BACKGROUND:A previous study by our group found that protein phosphatase 2Cm(PP2Cm)null mice developed significantly fewer symptoms of renal failure relative to wild-type mice,and thus it was speculated that PP2Cm may play an important protective role in the development of renal fibrosis,however,the molecular mechanisms remain undefined. OBJECTIVE:To investigate the effect of the PP2Cm gene on the transcriptome of human renal tubular epithelial cells. METHODS:Cultured human renal tubular epithelial cells were transfected with the PP2Cm gene into human renal tubular epithelial cells using plasmids.The expression of PP2Cm in the cells was detected by fluorescence quantitative PCR assay and western blot assay,and subsequently,cell RNA was separately extracted for transcriptome sequencing to look for differentially expressed genes between transfected and control groups.The resulting differential genes were further subjected to GO analysis and KEGG analysis using bioinformatics methods. RESULTS AND CONCLUSION:There were 796 differentially expressed genes,553 of which were downregulated genes and 243 upregulated genes,in human renal tubular epithelial cells transfected with the PP2Cm gene compared with untransfected blank cells by sequencing analysis.GO analysis results showed that the upregulated genes were significantly enriched in cellular biosynthetic processes,protein translation,intrinsic apoptotic signaling pathways,and so on.The downregulated expressed genes were significantly enriched in endothelial cell proliferation,cell adhesion and other signaling pathways.KEGG analysis results showed that the significantly up-regulated genes were enriched in metabolism-related signaling pathways such as amino acid metabolism and biosynthesis.The downregulated expressed genes were significantly enriched in signaling pathways such as pantothenate and coenzyme A biosynthesis.Our results show that PP2Cm overexpression can affect a number of signaling pathways related to a range of biological processes in renal tubular epithelial cells,which may be important in metabolism-related signaling pathways such as amino acid metabolism and biosynthesis.

Objective To study the pharmacokinetic characteristics of buspirone hydrochloride tablets in healthy adult populations under conditions of fasting and postprandial administration.Methods A single-center,randomized,three-cycle partially repeated crossover trial design was adopted,and 36 subjects were enrolled on fasting/postprandial,one tablet of the test preparation was taken in one cycle,one tablet of reference preparation(5 mg of buspirone tablets)was taken once in each of 2 cycles,the drug concentration of buspirone in plasma was determined by liquid chromatography-tandem mass spectrometry,and the pharmacokinetic parameters were calculated by WinNonlin software.Results Main pharmacokinetics of buspirone after oral administration of test and reference preparations in fasting group,the Cmax was(285.72±286.08)and(308.94±341.03)pg·mL-1;AUC0-t were(577.09±491.10)and(618.62±642.56)pg·mL-1·h;AUC0-∞ were(586.85±510.04)and(655.92±687.95)pg·mL-1·h;tmax was 0.75(0.33-4.00)and 0.75(0.33-1.75)h.Main pharmacokinetics of buspirone after oral administration of test and reference preparations in the postprandial group,the Cmax were(676.36±603.64)and(760.33±610.27)pg·mL-1;AUC0-t were(1 755.58±1 001.69)and(1 743.00±1 073.33)pg·h·mL-1;AUC0-∞ were(1 839.97±1 044.60)and(1 818.00±1 106.95)pg·mL-1·h;tmax was 1.25(0.25-4.50)and 1.00(0.25-3.50)h.The 90％confidence intervals of the AUC0-t and AUC0-∞ geometric mean ratios of the test preparation and the reference preparation in the fasting test and the postprandial test all fell between 80.00％and 125.00％,and the 95％upper confidence limit of of Cmax was ≤0 and geometric mean ratios point estimates fall between 80.00％and 125.00％.Conclusion Two kinds of buspirone hydrochloride are bioequivalent in Chinese healthy adult subject.

The current situation of medical simulation technology was introduced when applied in medical service of foreign armies.The current situation and problems of medical simulation technology in mobile medical service detachment training of the PLA were described.Some suggestions were put forward including completing medical simulation management system,optimizing personnel managment and training mode and promoting standardization and modular construction of medical simulation system.References were provided for enhancing combat-oriented training and medical service support capability of levels of medical service institutions and mobile medical service detachment of the PLA.[Chinese Medical Equipment Journal,2024,45(10):88-92]

Jumonji domain-containing protein D3(JMJD3)is a 2-oxoglutarate-dependent dioxygenase that specif-ically removes transcriptional repression marks di-and tri-methylated groups from lysine 27 on histone 3(H3K27me2/3).The erasure of these marks leads to the activation of some associated genes,thereby influencing various biological processes,such as development,differentiation,and immune response.However,comprehensive descriptions regarding the relationship between JMJD3 and inflammation are lacking.Here,we provide a comprehensive overview of JMJD3,including its structure,functions,and involvement in inflammatory pathways.In addition,we summarize the evidence supporting JMJD3's role in several inflammatory diseases,as well as the potential therapeutic applications of JMJD3 inhibitors.Additionally,we also discuss the challenges and opportunities associated with investigating the functions of JMJD3 and developing targeted inhibitors and propose feasible solutions to provide valuable insights into the functional exploration and discovery of potential drugs targeting JMJD3 for inflammatory diseases.

Objective To investigate the nutritional status of children with cystic fibrosis(CF)and understand the correlation between malnutrition and clinical characteristics as well as lung function.Methods A retrospective analysis was performed on clinical data of CF children admitted from January 2016 to June 2023.Clinical characteristics of CF children with different nutritional statuses were compared,and the correlation between malnutrition and lung function was analyzed.Results A total of 52 CF children were included,comprising 25 boys(48％)and 27 girls(52％),aged between 7 months and 17 years.Respiratory symptoms were the predominant clinical manifestations(96％,50/52).The prevalence of malnutrition was 65％(34/52),with moderate/severe malnutrition being the most common(65％,22/34).The malnutrition group had a longer duration of illness,higher proportion of digestive system symptoms,and lower levels of serum albumin(P＜0.05).Pulmonary function parameters,including forced expiratory volume in one second as a percentage of the predicted value,ratio of forced expiratory volume in one second to forced vital capacity,forced expiratory flow at 25％of forced vital capacity exhaled,forced expiratory flow at 50％of forced vital capacity exhaled,forced expiratory flow at 75％of forced vital capacity exhaled,and maximum mid-expiratory flow as a percentage of the predicted value,were lower in the malnutrition group compared to the normal nutrition group(P＜0.05).Correlation analysis showed body mass index Z-score was positively correlated with the above six pulmonary function parameters(P＜0.05).Conclusions The prevalence of malnutrition is high in CF children and is associated with decreased lung function.CF children with higher body mass index have better lung function.Therefore,screening and evaluation of nutritional status as well as appropriate nutritional intervention should be emphasized in CF children.[Chinese Journal of Contemporary Pediatrics,2024,26(3):275-281]

Hemophilic arthritis(HA),caused by recurrent bleeding,can seriously affect patient quality of life and consumes extensive social and medical resources.There is thus a need to establish an animal model of HA for research;however,this is limited by ethical requirements.Here we review the recent literature and summarize research progress into animal models of HA at home and abroad,from the aspects of species selection,modeling method,histopathology,and imaging evaluation method.Species selection includes rodents such as mice,New Zealand rabbits,beagles,miniature pigs,and crab-eating macaques.Modeling method comprise gene knockout trauma models,gene knockout spontaneous models,and injection models.Among these,the gene knockout spontaneous model closely mimics the pathological process of spontaneous bleeding and concurrent arthritis in human HA,making it more relevant to human HA.However,due to high modeling costs,phenotypic instability,and low survival rates,this model is not the preferred choice for animal experimental studies.In contrast,gene knockout trauma models exhibit characteristics such as short modeling time,strong stability,and high success rates,thus being widely utilized in animal experimental research.Evaluation of HA models involves various imaging method including MRI,micro-CT,MSKUS/PD,in addition to various gross scoring method.By reviewing the progress of HA model research,more experimental evidence is provided for investigating the pathogenesis and validating the efficacy of HA treatments,thereby compensating for the lack of clinical data,particularly in the field of traditional Chinese medicine therapy.

NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors, but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown. Besides, the WW domain containing proteins can be recognized by NDFIP1, resulted in the loading of the target proteins into exosomes. However, whether WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) can be packaged into exosomes by NDFIP1 and if so, whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent. Here, we first found that NDFIP1 was low expressed in NSCLC samples and cell lines, which is associated with shorter OS. Then, we confirmed the interaction between TAZ and NDFIP1, and the existence of TAZ in exosomes, which requires NDFIP1. Critically, knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate. And the cellular TAZ level could be altered by exosome secretion. Furthermore, NDFIP1 inhibited proliferation in vitro and in vivo, and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout. Moreover, TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples, and the serum exosomal TAZ level was lower in NSCLC patients. In summary, our data uncover a new tumor suppressor, NDFIP1 in NSCLC, and a new exosome-related regulatory mechanism of TAZ.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Carrier Proteins/metabolism* ; Cell Line ; Cell Proliferation ; Exosomes/metabolism* ; Lung Neoplasms/genetics* ; Membrane Proteins/metabolism* ; Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism*

Purpose: We aimed to analyze the optimal timing of enteral nutrition (EN) in the treatment of sepsis and its effect on sepsis-associated acute kidney injury (SA-AKI.) Materials and Methods: The MIMIC-III database was employed to identify patients with sepsis who had received EN. With AKI as the primary outcome variable, receiver operating characteristic (ROC) curves were utilized to calculate the optimal cut-off time of early EN (EEN). Propensity score matching (PSM) was employed to control confounding effects. Logistic regressions and propensity score-based inverse probability of treatment weighting were utilized to assess the robustness of our findings. Comparisons within the EEN group were performed. Results: 2364 patients were included in our study. With 53 hours after intensive care units (ICU) admission as the cut-off time of EEN according to the ROC curve, 1212 patients were assigned to the EEN group and the other 1152 to the delayed EN group. The risk of SA-AKI was reduced in the EEN group (odds ratio 0.319, 95% confidence interval 0.245–0.413, p<0.001). The EEN patients received fewer volumes (mL) of intravenous fluid (IVF) during their ICU stay (3750 mL vs. 5513.23 mL, p<0.001). The mediating effect of IVF was significant (p<0.001 for the average causal mediation effect). No significant differences were found within the EEN group (0–48 hours vs. 48–53 hours), except that patients initiating EN within 48 hours spent fewer days in ICU and hospital. Conclusion EEN is associated with decreased risk of SA-AKI, and this beneficial effect may be proportionally mediated by IVF volume.

OBJECTIVE: To observe the clinical efficacy of lidong needling therapy (acupuncture technique combined with therapeutic movement of the body) on upper limb lymphedema after breast cancer surgery in combination with functional exercise. METHODS: A total of 73 patients with postoperative lymphedema of breast cancer in the upper limbs were randomized into an observation group (36 cases) and a control group (37 cases). The routine nursing care and functional exercise were given in the control group, twice a day, for about 10-15 min each time, lasting 8 weeks. On the basis of the treatment as the control group, lidong needling therapy was applied to the acupionts on the affected upper limb, i.e. Jianyu (LI 15), Waiguan (TE 5), Hegu (LI 4) and ashi points (the most obvious swelling sites), as well as to bilateral Yinlingquan (SP 9) and Zusanli (ST 36), etc. The needles were retained for 30 min. While the needles retained, the patients were asked to move the affected shoulder to 90° by the sagittal anteflexion and keep it elevated. Simultaneously, the hand on the affected side was clenched and opened slowly and coordinately. Lidong needling therapy was delivered once every two days, three times weekly for 8 weeks. Before and after treatment, the difference of the circumference between the affected and healthy limbs, the score of visual analogue scale (VAS) for swelling and the score of disability of arm, shoulder and hand (DASH) were compared in the patients of the two groups. The clinical efficacy was evaluated. RESULTS: After 2, 4, 6 and 8 weeks of treatment, except for the circumference of the area 10 cm below the cubitel crease in the control group, the differences in the circumferences of the rest parts between the affected and healthy limbs were reduced in comparison with those before treatment in the two groups (P<0.01, P<0.05). After 6 weeks of treatment, in the observation group, for the circumference at the level of hand between the thumb and the index finger and that of the wrist, the differences between the affected and healthy limbs was smaller compared with those in the control group (P<0.05). After 8 weeks of treatment, except for the areas 5 cm below and above the cubitel crease, the differences of circumferences between the affected and healthy limbs in the observation group were smaller than those in the control group in the rest parts (P<0.01, P<0.05). After 8 weeks of treatment, the swelling VAS scores were reduced when compared with those before treatment in the two groups (P<0.05), and the score in the observation group was lower than that in the control group (P<0.01). After 4 and 8 weeks of treatment, DASH scores were reduced in comparison with those before treatment in the two groups (P<0.01). The total effective rate of the observation group was 83.3% (30/36), which was higher than that of the control group (35.1%, 13/37, P<0.01). CONCLUSION Lidong needling therapy combined with the functional exercise obtains the satisfactory clinical effect on the upper limb lymphedema after breast cancer surgery. This treatment effectively relieves swelling and improves the upper limb function.
Humans ; Female ; Breast Neoplasms/surgery* ; Acupuncture Points ; Acupuncture Therapy/methods* ; Upper Extremity ; Treatment Outcome ; Lymphedema/therapy*

The study aims to observe the effects and explore the mechanisms of Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination in the treatment of the inflammatory response of mice with atherosclerosis(AS) via the Toll-like receptor 4(TLR4)/myeloid differentiation primary response protein 88(MyD88)/nuclear factor-κB(NF-κB) signaling pathway. Male ApoE~(-/-) mice were randomly assigned into a model group, a Buyang Huanwu Decoction group, an Astragali Radix-Angelicae Sinensis Radix combination group, and an atorvastatin group, and male C57BL/6J mice of the same weeks old were used as the control group. Other groups except the control group were given high-fat diets for 12 weeks to establish the AS model, and drugs were administrated by gavage. Aortic intimal hyperplasia thickness, blood lipid level, plasma inflammatory cytokine levels, M1/M2 macrophage markers, and expression levels of proteins in TLR4/MyD88/NF-κB pathway in the vessel wall were measured to evaluate the effects of drugs on AS lesions and inflammatory responses. The results showed that the AS model was successfully established with the ApoE~(-/-) mice fed with high-fat diets. Compared with the control group, the model group showed elevated plasma total cholesterol(TC), triglyceride(TG), and low-density lipoprotein cholesterol(LDL-c) levels(P<0.05), thickened intima(P<0.01), and increased plasma tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) levels(P<0.01). Moreover, the model group showed increased expression of vascular cell adhesion molecule-1(VCAM-1) and inducible nitric oxide synthase(iNOS)(P<0.01), inhibited expression of endothelial nitric oxide synthase(eNOS) and cluster of differentiation 206(CD206)(P<0.01), and up-regulated mRNA and protein levels of TLR4, MyD88, NF-κB inhibitor alpha(IκBα), and NF-κB in the vessel wall(P<0.05). Compared with the model group, Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination lowered the plasma TC and LDL-c levels(P<0.01), alleviated the intimal hyperplasia(P<0.01), and reduced the plasma TNF-α and IL-6 levels(P<0.05). Moreover, the two interventions promoted the expression of eNOS and CD206(P<0.05), inhibited the expression of VCAM-1 and iNOS(P<0.01), and down-regulated the mRNA and protein levels of TLR4, MyD88, IκBα, and NF-κB(P<0.05) in the vessel wall. This study indicated that Buyang Huanwu Decoction and Astragali Radix-Angelicae Sinensis Radix combination could delay the progression of AS, inhibit the polarization of vascular wall macrophages toward M1 type, and attenuate vascular inflammatory response by inhibiting the activation of TLR4/MyD88/NF-κB signaling pathway in the vascular wall. Astragali Radix and Angelicae Sinensis Radix were the main pharmacological substances in Buyang Huanwu Decoction for alleviating the AS vascular inflammatory response.
Mice ; Male ; Animals ; NF-kappa B/metabolism* ; Toll-Like Receptor 4/metabolism* ; NF-KappaB Inhibitor alpha/metabolism* ; Tumor Necrosis Factor-alpha/metabolism* ; Interleukin-6/metabolism* ; Myeloid Differentiation Factor 88/metabolism* ; Vascular Cell Adhesion Molecule-1/metabolism* ; Cholesterol, LDL ; Hyperplasia ; Mice, Inbred C57BL ; Atherosclerosis/genetics* ; Apolipoproteins E/therapeutic use* ; RNA, Messenger