BACKGROUND:Bone relies on the close connection between blood vessels and bone cells to maintain its integrity.Bones are in a physiologically hypoxic environment.Therefore,the study of angiogenesis and osteogenesis in hypoxic environment is closer to the microenvironment in vivo. OBJECTIVE:To explore the influence of Wenshen Tongluo Zhitong(WSTLZT)formula on H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell co-culture system in hypoxia environment and its related mechanism. METHODS:Enzyme digestion method and flow sorting technique were used to isolate and identify H-type bone microvascular endothelial cells.Mouse bone marrow mesenchymal stem cells were isolated and obtained by bone marrow adhesion method.H-type bone microvascular endothelial cell/bone marrow mesenchymal stem cell hypoxic co-culture system was established using Transwell chamber and anoxic culture workstation.WSTLZT formula powder was used to intervene in each group at a mass concentration of 50 and 100 μg/mL.The angiogenic function of H-type bone microvascular endothelial cells in the co-culture system was evaluated by scratch migration test and tube formation test.The osteogenic differentiation ability of bone marrow mesenchymal stem cells in the co-cultured system was evaluated by alkaline phosphatase staining and alizarin red staining.The protein and mRNA expression changes of PDGF/PI3K/AKT signal axis related molecules in H-type bone microvascular endothelial cells in the co-cultured system were detected by Western Blotting and q-PCR,respectively. RESULTS AND CONCLUSION:(1)Compared with the normal oxygen group,the scratch mobility and new blood vessel length of H-type bone microvascular endothelial cells were significantly higher(P<0.05);the osteogenic differentiation capacity of bone marrow mesenchymal stem cells was higher(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular protein and mRNA increased(P<0.05)in the hypoxia group.(2)Compared with the hypoxia group,scratch mobility and new blood vessel length were significantly increased in the H-type bone microvascular endothelial cells(P<0.05);bone marrow mesenchymal stem cells had stronger osteogenic function(P<0.05);the expression of PDGF/PI3K/AKT axis-related molecular proteins and mRNA further increased(P<0.05)after treatment with different dose concentrations of WSTLZT formula.These findings conclude that H-type angiogenesis and osteogenesis under hypoxia may be related to the PDGF/PI3K/AKT signaling axis,and WSTLZT formula may promote H-type vasculo-dependent bone formation by activating the PDGF/PI3K/AKT signaling axis,thereby preventing and treating osteoporosis.

The doctor-patient relationship is a set of social relationships based on shared interests， mutual trust， and emotional bonds， to relieve illnesses and promote health. However， the doctor-patient relationship often falls into tensions and conflicts. How to build a trusting and harmonious doctor-patient destiny community has become one of the most important issues of concern to the whole society. Based on the biopsychosocial concept of disease， the emotion management technique （EMT） emphasizes that doctors take the patient’s emotion as a clue in clinical diagnosis and treatment， regard emotions as one of the important indicators for disease diagnosis， understand the emotional events behind the disease， and provide patients with appropriate empathy and emotional management， so as to provide clinical methods for managing diseases and building a trusting and harmonious doctor-patient relationship.

Acute lung injury (ALI) is a significant complication of sepsis, characterized by high morbidity, mortality, and poor prognosis. Neutrophils, as critical intrinsic immune cells in the lung, play a fundamental role in the development and progression of ALI. During ALI, neutrophils generate neutrophil extracellular traps (NETs), and excessive NETs can intensify inflammatory injury. Research indicates that Taohe Chengqi decoction (THCQD) can ameliorate sepsis-induced lung inflammation and modulate immune function. This study aimed to investigate the mechanisms by which THCQD improves ALI and its relationship with NETs in sepsis patients, seeking to provide novel perspectives and interventions for clinical treatment. The findings demonstrate that THCQD enhanced survival rates and reduced lung injury in the cecum ligation and puncture (CLP)-induced ALI mouse model. Furthermore, THCQD diminished neutrophil and macrophage infiltration, inflammatory responses, and the production of pro-inflammatory cytokines, including interleukin-1β (IL-1β), IL-6, and tumor necrosis factor α (TNF-α). Notably, subsequent experiments confirmed that THCQD inhibits NET formation both in vivo and in vitro. Moreover, THCQD significantly decreased the expression of peptidyl arginine deiminase 4 (PAD4) protein, and molecular docking predicted that certain active compounds in THCQD could bind tightly to PAD4. PAD4 overexpression partially reversed THCQD's inhibitory effects on PAD4. These findings strongly indicate that THCQD mitigates CLP-induced ALI by inhibiting PAD4-mediated NETs.
Extracellular Traps/immunology* ; Acute Lung Injury/immunology* ; Animals ; Sepsis/immunology* ; Drugs, Chinese Herbal/pharmacology* ; Mice ; Neutrophils/immunology* ; Male ; Protein-Arginine Deiminase Type 4/genetics* ; Mice, Inbred C57BL ; Humans ; Disease Models, Animal ; Cytokines/metabolism*

Nonalcoholic steatohepatitis （NASH） is a chronic liver disease with the main pathological features of hepatic steatosis， inflammatory cell infiltration， and interstitial fibroplasia， and it is an important risk factor for liver fibrosis， liver cirrhosis， and hepatocellular carcinoma. NOD-like receptor protein 3 （NLRP3） inflammasome is the core of innate immunity， and the abnormal activation of NLRP3 inflammasome is closely associated with the development and progression of NASH， which involves multiple links such as inflammatory response and oxidative stress. A large number of studies have shown that the active ingredients of traditional Chinese medicine （TCM） and TCM compound prescriptions can improve oxidative stress， regulate lipid metabolism， and alleviate liver inflammation by regulating NLRP3 inflammasome. TCM treatment applied in clinical practice has achieved a good therapeutic effect， while inflammasome is one of the key pathways or targets for TCM in improving NASH. This article reviews the mechanism of action of NLRP3 inflammasome in NASH and the research advances in TCM intervention of NLRP3 inflammasome， in order to provide ideas for the clinical TCM treatment of NASH， as well as reference targets and research directions for the research and development of new TCM drugs.

Objective: To investigate the characteristics of temporal and spatial distribution of tuberculosis epidemics in Shache County, Kashgar Region, Xinjiang. Methods: Information on the incidence of tuberculosis in Sacha County from 2019—2021 was collected and spatiotemporally analyzed by applying the circular distribution method, local spatial autocorrelation analysis, hot and cold spot analysis, directional distribution and spatial center of gravity methods. Results : The total number of tuberculosis cases in Shache County in 2019—2021 was 8 345, of which 52.03%were male and 47.97% were female, and the patients were predominantly 60-75 years old. The number of reported incidences of TB in Tagarqi Township, Shache Township, and Chajek Township ranked among the top three in the county. Spring and summer were the disease-prone seasons for TB, and mid-March to mid-July was the period of high disease incidence. Misha Township and Ishkuli Township are the “high and high” gathering areas, while the “low and low” gathering areas are mainly concentrated in Khoshrav Township and Karasu Township. The hotspots of TB incidence in Shache county were Tagarqi township, Misha township, and Ishkuli township. During the study period, the center of gravity of TB incidence in Shache county of Kashgar area gradually shifted from the southwest to the northeast. Conclusion In Shache county, there is a certain degree of aggregation of tuberculosis outbreaks, with more men than women reporting illnesses, a larger proportion of older people, and a strong seasonal incidence of the disease, with Mixia township and Ishikuli township being the key areas of incidence. Relevant departments should continue to strengthen the disease surveillance of key populations and regions during the high incidence of tuberculosis, and take appropriate intervention measures to reduce the risk of tuberculosis transmission.

Objective To investigate the relationship between interleukin-1β (IL-1β) and miR-185-5p in the process of joint injury in acute gouty arthritis (AGA). Methods The serum miR-185-5p levels of 89 AGA patients and 91 healthy volunteers were detected by real-time quantitative PCR. The correlation between miR-185-5p expression level and VAS score or IL-1β expression level was evaluated by Pearson correlation coefficient method. Receiver operating characteristic (ROC) curve was used to evaluate the diagnostic value of miR-185-5p in AGA. THP-1 cells were induced by sodium urate (MSU) to construct an in vitro acute gouty inflammatory cell model. After the expression level of miR-185-5p in THP-1 cells was upregulated or downregulated by transfection of miR-185-5p mimics or inhibitors in vitro, inflammatory cytokines of THP-1 cells, such as IL-1β, IL-8 and tumor necrosis factor α (TNF-α), were detected by ELISA. The luciferase reporter gene assay was used to determine the interaction between miR-185-5p and the 3'-UTR of IL-1β. Results Compared with the healthy control group, the expression level of serum miR-185-5p in AGA patients was significantly reduced. The level of serum miR-185-5p was negatively correlated with VAS score and IL-1β expression level. The area under the curve (AUC) was 0.905, the sensitivity was 80.17% and the specificity was 83.52%. Down-regulation of miR-185-5p significantly promoted the expression of IL-1β, IL-8 and tumor necrosis factor (TNF-α), while overexpression of miR-185-5p showed the opposite results. Luciferase reporter gene assay showed that IL-1β was the target gene of miR-185-5p, and miR-185-5p negatively regulated the expression of IL-1β. Conclusion miR-185-5p alleviates the inflammatory response in AGA by inhibiting IL-1β.
Humans ; 3' Untranslated Regions ; Arthritis, Gouty/genetics* ; Interleukin-1beta/genetics* ; Interleukin-8 ; Luciferases ; MicroRNAs/genetics* ; Tumor Necrosis Factor-alpha

Objective:To investigate long-term auditory changes and characteristics of Alport syndrome（AS） patients with different degrees of renal injury. Methods:Retrospectively analyzing clinical data of patients diagnosed AS from January 2007 to September 2022, including renal pathology, genetic detection and hearing examination. A long-term follow-up focusing on hearing and renal function was conducted. Results:This study included 70 AS patients, of which 33（25 males, 8 females, aged 3.4-27.8 years） were followed up, resulting in a loss rate of 52.9%.The follow-up period ranged from 1.1to 15.8 years, with 16 patients followed-up for over 10 years. During the follow-up, 10 patients presenting with hearing abnormalities at the time of diagnosis of AS had progressive hearing loss, and 3 patients with new hearing abnormalities were followed up, which appeared at 5-6 years of disease course. All of which were sensorineural deafness. While only 3 patients with hearing abnormalities among 13 patients received hearing aid intervention. Of these patients,7 developed end-stage renal disease（ESRD）, predominantly males （6/7）. The rate of long-term hearing loss was significantly different between ESRD group and non-ESRD group（P=0.013）. There was no correlation between the progression of renal disease and long-term hearing level（P>0.05）. kidney biopsies from 28 patients revealed varying degrees of podocyte lesion and uneven thickness of basement membrane. The severity of podocyte lesion was correlated with the rate of long-term hearing loss（P=0.048）, and there was no correlation with the severity of hearing loss（P>0.05）. Among 11 cases, theCOL4A5mutationwas most common （8 out of 11）, but there was no significant correlation between the mutation type and hearing phenotype（P>0.05）. Conclusion:AS patients exhibit progressive hearing loss with significant heterogeneity over the long-term.. THearing loss is more likely to occur 5-6 years into the disease course. Hearing abnormalities are closely related to renal disease status, kidney tissue pathology, and gene mutations, emphasizing the need for vigilant long-term hearing follow-up and early intervention.
Male ; Child ; Female ; Humans ; Nephritis, Hereditary/pathology* ; Retrospective Studies ; Kidney ; Deafness ; Hearing Loss/genetics* ; Kidney Failure, Chronic/pathology* ; Mutation

Objective To investigate the effects of nuclear respiratory factor 1(NRF1)on mitochondrial and cog-nitive dysfunction in Alzheimer's disease(AD)model mice.Methods The 5 × FAD mice were utilized as a mod-el for Alzheimer's disease,and the sparsely labeled AAV virus overexpressing NRF1(AAV-NRF1)was adminis-tered via stereotaxic injection into the brain.The expression of NRF1 in hippocampus was determined by Western blot,the morphology of mitochondria in hippocampus was observed by transmission electron microscope,the den-dritic spines of sparsely labeled neurons in the CA1 region were visualized and quantified using confocal laser mi-croscopy,cognitive and memory functions of mice were evaluated using the Morris water maze test,while electro-physiological methods were employed to detect long-term potentiation(LTP)of synaptic efficacy.Results The ex-pression of NRF1 in the hippocampus was significantly upregulated following stereotactic injection of AAV-NRF1(P＜0.001).This intervention led to notable improvements in mitochondrial morphology within hippocampal neurons,as well as enhanced cognitive and memory functions in mice(P＜0.01).Moreover,there was a significant in-crease in dendritic spine density among neurons located in the CA1 region of the hippocampus(P＜0.001),ac-companied by long-lasting and stable long-term potentiation(LTP)and a substantial elevation in fEPSP slope(P＜0.01).Conclusion The overexpression of NRF1 in a 5 × FAD mouse model of Alzheimer's disease(AD)initia-ted the restoration of mitochondrial dysfunction and enhanced synaptic plasticity,indicating that these alterations may contribute to the therapeutic efficacy of NRF1 overexpression in ameliorating cognitive dysfunction associated with AD.

OBJECTIVE To analyze the factors affecting the inclusion of Chinese patent medicines in China’s National reimbursement drug list （NRDL）， and assist these medicines in fully reflecting their actual value in the reimbursement admission process. METHODS From the official website of the China’s National Healthcare Security Administration， the application materials of Chinese patent medicines outside the list that passed the formal review from 2021 to 2023 were obtained， including basic information on the medicines， safety， efficacy， innovation and heritage information， and supplemented with references from the pharmacopeia and the Yaozhi Database. Economic information and enterprise information were obtained through websites such as the Yaozhi Database. Univariate analysis， multivariate Logistic regression analysis and stepwise regression analysis were conducted on the initial application information and admission outcomes of the medicines. Sensitivity analysis was also performed on medicines that applied multiple times in different years as independent samples. RESULTS & CONCLUSIONS There were 27 Chinese patent medicines that passed the formal review from 2021 to 2023， involving 37 applications. The univariate analysis results showed that medicines with descriptions of traditional Chinese medicine （TCM） syndrome types， clear adjustment information for medication plans for specific population groups， short time to market in the indications of the package insert， registered as Class 1 to 6 following or class Ⅰ innovative TCM/class Ⅲ ancient classic prescription compound TCM registered， and those produced by enterprises listed in the “Top 100 Chinese Pharmaceutical Industry Enterprises” list for the current year were more likely to be included in the NRDL （P＜0.05）. The results of the multivariate Logistic regression analysis were not statistically significant， but the stepwise regression results indicated good consistency with the univariate analysis. The results of the sensitivity analysis were consistent with the trend of basic analysis. It is recommended that Chinese patent medicine enterprises further clarify the description of product instructions， expand innovation capabilities， inherit and develop ancient classic prescriptions， and promptly complete clinical trial evidence.

Objective:This study aimed to compare the audiological characteristics between children with unilateral auditory neuropathy (UAN) and single-sided deafness (SSD) to establish a valid basis for the differential diagnosis of children with UAN.Methods:A retrospective analysis was conducted on audiological and imaging evaluations of children with UAN and SSD who were treated at Beijing Children′s Hospital of Capital Medical University between May 2015 and June 2023. There were 17 children with UAN, comprising 10 males and 7 females, with an average age of 4.7 years. Additionally, there were 43 children with SSD, consisting of 27 males and 16 females, with an average age of 6.5 years. Audiological assessments included Auditory brainstem response (ABR), Steady-state auditory evoked potential (ASSR), Behavioural audiometry, Cochlear microphonic potential (CM), Distortino-product otoacoustic emission (DPOAE), and acoustic immittance test. The results of the audiological assessment and imaging phenotypic between the two groups of children were compared and analyzed by applying SPSS 27.0 statistical software.Results:(1) The UAN group (77.8%) had a significantly higher rate of ABR wave III L than the SSD group (20.9%) ( P<0.01). The PA thresholds at 500 Hz and 1 000 Hz of children with SSD were higher than those of children with UAN, while the ASSR thresholds at 500 Hz, 1000 Hz, 2 000 Hz, and 4 000 Hz of children with SSD were significantly higher than those of children with UAN ( P<0.05). (2) The degree of hearing loss in both UAN and SSD children was predominantly complete hearing loss. The percentage of complete hearing loss was significantly higher (χ2=4.353, P=0.037) in the SSD group (93.0%, 40/43) than in the UAN group (63.6%, 7/11). However, the percentage of profound hearing loss was significantly higher in the UAN group (27.3%, 3/11) than in the SSD group (2.3%, 1/43) ( Fisher′s exact test, P=0.023). In terms of hearing curve configuration, the percentage of flat type was significantly higher in the SSD group (76.7%, 33/43) than in the UAN group (36.4%, 4/11). The proportion of the UAN group (27.3%, 3/11) was significantly higher than that in the SSD group (2.3%, 1/43) in ascending type ( P<0.05). There were no statistically significant differences in the hearing curves of the declining type and other types between the two groups ( P>0.05). (3) The proportion of imaging assessment without abnormality was significantly more common in the UAN group (81.8%) than in the SSD group (37.1%) (χ2=6.695, P=0.015). Conclusions:Compared to children with SSD, the occurrence of wave III L on the ABR test was significantly more common in children with UAN. The percentage of ascending hearing curves was significantly higher in children with UAN than in children with SSD. ASSR thresholds were significantly lower in children with UAN. The normal imaging phenotype was significantly more common in children with UAN than in children with SSD.