorescence probe with lysosome-targeting ability.

In recent years, hemi-cyanine dyes have been widely used as biological probes due to their red-light emission characteristics and high fluorescence quantum yield. In this study, we synthesized a novel hemi-cyanine dye containing a tetrahydropyridine ring. A lysosomal target was introduced into its structure to create a new pH-sensitive near-infrared fluorescent probe that successfully targeted lysosomes. The results showed that when the probe solution was excited at the absorption wavelength of 650 nm, its fluorescence emission wavelength was about 700 nm, and the peak intensity changed with different pH values in a wide range. Therefore, this probe enabled non-invasive detection of changes in the acidic environment of lysosomes in living organisms and showed good imaging capabilities. Moreover, the probe displays high sensitivity and good stability. The theoretical calculation of a probe structure has also been completed to discuss the relationship between structure and property.

Multi-Level Structural Enhancement Mechanism of the Excellent Mechanical Properties of Dung Beetle Leg Joint.

The multi-level structure is a strategy to enhance the mechanical properties of dung beetle leg joints. Under external loads, the microstructure facilitates energy dissipation and prevents crack extension. The macrostructure aids in transferring the load to more reliable parts. The connection established by the two hemispheres is present in the dung beetle leg joint. The micron-layered and nanoscale crystal structures further constitute the leg joint with excellent mechanical properties. The maximum compression fracture force is ≈101000 times the weight of the leg. Here, the structural design within the dung beetle leg joints and reveal the resulting mechanical response and enhancement mechanisms is determined. A series of beetle leg joints where the macrostructure and microstructure of the dung beetle leg provide mechanical strength at critical strains while avoiding catastrophic failure by transferring the load from the joint to the exoskeleton of the femur is highlighted. Nanocrystalline structures and fiber layers contribute to crack propagation of the exoskeleton. Based on this, the bionic joint with multi-level structures using resin and conducted a series of tests to verify their effectiveness is prepared. This study provides a new idea for designing and optimizing high-load joints in engineering.

Tunable Surface Wettability via Terahertz Electrowave Controlled Vicinal Subnanoscale Water Layer.

Achieving timely, reversible, and long-range remote tunability over surface wettability is highly demanded across diverse fields, including nanofluidic systems, drug delivery, and heterogeneous catalysis. Herein, using molecular dynamic simulations, we show, for the first time, a theoretical design of electrowetting to achieve remotely controllable surface wettability via using a terahertz wave. The key idea driving the design is the unique terahertz collective vibration identified in the vicinal subnanoscale water layer, which is absent in bulk water, enabling efficient energy transfer from the terahertz wave to the rotational motion of the vicinal subnanoscale water layer. Consequently, a frequency-specific alternating terahertz electric field near the critical strength can significantly affect the local hydrogen-bonding network of the contact water layer on the solid surface, thereby achieving tunable surface wettability.

Comparison of Percutaneous Transforaminal Endoscopic Decompression and Full Endoscopic Lamina Fenestration Decompression in the Treatment of Degenerative Lumbar Spinal Stenosis with Unilateral Radicular Pain: A Retrospective Study.

BACKGROUND: Endoscopic decompression of the spinal canal is an emerging procedure for the treatment of degenerative lumbar spinal stenosis, but there are few reports of comparative studies of endoscopic techniques for transforaminal and non-transforaminal approaches. OBJECTIVE: To compare the clinical application of percutaneous transforaminal endoscopic decompression (PTED) and full endoscopic lamina fenestration decompression (Endo-LOVE) for treating degenerative lumbar spinal stenosis with unilateral radicular pain. METHODS: A total of 58 patients with degenerative lumbar spinal stenosis (DLSS) with unilateral radicular pain in the lower extremities who underwent endoscopic decompression treatment from June 2020 to December 2021 were retrospectively identified and divided into two groups (PTED vs Endo-LOVE). The two groups' perioperative data were analyzed according to surgical modalities. The Visual Analogue Score (VAS) for pain, Oswestry Disability Index (ODI), modified MacNab criteria, and dural sac cross-sectional area (DSCSA) were used to assess the post-operative outcomes of the two groups. RESULTS: All 58 patients completed the operation and received more than 12 months of follow-up. There was no significant difference in the operation time, number of intraoperative fluoroscopies, intraoperative bleeding, or postoperative hospitalization time between the two groups (p > 0.05); VAS scores and ODIs of the two groups at all postoperative time points were significantly lower than before the operation (p < 0.05), and there was no significant difference in the comparison of the clinical efficacy between the two groups (p > 0.05); the DSCSA of the two groups at the last postoperative follow-up was significantly larger than before the operation (p < 0.05), and there was no significant difference in the improvement of DSCSA between them (p > 0.05). CONCLUSIONS: Both procedures are safe and effective in the treatment of DLSS with unilateral lower extremity radicular pain, and we should be specific about the choice of spinal stenosis treatment.

New daphnane diterpenoidal 1,3,4-oxdiazole derivatives as potential anti-hepatoma agents: Synthesis, biological evaluation and molecular modeling studies.

Hepatocellular carcinoma (HCC) is a major challenge for human healthy. Daphnane-type diterpenes have attracted increasingly attention due to remarkable pharmaceutical potential including anti-HCC activity. To further develop this class of compounds as inhibitors of HCC, the daphnane diterpenoids 12-O-debenzoyl-Yuanhuacine (YHC) and 12-hydroxydaphnetoxin (YHE) were prepared by a standard chemical transformation from dried flower buds of the Daphne genkwa plant. Subsequently, 22 daphnane diterpenoidal 1,3,4-oxdiazole derivatives were rationally designed and synthesized based on YHC and YHE. The assessment of the target compound's anti-hepatocellular carcinoma activity revealed that YHC1 exhibited comparable activity to sorafenib in the Hep3B cell line, while demonstrating higher selectivity. The mechanistic investigation demonstrates that compound YHC1 induces cell cycle arrest at the G0/G1 phase, cellular senescence, apoptosis, and elevates cellular reactive oxygen species levels. Moreover, molecular docking and CETSA results confirm the interaction between YHC1 and YAP1 as well as TEAD1. Co-IP experiments further validated that YHC1 can effectively inhibit the binding of YAP1 and TEAD1. In conclusion, YHC1 selectively targets YAP1 and TEAD1, exhibiting its anti-hepatocellular carcinoma effects through the inhibition of their interaction.

Environmental Concentrations of Herbicide Prometryn Render Stress-Tolerant Corals Susceptible to Ocean Warming.

Global warming has caused the degradation of coral reefs around the world. While stress-tolerant corals have demonstrated the ability to acclimatize to ocean warming, it remains unclear whether they can sustain their thermal resilience when superimposed with other coastal environmental stressors. We report the combined impacts of a photosystem II (PSII) herbicide, prometryn, and ocean warming on the stress-tolerant coral Galaxea fascicularis through physiological and omics analyses. The results demonstrate that the heat-stress-induced inhibition of photosynthetic efficiency in G. fascicularis is exacerbated in the presence of prometryn. Transcriptomics and metabolomics analyses indicate that the prometryn exposure may overwhelm the photosystem repair mechanism in stress-tolerant corals, thereby compromising their capacity for thermal acclimation. Moreover, prometryn might amplify the adverse effects of heat stress on key energy and nutrient metabolism pathways and induce a stronger response to oxidative stress in stress-tolerant corals. The findings indicate that the presence of prometryn at environmentally relevant concentrations would render corals more susceptible to heat stress and exacerbate the breakdown of coral Symbiodiniaceae symbiosis. The present study provides valuable insights into the necessity of prioritizing PSII herbicide pollution reduction in coral reef protection efforts while mitigating the effects of climate change.

Whole-Transcriptome Profiling and Functional Prediction of Long Non-Coding RNAs Associated with Cold Tolerance in Japonica Rice Varieties.

Low-temperature chilling is a major abiotic stress leading to reduced rice yield and is a significant environmental threat to food security. Low-temperature chilling studies have focused on physiological changes or coding genes. However, the competitive endogenous RNA mechanism in rice at low temperatures has not been reported. Therefore, in this study, antioxidant physiological indices were combined with whole-transcriptome data through weighted correlation network analysis, which found that the gene modules had the highest correlation with the key antioxidant enzymes superoxide dismutase and peroxidase. The hub genes of the superoxide dismutase-related module included the UDP-glucosyltransferase family protein, sesquiterpene synthase and indole-3-glycerophosphatase gene. The hub genes of the peroxidase-related module included the WRKY transcription factor, abscisic acid signal transduction pathway-related gene plasma membrane hydrogen-ATPase and receptor-like kinase. Therefore, we selected the modular hub genes and significantly enriched the metabolic pathway genes to construct the key competitive endogenous RNA networks, resulting in three competitive endogenous RNA networks of seven long non-coding RNAs regulating three co-expressed messenger RNAs via four microRNAs. Finally, the negative regulatory function of the WRKY transcription factor OsWRKY61 was determined via subcellular localization and validation of the physiological indices in the mutant.

Pelvic floor dysfunction after intervention, compared with expectant management, in prolonged second stage of labour: A population-based questionnaire and cohort study.

OBJECTIVE: To investigate the effect of vacuum extraction (VE) or caesarean section (CS), compared with expectant management, on pelvic floor dysfunction (PFD) 1-2 years postpartum in primiparous women with a prolonged second stage of labour. DESIGN: A population-based questionnaire and cohort study. SETTING: Stockholm, Sweden. POPULATION: A cohort of 1302 primiparous women with a second stage duration of ≥3 h, delivering from December 2017 to November 2018. METHODS: The 1-year follow-up questionnaire from the Swedish National Perineal Laceration Register was distributed 12-24 months postpartum. Exposure was VE or CS at 3-4 h or 4-5 h, compared with expectant management. MAIN OUTCOME MEASURES: Pelvic floor dysfunction was defined as at least weekly symptoms of urinary incontinence, pelvic organ prolapse or a Wexner score of ≥4. The risk of PFD was calculated using Poisson regression with robust variance estimation, presented as crude and adjusted relative risks (RRs and aRRs) with 95% confidence intervals (95% CIs). The implication of obstetric anal sphincter injury (OASI) on pelvic floor disorders was investigated through mediation analysis. RESULTS: In total, 35.1% of women reported PFD. Compared with expectant management, the risk of PFD was increased after VE at 3-4 h (aRR 1.33, 95% CI 1.06-1.65) and 4-5 h (aRR 1.34, 95% CI 1.05-1.70), but remained unchanged after CS. The increased risk after VE was not mediated by OASI. CONCLUSIONS: Pelvic floor dysfunction was common in primiparous women after a prolonged second stage, and the risk of PFD increased after VE but was unaffected by CS, compared with expectant management. If a spontaneous vaginal delivery eventually occurred, allowing an extended duration of labour did not increase the risk of PFD.

The effect of diabetes mellitus on lumbar disc degeneration: an MRI-based study.

PURPOSE: This study aims to analyse the effect of diabetes mellitus (DM) on the radiological changes of Magnetic Resonance Imaging (MRI) on the intervertebral discs and paravertebral muscle to investigate the effect of DM on spinal degeneration. METHODS: This retrospective study initially included 262 patients who underwent treatment between January 2020 and December 2021 because of lumbar disc herniation. Amongst these patients, 98 patients suffered from type 2 diabetes mellitus (T2DM) for more than five years; this is the poorly controlled group (haemoglobin A1c (HbA1c) ≥ 6.5%; BMI: 26.28 ± 3.60; HbA1c: 7.5, IQR = 1.3). Another 164 patients without T2DM are included in the control group. The data collected and analysed include gender, age, smoking, alcohol use, disease course, Charlson Comorbidity Index, BMI, and radiological parameters including disc height, modified Pfirrmann grading scores, percentage of fat infiltration area of paravertebral muscle, and pathological changes of the endplate. RESULTS: After propensity score-matched analysis, the difference in general data between the control and T2DM groups was eliminated, and 186 patients were analysed. The modified Pfirrmann grading scores showed statistical differences in every lumbar segment, suggesting that the T2DM group suffered from greater disc degeneration at all L1-S1 segments compared with the control group. The disc height from L1/2 to L5/S1 was not statistically different between the two groups. Compared to the T2DM group, the control group had a lower percentage of fat infiltration areas in L4/5 and L5/S1 paravertebral muscle, whereas L1/2 to L3/4 showed no statistical difference. The T2DM group had more pathological changes of cartilage endplate compared with the control group. CONCLUSIONS: Prolonged uncontrolled hyperglycaemia may contribute to lumbar disc degeneration, fatty infiltration of the paraspinal muscles in the lower lumbar segments, and increased incidence of endplate cartilage pathological changes in patients with degenerative disc disease.