Differential cytokine expression in gastric tissues highlights helicobacter pylori's role in gastritis.

Helicobacter pylori (H. pylori), known for causing gastric inflammation, gastritis and gastric cancer, prompted our study to investigate the differential expression of cytokines in gastric tissues, which is crucial for understanding H. pylori infection and its potential progression to gastric cancer. Focusing on Il-1ß, IL-6, IL-8, IL-12, IL-18, and TNF-α, we analysed gene and protein levels to differentiate between H. pylori-infected and non-infected gastritis. We utilised real-time quantitative polymerase chain reaction (RT-qPCR) for gene quantification, immunohistochemical staining, and ELISA for protein measurement. Gastric samples from patients with gastritis were divided into three groups: (1) non-gastritis (N-group) group, (2) gastritis without H. pylori infection (G-group), and (3) gastritis with H. pylori infection (GH-group), each consisting of 8 samples. Our findings revealed a statistically significant variation in cytokine expression. Generally, cytokine levels were higher in gastritis, but in H. pylori-infected gastritis, IL-1ß, IL-6, and IL-8 levels were lower compared to H. pylori-independent gastritis, while IL-12, IL-18, and TNF-α levels were higher. This distinct cytokine expression pattern in H. pylori-infected gastritis underscores a unique inflammatory response, providing deeper insights into its pathogenesis.

Risk of heart disease and stroke among individuals with prehypertension or blood pressure progression: a national population-based cohort study.

OBJECTIVE: The purpose of our study was to analyze the association of blood pressure and blood pressure progression with heart disease and stroke among Chinese population. METHOD: We included a total of 10 122 adults aged 45 years and above free of heart disease or stroke at baseline from the China Health and Retirement Longitudinal Study cohort. We used Cox proportional hazards models to analyze the relationship between cardiovascular risk and prehypertension in subjects with or without progression to hypertension. RESULT: During a mean follow-up of 6.5 years, 1972 subjects were either diagnosed with heart disease or had a stroke (composite outcome). Compared with individuals with normotension at baseline, the fully adjusted hazard ratio (HR) [95% confidence interval (CI)] was 1.25 (1.10-1.42) and 1.52 (1.34-1.74) for composite outcome in individuals with prehypertension and hypertension at baseline, respectively. The subjects who progressed to hypertension had higher risk of cardiovascular outcomes than those who remained at normal blood pressure or prehypertension in a fully adjusted model. The subjects who progressed from prehypertension to hypertension had 1.72 times higher risk [HR (95% CI): 1.72 (1.37-2.16)] of cardiovascular outcomes than those who remained at normal blood pressure or prehypertension in a fully adjusted model. CONCLUSION: The cardiovascular risk of subjects with prehypertension is higher than that of subjects with normal blood pressure. After a diagnosis of hypertension, subjects who progressed from normal blood pressure to hypertension had an increased risk of heart disease and stroke.

Progranulin promotes regulatory T cells plasticity by mitochondrial metabolism through AMPK/PGC-1α pathway in ARDS.

As the aging population increases, the focus on elderly patients with acute respiratory distress syndrome (ARDS) is also increasing. In this article, we found progranulin (PGRN) differential expression in ARDS patients and healthy controls, even in young and old ARDS patients. Its expression strongly correlates with several cytokines in both young and elderly ARDS patients. PGRN has comparable therapeutic effects in young and elderly mice with lipopolysaccharide-induced acute lung injury, manifesting as lung injury, apoptosis, inflammation, and regulatory T cells (Tregs) differentiation. Considering that Tregs differentiation relies on metabolic reprogramming, we discovered that Tregs differentiation was mediated by mitochondrial function, especially in the aged population. Furthermore, we demonstrated that PGRN alleviated the mitochondrial damage during Tregs differentiation through the AMPK/PGC-1α pathway in T cells. Collectively, PGRN may regulate mitochondria function to promote Tregs differentiation through the AMPK/PGC-1α pathway to improve ARDS.

The Application of Preoperative Computed Tomography Angiography and Color Ultrasound Assisted Lower Limb Perforator Flap Design in the Repair of Lower Limb Soft Tissue Defects.

Objective: The goal of this study was to explore the application effect of preoperative computed tomography (CT) angiography and color ultrasound-assisted design of lower limb perforator flaps in the repair of lower limb soft tissue defects. Repair of soft tissue defects in the lower limbs is a challenging surgical task, and accurate preoperative location of vascular structures and detailed design of the surgical plan are crucial to the success of the surgery. This study aims to improve the accuracy and effectiveness of lower limb perforator flap repair surgery by introducing CT angiography and color ultrasound technology. Methods: Sixty-four patients who underwent lower limb soft tissue defect repair with perforator flaps were enrolled at our hospital from February 2020 to February 2023. According to their admission time, they were divided into two groups: 32 patients admitted before June 31, 2022, were included in the control group, and preoperative color Doppler ultrasound was used to assist in designing the lower limb perforator flap; 32 patients admitted after June 31, 2022, were included in the study group, and preoperative CT angiography and color Doppler ultrasound were used to assist in designing the lower limb perforator flap. Specifically, we conducted detailed records and analyzes of patients' age distribution, gender ratio, and relevant medical history. This demographic information will help reveal whether there are differences in the effectiveness of preoperative CT angiography and color ultrasound-assisted lower extremity perforator flap design among different patient groups. By considering these key factors, we can more accurately assess the actual utility of new technologies in different patient groups and provide more specific guidance for clinical practice.The therapeutic effects of the two groups of patients were recorded. The differences between the preoperative CT angiography measurements and intraoperative actual measurements of the study group were compared. Clinical indicators, sensory function in the graft area, flap survival rate, flap complication rate, and donor area complication rate were compared between the two groups. The satisfaction of patients in the two groups with the recovery of the surgical area was also compared. Results: The treatment success rate of the study group was higher than that of the control group (P < .05). There was no significant difference in the preoperative CT angiography measurements (shallow branch localization, shallow branch starting diameter, shallow branch length, deep branch starting diameter) and intraoperative actual measurements of the study group (P > .05). The operation time and intraoperative blood loss of the study group were shorter than those of the control group (P < .05), and there was no significant difference in flap harvesting area and length of hospital stay between the two groups (P > .05). There was a difference in sensory function in the graft area between the two groups, with a higher proportion of S4 grade in the study group and better recovery compared to the control group (P < .05). There was no significant difference in satisfaction evaluation between the two groups (P > .05). Conclusion: Preoperative CT angiography and color ultrasound-assisted design of lower limb perforator flaps have shown significant clinical advantages in repairing lower limb soft tissue defects, improving treatment effects and surgical efficiency. In clinical practice, this technology is expected to reduce surgical complexity, shorten surgical time, reduce the risk of intraoperative bleeding, and achieve effective defect repair while maintaining or improving the patient's sensory function.However, there are some limitations to the study, such as the relatively small sample size and single-center nature. Future research can optimize the operation process of this technology, expand the scope of research, and explore its application in the repair of soft tissue defects caused by specific causes. This technology may provide more precise and effective options for personalized treatment, especially for patients who need to preserve more sensory function.

Effects of pelvic floor myofascial manipulation intervention on primiparas and neonates during the second stage of vaginal delivery.

A prolonged second stage of vaginal delivery increases the risk of shoulder dystocia, unnecessary episiotomies and cesarean sections. However, no standardized method has been proposed to tackle this issue. The effects of pelvic floor myofascial manipulation intervention during the second stage of labor in primiparas and its prognostic value in neonatal postpartum outcomes remain unknown. In the present study, a total of 60 primiparas who were expecting a vaginal delivery in the Second Affiliated Hospital of Hainan Medical College (Haikou, China) between October 2021 and January 2022 were selected. These women were randomly assigned to a control group (standard intrapartum care) or an experimental group (pelvic floor myofascial manipulation for 15-20 min during the second stage of labor along with standard intrapartum care) using a random number table, with 28 patients in each group. There was no significant difference in age, gestational time or body mass index between the two groups before delivery, indicating that the baseline data were comparable. The second stage of labor duration, forced breath-holding time and postpartum hemorrhage volume in the experimental group were significantly lower than those in the control group. The pain visual analog scale scores, fatigue scores and neonatal Apgar scores in the experimental group were also significantly lower than those in the control group. The rate of episiotomy in the experimental group was lower than that in the control group, but the difference was not statistically significant. In conclusion, pelvic floor myofascial manipulation intervention during the second stage of labor for primiparas with vaginal delivery can reduce the duration of the second stage of labor, the amount of bleeding during labor and the pain during labor. Meanwhile, it has the potential to improve neonatal outcomes.

Creating a near-perfect circularly polarized terahertz beam through the nonreciprocity of a magnetoplasma.

Compared to other parts of the electromagnetic spectrum, the terahertz frequency range lacks efficient polarization manipulation techniques, which is impeding the proliferation of terahertz technology. In this work, we demonstrate a tunable and broadband linear-to-circular polarization converter based on an InSb plate containing a free-carrier magnetoplasma. In a wide spectral region (∼ 0.45 THz), the magnetoplasma selectively absorbs one circularly polarized mode due to electron cyclotron resonance and also reflects it at the edges of the absorption band. Both effects are nonreciprocal and contribute to form a near-zero transmission band with a high isolation of -36 dB, resulting in the output of a near-perfect circularly polarized terahertz wave for an incident linearly polarized beam. The near-zero transmission band is tunable with magnetic field to cover a wide frequency range from 0.3 to 4.8 THz.

NRTPredictor: identifying rice root cell state in single-cell RNA-seq via ensemble learning.

BACKGROUND: Single-cell RNA sequencing (scRNA-seq) measurements of gene expression show great promise for studying the cellular heterogeneity of rice roots. How precisely annotating cell identity is a major unresolved problem in plant scRNA-seq analysis due to the inherent high dimensionality and sparsity. RESULTS: To address this challenge, we present NRTPredictor, an ensemble-learning system, to predict rice root cell stage and mine biomarkers through complete model interpretability. The performance of NRTPredictor was evaluated using a test dataset, with 98.01% accuracy and 95.45% recall. With the power of interpretability provided by NRTPredictor, our model recognizes 110 marker genes partially involved in phenylpropanoid biosynthesis. Expression patterns of rice root could be mapped by the above-mentioned candidate genes, showing the superiority of NRTPredictor. Integrated analysis of scRNA and bulk RNA-seq data revealed aberrant expression of Epidermis cell subpopulations in flooding, Pi, and salt stresses. CONCLUSION: Taken together, our results demonstrate that NRTPredictor is a useful tool for automated prediction of rice root cell stage and provides a valuable resource for deciphering the rice root cellular heterogeneity and the molecular mechanisms of flooding, Pi, and salt stresses. Based on the proposed model, a free webserver has been established, which is available at https://www.cgris.net/nrtp .

Genomic characteristics of Mycobacterium tuberculosis isolates of cutaneous tuberculosis.

Objectives: Cutaneous tuberculosis with various manifestations can be divided into several clinical types according to the host's immune status and infective route. However, the etiological factors of this disease remain unclear. The objective of this study is to investigate the pathogens associated with the occurrence and different types of cutaneous tuberculosis. Methods: 58 Mycobacterium tuberculosis strains isolated from cutaneous tuberculosis over the last 20 years were sequenced and analyzed for genomic characteristics including lineage distribution, drug-resistance mutations, and mutations potentially associated with different sites of infection. Results: The M. tuberculosis strains from four major types of cutaneous tuberculosis and pulmonary tuberculosis shared similar genotypes and genomic composition. The strains isolated from cutaneous tuberculosis had a lower rate of drug resistance. Phylogenic analysis showed cutaneous tuberculosis and pulmonary tuberculosis isolates scattered on the three. Several SNPs in metabolism related genes exhibited a strong correlation with different infection sites. Conclusions: The different infection sites of TB may barely be affected by large genomic changes in M. tuberculosis isolates, but the significant difference in SNPs of drug resistance gene and metabolism-related genes still deserves more attention.

Guselkumab for the treatment of patients with moderate-to-severe hidradenitis suppurativa: A phase 2 randomized study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that causes substantial physical, emotional and psychological burdens. Guselkumab, a monoclonal antibody that binds to the p19 subunit of interleukin-23, has demonstrated high levels of efficacy in the treatment of inflammatory diseases, including psoriasis and psoriatic arthritis. OBJECTIVE: To evaluate the effect of guselkumab on the treatment of HS, a phase 2, multicentre, randomized, placebo-controlled, double-blind, proof-of-concept study was conducted. METHODS: Patients ≥18 years of age with moderate-to-severe HS for ≥1 year were randomized to (1) guselkumab 200 mg by subcutaneous (SC) injection every 4 weeks (q4w) through Week 36 (guselkumab SC); (2) guselkumab 1200 mg intravenously (IV) q4w for 12 weeks, then switched to guselkumab 200 mg SC q4w from Weeks 12 through 36 (guselkumab IV); or (3) placebo for 12 weeks, with re-randomization to guselkumab 200 mg SC q4w at Weeks 16 through 36 (placebo → guselkumab 200 mg) or guselkumab 100 mg SC at Weeks 16, 20, 28 and 36 and placebo at Weeks 24 and 32 (placebo → guselkumab 100 mg). End points included HS clinical response (HiSCR) and patient-reported outcomes. RESULTS: Although guselkumab SC or guselkumab IV resulted in numerically higher HiSCR versus placebo at Week 16 (50.8%, 45.0%, 38.7%, respectively), statistical significance was not achieved. Numerically greater improvements in patient-reported outcomes were also observed for guselkumab SC and guselkumab IV versus placebo at Week 16. Through Week 40, no clear differences to suggest a dose response were observed for HiSCR and patient-reported outcomes. CONCLUSIONS: Despite modest improvements, the primary end point was not met and the overall findings do not support the efficacy of guselkumab in the treatment of HS. CLINICALTRIALS: gov: NCT03628924.

Neuronal Correlates of Task Irrelevant Distractions Enhance the Detection of Attention Deficit/Hyperactivity Disorder.

Early diagnosis and treatment can reduce the symptoms of Attention Deficit/Hyperactivity Disorder (ADHD) in children, but medical diagnosis is usually delayed. Hence, it is important to increase the efficiency of early diagnosis. Previous studies used behavioral and neuronal data during GO/NOGO task to help detect ADHD and the accuracy differed considerably from 53% to 92%, depending on the employed methods and the number of electroencephalogram (EEG) channels. It remains unclear whether data from a few EEG channels can still lead to a good accuracy of detecting ADHD. Here, we hypothesize that introducing distractions into a VR-based GO/NOGO task can augment the detection of ADHD using 6-channel EEG because children with ADHD are easily distracted. Forty-nine ADHD children and 32 typically developing children were recruited. We use a clinically applicable system with EEG to record data. Statistical analysis and machine learning methods were employed to analyze the data. The behavioral results revealed significant differences in task performance when there are distractions. The presence of distractions leads to EEG changes in both groups, indicating immaturity in inhibitory control. Importantly, the distractions additionally enhanced the between-group differences in NOGO α and γ power, reflecting insufficient inhibition in different neural networks for distraction suppression in the ADHD group. Machine learning methods further confirmed that distractions enhance the detection of ADHD with an accuracy of 85.45%. In conclusion, this system can assist in fast screenings for ADHD and the findings of neuronal correlates of distractions can help design therapeutic strategies.

Guselkumab More Effectively Neutralizes Psoriasis-Associated Histologic, Transcriptomic, and Clinical Measures than Ustekinumab.

Given the key role of the IL-23/Th17 axis in the pathogenesis of moderate-to-severe plaque psoriasis, several specific inhibitors of the p19 subunit of IL-23 have been approved to treat this chronic inflammatory disease. Clinical data indicate that guselkumab, one such selective IL-23 inhibitor, achieves greater clinical efficacy compared with ustekinumab, which inhibits both IL-12 and IL-23 via binding their shared p40 subunit. To understand mechanisms underlying the enhanced efficacy observed with the p19 subunit of IL-23-specific inhibition, we explored cellular and molecular changes in skin of psoriasis patients treated with ustekinumab or guselkumab and in ustekinumab inadequate responders (Investigator's Global Assessment of psoriasis score ≥ 2) subsequently treated with guselkumab (ustekinumab→guselkumab). Skin biopsies were collected pretreatment and posttreatment to assess histologic changes and molecular responses in ustekinumab- and guselkumab-treated patients. Serum cytokines and skin transcriptomics from the subset of ustekinumab→guselkumab-treated patients were also analyzed to characterize differential treatment effects. Ustekinumab and guselkumab demonstrated differential effects on secretion of pathogenic Th17-related cytokines induced by IL-23 in in vitro assays, which suggest guselkumab is a more potent therapeutic agent. Consistent with these findings, guselkumab elicited a significantly greater reduction in cellular and molecular psoriasis-related disease indicators than ustekinumab. In ustekinumab→guselkumab patients, suppression of serum IL-17A and IL-17F levels and neutralization of molecular scar and psoriasis-related gene markers in skin were significantly greater compared with patients continuing ustekinumab. This comparative study demonstrates that guselkumab inhibits psoriasis-associated pathology, suppresses Th17-related serum cytokines, and normalizes the psoriasis skin gene expression profile more effectively than ustekinumab.

[Visual analysis of research on traditional Chinese medicine treatment of Alzheimer's disease in recent ten years].

This study employed bibliometrics tools to review the studies of traditional Chinese medicine(TCM) treatment of Alzheimer's disease(AD) in recent ten years, aiming to explore the research status, hotspots, and future trends in this field at home and abroad. The relevant literature published from January 1, 2012 to August 15, 2022 was retrieved from Web of Science and CNKI. CiteSpace 6.1R2 and VOSviewer 1.6.15 were used for the visual analysis of authors, countries, institutions, keywords, journals, etc. A total of 2 254 Chinese articles and 545 English articles were included. The annual number of articles published showed a rising trend with fluctuations. The country with the largest number of relevant articles published and the largest centrality was China. SUN Guo-jie and WANG Qi were the authors publishing the most Chinese articles and English articles, respectively. Hubei University of Chinese Medicine and Beijing University of Chinese Medicine published the most articles in Chinese and English, respectively. Journal of Ethnopharmacology and Neuroscience Letters published the articles with the highest cited frequency and the highest centrality. According to the keywords, the research on TCM treatment of AD mainly focused on the mechanism of action and treatment methods. Metabolomics, intestinal flora, oxidative stress, tau hyperphosphorylation, ß-amyloid(Aß), inflammatory cytokines, and autophagy were the focuses of the research on mechanism of action. Acupuncture, clinical effect, kidney deficiency and phlegm stasis, and dredging governor vessel to revitalize mind were the hotspots of clinical research. This research field is still in the stage of exploration and development. Exchanges and cooperation among institutions should be encouraged to carry out more high-quality basic research on TCM treatment of AD, obtain high-level evidence, and clarify the pathogenesis and prescription mechanism.

Individualized red-cell transfusion strategy for non-cardiac surgery in adults: a randomized controlled trial.

BACKGROUND: Red-cell transfusion is critical for surgery during the peri-operative period; however, the transfusion threshold remains controversial mainly owing to the diversity among patients. The patient's medical status should be evaluated before making a transfusion decision. Herein, we developed an individualized transfusion strategy using the West-China-Liu's Score based on the physiology of oxygen delivery/consumption balance and designed an open-label, multicenter, randomized clinical trial to verify whether it reduced red cell requirement as compared with that associated with restrictive and liberal strategies safely and effectively, providing valid evidence for peri-operative transfusion. METHODS: Patients aged >14 years undergoing elective non-cardiac surgery with estimated blood loss > 1000 mL or 20% blood volume and hemoglobin concentration <10 g/dL were randomly assigned to an individualized strategy, a restrictive strategy following China's guideline or a liberal strategy with a transfusion threshold of hemoglobin concentration <9.5 g/dL. We evaluated two primary outcomes: the proportion of patients who received red blood cells (superiority test) and a composite of in-hospital complications and all-cause mortality by day 30 (non-inferiority test). RESULTS: We enrolled 1182 patients: 379, 419, and 384 received individualized, restrictive, and liberal strategies, respectively. Approximately 30.6% (116/379) of patients in the individualized strategy received a red-cell transfusion, less than 62.5% (262/419) in the restrictive strategy (absolute risk difference, 31.92%; 97.5% confidence interval [CI]: 24.42-39.42%; odds ratio, 3.78%; 97.5% CI: 2.70-5.30%; P <0.001), and 89.8% (345/384) in the liberal strategy (absolute risk difference, 59.24%; 97.5% CI: 52.91-65.57%; odds ratio, 20.06; 97.5% CI: 12.74-31.57; P <0.001). No statistically significant differences were found in the composite of in-hospital complications and mortality by day 30 among the three strategies. CONCLUSION: The individualized red-cell transfusion strategy using the West-China-Liu's Score reduced red-cell transfusion without increasing in-hospital complications and mortality by day 30 when compared with restrictive and liberal strategies in elective non-cardiac surgeries. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01597232.

[Effect of continuous blood purification on immunity and endothelial cell function in patients with sepsis].

OBJECTIVE: To explore the effect of continuous blood purification (CBP) on the immunity and endothelial cell function of patients with sepsis. METHODS: A prospective study was conducted. The patients aged ≥ 18 years old and meeting the diagnostic criteria of sepsis admitted to the department of critical care medicine of Binzhou Medical University Hospital from March 2019 to October 2020 were selected as the research subjects, and the patients were divided into standard treatment group and CBP treatment group according to random number table method. Both groups were given standard treatment including initial fluid resuscitation, infection source control and antibiotics according to the 2016 international guidelines for the management of sepsis and septic shock. CBP treatment group was additionally given continuous veno-venous hemofiltration (CVVH) at a dose of 25-30 mL×kg-1×h-1 and blood flow rate of 150-200 mL/min for more than 20 hours a day for 3 days. The clinical data of patients including blood lactic acid (Lac), procalcitonin (PCT), lymphocyte count (LYM), acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score were recorded before treatment and 1 day and 3 days after treatment. At the same time, the venous blood was collected, and the immune function related indexes [interleukins (IL-4, IL-7), programmed death receptor-1 (PD-1), programmed death ligand-1 (PD-L1), interferon-γ (IFN-γ)] and endothelial cell injury related markers [soluble thrombomodulin (sTM), angiopoietin-2 (Ang-2), von Willebrand factor (vWF), heparan sulfate (HS), syndecan-1 (SDC-1)] levels in serum were determined by enzyme-linked immunosorbent assay (ELISA). The length of intensive care unit (ICU) stay of patients in the two groups was recorded, and the outcomes of patients in the two groups were followed up for 28 days. RESULTS: Finally, 20 patients were enrolled in the standard treatment group, and 19 patients were enrolled in the CBP treatment group. There were no significant differences in gender, age and infection site between the two groups. The length of ICU stay in the standard treatment group was (10±5) days, and 5 patients died and 15 patients survived after 28 days. The length of ICU stay in the CBP treatment group was (9±4) days, and 8 patients died and 11 patients survived after 28 days. There were no significant differences in the length of ICU stay and number of patients who died within 28 days between the two groups (both P > 0.05). There were no significant differences in the Lac, PCT, LYM, APACHE II score, SOFA score and immune function and endothelial cell injury related indexes before treatment and 1 day after treatment between the two groups. After 3 days of treatment, the Lac, PCT, APACHE II score and SOFA score of the CBP treatment group were significantly lower than those before treatment, and pro-inflammatory and anti-inflammatory cytokines such as IFN-γ and IL-4, apoptosis-related indicators such as PD-1 and IL-7, and endothelial injury related factors such as sTM, SDC-1 and HS were significantly improved compared with the pre-treatment, the improvement degree of the above indicators was more obvious than that of the standard treatment group, and LYM was significantly higher than that of the standard treatment group (×109/L: 1.3±0.3 vs. 0.9±0.4, P < 0.05), IL-4, IFN-γ, IFN-γ/IL-4 ratio, IL-7, PD-1, sTM, SDC-1, HS, and Ang-2 were significantly lower than those of the standard treatment group [IL-4 (ng/L): 2.8 (1.5, 3.2) vs. 3.3 (2.7, 5.2), IFN-γ (ng/L): 6.3 (5.4, 106.5) vs. 217.9 (71.4, 517.1), IFN-γ/IL-4 ratio: 3.7 (1.8, 70.3) vs. 59.1 (18.3, 124.9), IL-7 (ng/L): 4.6 (3.2, 5.1) vs. 6.3 (5.2, 8.0), PD-1 (µg/L): 0.04 (0.03, 0.06) vs. 0.08 (0.05, 0.12), sTM (µg/L): 4.9 (4.3, 7.4) vs. 8.7 (6.0, 10.8), SDC-1 (µg/L): 0.6 (0.3, 1.1) vs. 0.9 (0.8, 2.5), HS (ng/L): 434.8 (256.2, 805.0) vs. 887.9 (620.1, 957.3), Ang-2 (ng/L): 934.0 (673.3, 1 502.1) vs. 2 233.9 (1 472.5, 3 808.4)], the differences were statistically significant (all P < 0.05). CONCLUSIONS: CBP treatment can eliminate the patient's immunosuppressive state, reduce a variety of endothelial injury markers and the degradation of glycocalyx, but cannot decrease the 28-day death risk or shorten the length of ICU stay.

Pelvic floor myofascial manipulation combined with Kegel exercise and mecobalamin in the treatment of atypical diabetic neurogenic bladder: a case report.

Background: Diabetic neurogenic bladder (DNB) is one of the autonomic neuropathies of diabetes mellitus (DM), with an incidence rate reaching 40-60%. This study combined bladder function rehabilitation training and mecobalamin to treat a patient with DNB to provide reference for clinical work. Case Description: A 67-year-old woman was admitted to our hospital on 5 December 2018, with a 3-year history of dysuria that had progressively worsened for 15 days. The patient was treated with pelvic floor myofascial manipulation combined with Kegel training and mecobalamin for 6 months. Pelvic organ prolapse (POP), pelvic floor surface electromyography (EMG), psychological status, and quality of life were evaluated before, during, and after treatment, and the changes in urodynamics were observed. After comprehensive rehabilitation treatment, the patient's POP, pelvic floor muscle strength, mental state, and quality of life were significantly improved. The results of the urodynamic examination showed that the patient's safe bladder capacity reached 500 mL after treatment, in contrast to the first safe bladder capacity measurement of 90 mL. The symptoms of ureteral reflux disappeared, the detrusor compliance increased from 2 to 20 mL/cmH2O, which roughly indicated a return to healthy function. However, there was no detrusor contraction in the bladder during urination. Conclusions: This patient achieved good curative effect after the treatment of comprehensive pelvic floor rehabilitation combined with mecobalamin. However, the safe capacity of the patient reported in this case showed a small bladder safe capacity, and the patient's detrusor muscle did not contract during urination. Thus, urination in this patient may be accomplished by increasing abdominal pressure. When treating patients with atypical neurogenic bladder, the adverse effects caused by excessive abdominal pressure and abdominal wall relaxation need to be considered.

Guselkumab for hidradenitis suppurativa: a phase II, open-label, mode-of-action study.

BACKGROUND: The effectiveness of available biologics for the treatment of hidradenitis suppurativa (HS) is limited. Additional therapeutic options are needed. OBJECTIVES: To investigate the efficacy and mode of action of guselkumab [an anti-interleukin (IL)-23p19 monoclonal antibody] 200 mg subcutaneously every 4 weeks for 16 weeks in patients with HS. METHODS: An open-label, multicentre, phase IIa trial in patients with moderate-to-severe HS was carried out (NCT04061395). The pharmacodynamic response in skin and blood was measured after 16 weeks of treatment. Clinical efficacy was assessed using the Hidradenitis Suppurativa Clinical Response (HiSCR), the International Hidradenitis Suppurativa Severity Score System (IHS4), and the abscess and inflammatory nodule (AN) count. The protocol was reviewed and approved by the local institutional review board (METC 2018/694), and the study was conducted in accordance with good clinical practice guidelines and applicable regulatory requirements. RESULTS: Thirteen of 20 patients (65%) achieved HiSCR with a statistically significant decrease in median IHS4 score (from 8.5 to 5.0; P = 0.002) and median AN count (from 6.5 to 4.0; P = 0.002). The overall patient-reported outcomes did not show a similar trend. One serious adverse event, likely to be unrelated to guselkumab treatment, was observed. In lesional skin, transcriptomic analysis revealed the upregulation of various genes associated with inflammation, including immunoglobulins, S100, matrix metalloproteinases, keratin, B-cell and complement genes, which decreased in clinical responders after treatment. Immunohistochemistry revealed a marked decrease in inflammatory markers in clinical responders at week 16. CONCLUSIONS: Sixty-five per cent of patients with moderate-to-severe HS achieved HiSCR after 16 weeks of treatment with guselkumab. We could not demonstrate a consistent correlation between gene and protein expression and clinical responses. The main limitations of this study were the small sample size and absence of a placebo arm. The large placebo-controlled phase IIb NOVA trial for guselkumab in patients with HS reported a lower HiSCR response of 45.0-50.8% in the treatment group and 38.7% in the placebo group. Guselkumab seems only to be of benefit in a subgroup of patients with HS, indicating that the IL-23/T helper 17 axis is not central to the pathophysiology of HS.

Association of Blood Glucose Variability with Sepsis-Related Disseminated Intravascular Coagulation Morbidity and Mortality.

Purpose: Sepsis-related disseminated intravascular coagulation (DIC) is closely associated with poor prognosis and high mortality. Higher blood glucose (BG) variability indicates an increased risk of mortality in sepsis; however, its relationship with sepsis-related DIC has not been investigated. This study aimed to determine the association between glucose variability and sepsis-related DIC. Patients and Methods: Patients with sepsis admitted to the intensive care unit were enrolled between October 2017 and January 2021. Baseline data and BG records from the first 72 h were collected. We calculated the glucose liability index (GLI), largest amplitude of glucose excursion, BG standard deviation, and coefficient of variation on days 1 and 3. The relationship between GLI and morbidity of sepsis-related DIC was explored using a competing risk model. In subgroup analysis, we divided patients with and without diabetes into three groups according to the BG range. Results: Of the 238 patients enrolled, 28.2% developed DIC during hospitalization (n=67). GLI on day 3 was found to have the closest relationship with DIC incidence as it has the largest area under the ROC curve and the highest associated odds ratio of death per unit change (GLI3-day: AUC=0.891 OR=1.84), also independently increased the occurrence of DIC after adjusting for the competing risk of death (sub-distribution hazard ratios=1.866, p<0.01). In subgroup analysis, patients with diabetes had worse outcomes under hypoglycemia than under hyperglycemia. Patients without diabetes having stable BG had the best outcomes. Conclusion: Our study suggested that a higher GLI in patients with sepsis at 72 h was independently associated with an increased risk of sepsis-related DIC, which was not associated with pre-existing diabetes.

Andrographolide exerted anti-inflammatory effects thereby reducing sex hormone synthesis in LPS-induced female rats, but had no effect on hormone production in healthy ones.

Females have higher inflammatory tolerance because they have some special sex-related anti-inflammatory pathways. Andrographolide, a diterpene lactone compound from Andrographis paniculata (Burm.f.) Nees, has a powerful anti-inflammatory effect. But whether andrographolide regulates sex-related anti-inflammatory pathways in females has yet to be reported. A non-targeted metabonomics method was employed to investigate the metabolic pathways of andrographolide in LPS-induced inflammatory female rats. Substances and genes were then selected out of gender-related pathways discovered by metabonomics experiments and their quantities or expressions were evaluated. Furthermore, the effects of andrographolide on these chemicals or genes in non-inflammatory female rats were also examined in order to investigate the cascade interaction between anti-inflammatory mechanisms and metabolites. The biomarkers of 24 metabolites in plasma were identified. Following pathway enrichment analysis, these metabolic markers were clustered into glycerophosphate, glycerolipids, inositol phosphate and steroid hormone synthesis pathways. Validation experiments confirmed that andrographolide lowered post-inflammatory female sex hormones such as progesterone, estradiol, corticosterone, and testosterone rather than increasing them. Andrographolide may have these effects via inhibiting the overexpression of CYP11a1 and StAR. However, andrographolide had no effect on the expression of these two genes or the four types of hormones in non-inflamed female rats. Similarly, andrographolide decreased TNF-α, IL-6 and IL-1ß production in inflammatory rats but showed no effect on these inflammatory markers in non-inflammatory rats. LPS and other inflammatory cytokines promote hormone production, which in turn will prevent increased inflammation. Therefore, it may be hypothesized that andrographolide's reduction of inflammatory cytokine is what generates its inhibitory action on sex hormones during inflammation. By blocking the activation of inflammatory pathways, andrographolide prevented the stimulation of inflammatory factors on the production of sex hormones. It does not, however, directly inhibit or enhance the synthesis of sex hormones.