Objective To investigate the dietary structure and nutritional metabolism indicators in patients with type 2 diabetic nephropathy and to analyze the relationship with renal injury. Methods From January 2022 to February 2024, 296 patients with type 2 diabetic nephropathy were included in the hospital for investigation. According to the measurement results of 24h urinary protein quantification, these patients were divided into mild, moderate and severe renal injury groups. The diet, nutritional metabolism and renal injury indicators were compared, and the correlation was analyzed. Results The total energy intake, protein, fat and carbohydrate energy supply ratio were decreased with the aggravation of renal injury while the levels of hemoglobin (Hgb), total protein (TP), globulin (GLB), albumin (ALB), triglyceride (TG) and high density lipoprotein cholesterol (HDL-C) were enhanced (P<0.05), and the total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) were manifested as severe injury group>moderate injury group>mild injury group (P<0.05). Total intake, carbohydrate energy supply ratio, Hgb, TP, GLB, ALB, TG and HDL-C were positively correlated with 24h urinary protein quantification, and the other indicators were negatively correlated with 24h urinary protein quantification (P<0.05). Conclusion The patients with type 2 diabetic nephropathy generally have unreasonable dietary structure and poor nutritional metabolism, both of which are associated with the degree of renal injury. It is recommended to strengthen the diet management, optimize the energy supply ratio, monitor the biochemical indicators and adjust the treatment regimen.

ObjectiveTo establish a tumor prognostic risk assessment model related to target genes of the miR-34 family. MethodsTarget genes of the miR-34 family were screened， and the scores of miR-34 target genes were assessed in 16 tumor types. Univariate Cox regression analysis was used to identify the tumor type with the strongest correlation between miR-34 target gene scores and overall survival （OS）. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses were performed to elucidate the functional roles and signaling pathways of miR-34 target genes. A prognostic risk model based on the miR-34 target genes was constructed using univariate Cox and LASSO regression analyses. Quantitative real-time PCR （qPCR） and dual-luciferase reporter assays were conducted to validate whether the target genes bind to miR-34 and measure their RNA expression levels in the relevant tumors. Additionally， the risk score was integrated with other clinical indicators to develop a nomogram prediction model for patient survival. ResultsA total of 65 target genes of the miR-34 family were screened. The cancer type exhibiting stronger correlation between the target gene scores and OS was lung adenocarcinoma （P = 0.003， HR= 5.150）. Furthermore， miR-34 target genes were predominantly enriched in oxidative stress pathways and various tumor-related processes. Three genes， LDHA， GALNT7， and SATB2， were identified as core components of the prognostic analysis model for lung adenocarcinoma. Additionally， the constructed nomogram model demonstrated robust predictive performance. ConclusionThe risk model and prognosis model of lung adenocarcinoma constructed based on the key target genes of miR-34 have good predictive performance.

Charcoal-processed traditional Chinese herbal medicine has various therapeutic effects， including astringing， hemostasis， anti-diarrhea， clearing heat， tonifying， and warming the interior. This paper summarizes the clinical application features， compatible experiences， dosages， and precautions for over 20 types of charcoal-processed herbal medicine in the treatment of gynecological bleeding disorders caused by dysfunctions such as dysfunctional uterine bleeding， endometriosis， uterine incision pseudocavity， and vaginal bleeding resulting from threatened miscarriage. The charcoal-processed herbal medicine include Huangqin （Scutellaria Baicalensis） Charcoal， Dahuang （Rheum Palmatum） Charcoal， Cebai （Platycladus Orientalis） Charcoal， Diyu （Sanguisorba Officinalis） Charcoal， Daji （Cirsium Setosum） Charcoal， Xiaoji （Cirsium Japonicum） Charcoal， Shengdi （Rehmannia Glutinosa） Charcoal， Aiye （Artemisia Argyi） Charcoal， Paojiang （Zingiber Officinale） Charcoal， Xuduan （Dipsacus Asper） Charcoal， Duzhong （Eucommia Ulmoides） Charcoal， Qiancao （Rubia Cordifolia） Charcoal， Puhuang （Typha Angustifolia） Charcoal， Shanzha （Crataegus Pinnatifida） Charcoal， Jingjie （Schizonepeta Tenuifolia） Charcoal， Xueyu （Carthamus Tinctorius） Charcoal， Zonglyu （Areca Catechu） Charcoal， Wumei （Prunus Mume） Charcoal， Shudahuang （Rheum Officinale） Charcoal， Lianfang （Nymphaea Alba） Charcoal， Mianmaguanzhong （Clematis Armandii） Charcoal， and Oujie （Nelumbo Nucifera） Charcoal.

BACKGROUND:As the end bearing joint of the human body,the ankle joint bears the top-down pressure of the body,which leads to the ankle joint is easy to be damaged in the movement,can induce functional ankle instability,which negatively affects daily life.The study of lower extremity biomechanics in patients with functional ankle instability during counter movement jump is of great significance for scientific training,prevention of ankle injury,and clinical rehabilitation after injury. OBJECTIVE:To investigate the kinetics and kinematics of lower limbs in the longitudinal jumping of functional ankle instability population. METHODS:From March to September 2023,15 male patients with functional ankle instability and 15 healthy people,aged 22-28 years old,were recruited in Soochow University.All subjects completed counter movement jump experiment.Vicon infrared high-speed motion capture system and Kistler three-dimensional force measuring table were used to simultaneously collect the lower limb kinematics and kinetics indexes of the two groups of subjects at the take-off stage of counter movement jump,the instant off the ground,the initial landing moment and the peak moment of vertical ground reaction force. RESULTS AND CONCLUSION:(1)At the instant off the ground,the affected side of the functional ankle instability group showed smaller knee internal rotation moment(P=0.020)and smaller ankle internal rotation moment(P=0.009)compared with the affected side of the healthy control group.(2)At the moment of landing,the affected side of the functional ankle instability group showed a smaller hip flexion angle than the affected side of the healthy control group(P=0.039).Compared with the healthy control group,functional ankle instability group showed smaller hip abduction angle(P=0.022),smaller knee varus angle(P=0.010),larger knee external rotation angle(P=0.021),smaller ankle varus angle(P=0.004),and smaller external ankle rotation angle(P=0.008).(3)At the peak of vertical ground reaction force,functional ankle instability group showed a smaller ankle varus angle than healthy control group(P=0.044).(4)The results showed that the lower limb biomechanical characteristics of the patients with functional ankle instability were abnormal compared with the healthy people during counter movement jump,which mainly showed the changes of the kinematics and kinetics indexes of the lower limb joints in the sagittal plane and the frontal plane at the moment of lift-off and landing.These changes reflect that people with functional ankle instability adopt rigid take-off and landing patterns when performing counter movement jump,tend to transfer the load of the affected ankle joint to other joints of the lower limb,and show compensatory phenomenon of the healthy lower limb.Therefore,detection and correction of abnormal biomechanical features should be a part of rehabilitation training for those with functional ankle instability.

Objective:To establish a quality control method for the standard decoction of Polygoni Avicularis Herba.Methods:Totally 12 batches of decoction pieces from different origins were collected, the standard decoction was prepared and the quality evaluation method was established, the content of index components in the decoction pieces and the standard decoction was determined with HPLC, the index components, solution pH and other parameters were calculated, and the similarity analysis was carried out against the fingerprints.Results:The total content of myricetin in 12 batches of decoction pieces was >0.12%, and the content of myricetin in the standard decoction was >0.03%, which met the standard of the 2020 edition of the Chinese Pharmacopoeia. The pH value was 5.1-5.5, the transfer rate of myricetin components ranged from 50.0%-106.3%, and the fingerprint study showed that there were 7 common peaks. The similarity analysis results indicated that the standard decoction of 12 batches of decoction pieces of Polygoni Avicularis Herba had good consistency.Conclusion:The preparation process is stable and feasible in line with the traditional decoction preparation method, and can be used for the research and quality evaluation of the standard decoction.

Objective To explore the effects of Jingling Oral Liquid(mainly composed of Polygoni Multiflori Radix,Polygonati Rhizoma,Platycladi Semen,Nelumbinis Semen,Ligustri Lucidi Fructus,Poria,and Lilii Bulbus)as an adjunctive therapy on cognitive,motor,and social abilities in children with global developmental delay(GDD).Methods A total of 120 children with GDD who visited the Department of Neurological Rehabilitation at Hebei Children's Hospital from July 2021 to November 2023 were selected as the study subjects.The children were randomly divided into a control group and a trial group using a random number table,with 60 children in each group.The control group received conventional comprehensive rehabilitation training,while the trial group received Jingling Oral Liquid as an adjunctive therapy in addition to the control group's treatment.The treatment course lasted 12 weeks.Before and after treatment,the changes in Gesell Developmental Scale(GDS)scores,Peabody Developmental Motor Scales(PDMS)scores,motor function scores,and language ability scores in both groups were observed to evaluate the cognitive,motor,and social abilities of the children.Results(1)After treatment,the scores of all dimensions of the GDS,including adaption,developmental quotient of fine motor,language developmental quotient,and personal-social developmental quotient,were significantly increased in both groups compared to those before treatment(P＜0.01),and the improvement of GDS scores in the trial group was significantly superior to that in the control group(P＜0.01).(2)After treatment,the scores of all dimensions of the PDMS,including fine developmental quotient score,standardized score of visual-motor integration,and standardized score of grasping,were significantly increased in both groups compared to those before treatment(P＜0.01),and the improvement of PDMS scores in the trial group was significantly superior to that in the control group(P＜0.01).(3)After treatment,the scores of motor function indicators of fine motor quotient(FMQ),gross motor quotient(GMQ),and total motor quotient(TMQ)were significantly increased in both groups compared to those before treatment(P＜0.01),and the improvement of motor function scores in the trial group was significantly superior to that in the control group(P＜0.01).(4)After treatment,the language ability scores were significantly increased in both groups compared to those before treatment(P＜0.01),and the improvement of language ability scores in the trial group was significantly superior to that in the control group(P＜0.01).Conclusion The combination of Jingling Oral Liquid with conventional comprehensive rehabilitation training can effectively improve the cognitive,motor,and social abilities of children with GDD.

Objective: To investigate the mechanism of miR-224-5p on proliferation, apoptosis, invasion and migration of human hepatocellular carcinoma HepG2 cells. Methods : The RNA expression levels of miR-224-5p and early growth responsive gene 2(EGR2) in patients with hepatocellular carcinoma were obtained from the TCGA dataset. Normal human hepatocytes LO2 and hepatoma cells HepG2 were cultured in vitro, and the HepG2 cells were transfected with lentiviral vectors(knockdown of miR-224-5p), small interfering RNA fragments or overexpression vectors(interference and overexpression of EGR2). The expression levels of miR-224-5p and EGR2 in hepatocellular carcinoma cDNA chips and cells were detected by quantitative real-time PCR(qPCR). The expression level of EGR2 protein was detected by Western blot. Dual luciferase reporter gene assay was used to detect the binding of miR-224-5p to EGR2. HepG2 cells positive rate were detected by EdU assay, apoptosis rate was detected by flow cytometry, cell invasion number was detected by Transwell assay, and cell mobility was detected by scratch assay. Results : Compared with paracancerous tissues, the expression of miR-224-5p was increased and the expression of EGR2 mRNA decreased in HCC tissues. Compared with LO2 group, the expression of miR-224-5p in HepG2 cells increased, and the expression of EGR2 mRNA and protein decreased. Compared with the Lv-sh-NC group, the 24 h EdU positive cell rate, cell invasion number, and 48 h cell mobility of HepG2 cells in the Lv-sh-miR-224-5p group decreased, while the apoptosis rate increased. Compared with Oe-NC group, 24 h EdU positive cell rate, cell invasion number, and 48 h cell mobility of HepG2 cells in Oe-EGR2 group decreased, while apoptosis rate increased. Compared with Lv-sh-NC group, the expression of EGR2 protein in Lv-sh-miR-224-5p group increased. Compared with Lv-sh-miR-224-5p+si-NC group, 24 h EdU positive cell rate, cell invasion rate, and 48 h cell mobility of HepG2 cells in Lv-sh-miR-224-5p+si-EGR2 group increased, while apoptosis number decreased. Conclusion miR-224-5p can promote proliferation, invasion, and migration of HepG2 cells and inhibit apoptosis via binding with EGR2.

OBJECTIVES: Acute lung injury (ALI) is an acute respiratory failure syndrome characterized by impaired gas exchange. Due to the lack of effective targeted drugs, it is associated with high mortality and poor prognosis. Tripterygium wilfordii (TW) has demonstrated anti-inflammatory activity in the treatment of various diseases. This study aims to investigate the effects and underlying mechanisms of TW on myeloid-derived suppressor cells (MDSCs) in ALI, providing experimental evidence for TW as a potential adjuvant therapy for ALI. METHODS: Eighteen specific pathogen-free (SPF) C57BL/6 mice were randomly divided into normal control (NC; intranasal saline), lipopolysaccharide (LPS; 5 mg/kg intranasally to induce ALI), and LPS+TW (50 mg/kg TW by gavage on the first day of modeling, followed by 5 mg/kg LPS intranasally to induce ALI) groups (n=6 each). Lung injury and edema were assessed by histopathological scoring and wet-to-dry weight ratio. Cytokine levels [interleukin (IL)-1β, IL-6, IL-18, tumor necrosis factor-α (TNF-α)] in lung tissue lavage fluid were measured by enzyme-linked immunosorbent assay (ELISA). Flow cytometry was used to assess the proportions of MDSCs, polymorphonuclear MDSCs (PMN-MDSCs), and monocytic MDSCs (M-MDSCs) in bone marrow, spleen, peripheral blood, and lung tissue, as well as reactive oxygen species (ROS) levels in lung tissues. Messenger RNA (mRNA) expression levels of inducible nitric oxide synthase (iNOS) and arginase-1 (ARG-1) in lung tissues were determined by real-time fluorescence quantitative polymerase chain reaction (RT-qPCR). PMN-MDSCs sorted from the lungs of LPS-treated mice were co-cultured with splenic CD3⁺ T cells and divided into NC, triptolide (TPL)-L, and TPL-H groups, with bovine serum albumin, 25 nmol/L TPL, and 50 nmol/L TPL, respectively. Flow cytometry was used to detect the effect of PMN-MDSCs on T-cell proliferation, and RT-qPCR was used to measure iNOS and ARG-1 mRNA expression. RESULTS: Compared with the NC group, the LPS group showed marked lung pathology with significantly increased histopathological scores and wet-to-dry ratios (both P<0.001). TW treatment significantly alleviated lung injury and reduced both indices compared with the LPS group (both P<0.05). Cytokine levels were significantly decreased in the LPS+TW group compared with the LPS group (all P<0.001). The proportions of MDSCs in CD45⁺ cells from spleen, bone marrow, peripheral blood, and lung, as well as PMN-MDSCs from spleen, peripheral blood, and lung, were significantly reduced in the LPS+TW group compared with the LPS group (all P<0.05), accompanied by reduced ROS levels in lung tissues (P<0.001). iNOS and ARG-1 mRNA expression in lung tissues was significantly lower in the LPS+TW group than in the LPS group (both P<0.001). In vitro, compared with the TPL-L group, the TPL-H group showed significantly increased CD3⁺ T-cell proliferation (P<0.001), and decreased iNOS and ARG-1 mRNA expression (all P<0.05). CONCLUSIONS TW alleviates the progression of LPS-induced ALI in mice, potentially by reducing the proportion of MDSCs in lung tissues and attenuating the immunosuppressive function of PMN-MDSCs.
Animals ; Acute Lung Injury/chemically induced* ; Myeloid-Derived Suppressor Cells/cytology* ; Tripterygium/chemistry* ; Mice, Inbred C57BL ; Mice ; Cell Differentiation/drug effects* ; Male ; Lipopolysaccharides ; Nitric Oxide Synthase Type II/genetics* ; Cytokines/metabolism* ; Reactive Oxygen Species/metabolism* ; Diterpenes/pharmacology* ; Epoxy Compounds ; Phenanthrenes

Alzheimer's disease (AD) is the major form of dementia in the elderly and is closely related to the toxic effects of microglia sustained activation. In AD, sustained microglial activation triggers impaired synaptic pruning, neuroinflammation, neurotoxicity, and cognitive deficits. Accumulating evidence has demonstrated that aberrant expression of deubiquitinating enzymes is associated with regulating microglia function. Here, we use RNA sequencing to identify a deubiquitinase YOD1 as a regulator of microglial function and AD pathology. Further study showed that YOD1 knockout significantly improved the migration, phagocytosis, and inflammatory response of microglia, thereby improving the cognitive impairment of AD model mice. Through LC-MS/MS analysis combined with Co-IP, we found that Myosin heavy chain 9 (MYH9), a key regulator maintaining microglia homeostasis, is an interacting protein of YOD1. Mechanistically, YOD1 binds to MYH9 and maintains its stability by removing the K48 ubiquitin chain from MYH9, thereby mediating the microglia polarization signaling pathway to mediate microglia homeostasis. Taken together, our study reveals a specific role of microglial YOD1 in mediating microglia homeostasis and AD pathology, which provides a potential strategy for targeting microglia to treat AD.

OBJECTIVES: To investigate the regulatory role of nucleotide-bound oligomerized domain-like receptor containing pyrin-domain protein 6 (NLRP6) in liver lipid metabolism and non-alcoholic fatty liver disease (NAFLD). METHODS: Mouse models with high-fat diet (HFD) feeding for 16 weeks (n=6) or with methionine choline-deficient diet (MCD) feeding for 8 weeks (n=6) were examined for the development of NAFLD using HE and oil red O staining, and hepatic expressions of NLRP6 were detected with RT-qPCR, Western blotting, and immunohistochemical staining. Cultured human hepatocytes (LO2 cells) with adenovirus-mediated NLRP6 overexpression or knock-down were treated with palmitic acid (PA) in the presence or absence of compound C (an AMPK inhibitor), and the changes in cellular lipid metabolism were examined by measuring triglyceride, ATP and β-hydroxybutyrate levels and using oil red staining, RT-qPCR, and Western blotting. RESULTS: HFD and MCD feeding both resulted in the development of NAFLD in mice, which showed significantly decreased NLRP6 expression in the liver. In PA-treated LO2 cells, NLRP6 overexpression significantly decreased cellular TG content and lipid deposition, while NLRP6 knockdown caused the opposite effects. NLRP6 overexpression in PA-treated LO2 cells also increased mRNA and protein expressions of PGC1A and CPT1A, levels of ATP and β-hydroxybutyrate, and the phosphorylation level of AMPK pathway; the oxidative decomposition of lipids induced by Ad-NLRP6 was inhibited by the use of AMPK inhibitors. CONCLUSIONS NLRP6 overexpression promotes lipid oxidation and decomposition through AMPK/CPT1A/PGC1A to alleviate lipid deposition in hepatocytes.
Non-alcoholic Fatty Liver Disease/metabolism* ; Animals ; Hepatocytes/metabolism* ; Lipid Metabolism ; Mice ; Humans ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ; AMP-Activated Protein Kinases/metabolism* ; Carnitine O-Palmitoyltransferase/metabolism* ; Diet, High-Fat ; Male ; Mice, Inbred C57BL ; Signal Transduction