Clinical therapeutic effect of self-prescribed Sanhanchushi Tongbi on lumbar disc herniation.

BACKGROUND: Lumbar disc herniation (LDH) commonly occurs during spinal surgery; LDH is on the increase in younger patients and is classified as "paralysis" and "back pain." Sanhanchushi Tongbi (SPST) is a customized prescription. It disperses cold, relieves pain, removes cold from the meridians and viscera, and treats neuropathic pain. However, few studies have investigated its mechanism of pain relief. AIM: To observe the clinical therapeutic effects on LDH treated with self-prescribed SPST. METHODS: A total of 211 patients with LDH syndrome were divided into two groups: 107 patients in the control group were treated with conventional massage combined with traction, and 104 patients in the observation group were treated with a combination of the control regimen and self-prescribed oral SPST. The patients were treated for 4 wk. Indices of traditional Chinese medicine (TCM) syndrome score and serum inflammatory factor levels were measured. RESULTS: After therapy, the TCM syndrome score in the observation group was significantly lower than that in the control group (P < 0.05). The main symptoms, clinical signs, daily activities, and Japanese Orthopedic Association scores in the observation group were significantly higher than those in the control group after therapy (P < 0.05). The levels of tumor necrosis factor-α, interleukin-6, and C-reactive protein were lower in the observation group than in the control group (P < 0.05). In the observation group, superoxide dismutase levels were significantly higher, whereas malondialdehyde levels were significantly lower, compared with the control group (P < 0.05). The overall efficacy rate in the observation group was 96.15%, which was substantially higher than that in the control group (88.79%; P < 0.05). CONCLUSION: Self-prescribed SPST can reduce the levels of inflammatory and pain-causing factors as well as lumbar pain in patients with LDH.

Jingqianshu granules mitigates premenstrual depression by regulating orexin signaling.

Introduction: Premenstrual dysphoric disorder (PMDD), a severe form of premenstrual syndrome (PMS), is a serious health disorder that affects patient moods. It is caused by cyclic psychological symptoms and its pathogenesis is still unclear. Abnormalities in the basolateral amygdala (BLA) orexin system, which are important causes of the development of depressive mood, have not been reported in PMDD, so exploring its intrinsic mechanisms is meaningful for enriching the pathomechanisms of PMDD. Methods: High performance liquid chromatography was used for the determination of the active ingredients of Jingqianshu granules. Developing a rat model of premenstrual depression using the forced swimming test (FST). The experiment consisted of two parts. In Part 1, the rats were divided into the control group, the model group, the model + Jingqianshu group, and the model + fluoxetine group. The FST, open field test, and elevated plus maze test, were used to assess the behavior of the rats as well as to evaluate the effect of drug intervention. Immunofluorescence and RT-qPCR were used to detect the expression of orexin and its receptors OX1R and OX2R genes and proteins. The expression of Toll-like receptor 4, nuclear factor kappa-B, tumor necrosis factor-α, interleukin 6, and interleukin-1ß in the BLA brain region was detected by Western-Blot. In part 2, the rats were injected intracerebrally with orexin-A. Observe the behavioral activities of rats in the control group, model group, and model+orexin-A group. Immunofluorescence was used to detect microglia in the BLA area of rats, and the expression levels of the above inflammatory factors were detected by Western-Blot. Results: The five components of Jingqianshu granules are: paeoniflorin, erulic acid, liquiritin, hesperidin, and paeonol. During the estrous cycle, rats exhibited depressive-like behavior during the non-receptive phase of the behavioral test, which disappeared during the receptive phase. Immunofluorescence and RT-qPCR showed reduced gene and protein expression of orexin, OX1R, and OX2R in the BLA region of rats in the model group.WB showed elevated levels of inflammatory factors. All returned to control levels after drug treatment. In part 2, injection of orexin-A into the BLA brain region of model rats resulted in reduced immunoreactivity of microglia and decreased expression levels of inflammatory factors. Discussion: Jianqianshu granules can achieve the purpose of treating premenstrual depression by regulating orexin-mediated inflammatory factors, which provides a new idea for further research on the pathogenesis of PMDD. However, the current study is still preliminary and the pathogenesis of PMDD is complex. Therefore, more in-depth exploration is needed.

A prognostic model based on CLEC6A predicts clinical outcome of breast cancer patients.

CLEC6A, (C-type lectin domain family 6, member A), plays a prominent role in regulating innate immunity and adaptive immunity. CLEC6A has shown great potential as a target for cancer immunotherapy. This study aims to explore the prognostic value of CLEC6A, and analyze the relationship associated with the common hematological parameters in breast cancer patients. We performed a retrospective analysis on 183 breast cancer patients data in hospital information system from January 2013 to December 2015. The expression of CLEC6A was recorded via semiquantitative immunohistochemistry in breast cancer. The association between expression of CLEC6A and relative parameters were performed by Chi-square test and Fisher's exact test. Kaplan-Meier assay and Log-rank test were performed to evaluate the survival time. The Cox proportional hazards regression analysis was applied to identify prognostic factors. Nomograms were conducted to predict 1-, 3-, and 5-year disease free survival (DFS) and overall survival (OS) for breast cancer, which could be a good reference in clinical practice. The nomogram model was estimated by calibration curve analysis for its function of discrimination. The accuracy and benefit of the nomogram model were appraised by comparing it to only CLEC6A via decision curve analysis (DCA). The prediction accuracy of CLEC6A was also determined by time-dependent receiver operating characteristics (TDROC) curves, and the area under the curve (AUC) for different survival time. There were 94 cases in the CLEC6A low-expression group and 89 cases in CLEC6A high-expression group. Compared to CLEC6A low-expression group, the CLEC6A high-expression group had better survival (DFS: 56.95 vs. 70.81 months, P = 0.0078 and OS: 67.98 vs. 79.05 months, P = 0.0089). The CLEC6A was a potential prognostic factor in multivariate analysis (DFS: P = 0.023, hazard ratio (HR): 0.454, 95 % confidence interval (CI): 0.229-0.898; OS: P = 0.020, HR: 0.504, 95 %CI: 0.284-0.897). The nomogram in accordance with these potential prognostic factors was constructed to predict survival and the calibration curve analysis had indicated that the predicted line was well-matched with reference line in 1-, 3-, and 5-year DFS and OS category. The 1-, 3-, and 5-year DCA curves have revealed that nomogram model yielded larger net benefits than CLEC6A alone. Finally, the TDROC curve indicated that CLEC6A could better predict 1-year DFS and OS than others. Furthermore, we combined these potential independent prognostic factors to analyze the relationship among these hematologic index and oxidative stress indicators, and indicated that higher CLEC6A level, higher CO2 level or low CHOL level or high HDL-CHO level would have survived longer and better prognosis. In breast cancer, high expression of CLEC6A can independently predict better survival. Our nomogram consisted of CLEC6A and other indicators has good predictive performance and can facilitate clinical decision-making.

Choledochoscopy combined with double-cannula lavage in the treatment of acute pancreatitis with encapsulated necrosis and the analysis of related inflammatory indexes.

OBJECTIVE: This study aimed to evaluate the application of choledochoscopy combined with double-cannula lavage in the treatment of acute pancreatitis (AP) with encapsulated necrosis and analyzed related inflammatory indexes. METHODS: Thirty patients with AP with encapsulated necrosis were enrolled and treated with choledochoscopy and double-cannula lavage. Serum white blood cell (WBC), procalcitonin (PCT), C-reactive protein (CRP), interleukin 6 (IL-6), IL-8, tumor necrosis factor alpha (TNF-α), and related inflammatory indexes were detected before and after surgery. RESULTS: All of the participants who underwent the surgery recovered well and were discharged without serious complications; no deaths occurred. The serum WBC, PCT, and CRP of patients after surgery decreased compared with before the procedure, and the differences in WBC and CRP were statistically significant (P < 0.05); the difference in PCT was not statistically significant (P > 0.05). Postoperatively, IL-6, IL-8, and TNF-α levels were higher than before surgery, and the differences were statistically significant (P < 0.05). CONCLUSION: The surgical method presented herein effectively controlled and alleviated the infection of patients; it also did not increase the risk of infection and can thus be considered a safe and effective surgical method.

Pyroptosis mediates osteoporosis via the inflammation immune microenvironment.

Osteoporosis represents a systemic imbalance in bone metabolism, augmenting the susceptibility to fractures among patients and emerging as a notable mortality determinant in the elderly population. It has evolved into a worldwide concern impacting the physical well-being of the elderly, imposing a substantial burden on both human society and the economy. Presently, the precise pathogenesis of osteoporosis remains inadequately characterized and necessitates further exploration. The advancement of osteoporosis is typically linked to the initiation of an inflammatory response. Cells in an inflammatory environment can cause inflammatory death including pyroptosis. Pyroptosis is a recently identified form of programmed cell death with inflammatory properties, mediated by the caspase and gasdermin families. It is regarded as the most inflammatory form of cell death in contemporary medical research. Under the influence of diverse cytokines, macrophages, and other immune cells may undergo pyroptosis, releasing inflammatory factors, such as IL-1ß and IL-18. Numerous lines of evidence highlight the pivotal role of pyroptosis in the pathogenesis of inflammatory diseases, including cancer, intestinal disorders, hepatic conditions, and cutaneous ailments. Osteoporosis progression is frequently associated with inflammation; hence, pyroptosis may also play a role in the pathogenesis of osteoporosis to a certain extent, making it a potential target for treatment. This paper has provided a comprehensive summary of pertinent research concerning pyroptosis and its impact on osteoporosis. The notion proposing that pyroptosis mediates osteoporosis via the inflammatory immune microenvironment is advanced, and we subsequently investigate potential targets for treating osteoporosis through the modulation of pyroptosis.

Current status of sevoflurane anesthesia in association with microglia inflammation and neurodegenerative diseases.

Sevoflurane is one of the most commonly used volatile anesthetics in clinical practice and is often used in pediatric anesthesia and intraoperative maintenance. Microglia exist in the central nervous system and are innate immune cells in the central nervous system. Under external stimulation, microglia are divided into two phenotypes: proinflammatory (M1 type) and anti-inflammatory (M2 type), maintaining the stability of the central nervous system through induction, housekeeping, and defense functions. Sevoflurane can activate microglia, increase the expression of inflammatory factors through various inflammatory signaling pathways, release inflammatory mediators to cause oxidative stress, damage nerve tissues, and eventually develop into neurodegenerative diseases. In this article, the relationship between sevoflurane anesthesia and microglia inflammation expression and the occurrence of neurodegenerative diseases is reviewed as follows.

U-Shaped Relationship Between Fibrinogen Level and 10-year Mortality in Patients With Acute Coronary Syndrome: Prospective Cohort Study.

This study demonstrated that fibrinogen is an independent risk factor for 10-year mortality in patients with acute coronary syndrome (ACS), with a U-shaped nonlinear relationship observed between the two. These findings underscore the importance of monitoring fibrinogen levels and the consideration of long-term anti-inflammatory treatment in the clinical management of patients with ACS.

Effectiveness of resistance training in modulating inflammatory biomarkers among Asian patients with sarcopenia: a systematic review and meta-analysis of randomized controlled trials.

Objective: Given the high incidence of sarcopenia among Asians, it is imperative to identify appropriate intervention methods. The International Clinical Practice Guidelines for Sarcopenia, developed by the International Conference on Sarcopenia and Frailty Research (ICFSR) task force, recommends resistance training (RT) as a primary treatment for managing sarcopenia. Inflammatory biomarkers serve as indicators of sarcopenia. However, there is currently insufficient conclusive evidence regarding the effectiveness of RT in modulating inflammatory biomarker levels among Asian participants with sarcopenia. Data sources: Four databases were utilized for this study until October 9, 2023. This study focused on randomized controlled trials (RCTs) that examined the effects of RT on interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), and interleukin-10 (IL-10) about sarcopenia. This study has been registered in the PROSPERO database (CRD42024501855). Results: The meta-analysis included six studies from Asians involving 278 participants. The results showed a significant decrease in RT for IL-6 (weighted mean difference (WMD) = -0.73, 95% confidence interval (CI) = -1.02 to -0.44; n=5). However, no significant differences were found for TNF-α (WMD = -1.00, 95% CI = -2.47 to 0.46; n=5), CRP (WMD = -0.45, 95% CI = -1.14 to 0.23; n=3), and IL-10 (WMD = 0.13, 95% CI = -3.99 to 4.25; n=2). Subgroup analysis revealed that factors including gender selection, intervention methods, frequency, period, and duration could have a particular effect on the part of inflammatory biomarkers. Conclusion: RT has been shown to reduce part of the level of inflammatory markers, specifically IL-6, in Asian sarcopenia participants. However, other inflammatory factors, such as TNF-α, CRP, and IL-10, did not show significant changes. Further research should confirm the impact of RT on these indicators and explore the potential effects of various factors on different inflammatory markers, such as diet, body composition, and medications. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=501855, identifier CRD42024501855.

Association between serum copper and blood glucose: a mediation analysis of inflammation indicators in the NHANES (2011-2016).

Background: The rising prevalence of diabetes underscores the need for identifying effective prevention strategies. Recent research suggests environmental factors, particularly heavy metals like copper, significantly influence health outcomes, including diabetes, through mechanisms involving inflammation and oxidative stress. This study aims to explore how serum copper levels affect blood glucose, employing NHANES data from 2011 to 2016, to provide insights into environmental health's role in diabetes prevention and management. Methods: The study analyzed data from 2,318 NHANES participants across three cycles (2011-2016), focusing on those with available data on serum copper, inflammatory markers, and blood glucose levels. We utilized principal component analysis for selecting inflammatory markers, mediation analysis to examine direct and indirect effects, multiple linear regression for assessing relationships between markers and glucose levels, and weighted quantile sum regression for evaluating individual and collective marker effects, adjusting for demographic variables and serum copper. Results: Participants averaged 42.70 years of age, with a near-even split between genders. Average serum copper was 119.50 µg/dL, white blood cell count 6.82 × 109/L, and fasting blood glucose 107.10 mg/dL. Analyses identified significant mediation by inflammatory markers (especially white blood cells: 39.78%) in the copper-blood glucose relationship. Regression analyses highlighted a positive correlation between white blood cells (estimate: 1.077, 95% CI: 0.432 to 2.490, p = 0.013) and copper levels and a negative correlation for monocyte percentage (estimate: -1.573, 95% CI: 0.520 to -3.025, p = 0.003). Neutrophil percentage was notably influential in glucose levels. Sensitive analyses confirmed the study's findings. Conclusion: Serum copper levels significantly impact blood glucose through inflammatory marker mediation, highlighting the importance of considering environmental factors in diabetes management and prevention. These findings advocate for public health interventions and policies targeting environmental monitoring and heavy metal exposure reduction, emphasizing the potential of environmental health measures in combating diabetes incidence.

VX-702 Ameliorates the Severity of Sepsis-Associated Acute Kidney Injury by Downregulating Inflammatory Factors in Macrophages.

Purpose: Sepsis-associated acute kidney injury (S-AKI) contributes to high mortality, but it is lack of specific treatments. We aimed to investigate the underlying mechanism of S-AKI and to identify target drugs to alleviate AKI. Methods: We establish a stable mouse model of S-AKI by Pseudomonas aeruginosa incision infection. Based on high-throughput sequencing and bioinformatics analysis, we investigated the underlying mechanism and selected the target drug (VX-702) for S-AKI. An in vitro model established by co-cultured of kidney tubular epithelial cell line (TCMK-1) cells with lipopolysaccharide (LPS)-induced leukemic monocyte/macrophage cells (RAW264.7), we explored the effect of VX-702 on S-AKI. Results: The data showed interleukin (IL)-6 and IL-1ß were the hub genes, and the mitogen-activated protein kinase (MAPK) signaling pathway was the main pathway involved in S-AKI. Administration of VX-702 by oral gavage decreased the elevated concentrations of IL-6, IL-1ß, serum creatinine, and blood urea nitrogen in mice with S-AKI. Moreover, VX-702 reduced the number of apoptotic cells in damaged kidney tissues. Cell viability was decreased, and the number of apoptotic cells was increased in TCMK-1 cells co-cultured with LPS-induced RAW264.7 cells compared to LPS-induced TCMK-1 cells. VX-702 treatment reversed this effect. VX-702 treatment reduced the levels of phosphorylated p38 MAPK and proinflammatory cytokines in RAW264.7 cells and the supernatant. VX-702 could bind IL-6, IL-1ß and MAPK, and affect the binding of IL-1ß and its receptor, as demonstrated by molecular docking. Conclusion: VX-702 ameliorated S-AKI by inhibiting the release of proinflammatory cytokines from macrophages, indicating its potential as a novel therapeutic for S-AKI treatment.

Exposure to coal dust exacerbates cognitive impairment by activating the IL6/ERK1/2/SP1 signaling pathway.

Coal dust (CD) is a common pollutant, and epidemiological surveys indicate that long-term exposure to coal dust not only leads to the occurrence of pulmonary diseases but also has certain impacts on cognitive abilities. However, there is little open-published literature on the effects and specific mechanisms of coal dust exposure on the cognition of patients with Mild Cognitive Impairment (MCI) and Alzheimer's Disease (AD). An animal model has been built in this study with clinical population samples to explore the changes in neuroinflammation and cognitive abilities with coal dust exposure. In the animal model, compared to C57BL/6 mice, APP/PS1 mice exposed to coal dust exhibited more severe cognitive impairment, accompanied by significantly elevated levels of neuroinflammatory factors Apolipoprotein E4 (AOPE4) and Interleukin-6 (IL6) in the hippocampus, and more severe neuronal damage. In clinical sample sequencing, it was found that there is significant upregulation of AOPE4, neutrophils, and IL6 expression in the peripheral blood of MCI patients compared to normal individuals. Mechanistically, cell experiments revealed that IL6 could promote the phosphorylation of ERK1/2 and enhance the expression of transcription factor SP1, thereby promoting AOPE4 expression. The results of this study suggest that coal dust can promote the upregulation of IL6 and AOPE4 in patients, exacerbating cognitive impairment.

Meta-analysis of the relationship between ocular and peripheral serum IL-17A and diabetic retinopathy.

Purpose: A systematic evaluation and Meta-analysis were performed to determine the relationship between IL-17A levels in ocular aqueous and peripheral venous serum samples and diabetic retinopathy (DR). Methods: PubMed, Embase, Web of Science, and CNKI databases were searched from the time of library construction to 2023-09-20.The results were combined using a random-effects model, sensitivity analyses were performed to determine whether the arithmetic was stable and reliable, and subgroup analyses were used to look for possible sources of heterogeneity. Results: A total of 7 case-control studies were included. The level of IL-17A was higher in the Nonproliferative DR(NPDR) group than in the Non-DR(NDR) group [SMD=2.07,95%CI(0.45,3.68),P=0.01], and the level of IL-17A in the proliferating DR(PDR) group was higher than that of the NDR group [SMD=4.66,95%CI(1.23,8.08),P<0.00001]. IL-17A levels in peripheral serum and atrial fluid were significantly higher in NPDR and PDR patients than in non-DR patients in subgroup analyses, and detection of peripheral serum IL-17A concentrations could help to assess the risk of progression from NPDR to PDR. Sensitivity analyses suggested that the results of the random-effects arithmetic were stable and reliable. Subgroup analyses based on assay method and sample source showed that the choice of these factors would largely influence the relationship between IL-17A levels and DR. Conclusion: Elevated peripheral serum and ocular aqueous humor IL-17A levels in diabetic patients are associated with the risk of DR, IL-17A may serve as a potential predictor or therapeutic target for DR, and IL-17A may be an important predictor of inflammation for the progression of NPDR to PDR. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024532900.

Oroxylin A inhibits inflammatory cytokines in periodontitis via HO­1.

Periodontal disease is a common infectious disease that can lead to the loss of teeth. Hower how to effectively suppress the inflammation with medication is unclear. The aim of the present study was to investigate the anti­inflammatory effect of Oroxylin A in periodontitis and its potential role through heme oxygenase­1 (HO­1). Primary rat gingival fibroblasts (RGFs) were cultured using the tissue block method and identified by immunofluorescence. Following lipopolysaccharide (LPS) stimulation of RGFs, Oroxylin A was administered at 50, 100, 200 or 400 µg/ml. Reverse transcription­quantitative PCR was used to assess mRNA expression of cyclooxygenase (COX)­2, TNF­α, RANKL and osteoprotegerin (OPG). Western blotting was used to detect protein expression levels of COX ­2, TNF­α, RANKL and OPG. Following HO­1 knockdown, the same treatment was performed. The expression of COX­2 in rat gingival tissue was observed by immunohistochemistry. One­way analysis of variance and Student's t test were used for statistical analysis. Oroxylin A downregulated mRNA expression of COX­2, TNF­α, RANKL and OPG in LPS­induced RGFs. With increase of Oroxylin A dose, the expression of HO­1 was gradually upregulated. When HO­1 was knocked down, Oroxylin A did not downregulate the expression of COX­2, TNF­α, RANKL and OPG in LPS­induced RGFs. Immunohistochemical results showed that expression of COX­2 was downregulated by Oroxylin A, and the expression of TNF­α, RANKL and OPG were also downregulated. Oroxylin A decreased expression of inflammatory cytokines in LPS­induced RGFs and had a good inhibitory effect on periodontitis in rats.

Weissella cibaria Relieves Gut Inflammation Caused by Escherichia coli through Inflammation Modulation and Gut Microbiota Regulation.

The emergence of multi-drug-resistant (MDR) pathogens has considerably challenged the development of new drugs. Probiotics that inhibit MDR pathogens offer advantages over chemical antibiotics and drugs due to their increased safety and fewer side effects. This study reported that Weissella cibaria P-8 isolated from pickles showed excellent antibacterial activity against intestinal pathogens, particularly the antibacterial activity against MDR Escherichia coli B2 was the highest. This study showed that the survival rates of W. cibaria P-8 at pH 2.0 and 0.3% bile salt concentration were 72% and 71.56%, respectively, and it still had antibacterial activity under pepsin, trypsin, protease K, and catalase hydrolysis. Moreover, W. cibaria P-8 inhibits the expression of inflammatory factors interleukin-1ß, tumor necrosis factor-α, and interleukin-6, upregulates the interleukin-10 level, and increases total antioxidant capacity and superoxide dismutase enzyme activity in serum. W. cibaria P-8 also efficiently repairs intestinal damage caused by E. coli infection. The gut microbiota analysis demonstrated that W. cibaria P-8 colonizes the intestine and increases the abundance of some beneficial intestinal microorganisms, particularly Prevotella. In conclusion, W. cibaria P-8 alleviated MDR E. coli-induced intestinal inflammation by regulating inflammatory cytokine and enzyme activity and rebalancing the gut microbiota, which could provide the foundation for subsequent clinical analyses and probiotic product development.

Treatment Effects of Bifidobacterium Quadruple Viable Tablets Combined With Quadruple Therapy on Helicobacter Pylori-Infected Peptic Ulcer in Children.

This study aimed to investigate the treatment effects of Bifidobacterium quadruple viable tablets combined with quadruple therapy on Helicobacter pylori (Hp)-infected peptic ulcer in children. A total of 124 children with Hp-infected peptic ulcers were allocated into 2 treatment groups: control group (quadruple therapy) and observation group (quadruple therapy plus Bifidobacterium quadruple viable tablets). After treatment, the 2 groups were compared in terms of ulcer healing, serum inflammatory cytokines, Hp elimination, gastrointestinal hormones, and intestinal flora. After treatment, the children in the observation group possessed lower serum interleukin-6, tumor necrosis factor α, procalcitonin, C-reactive protein, gastrin, and motilin levels, and higher ulcer healing rate, Hp clearance rate, somatostatin levels and bifidobacterium and lactobacillus versus those in the control group. Bifidobacterium quadruple viable tablets combined with quadruple therapy has good efficacy in Hp-associated peptic ulcer disease.

Multiple pretreatments can effectively improve the functionality of mesenchymal stem cells.

In this editorial, we offer our perspective on the groundbreaking study entitled "Hypoxia and inflammatory factor preconditioning enhances the immunosuppressive properties of human umbilical cord mesenchymal stem cells", recently published in World Journal of Stem Cells. Despite over three decades of research on the clinical application of mesenchymal stem cells (MSCs), only a few therapeutic products have made it to clinical use, due to multiple preclinical and clinical challenges yet to be addressed. The study proved the hypoxia and inflammatory factor preconditioning led to higher immunosuppressive effects of MSCs without damaging their biological characteristics, which revealed the combination of inflammatory factors and hypoxic preconditioning offers a promising approach to enhance the function of MSCs. As we delve deeper into the intricacies of pretreatment methodologies, we anticipate a transformative shift in the landscape of MSC-based therapies, ultimately contributing to improved patient outcomes and advancing the field as a whole.

Characterization of preclinical Alzheimer's disease model: spontaneous type 2 diabetic cynomolgus monkeys with systemic pro-inflammation, positive biomarkers and developing AD-like pathology.

BACKGROUND: The key to the prevention and treatment of Alzheimer's disease (AD) is to be able to predict and diagnose AD at the preclinical or early stage, but the lack of a preclinical model of AD is the critical factor that causes this problem to remain unresolved. METHODS: We assessed 18 monkeys in vivo evaluation of pro-inflammatory cytokines and AD pathological biomarkers (n = 9 / type 2 diabetic mellitus (T2DM) group, age 20, fasting plasma glucose (FPG) ≥ 100 mg/dL, and n = 9 / negative control (NC) group, age 17, FPG < 100 mg/dL). Levels of pro-inflammatory cytokines and AD pathological biomarkers was measured by ELISA and Simoa Technology, respectively. 9 monkeys evaluated ex vivo for AD-like pathology (n = 6 / T2DM group, age 22.17, FPG ≥ 126 mg/dL, and n = 3 / NC group, age 14.67, FPG < 100 mg/dL). To evaluate the pathological features of AD in the brains of T2DM monkeys, we assessed the levels of Aß, phospho-tau, and neuroinflammation using immunohistochemistry, which further confirmed the deposition of Aß plaques by Bielschowsky's silver, Congo red, and Thioflavin S staining. Synaptic damage and neurodegeneration were assessed by immunofluorescence. RESULTS: We found not only increased levels of pro-inflammatory cytokines such as tumor necrosis factor-α (TNF-α) in peripheral blood (PB) and brain of T2DM monkeys but also changes in PB of AD pathological biomarkers such as decreased ß-amyloid (Aß) 42 and Aß40 levels. Most notably, we observed AD-like pathological features in the brain of T2DM monkeys, including Aß plaque deposition, p-tau from neuropil thread to pre-neurofibrillary tangles (NFTs), and even the appearance of extracellular NFT. Microglia were activated from a resting state to an amoeboid. Astrocytes showed marked hypertrophy and an increased number of cell bodies and protrusions. Finally, we observed impairment of the postsynaptic membrane but no neurodegeneration or neuronal death. CONCLUSIONS: Overall, T2DM monkeys showed elevated levels of peripheral and intracerebral inflammation, positive AD biomarkers in body fluids, and developing AD-like pathology in the brain, including Aß and tau pathology, glial cell activation, and partial synaptic damage, but no neuronal degeneration or death as compared to the healthy normal group. Hereby, we consider the T2DM monkeys with elevation of the peripheral pro-inflammatory factors and positive AD biomarkers can be potentially regarded as a preclinical AD model.

Clinical efficacy of recombinant human basic fibroblast growth factor combined with ranitidine in the treatment of recurrent oral ulcer and its effect on serum TNF, IL-2 and T-lymphocyte subsets.

Objective: To evaluate the clinical efficacy of recombinant human basic fibroblast growth factor (rh-bFGF) combined with ranitidine in the treatment of recurrent oral ulcer and its effects on serum TNF, IL-2 and T-lymphocyte subsets. Methods: This was a retrospective study. Eighty patients with oral ulcers admitted to First Medical Center, Chinese PLA General Hospital from July 2021 to June 2022 were randomly divided into the control group and the experimental group (n=40). Patients in the control group were given topical treatment with rh-bFGF gel, while those in the experimental group were given oral treatment combined with ranitidine based on the control group, and both groups were treated continuously for 14 days. The therapeutic effect, pain relief time, ulcer healing time, as well as the differences in the levels of inflammatory factors and T-lymphocyte subsets were compared and analyzed between the two groups. Results: The overall response rate of the experimental group was 92.5%, while that of the control group was 75%, with a statistically significant difference(P=0.03). After treatment, inflammatory factors indexes in the experimental group were significantly lower than those in the control group, with statistically significant differences (P=0.00). The indexes of T-lymphocyte subsets in the experimental group were significantly higher than those in the control group after treatment, with statistically significant differences (P=0.00). Conclusion: Recombinant human basic fibroblast growth factor combined with ranitidine is effective in the treatment of recurrent oral ulcers, boasting various benefits such as effectively promoting ulcer healing, reducing pain and inflammatory response, and enhancing immune function.

Effects of staged rehabilitation training on inflammatory factor levels and red blood cell distribution width followingcardiac valve replacement.

BACKGROUND: The current study was conducted aimed atexploring the effects of staged rehabilitation training on the levels of inflammatory factors and red blood cell distribution in patients who underwent cardiac valve replacement. METHODS: A total of 140 patients who underwent cardiac valve replacement at The First Hospital of Hebei Medical University between April 2021 and November 2022 were included in this study. During the postoperative rehabilitation phase, the patients were randomly assigned to either the control group or the experimental group. The experimental group received staged rehabilitation training (n = 70), while the control group received conventional care and rehabilitation suggestions without specialized staged rehabilitation training (n = 70). Informed consent was obtained from all patients prior to theirinclusion in the study. Clinical data of the patients were collected andanalyzed. RDW was measured using an automated blood cell analyzer on postoperative day 1, 14, and 28. Levels ofTNF-α, IL-6 and CRP were measured using ELISA. Quality of life was evaluated usingthe WHOQOL-BREF questionnaire. The effects of postoperative rehabilitation were assessed using the 6MWD test. The occurrence of adverse events in the postoperative periodwas alsoanalyzed. RESULTS: There were no significant differences in the general characteristics of the two groups of patients (P > 0.05). On the first day after surgery, no significant differences were seen in RDW between the two groups (P > 0.05). However, on the 14th and 28th day after surgery, the experimental group exhibited a significant reduction in RDW compared to the control group (P < 0.05). On the first day after surgery, the levels of serum TNF-α, IL-6 and CRP were comparable between the two groups (P > 0.05). However, on the 14th and the 28th after surgery, the experimental group showed evidently lower levels of TNF-α, IL-6 and CRP compared to the control group (P < 0.05). The experimental group demonstrated higher scores in the domains of physical health, psychological state, social relationships, and environment in the WHOQOL-BREF questionnaire compared to the control group (P < 0.05). Furthermore, the experimental group exhibited increased average,minimum,maximum walking distances in the6-minute walking test compared to the control group (P < 0.05). There were no significant differences in the incidence of postoperative adverse events between the two groups of patients (P > 0.05). CONCLUSION: Staged rehabilitation training exerteda positive effect on the levels of inflammatory factors and red blood cell distribution in patients following cardiac valve replacement. This type of rehabilitation training facilitated the patient's recovery process by reducing the inflammatory response and improving the condition of red blood cells. Additionally, it enhanced the quality of life and rehabilitation outcomes for patients.

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OBJECTIVES: To observe the effect of electroacupuncture (EA) on the changes of behavior and hippocampal inflammatory factors in rats with chronic fatigue syndrome (CFS), so as to explore its possible mechanisms in the treatment of CFS. METHODS: Twenty-seven SD rats were randomly divided into control, model and electroacupuncture (EA) groups (n=9 rats in each group). The CFS model was established by multi-factor compound stress stimulation method. Rats of the EA group received EA (10 Hz) at "Shenting" (GV24) penetrating "Baihui" (GV20), "Dazhui" (GV14) for 15 min, twice a day for 14 days. The general conditions, Morris water maze test, open field test, the exhausted running platform were conducted for determining the rats' locomotor and learning-memory activities. H.E. staining was used to observe the morphological structure of neurons in hippocampal CA1 region. The contents of interleukin (IL)-10, IL-17 and transforming growth factor (TGF) ß1 in hippocampus and serum of rats were detected by ELISA, and the positive expressions of IL-10, IL-17 and TGF-ß1 in hippocampal CA1 region were detected by immunofluorescence staining. RESULTS: Compared with the control group, the score of general condition was increased (P<0.05), the escape latency was prolonged (P<0.05), the number of crossing the original platform was decreased (P<0.05), the numbers of crossing the grid and entering the central area were increased (P<0.05), and the exhaustive treadmill time was shortened (P<0.05) in the model group. The contents of IL-10 in the hippocampus and serum were decreased (P<0.05), while IL-17 and TGF-ß1 contents were increased (P<0.05). The immunofluorescence intensity of IL-10 in the hippocampus was decreased (P<0.05), while the intensity of IL-17 and TGF-ß1 were increased (P<0.05). After treatment, compared with the model group, the score of general condition was decreased (P<0.05), the escape latency was shortened (P<0.05), the number of crossing the original platform was increased (P<0.05), the numbers of crossing the grid and entering the central area were decreased (P<0.05), and the exhaustive treadmill time was prolonged (P<0.05) in the EA group. The contents of IL-10 in the hippocampus and serum were increased (P<0.05), while IL-17 and TGF-ß1 levels were decreased (P<0.05). The immunofluorescence intensity of IL-10 in the hippocampus was increased (P<0.05), while the intensity of IL-17 and TGF-ß1 were decreased (P<0.05). H.E. staining showed that in the model group, the number of neurons in the hippocampus decreased, with disordered arrangement and loose structure, and a small numbers of neuronal nuclei were missing. The degree of tissue damage of the EA group was milder than that of the model group. CONCLUSIONS: EA can alleviate fatigue and spatial learning and memory impairment in CFS rats, which may be related to the regulation of peripheral and central inflammation.