ObjectiveTo investigate the molecular mechanism by which the Bushen Kaixuan Tongluo prescription exerts a renal protective effect in mice with diabetic kidney disease （DKD） by regulating the cyclic adenosine monophosphate （cAMP） signaling pathway. MethodsThirty specific pathogen-free （SPF） male db/db mice were adaptively fed for three weeks. Mice with a random tail vein blood glucose level ≥ 11.1 mmol·L^-1 and urinary albumin-creatinine ratio （ACR） ≥ 30 mg·g^-1 were considered successfully modeled. The successfully modeled mice were randomly divided into five groups with six mice in each group： the model group， the low-， medium-， and high-dose Bushen Kaixuan Tongluo prescription groups （administered at doses of 7， 14， 28 g·kg^-1·d^-1 respectively）， and the positive drug irbesartan group （administered at a dose of 20 mg·kg^-1·d^-1）. Additionally， six db/m mice were selected as the blank group. Mice in each group were given intragastric administration of the Bushen Kaixuan Tongluo prescription at the corresponding concentrations， irbesartan， or an equal volume of pure water， and the intervention lasted for 12 weeks. During the experiment， the general conditions， body weight changes， and renal function indicators of the mice were dynamically monitored. After the intervention， a blood glucose meter was used to measure the fasting blood glucose （FBG） of the mice. An automatic biochemical analyzer was employed to detect the levels of serum creatinine （SCr）， blood urea nitrogen （BUN）， urinary microalbumin （uALB）， ACR， aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， total cholesterol （TC）， triglycerides （TG）， leptin （LEP）， glycosylated serum protein （GSP）， and insulin （INS） in the mice. Renal tissues were collected for hematoxylin-eosin （HE） staining， periodic acid-Schiff （PAS） staining， and Masson's trichrome staining to observe the histopathological changes. Immunohistochemistry （IHC） was used to detect the expressions of protein kinase A （PKA） and cAMP response element-binding protein （CREB） in the mice. Western blot analysis was performed to determine the expression levels of PKA， phosphorylated protein kinase A （p-PKA）， CREB， phosphorylated cAMP response element-binding protein （p-CREB）， and B-cell lymphoma-2 （Bcl-2） proteins in the renal tissues of the mice. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression levels of PKA， CREB， and Bcl-2 in the renal tissues of the mice. ResultsCompared with the blank group， the mice in the model group showed listlessness， decreased activity， and a significant increase in body weight （P<0.01）. Biochemical indicators revealed that the levels of BUN， uALB， ACR， AST， ALT， TC， TG， FBG， LEP， GSP， and INS were significantly increased （P<0.01）， while SCr showed an increasing trend with no statistically significant difference. Compared with the model group， the mice in the Bushen Kaixuan Tongluo prescription intervention groups had improved general conditions and a decreasing trend in body weight. Biochemical indicators showed that the levels of BUN， uALB， ACR， TC， GSP， and INS were significantly decreased （P<0.05）， while SCr， AST， ALT， TG， and LEP showed a decreasing trend with no statistically significant difference. Renal histopathological analysis showed that the model group exhibited typical DKD pathological features such as thickening of the glomerular basement membrane， expansion of the mesangial matrix， and deposition of collagen fibers in the renal tubulointerstitium， and all treatment groups could alleviate the above pathological damages. The IHC results showed that compared with the blank group， the expression levels of p-PKA and p-CREB in the renal tissues of the model group were significantly decreased （P<0.01）. Compared with the model group， the expression level of p-PKA in the medium-dose Bushen Kaixuan Tongluo prescription group was significantly increased （P<0.01）， while the expression level of p-CREB showed an increasing trend with no statistically significant difference. Western blot results showed that compared with the blank group， the expression levels of p-PKA/PKA， p-CREB/CREB， and Bcl-2 in the model group were significantly decreased （P<0.05）. Compared with the model group， the expression levels of these proteins in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly increased （P<0.01）. Real-time PCR results showed that compared with the blank group， the mRNA expressions of PKA， CREB， and Bcl-2 in the model group were significantly down-regulated （P<0.05）. Compared with the model group， the mRNA expressions of these genes in the medium-dose Bushen Kaixuan Tongluo prescription group were significantly up-regulated （P<0.05）. ConclusionThe Bushen Kaixuan Tongluo prescription can improve the liver and kidney functions of db/db mice， correct lipid metabolism disorders and glucose metabolism imbalance. Its renal protective effect is associated with up-regulating the cAMP signaling pathway to improve renal fibrosis and reduce the level of oxidative stress， thereby protecting renal function.

ObjectiveTo provide a reference for the rational clinical use of cold Chinese medicines by sorting and analyzing their properties， flavors， meridian tropism， primary therapeutic indications， methods of administration， dosages， and precautions as recorded in the 2020 edition of Pharmacopoeia of the People's Republic of China （Chinese Pharmacopoeia）. MethodsCold Chinese medicines for internal and external use included in the 2020 edition of Chinese Pharmacopoeia were entered one by one， and their efficacy， properties， flavors， meridian tropism， methods of administration， dosages， and usage precautions were statistically classified and summarized to guide clinical medication use. ResultsA total of 259 cold Chinese medicines for internal use were included and categorized into 18 efficacy groups， mainly comprising heat-clearing drugs， water-excreting and dampness-draining drugs， and phlegm-resolving， cough- and asthma-relieving drugs. Their predominant flavors were bitter， sweet， and pungent， and they primarily entered the liver， lung， and stomach meridians. The main methods of administration included decocting first， grinding into powder for oral use， or preparing into pills or powders， with most dosages ranging from 9 to 15 g. A total of 83 cold Chinese medicines for external use were included， involving 16 efficacy categories. Their main flavors were bitter， sweet， and pungent， primarily entering the liver， lung， and large intestine meridians. The main external application methods were grinding into powder for topical use or preparing decoctions for fumigation and washing， with most dosages ranging from 9 to 15 g. Whether for internal or external use， cold Chinese medicines should be used with caution or contraindicated in pregnant women. ConclusionThe cold Chinese medicines included in the 2020 edition of the Chinese Pharmacopoeia are mainly suitable for patients with carbuncles， swellings， and coughs. However， in clinical practice， it is necessary to strictly follow the principles of syndrome differentiation and treatment， pay attention to administration methods and dosages， and use cold medicines rationally and effectively to improve clinical efficacy.

OBJECTIVES: To evaluate the efficacy of molecular targeted agents in children with progressive pediatric low-grade gliomas (pLGG). METHODS: A retrospective analysis was conducted on pLGG patients treated with oral targeted therapies at the Department of Pediatrics, Beijing Shijitan Hospital, Capital Medical University, from July 2021. Treatment responses and safety profiles were assessed. RESULTS: Among the 20 enrolled patients, the trametinib group (n=12, including 11 cases with BRAF fusions and 1 case with BRAF V600E mutation) demonstrated 4 partial responses (33%) and 2 minor responses (17%), with a median time to response of 3.0 months. In the vemurafenib group (n=6, all with BRAF V600E mutation), 5 patients achieved partial responses (83%), showing a median time to response of 1.0 month. Comparative analysis revealed no statistically significant difference in progression-free survival rates between the two treatment groups (P>0.05). The median duration of clinical benefit (defined as partial response + minor response + stable disease) was 11.0 months for vemurafenib and 18.0 months for trametinib. Two additional cases, one with ATM mutation treated with olaparib for 24 months and one with NF1 mutation receiving everolimus for 21 months, discontinued treatment due to sustained disease stability. No severe adverse events were observed in any treatment group. CONCLUSIONS Molecular targeted therapy demonstrates clinical efficacy with favorable tolerability in pLGG. Vemurafenib achieves high response rates and induces early tumor shrinkage in patients with BRAF V600E mutations, supporting its utility as a first-line therapy.
Humans ; Glioma/genetics* ; Male ; Female ; Child ; Child, Preschool ; Retrospective Studies ; Brain Neoplasms/genetics* ; Molecular Targeted Therapy/adverse effects* ; Adolescent ; Infant ; Proto-Oncogene Proteins B-raf/genetics* ; Pyrimidinones/therapeutic use* ; Mutation

Inflammatory bowel disease is a chronic, idiopathic, and recurrent gastrointestinal disorder with an unclear etiology and uncertain pathogenesis. Traditional treatment strategies rely on frequent administration of high doses of medication to reduce inflammation, whereas these approaches have limitations and may induce potential complications. Therefore, finding more effective and safe therapeutic drugs and methods is particularly important. Plant-derived exosome-like nanovesicles(PDELNs) are nano-sized vesicles with a lipid bilayer structure that are secreted by plant cells. The bioactive molecules contained within, such as lipids, proteins, and nucleic acids, can serve as information carriers, playing a role in the transmission of information and substances between cells and across species. PDELNs can carry and transfer their own bioactive substances or act as carriers for delivering other active components or drugs. Due to the high biocompatibility, low toxicity, and significant bioactivity, PDELNs have garnered widespread attention. Compared with other exosomes, PDELNs are not destroyed in the gastrointestinal tract when taken orally and can reach the intestines. This unique property makes PDELNs a promising oral nanodrug for treating intestinal diseases, showing great potential in this area. This article reviews recent research literature on PDELNs regarding the physicochemical characteristics, extraction and purification methods, functions, application characteristics and mechanisms in the treatment of intestinal diseases, and use as a carrier for treating intestinal diseases, aiming to provide a reference for the use of PDELNs in the treatment of intestinal diseases.
Humans ; Exosomes/metabolism* ; Animals ; Intestinal Diseases/metabolism* ; Plants/metabolism* ; Drug Carriers/chemistry* ; Drugs, Chinese Herbal/chemistry* ; Drug Delivery Systems ; Nanoparticles/chemistry*

Objective To analyze the clinical manifestations of intestinal pneumatosis cystoid(IPC)and explore the prognosis of IPC patients,to provide a reference for clinical treatment.Methods The clinical data of 4 IPC patients admitted to Jining First People's Hospital from June 2024 to March 2025 were retrospectively analyzed,and the treatment experience was summarized.Results Case 1:a 65-year-old male patient presented with lower abdominal pain,fever,nausea,and vomiting(vomitus was intestinal contents)without obvious trigger on July 15,2024.CT showed thickening of the distal transverse colon wall and multiple cystic gas-density shadows in the submucosa,suggesting transverse colon pneumatosis cystoides with surrounding infection.The patient was discharged after conservative treatment in our hospital,including anti-inflammatory therapy and fasting.However,the patient repeatedly developed intestinal obstruction symptoms after discharge,but the patient and family refused surgery and chose conservative treatment until automatic discharge.Due to recurrent abdominal pain,the patient was later treated in an external hospital,where incomplete intestinal obstruction of the transverse colon was diagnosed.Given the poor response to conservative treatment and recurrent obstruction,multidisciplinary discussion recommended surgery.Intraoperative exploration revealed stenosis in part of the transverse colon,and partial transverse colon resection with end-to-side anastomosis was performed.The operation was successful,and the patient recovered well postoperatively.The other 3 IPC patients had milder symptoms and were discharged after conservative treatment.Conclusion Most cases of intestinal pneumatosis cystoid can improve with conservative treatment.It is of great significance to determine the need for surgery and prevent colonic stricture after conservative treatment.

AIM To optimize the extraction process for Bletillae Rhizoma,and to evaluate its anti-oxidant,tyrosinase inhibitory activities.METHODS With ultrasound time,ethanol concentration and solid-liquid ratio as influencing factors,the total extraction content of gastrodin,protocatechualdehyde,p-hydroxybenzaldehyde,1,4-bis[4-(gluconoxy)benzyl]-2-isobutylmalate-2-glucoside,1,4-bis[4-(gluconoxy)benzyl]-2-isobutylmalate,yam Ⅲ,dihydropinosin and 3'-O-methylyam Ⅲ as an evaluation index,the extraction process was optimized by Box-Behnken response surface method.Subsequently,the extract's scavenging effects on DPPH,ABTS+free radicals,and inhibitory ability on tyrosinase were determined.RESULTS The optimal conditions were determined to be 49 min for ultrasound time,55％for ethanol concentration,1∶30 for solid-liquid ratio,and 2 times for extraction frequency,the total extraction content was 13.18 mg/g.The extract demonstrated the IC50 of 10.12,314.07 and 1.70 μg/g on DPPH,ABTS+free radicals and tyrosinase,respectively.CONCLUSION This simple,reliable and stable method can be used for the extraction for Bletillae Rhizoma with strong anti-oxidant,tyrosinase inhibitory activities.

Objective:To compare the diagnostic value of semi-quantitative parameters of fluorine 18-labelled prostate-specific membrane antigen( 18F-PSMA)positron emission tomography /computed tomography(PET/CT)and the Prostate-specific Membrane Antigen Reporting and Data System(PSMA-RADS)score for identifying benign and malignant oligo-PSMA-avid bone lesions(1-5 lesions)in elderly patients with prostate cancer. Methods:A retrospective analysis was conducted on 157 prostate cancer patients who underwent 18F-PSMA PET/CT examinations at Beijing Hospital from October 2022 to August 2024.According to the inclusion and exclusion criteria, a total of 63 patients were selected.All patients underwent 18F-PSMA PET/CT examination for the purpose of initial staging or detecting lesions with biochemical recurrence.PSMA-avid bone lesions were evaluated using the PSMA-RADS version 2.0 scoring system and the semi-quantitative parameters were measured on PSMA PET/CT images.According to the comprehensive diagnostic criteria, PSMA-avid bone lesions were divided into metastatic group and non-metastatic group.The differences in PSMA-RADS scores, semi-quantitative parameters, bone density abnormalities, and lesion distribution were compared between the two groups.Multivariate logistic regression analysis was performed to determine the factors related to the bone metastasis in prostate cancer.By plotting the receiver operating characteristic(ROC)curves and calculating the area under the curve(AUC), factors with better diagnostic performance were evaluated and screened, and the optimal diagnostic threshold for each factor in diagnosing bone metastasis was determined. Results:There were a total of 129 PSMA-avid bone lesions for 63 patients(aged 60-84 years, median age 69 years), including 35 lesions(27.1%)in the metastatic group and 94 lesions(72.9%)in the non-metastatic group.The differences between metastatic group and non-metastatic group in PSMA-RADS scores[5(4, 5) vs.3(3, 3)], maximum standardized uptake value(SUV max)[12.6(7.0, 18.4) vs.4.7(3.5, 5.9)], lesion SUV max/mediastinal blood pool SUV max ratio(lesion-to-blood pool ratio, LBR)[5.4(3.0, 8.3) vs.1.7(1.4, 2.2)], lesion SUV max/liver SUV max ratio(lesion-to-liver ratio, LLR)[2.6(1.6, 4.1) vs.0.8(0.7, 1.1)], PSMA receptor expressing tumor volume(PSMA-TV)[0.6(0.3, 1.0) vs.1.0(0.7, 1.5)], total lesion of PSMA(TL-PSMA)[4.4(2.4, 7.0) vs.2.4(1.7, 3.9)], proportion of changes in osteogenic bone density[77.1%(27/35) vs.2.1%(2/94)], proportion of lesions located in the ribs[14.3%(5/35) vs.46.8%(44/94)], and proportion of lesions located in the pelvis[54.3%(19/35) vs.20.2%(19/94)]were all statistically significant(all P<0.05). Multivariate logistic regression analysis indicated that none of the variables with statistically significant differences between groups above were independent risk factors for osseous metastasis in prostate cancer(all P>0.05). Among them, The PSMA-RADS score, LLR, LBR, and SUV max all had good diagnostic efficacy for osseous metastasis, with 0.995(95% CI: 0.987-1.000), 0.923(95% CI: 0.869-0.977), 0.898(95% CI: 0.828-0.967), and 0.890(95% CI: 0.820-0.961), respectively.The cut-off values for diagnosing osseous metastasis were 4 score for PSMA-RADS score, 0.934 for LLR, 1.990 for LBR, and 5.47 for SUV max, respectively.According to Delong's test, there were statistically significant differences in AUC between PSMA-RADS score and 18F-PSMA PET/CT semi-quantitative parameters(LLR, LBR, and SUV max)( Z-values were 2.677, 2.776, and 2.929, respectively, and P-values were 0.007, 0.006, and 0.003, respectively). Conclusions:The PSMA-RADS score(Version 2.0)and 18F-PSMA PET/CT semi-quantitative parameters(LLR, LBR, and SUV max)both have good diagnostic value in differentiating benign and malignant PSMA-avid bone lesions in elderly patients with prostate cancer, among which the PSMA-RADS score has the best diagnostic efficacy.

BACKGROUND: Congenital heart disease (CHD) is a leading cause of birth defect-related mortality. However, more recent CHD mortality data for China are lacking. Additionally, limited studies have evaluated sex, rural-urban, and region-specific disparities of CHD mortality in China. METHODS: We designed a population-based study using data from the Dataset of National Mortality Surveillance in China between 2008 and 2021. We calculated age-adjusted CHD mortality using the sixth census data of China in 2010 as the standard population. We assessed the temporal trends in CHD mortality by age, sex, area, and region from 2008 to 2021 using the joinpoint regression model. RESULTS: From 2008 to 2021, 33,534 deaths were attributed to CHD. The period witnessed a two-fold decrease in the age-adjusted CHD mortality from 1.61 to 0.76 per 100,000 persons (average annual percent change [AAPC] = -5.90%). Females tended to have lower age-adjusted CHD mortality than males, but with a similar decline rate from 2008 to 2021 (females: AAPC = -6.15%; males: AAPC = -5.84%). Similar AAPC values were observed among people living in urban (AAPC = -6.64%) and rural (AAPC = -6.12%) areas. Eastern regions experienced a more pronounced decrease in the age-adjusted CHD mortality (AAPC = -7.86%) than central (AAPC = -5.83%) and western regions (AAPC = -3.71%) between 2008 and 2021. Approximately half of the deaths (46.19%) due to CHD occurred during infancy. The CHD mortality rates in 2021 were lower than those in 2008 for people aged 0-39 years, with the largest decrease observed among children aged 1-4 years (AAPC = -8.26%), followed by infants (AAPC = -7.01%). CONCLUSIONS CHD mortality in China has dramatically decreased from 2008 to 2021. The slower decrease in CHD mortality in the central and western regions than in the eastern regions suggested that public health policymakers should pay more attention to health resources and health education for central and western regions.
Humans ; Heart Defects, Congenital/mortality* ; Male ; Female ; China/epidemiology* ; Infant ; Child, Preschool ; Adult ; Child ; Adolescent ; Infant, Newborn ; Middle Aged ; Young Adult ; Aged ; Rural Population

This study aims to explore the role and mechanism of CXC chemokine receptor 3 (CXCR3) in cisplatin-induced skeletal muscle atrophy. Wild-type mice were divided into two groups: cisplatin group and control group (treated by normal saline). The results showed that, compared to the control group, the expression levels of CXCR3 mRNA and protein were significantly up-regulated in the skeletal muscle of the cisplatin group, suggesting that CXCR3 may play an important role in the model of cisplatin-induced skeletal muscle atrophy. To further investigate its role and potential mechanisms, CXCR3 knockout mice and wild-type mice were treated with cisplatin to induce skeletal muscle atrophy. The results revealed that CXCR3 knockout not only failed to alleviate cisplatin-induced skeletal muscle atrophy, but also further reduced body weight, skeletal muscle mass, and muscle fiber cross-sectional area. Further analysis showed that, in the cisplatin-induced muscle atrophy model, CXCR3 knockout significantly up-regulated the expression levels of E3 ubiquitin ligases in skeletal muscle and down-regulated the expression levels of myogenic regulatory factors. To explore the molecular mechanism by which CXCR3 gene deletion exacerbated cisplatin-induced skeletal muscle atrophy, transcriptomic sequencing was performed on the atrophied skeletal muscles of wild-type and CXCR3 knockout mice. The results showed that, compared to wild-type mice, 14 genes were significantly up-regulated and 12 genes were significantly down-regulated in the skeletal muscle of CXCR3 knockout mice. Gene set enrichment analysis (GSEA) revealed a significant enrichment of genes related to fatty acid β-oxidation. Quantitative real-time PCR validation results were consistent with the transcriptomic sequencing results. These findings suggest that CXCR3 may counteract cisplatin-induced skeletal muscle atrophy by up-regulating E3 ubiquitin ligases, down-regulating myogenic regulatory factors, and enhancing the recruitment of fatty acid β-oxidation-related genes.
Animals ; Cisplatin/adverse effects* ; Muscular Atrophy/physiopathology* ; Mice ; Receptors, CXCR3/metabolism* ; Ubiquitin-Protein Ligases/metabolism* ; Mice, Knockout ; Oxidation-Reduction ; Fatty Acids/metabolism* ; Muscle, Skeletal/metabolism* ; Mice, Inbred C57BL ; Male