Objective: To investigate the nutritional status and influencing factors among Tibetan and Mongolian children and adolescents aged 7-18 years in high-altitude regions, so as to provide evidence for early prevention and control of malnutrition in this population. Methods: From May to June 2022, a cluster sampling method was employed to recruit 1 019 Tibetan and Mongolian children and adolescents aged 7-18 years from two primary and secondary schools in Golmud City. Physical examinations, dietary frequency questionnaires, and physical activity assessments were conducted. Nutritional status was classified as obesity, combined overweight/obesity, underweight, or central obesity according to national standards including Screening for Overweight and Obesity among School-age Children and Adolescents, Screening Standard for Malnutrition of School-age Children and Adolescents, Blue Book on Obesity Prevention and Control in China. Chi-square tests, t-test and Logistic regression analyses were performed to identify factors associated with different nutritional statuses. Results: The detection rates of obesity, combined overweight/obesity, underweight, and central obesity were 8.0%, 18.1%, 5.2%, and 19.7%, respectively. The height of children and adolescents across all age groups was generally lower than the national standard values. Tibetan participants exhibited significantly lower height-for-age Z-scores (HAZ)(9-10, 13-17 years, Z =2.01, 2.78, 4.16, 3.38, 4.12, 3.63, 3.00) and BMI-for-age Z-scores (BAZ) compared to Mongolian participants ( Z =-2.95, -2.47, -2.31, -2.89, -2.14, -2.17)( P < 0.05 ). Multivariate Logistic regression revealed that Mongolian children and adolescents had higher risks of obesity ( OR =2.20) and combined overweight/obesity ( OR = 2.18 ) ( P <0.05). Additionally, insufficient moderate-to-vigorous physical activity (MVPA) was associated with an increased risk of central obesity ( OR =1.48, P <0.05), compared with children and adolescents who meet the standard of MVPA. Conclusions The rates of overweight and obesity among Tibetan and Mongolian children and adolescents in Golmud City are higher, influenced by multiple factors. Nutrition interventions and physical activity strategies tailored to ethnic characteristics should be implemented, with emphasis on promoting MVPA to improve nutritional outcomes in this population.

Two novel diketopiperazines (1 and 5), along with ten known compounds (2-4, 6-12) demonstrating significant skin inflammation inhibition, were isolated from a marine-derived fungus identified as Aspergillus sp. FAZW0001. The structural elucidation and configurational reassessments of compounds 1-5 were established through comprehensive spectral analyses, with their absolute configurations determined via single crystal X-ray diffraction using Cu Kα radiation, Marfey's method, and comparison between experimental and calculated electronic circular dichroism (ECD) spectra. Compounds 1, 2, and 8 exhibited significant anti-inflammatory activities in Propionibacterium acnes (P. acnes)-induced human monocyte cell lines. Compound 8 demonstrated the ability to down-regulate interleukin-1β (IL-1β) expression by inhibiting Toll-like receptor 2 (TLR2) expression and modulating the activation of myeloid differentiation factor 88 (MyD88), mitogen-activated protein kinase (MAPK), and nuclear factor κB (NF-κB) signaling pathways, thus reducing the cellular inflammatory response induced by P. acnes. Additionally, compound 8 showed the capacity to suppress mitochondrial reactive oxygen species (ROS) production and nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome activation, thereby reducing IL-1β maturation and secretion. A three-dimensional quantitative structure-activity relationships (3D-QSAR) model was applied to compounds 5-12 to analyze their anti-inflammatory structure-activity relationships.
Humans ; Aspergillus/chemistry* ; Diketopiperazines/isolation & purification* ; Anti-Inflammatory Agents/isolation & purification* ; Interleukin-1beta/genetics* ; Toll-Like Receptor 2/immunology* ; Propionibacterium acnes/drug effects* ; NF-kappa B/genetics* ; Molecular Structure ; Myeloid Differentiation Factor 88/immunology* ; Monocytes/immunology* ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Cell Line

BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Objective To investigate the clinical features of thyroid dysfunction in lung cancer patients treated with programmed cell death receptor-1(PD-1)or programmed cell death receptor-ligand 1(PD-L1)and their value for predicting therapeutic efficacy.Methods Lung cancer patients treated with PD-1/PD-L1 inhibitors at West China Hospital,Sichuan University between March 2018 and September 2022 were retrospectively enrolled.Data concerning the medical records,therapeutic efficacy,and thyroid function indicators of the patients were retrieved from the hospital electronic medical record information system.The data were then analyzed to identify risk factors and predictive factors for immune-related adverse events(irAEs)of the thyroid.The predictive value of thyroid irAEs for treatment efficacy and prognosis was assessed.Objective response rate(ORR)was defined as the indicator for therapeutic efficacy and progression-free survival(PFS)was defined as the prognostic indicator.Results A total of 368 lung cancer patients were enrolled.Among them,31.5％(116/368)developed thyroid irAEs.According to the results of logistic regression analysis,baseline thyroid stimulating hormone(TSH)concentration and baseline positive results for thyroglobulin antibody(TGAb)and thyroid peroxidase antibody(TPOAb)were risk factors for thyroid dysfunction caused by PD-1/PD-L1 inhibitors.Among the three measures,baseline TPOAb concentration demonstrated good predictive value for thyroid irAEs,with an area under the receiver-operating characteristic(ROC)curve(AUC)of 0.745.Patients with thyroid irAEs had a longer median PFS(16.0 months vs.9.7 months,P＜0.001)and a higher ORR(55.2％vs.34.9％,P＜0.001)compared to those without thyroid irAEs.Patients with thyroid irAEs had a better ORR than those without thyroid irAEs did.It was more likely for patients with thyroid irAEs to achieve an objective response compared to those without thyroid irAEs(odds ratio[OR]=2.29;95％CI,1.46-3.60).Conclusion In lung cancer patients treated with the PD-1/PD-L1 inhibitors,the TPOAb antibody demonstrates good predictive value for thyroid irAEs.Patients who develop thyroid irAEs have better treatment outcomes and prognosis.

Objective To explore the protective effects and mechanism of Shenqi Qiangjing granules containing serum on hydrogen peroxide(H2O2)induced oxidative damage and ferroptosis in mouse spermatogonia(GC-1 spg).Methods Thir-ty SPF grade healthy male SD rats were selected and randomly divided into blank group,levocarnitine group,and Shenqi Qiangjing granules group.After 7 days of intragastric administration,drug-containing serum was collected from each group.Using mouse sper-matogonia as a cell model,they were randomly divided into the normal control group,the model control group,blank serum group,levocarnitine containing serum group,and Shenqi Qiangjing granules containing serum group.Except for the normal control group,the other groups used hydrogen peroxide at a concentration of 600 μmol·L-1 to induce injury to mouse spermatogonia for 4 hours,and then established oxidative stress injury models,after 24 hours of medication intervention in each group.The survival rate of cells was detected using CCK-8 method;The levels of intracellular reactive oxygen species(ROS),malondialdehyde(MDA),catalase(CAT),glutathione(GSH),and superoxide dismutase(SOD)were detected by ELISA;The intracellular iron level was detected by iron ion colorimetry;The activities of Caspase-3 and Caspase-9 were detected by colorimetry;The mRNA levels of glu-tathione peroxidase 4(GPX4)and ACSL4 were determined by qRT-PCR.Results Compared with the normal control group,the cell proliferation activity of the model control group decreased significantly,the levels of ROS,MDA and Fe3+were significantly increased,while the activities of CAT,GSH and SOD were significantly decreased in the model control group,however,Caspase-3 and Caspase-9 activities were significantly increased,the results showed significant difference(P＜0.05).Compare with the model control group,Shenqi Qiangjing granules containing serum could significantly increase the cell proliferation activity,decrease the levels of ROS,MDA and Fe3+,increase the activities of CAT,GSH and SOD,and decrease the activities of Caspase-3 and Caspase-9,the results showed significant difference(P＜0.05).The qRT PCR results showed that compared with the model control group,the expression of GPX4 mRNA was upregulated and ACSL4 mRNA was downregulated in blank serum group containing Shenqi Qiangjing granules,and the differences were statistically significant(P＜0.05).Conclusions Shenqi Qiangjing granules have significant protective effects on hydrogen peroxide-induced oxidative stress injury and ferroptosis of spermatogonia in mice.The mechanism may be related to the decrease of Caspase-3 and Caspase-9 activities and the inhibition of oxidative stress injury and ferroptosis.

Objective To explore the protective effects and mechanism of Shenqi Qiangjing granules containing serum on hydrogen peroxide(H2O2)induced oxidative damage and ferroptosis in mouse spermatogonia(GC-1 spg).Methods Thir-ty SPF grade healthy male SD rats were selected and randomly divided into blank group,levocarnitine group,and Shenqi Qiangjing granules group.After 7 days of intragastric administration,drug-containing serum was collected from each group.Using mouse sper-matogonia as a cell model,they were randomly divided into the normal control group,the model control group,blank serum group,levocarnitine containing serum group,and Shenqi Qiangjing granules containing serum group.Except for the normal control group,the other groups used hydrogen peroxide at a concentration of 600 μmol·L-1 to induce injury to mouse spermatogonia for 4 hours,and then established oxidative stress injury models,after 24 hours of medication intervention in each group.The survival rate of cells was detected using CCK-8 method;The levels of intracellular reactive oxygen species(ROS),malondialdehyde(MDA),catalase(CAT),glutathione(GSH),and superoxide dismutase(SOD)were detected by ELISA;The intracellular iron level was detected by iron ion colorimetry;The activities of Caspase-3 and Caspase-9 were detected by colorimetry;The mRNA levels of glu-tathione peroxidase 4(GPX4)and ACSL4 were determined by qRT-PCR.Results Compared with the normal control group,the cell proliferation activity of the model control group decreased significantly,the levels of ROS,MDA and Fe3+were significantly increased,while the activities of CAT,GSH and SOD were significantly decreased in the model control group,however,Caspase-3 and Caspase-9 activities were significantly increased,the results showed significant difference(P＜0.05).Compare with the model control group,Shenqi Qiangjing granules containing serum could significantly increase the cell proliferation activity,decrease the levels of ROS,MDA and Fe3+,increase the activities of CAT,GSH and SOD,and decrease the activities of Caspase-3 and Caspase-9,the results showed significant difference(P＜0.05).The qRT PCR results showed that compared with the model control group,the expression of GPX4 mRNA was upregulated and ACSL4 mRNA was downregulated in blank serum group containing Shenqi Qiangjing granules,and the differences were statistically significant(P＜0.05).Conclusions Shenqi Qiangjing granules have significant protective effects on hydrogen peroxide-induced oxidative stress injury and ferroptosis of spermatogonia in mice.The mechanism may be related to the decrease of Caspase-3 and Caspase-9 activities and the inhibition of oxidative stress injury and ferroptosis.

[Objective]To analyze the clinical characteristics and imaging features of effectively treated pediatric Mycoplasma pneumoniae pneumonia(MPP)with pulmonary consolidation,follow up the volume changes of pulmonary consolidation on lung CT scans of the affected children,and investigate the resolution patterns of pulmonary consolidation,and predict the time required for complete resolution.[Methods]We enrolled children with MPP and pulmonary consolidation hospitalized in the Department of General Pediatrics at Children's Hospital of Chongqing Medical University between January 2018 and May 2024.Data collected included demographics,clinical symptoms,laboratory indicators,treatment status,imaging data during hospitalization,as well as follow-up lung CT data and reexamination intervals after discharge.Consolidation volumes were measured before and after the treatment to calculate the resolution rate and resolution velocity.Descriptive statistical analysis was performed on clinical characteristics,imaging features and consolidation resolution.[Results]Among 238 children with MPP and lung consolidation,females slightly outnumbered males(the male to female ratio is 109 vs.129),with a mean age of approximately 5 years.At admission,the median cough and fever durations were 7(5-9)days and 6(4-7)days,respectively.No significant increase was found in white blood cells count or lactate dehydrogenase(LDH),and hypersensitive high-sensitivity C-reactive protein(CRP)slightly increased.Azithromycin was the first line of treatment in most cases,though second-line drugs increased in the recent two years due to the rising resistance.Bronchoalveolar lavage was performed in 66.8%(159/238)of children,and 33.2%(79/238)did not receive lavage.Consolidation was predominantly unilateral(206 unilateral vs.32 bilateral)and right-sided(117 right-sided vs.89 left-sided).The ratio of consolidation volume to total lung volume was 4.48(2.61-7.35)%,the consolidation resolution rate at follow-up was 96.08(88.02-98.95)%,the reexamination interval was 17(15-21)days,the resolution velocity was 2.15(1.23-4.01)cm3/d,and the time to complete resolution was 18.96(16.14-23.33)days.[Conclusions]Pulmonary consolidation in pediatric MPP achieves substantial resolution on CT within 2-3 weeks after effective clinical treatment.Initial consolidation volume and resolution velocity can predict the time required for complete resolution,thereby clinically guiding optimal CT follow-up scheduling.

OBJECTIVE To investigate the protective effect and potential mechanism of cornuside on diabetic nephropathy （DN） model mice. METHODS Male KK-Ay mice were fed with high-fat and high-sugar diet for two weeks to reproduce the DN model. The successfully modeled mice were randomly grouped into model group， aminoguanidine group （positive control，100 mg/kg） and cornuside group （100 mg/kg）， and male C57BL/6J mice were included as normal group， with 6 mice in each group. Administration groups were given relevant medicine intragastrically， and normal group and model group were given a constant volume of normal saline intragastrically， once a day， for 8 consecutive weeks. The levels of fasting blood glucose （FBG）， 24 h urinary protein， serum interleukin-12 （IL-12）， IL-10， blood urea nitrogen （BUN） and serum creatinine （Scr） were detected； the pathological injury， fibrotic change and glomerular microstructure of renal tissue were observed； the expressions of the receptor of advanced glycation end products （RAGE）， collagen type Ⅳ （COL-Ⅳ） and inducible nitric oxide synthase （iNOS） in renal cortex were detected in each group. RESULTS Compared with normal group， the renal cortex of mice in model group showed obvious inflammatory cell infiltration and fibrotic changes； the mesangial hyperplasia of glomerulus was serious and the basement membrane had a large number of irregular dark dense deposits； the levels of FBG and 24 h urinary protein， the serum levels of IL- 12， BUN and Scr， and the expression levels of RAGE， COL-Ⅳ and iNOS in the renal cortex were significantly increased， while the serum level of IL-10 was significantly decreased （P＜0.01）. Compared with the model group， the renal pathological injuries， fibrotic changes and glomerular microstructure of mice in administration groups were improved significantly， and the above quantitative indexes were generally improved （P＜0.05 or P＜0.01）. CONCLUSIONS Cornuside has a certain protective effect on DN model mice. It can inhibit the inflammatory response， reduce urinary protein excretion， and alleviate renal fibrosis， which may be related to the inhibition of the advanced glycation end products/RAGE signaling pathway.

Gouty arthritis is a condition resulting from the dysregulation of purine metabolism in the human body. It is characterized by redness, swelling, recurrent episodes of hot pain, and joint stiffness. Currently, Western medicine primarily relies on uric acid-lowering, anti-inflammatory, and analgesic drugs, but these medications often have significant side effects. In contrast, external therapies in traditional Chinese medicine are considered simpler, safer, and less likely to produce adverse reactions, thus making them more appealing to patients. This article summarizes the various external treatment methods used in traditional Chinese medicine to alleviate the clinical symptoms of gouty arthritis, offering a novel approach for clinical management.