ObjectiveTo optimize the processing technology of honey bran-fried Rosae Laevigatae Fructus（h-RLF）， formulate relevant quality standards， and explore its improving effect and mechanism on mice with ulcerative colitis（UC） induced by dextran sodium sulfate（DSS）. MethodsTaking the content of polysaccharides and water-soluble extract as the indexes， L₉（3⁴） orthogonal test was used to optimize parameters of the amount of honey bran， frying time and frying temperature. The quality of 15 batches of h-RLF decoction pieces was evaluated according to the optimized process， and the inspection limit standard was preliminarily drawn up. Eighty SPF male Kunming mice were randomly divided into 8 groups， including the blank group， model group， mesalazine group（0.13 g·kg^-1）， RLF group（3.77 g·kg^-1）， bran-fried RLF group（3.77 g·kg^-1）， h-RLF low， medium and high dose groups（1.89， 3.77， 7.54 g·kg^-1）， with 10 mice in each group. The mice in the blank group were free to drink pure water， and the other groups were free to drink 3% DSS solution for 7 days to prepare UC mouse model. Each treatment group was given corresponding drugs by intragastric administration， and the blank and model groups were given equal volume of normal saline. The body weight of mice was recorded daily and the disease activity index（DAI） was calculated. After the administration， the colon tissues of mice were collected to observe the pathological changes by hematoxylin-eosin（HE） staining. The levels of tumor necrosis factor（TNF）-α， interleukin（IL）-1β， IL-6 and IL-10 in the colon of mice were detected by enzyme-linked immunosorbent assay（ELISA）. Western blot was used to detect the expression levels of phosphorylation nuclear transcription factor-κB p65（p-NF-κB p65）， Toll-like receptor 4（TLR4）， p-p38 mitogen-activated protein kinase（p-p38 MAPK）， p-extracellular signal-regulated kinase（p-ERK） and p-c-Jun N-terminal kinase（p-JNK） proteins in colon tissues. ResultsThe optimum processing technology of h-RLF was 20 g honey bran per 100 g RLF， and stir-frying at 200 ℃ for 8 min. The limit standard under the examination of h-RLF was preliminarily formulated as follows：the polysaccharide content should not be less than 25% based on anhydrous glucose（C₆H₁₂O₆）， the content of water-soluble extract should not be less than 38%， the moisture content should not be more than 12.0%， the total ash content should not be more than 5.0%， and the acid-insoluble ash content should not be more than 1.0%. The cluster heat map analysis showed that the quality of RLF from Huanggang， Hubei province was better. Animal experiments showed that compared with the blank group， the DAI score of the model group was significantly increased， the levels of TNF-α， IL-1β and IL-6 in the colon tissue were significantly increased， the IL-10 level was significantly decreased， the colonic mucosa was seriously damaged， accompanied by a large number of inflammatory cell infiltration， tissue congestion and a significant reduction in glands， and the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins were significantly increased（P<0.01）. Compared with the model group， each administration group could alleviate the symptoms of colonic ulcer， the structure of colonic crypt was basically intact， and the glands were arranged in an orderly manner. Among them， the high-dose group of h-RLF had a better effect， which could significantly reduce the DAI score and the levels of TNF-α， IL-1β and IL-6 in colon tissue（P<0.01）， and significantly increase the level of IL-10（P<0.01）， alleviate the colonic mucosal injury， and effectively inhibit the expression levels of p-NF-κB p65， TLR4， p-p38 MAPK， p-ERK and p-JNK proteins（P<0.01）. ConclusionThe key parameters of the processing technology of h-RLF are determined， and the optimized technology is stable and feasible. The established quality standard is simple and reliable， and can be used for the quality control. h-RLF can effectively alleviate DSS-induced UC， and its mechanism may be related to inhibiting the activation of NF-κB/TLR4/MAPK pathway.

OBJECTIVE: To explore the clinical efficacy of conventional transforaminal endoscopic technique and I See transforaminal endoscopic technique in the treatment of recurrent L₅S₁ lumbar disc herniation with high iliac crest. METHODS: A total of 36 patients with recurrent L5S1 lumbar disc herniation with high iliac crest after posterior small-incision discectomy, admitted from May 2016 to May 2023, were selected. They were divided into the conventional transforaminal endoscopy group and the I See transforaminal endoscopy group according to the different transforaminal endoscopic techniques adopted, and all patients in both groups underwent lateral transforaminal spinal canal decompression and discectomy. There were 18 patients in the conventional transforaminal endoscopy group, including 11 males and 7 females, with an age of (52.24±6.68) years;the I See transforaminal endoscopy group also had 18 patients, including 12 males and 6 females, with an age of (50.75±7.79) years. The perioperative indicators (operation time, number of intraoperative radiographs, and length of hospital stay) were compared between two groups. The clinical efficacy was evaluated using the visual analogue scale(VAS) for pain, the Japanese Orthopaedic Association(JOA) low back pain score, and the modified MacNab criteria before and after surgery. RESULTS: All patients achieved gradeⅠincision healing, with no infection cases. The operation time of the I See group was (64.25±16.67) minutes, which was significantly shorter than that of the conventional transforaminal endoscopy group (89.11±17.24) minutes, and the difference was statistically significant(P<0.05). The number of intraoperative radiographs in the I See group was (5.20±2.29) times, which was significantly less than that in the conventional transforaminal endoscopy group(19.16±3.68) times, and the difference was statistically significant(P<0.05). The VAS and total JOA scores of both groups at the 3rd day, the 3rd month after surgery, and the last follow-up were significantly lower than those before surgery, with statistically significant differences(P<0.05);however, there were no statistically significant differences in VAS and total JOA scores between two groups at the 3rd day, the 3rd month after surgery, and the last follow-up (P>0.05). According to the modified MacNab criteria for efficacy evaluation:in the conventional transforaminal endoscopy group, 14 cases were excellent and 4 cases were good;in the I See transforaminal endoscopy group, 15 cases were excellent and 3 cases were good;there was no statistically significant difference in efficacy between two groups(Z=0.177, P=0.674). CONCLUSION Both transforaminal endoscopic techniques have good clinical effects in the treatment of recurrent L₅S₁ lumbar disc herniation with high iliac crest, resulting in significant improvement of postoperative symptoms, and they are safe, reliable, and minimally invasive surgical methods. Compared with the conventional transforaminal endoscopy, the I See transforaminal endoscopic technique has shorter operation time and fewer intraoperative radiographs, so it is generally the first choice.
Humans ; Male ; Female ; Intervertebral Disc Displacement/surgery* ; Endoscopy/methods* ; Middle Aged ; Lumbar Vertebrae/surgery* ; Ilium/surgery* ; Adult ; Diskectomy/methods*

Targeting T-cell is a strategy to control allogeneic response disorders, such as acute graft-versus-host disease (GVHD) which is an important cause of therapy-failure after allogeneic hematopoietic cell transplants. Free fatty acid receptor-4 (FFAR4) is a regulator of obesity but its role in T-cell and allogeneic reactions is unknown. Here, we found knockout of Ffar4 in donor T-cells in a mouse allograft model increased acute GVHD whereas the natural FFAR4 ligands and the synthetic FFAR4 agonists decreased it. FFAR4 agonist-mediated anti-acute GVHD effects depended on FFAR4-expression in donor T-cells. The FFAR4 agonist CpdA suppressed donor T-cell-mediated alloreaction by activating an aryl hydrocarbon receptor (AhR) pathway. CpdA recruited β-Arrestin2 to FFAR4 which facilitated nuclear translocation of AhR and upregulation of IL-22. The CpdA-mediated anti-acute GVHD effect was absent in mice receiving Ahr-knockout or Il22-knockout T-cells. Recipient-expressing Ffar4 was also important for the anti-acute GVHD effect of CpdA which inhibited activation of antigen presenting cells. Importantly, CpdA decreased acute GVHD in obese mice, an effect also depended on Ffar4-expression in donor T-cells and recipients. Our study shows the immunoregulatory effect of FFAR4 in T-cell, and targeting FFAR4 might be a relative option for controlling allogeneic reactions in obese patients.

Acute kidney injury (AKI) has high morbidity and mortality, but effective clinical drugs and management are lacking. Previous studies have suggested that macrophages play a crucial role in the inflammatory response to AKI and may serve as potential therapeutic targets. Emerging evidence has highlighted the importance of forkhead box protein O1 (FoxO1) in mediating macrophage activation and polarization in various diseases, but the specific mechanisms by which FoxO1 regulates macrophages during AKI remain unclear. The present study aimed to investigate the role of FoxO1 in macrophages in the pathogenesis of AKI. We observed a significant upregulation of FoxO1 in kidney macrophages following ischemia-reperfusion (I/R) injury. Additionally, our findings demonstrated that the administration of FoxO1 inhibitor AS1842856-encapsulated liposome (AS-Lipo), mainly acting on macrophages, effectively mitigated renal injury induced by I/R injury in mice. By generating myeloid-specific FoxO1-knockout mice, we further observed that the deficiency of FoxO1 in myeloid cells protected against I/R injury-induced AKI. Furthermore, our study provided evidence of FoxO1's pivotal role in macrophage chemotaxis, inflammation, and migration. Moreover, the impact of FoxO1 on the regulation of macrophage migration was mediated through RhoA guanine nucleotide exchange factor 1 (ARHGEF1), indicating that ARHGEF1 may serve as a potential intermediary between FoxO1 and the activity of the RhoA pathway. Consequently, our findings propose that FoxO1 plays a crucial role as a mediator and biomarker in the context of AKI. Targeting macrophage FoxO1 pharmacologically could potentially offer a promising therapeutic approach for AKI.

Loss of protein homeostasis is a hallmark of cellular senescence, and ribosome pausing plays a crucial role in the collapse of proteostasis. However, our understanding of ribosome pausing in senescent cells remains limited. In this study, we utilized ribosome profiling and G-quadruplex RNA immunoprecipitation sequencing techniques to explore the impact of RNA G-quadruplex (rG4) on the translation efficiency in senescent cells. Our results revealed a reduction in the translation efficiency of rG4-rich genes in senescent cells and demonstrated that rG4 structures within coding sequence can impede translation both in vivo and in vitro. Moreover, we observed a significant increase in the abundance of rG4 structures in senescent cells, and the stabilization of the rG4 structures further exacerbated cellular senescence. Mechanistically, the RNA helicase DHX9 functions as a key regulator of rG4 abundance, and its reduced expression in senescent cells contributing to increased ribosome pausing. Additionally, we also observed an increased abundance of rG4, an imbalance in protein homeostasis, and reduced DHX9 expression in aged mice. In summary, our findings reveal a novel biological role for rG4 and DHX9 in the regulation of translation and proteostasis, which may have implications for delaying cellular senescence and the aging process.
G-Quadruplexes ; Cellular Senescence ; Ribosomes/genetics* ; Humans ; Animals ; Mice ; DEAD-box RNA Helicases/genetics* ; Protein Biosynthesis ; RNA/chemistry* ; Neoplasm Proteins

OBJECTIVE: To investigate the value of difference between hematocrit (HCT) and albumin (Alb) in predicting the prognosis of patients with sepsis. METHODS: A retrospective study was conducted on the septic patients hospitalized at the First Affiliated Hospital of Guangxi Medical University from January to October in 2024. Clinical data including gender, age, body mass index (BMI), history of hypertension or diabetes, vital signs on admission, and sequential organ failure assessment (SOFA) score, acute physiology and chronic health evaluation II (APACHE II) score, blood lactic acid (Lac), oxygenation index (PaO₂/FiO₂), hemoglobin (Hb), white blood cell count (WBC), platelet count (PLT), lymphocyte count (LYM), HCT, Alb, difference between HCT and Alb, bilirubin, scrum creatinine (SCr), and fibrinogen (Fib) within 48 hours of admission were collected. The 28-day prognosis of patients was also recorded. Binary multivariate Logistic regression analysis was used to identify risk factors for 28-day death in patients with sepsis. The predictive efficacy of the difference between HCT and Alb on 28-day death was evaluated using the receiver operator characteristic curve (ROC curve). RESULTS: Among 180 enrolled septic patients, 140 survived and 40 died on 28 days. Compared with the survival group, the patients in the death group was significantly older (years old: 64±16 vs. 55±15, P < 0.05), and had higher SOFA score, APACHE II score, and SCr [SOFA score: 6 (4, 9) vs. 3 (2, 5), APACHE II score: 13 (10, 18) vs. 8 (6, 11), SCr (μmol/L): 136 (70, 416) vs. 77 (58, 126), all P < 0.05] as well as lower Hb, PLT, HCT, difference between HCT and Alb, and Fib within 48 hours of admission [Hb (g/L): 90±30 vs. 106±79, PLT (×10⁹/L): 158 (57, 240) vs. 215 (110, 315), HCT: 0.258±0.081 vs. 0.333±0.077, difference between HCT and Alb: -6.52±7.40 vs. 1.07±7.63, Fib (g/L): 3.72±1.57 vs. 4.59±1.55, all P < 0.05]. No significant difference in gender, BMI, history of hypertension or diabetes, vital signs on admission, or other laboratory indicators was found between the two groups. Binary multivariate Logistic regression analysis revealed that age [odds ratio (OR) = 1.040, 95% confidence interval (95%CI) was 1.004-1.078, P = 0.030], APACHE II score (OR = 1.218, 95%CI was 1.038-1.430, P = 0.016), Hb (OR = 1.040, 95%CI was 1.014-1.068, P = 0.003), and difference between HCT and Alb (OR = 0.804, 95%CI was 0.727-0.889, P < 0.001) were independent risk factors for 28-day death of septic patients. ROC curve analysis showed that the area under the ROC curve (AUC) of difference between HCT and Alb for predicting 28-day death of septic patients was 0.764 (95%CI was 0.679-0.849, P < 0.001). A cut-off value of difference between HCT and Alb ≤ -5.35 yielded a sensitivity of 80.7% and specificity of 65.0%. CONCLUSIONS The difference between HCT and Alb at early admission is a valuable predictor of prognosis in septic patients. A difference ≤ -5.35 indicates an increased death risk of septic patients.
Humans ; Prognosis ; Sepsis/blood* ; Retrospective Studies ; Hematocrit ; Serum Albumin/analysis* ; Male ; Female ; Middle Aged ; Aged ; APACHE

Background::Cardiovascular disease (CVD) has emerged as the leading cause of death from prostate cancer (PCa) in recent decades, bringing a great disease burden worldwide. Men with preexisting CVD have an increased risk for major adverse cardiovascular events when treated with androgen deprivation therapy (ADT). The present study aimed to explore the prevalence and risk evaluation of CVD among people with newly diagnosed PCa in China.Methods::Clinical data of newly diagnosed PCa patients were retrospectively collected from 34 centers in China from 2010 to 2022 through convenience sampling. CVD was defined as myocardial infarction, arrhythmia, heart failure, stroke, ischemic heart disease, and others. CVD risk was estimated by calculating Framingham risk scores (FRS). Patients were accordingly divided into low-, medium-, and high-risk groups. χ2 or Fisher’s exact test was used for comparison of categorical variables. Results::A total of 4253 patients were enrolled in the present study. A total of 27.0% (1147/4253) of patients had comorbid PCa and CVD, and 7.2% (307/4253) had two or more CVDs. The enrolled population was distributed in six regions of China, and approximately 71.0% (3019/4253) of patients lived in urban areas. With imaging and pathological evaluation, most PCa patients were diagnosed at an advanced stage, with 20.5% (871/4253) locally progressing and 20.5% (871/4253) showing metastasis. Most of them initiated prostatectomy (46.6%, 1983/4253) or regimens involving ADT therapy (45.7%, 1944/4253) for prostate cancer. In the present PCa cohort, 43.1% (1832/4253) of patients had hypertension, and half of them had poorly controlled blood pressure. With FRS stratification, as expected, a higher risk of CVD was related to aging and metabolic disturbance. However, we also found that patients with treatment involving ADT presented an originally higher risk of CVD than those without ADT. This was in accordance with clinical practice, i.e., aged patients or patients at advanced oncological stages were inclined to accept systematic integrative therapy instead of surgery. Among patients who underwent medical castration, only 4.0% (45/1118) received gonadotropin releasing hormone antagonists, in stark contrast to the grim situation of CVD prevalence and risk.Conclusions::PCa patients in China are diagnosed at an advanced stage. A heavy CVD burden was present at the initiation of treatment. Patients who accepted ADT-related therapy showed an original higher risk of CVD, but the awareness of cardiovascular protection was far from sufficient.

Cells are the fundamental structural and functional units of biological organisms,with inherent differences in composition and interactions with exogenous substances,known as cellular heterogeneity.Single cell inductively coupled plasma-mass spectrometry(SC-ICP-MS)allows for the high-throughput introduction of individual cells,enabling the highly sensitive detection and quantification of elements within a single cell,thus effectively providing information on cellular heterogeneity.This review outlined the SC-ICP-MS sample preparation process for different types of cells(single-cell systems,aggregation-prone and adherent cell systems,animal tissues,and plant tissues),including steps such as separation,washing,and fixation,as well as the advantages and existing issues of the current sample introduction systems and quantification methods.The recent applications of SC-ICP-MS in detecting endogenous substances(endogenous elements and proteins),exogenous substances(heavy metals,metal-based drugs and nanoparticles),and the simultaneous detection of both endogenous and exogenous substances were summarized.Finally,the perspectives on the future development of SC-ICP-MS in analytical methods and application fields were presented,including the optimization of single-cell sample preparation,transport efficiency,evaluation standards of ionization efficiency,and the establishment of multiparametric cell analysis platforms.

Objective To explore the correlation between serum lipid levels of total cholesterol(TC)and triglyceride(TG)and the survival prognosis in postoperative patients with early lung cancer,and to observe the effect of Fuzheng Quxie Prescription on serum lipid levels in postoperative patients with early lung cancer,so as to explore the mechanism of Fuzheng Quxie Prescription in improving the survival prognosis of postoperative patients with early lung cancer.Methods The correlation of serum TC and TG levels with survival prognosis of 257 postoperative patients with early lung cancer admitted in Shanghai Municipal Hospital of Traditional Chinese Medicine from July 2010 to December 2015 was retrospectively analyzed.The changes of serum TC and TG levels in postoperative patients with early lung cancer before and after treatment with Fuzheng Quxie Prescription were statistically analyzed.From January 2017 to April 2021,a prospective analysis of the one-year,two-year,three-year and four-year disease-free survival rates and serum TC and TG levels was carried out in 281 postoperative patients with early lung cancer treated with Fuzheng Quxie Prescription orally in Shanghai Municipal Hospital of Traditional Chinese Medicine(treatment group)and in 287 postoperative patients with early lung cancer who were followed up in clinic while had no medciation in Shanghai Pulmonary Hospital(control group).Results(1)The retrospective study showed that pre-treatment TC level was correlated with progression-free survival(PFS)in postoperative patients with early lung cancer,and the patients with high TC level had longer PFS.There was no significant correlation between pre-treatment TG level and PFS in postoperative patients with early lung cancer.The patients with high TG level had higher short-term survival rate while the patients with low TG level had higher long-term survival rate.(2)The prospective study showed that there were nine cases of recurrence in the treatment group and 24 cases of recurrence in the control group till the last follow-up time on April 1,2021.The one-year,two-year,three-year and four-year disease-free survival rates in the treatment group were 99.3％,96.8％,95.7％and 95.7％,respectively,which were superior to 97.6％,92.3％,89.2％and 87.1％in the control group(P＜0.05),indicating that the recurrence and metastasis in the postoperative patients with early lung cancer treated by Fuzheng Quxie Prescription were significantly reduced when compared with the control group,and the disease-free survival rate was significantly improved.After treatment,the serum levels of TC and TG in the treatment group were increased when compared with those before treatment(P＜0.05)while the control group showed no obvious changes(P＞0.05).The intergroup comparison showed that the increase of serum TC and TG levels in the treatment group was superior to that in the control group(P＜0.05),indicating that Fuzheng Quxie Prescription had regulatory effect on the blood lipid level of patients to a certain extent.Conclusion The analysis of the correlation between pre-treatment blood lipids and PFS prognosis in postoperative patients with early lung cancer indicated that lung cancer patients with high TC level had longer PFS;Fuzheng Quxie Prescription can regulate the blood lipid level of postoperative patients with early lung adenocarcinoma.It is speculated that Fuzheng Quxie Prescription may improve the survival prognosis of postoperative patients with early lung cancer probably by regulating the blood lipid level of the patients.