Radon, the only naturally occurring radioactive noble gas, is among the most common radioactive nuclides to which humans are exposed. Radon can induce various biological effects in the human body and is a risk factor for lung cancer. Circular RNAs (circRNAs) are stable, tissue-specific, and abundantly expressed in body fluids. circRNAs can regulate gene expression and play an important role in the development of cancer. In this paper, we summarized the changes in the expression and function of circRNAs, highlighting the potential mechanisms of circRNAs in radon exposure-induced cancers. Our results provided theoretical support for the use of circRNAs as a biomarker of radon exposure-induced radiation damage, and offer a theoretical basis for the early diagnosis, treatment, and prevention of radon exposure-induced diseases.

ObjectiveThis study aims to investigate the therapeutic effects of Wenweishu granule （WWSG） on functional dyspepsia （FD） with spleen-stomach deficiency cold syndrome in rats by integrating network pharmacology， molecular docking， and animal experiments. MethodsActive components and corresponding targets of WWSG were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform （TCMSP） and the Bioinformatics Analysis Tool for Molecular Mechanism of Traditional Chinese Medicine （BATMAN-TCM）. Disease-related targets for FD with spleen-stomach deficiency cold syndrome were screened using GeneCards and the Integrative Pharmacology-based Research Platform of Traditional Chinese Medicine （TCMIP）. Core therapeutic targets were identified via Cytoscape and validated by molecular docking. A rat model of FD with spleen-stomach deficiency cold syndrome was established using vinegar gavage combined with tail-clamping. The rats were randomly divided into a model group， low-， medium-， and high-dose WWSG groups （2.0， 4.0， 8.0 g·kg^-1）， a domperidone group （3.0 mg·kg^-1）， a Fuzi Lizhong pillwan （0.8 g·kg^-1）， and a normal control group （n=10 per group）. Drugs were administered once daily by gavage for 14 consecutive days. After treatment， body weight， symptom scores， and gastrointestinal motility indices were recorded. Gastric and duodenal pathologies changes were observed via hematoxylin-eosin （HE） staining. Brain-gut peptides were measured in serum and tissue using enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry and Western blot were performed to assess stem cell factor （SCF） and receptor tyrosine kinase （c-Kit） protein expression in gastric tissues. ResultsA total of 305 drug targets， 1 140 disease targets， and 116 overlapping targets were identified. Cytoscape analysis revealed 104 core targets. Enrichment analysis indicated that the SCF/c-Kit signaling pathway was the key mechanism. Molecular docking confirmed a strong binding affinity between active components of WWSG and SCF/c-Kit proteins （binding energy<-5.1 kcal·mol^-1）. Compared with the normal group， model rats exhibited slower weight gain （P<0.05）， reduced gastric emptying and intestinal propulsion （P<0.01）， mild gastric mucosal shedding， duodenal inflammatory cell infiltration， decreased levels of gastrin （GAS）， 5-hydroxytryptamine （5-HT）， and vasoactive intestinal peptide （VIP） （P<0.05， P<0.01）， and elevated somatostatin （SS） expression （P<0.05， P<0.01）. WWSG treatment ameliorated weight gain， symptom scores， and low-grade inflammation in gastric/duodenal tissues. High-dose WWSG significantly improved gastric emptying and intestinal propulsion， upregulated GAS， 5-HT， and VIP， and downregulated SS expression in serum and tissues （P<0.05， P<0.01）. Immunohistochemistry and Western blot demonstrated that SCF and c-Kit protein expression was decreased in the model group （P<0.05， P<0.01）， which was reversed by WWSG intervention （P<0.05）. ConclusionWWSG exerts therapeutic effects on FD with spleen-stomach deficiency cold syndrome in rats， potentially by regulating the SCF/c-Kit signaling pathway to enhance gastrointestinal motility.

BACKGROUND:Previous studies have confirmed that the new compound cottonrose hibiscus leaf gel plaster has a good effect in the treatment of acute soft tissue swelling. OBJECTIVE:To observe the clinical efficacy of compound cottonrose hibiscus leaf gel plaster in the treatment of synovitis of the knee joint. METHODS:Seventy-two patients with knee synovitis were selected from Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine from December 2019 to May 2021.These patients were randomly divided into a trial group and a control group,with 36 cases in each group.The trial group was treated with compound cottonrose hibiscus leaf gel plaster,once a day,12 hours each time,while the control group was treated with Diclofenac Diethylamine Emulgel,twice a day.After 28 days of treatment,visual analog scale score,WOMAC Osteoarthritis Index score,quality of life score(SF-36),thickness of knee synovium and comprehensive curative effect were compared between the two groups. RESULTS AND CONCLUSION:(1)Visual analog scale scores after treatment were lower than those before treatment(P<0.05).Visual analog scale scores in the trial group after 7,14 and 28 days of treatment were lower than those in the control group(P<0.05).The WOMAC Osteoarthritis Index scores of the two groups after treatment were lower than those before treatment(P<0.05),and the WOMAC Osteoarthritis Index scores in the trial group after 7,14 and 28 days of treatment were lower than those in the control group(P<0.05).(3)The SF-36 quality of life score in the two groups after 28 days of treatment was higher than that before treatment(P<0.05).SF-36 quality of life score in the trial group after 28 days of treatment was higher than that in the control group(P<0.05).(4)After 28 days of treatment,the thickness of knee synovium in the trial group was less than that in the control group(P<0.05),and the effective rate in the trial group was higher than that in the control group(P<0.05).(5)These findings indicate that compared with Diclofenac Diethylamine Emulgel,the compound cottonrose hibiscus leaf gel plaster can better relieve knee pain,enhance knee joint function,reduce synovial hyperplasia,and elevate the overall quality of life of patients.

In recent years,China has made great progress in basic nanomedicine,nanotoxicology and nanobiology research.Nanotechnology has been continuously applied in biomaterial and medical device,more and more medical devices applying nanomaterials are developed and manufactured.In order to gain more comprehension and accurate understanding of the research and industrial development in nanobiomaterial medical devices,this study reviewed the common nanomaterial in medical devices and the regulatory situation of nanomaterial medical devices at home and abroad,and discussed the current challenges in biological evaluation of nanomaterial medical devices,with a view to providing ideas for the safety evaluation and research of related products.

AIM:To explore the roles and associations of hepatocyte nuclear factor 4 alpha(HNF4A)and mu-protocadherin(MUCDHL)in the kidney of diabetic mice.METHODS:(1)A cohort of six 12-week-old db/m mice and six db/db mice were selected and maintained on a standard diet until 16 weeks.The protein levels of fibronectin(FN),collagen type III(Col-III),E-cadherin,α-smooth muscle actin(α-SMA),HNF4A,Snail and MUCDHL in renal tissues were scrutinized using Western blot.Immunohistochemical staining was conducted to observe the distribution and expres-sion of FN,HNF4A and MUCDHL.(2)Mouse renal tubular epithelial cells(mRTEC)were cultured in vitro and catego-rized into groups:normal glucose(NG)group,high glucose(HG)group,overexpression control groups(NG+vector and HG+vector),overexpression groups(NG+OE-MUCDHL,HG+OE-MUCDHL,NG+OE-HNF4A and HG+OE-HNF4A),knockdown control groups(NG+control and HG+control),and knockdown groups(NG+si-MUCDHL,HG+si-MUCDHL,NG+si-HNF4A and HG+si-HNF4A).The relevant protein levels were also detected by Western blot.RESULTS:(1)In db/db group,elevated body weight,blood glucose and urine albumin-to-creatinine ratio(UACR)indicated significant re-nal injury.Compared with db/m group,the mice in db/db group exhibited increased expression of FN,Col-III,α-SMA and Snail,and decreased expression of E-cadherin,HNF4A and MUCDHL.MUCDHL was predominantly expressed in the apical membrane of renal tubular epithelial cells,FN in the tubular mesenchyme,and HNF4A in the plasma and nu-cleus of renal tubular cells.(2)In HG group,there was an up-regulation in the expression of fibrosis-related proteins and a down-regulation in the expression of E-cadherin,HNF4A and MUCDHL compared with NG group.Overexpression of MUCDHL led to a decrease in the expression of FN,Col-III,α-SMA and Snail proteins,an increase in the expression of E-cadherin and MUCDHL proteins,and unaltered expression of HNF4A.Knockdown of MUCDHL resulted in a reversal of the aforementioned effects,with HNF4A expression remaining unaltered.Overexpression of HNF4A led to an increased ex-pression of MUCDHL,and the expression changes of the remaining indicators were consistent with the overexpression of MUCDHL.Knockdown of HNF4A reversed the aforementioned effects.MUCDHL may represent a downstream target gene of HNF4A.CONCLUSION:The diminished expression of HNF4A and MUCDHL in the renal tubules of diabetic mice implies their involvement in the progression of renal fibrosis in diabetic kidney disease(DKD).HNF4A may potentially impede the progression of renal fibrosis in DKD by up-regulating the expression of MUCDHL.

Brain computer interface(BCI)is a rapidly developing rehabilitation technology in recent years, which has been gradually used for cognitive rehabilitation of stroke patients.BCI can activate brain regions related to cognition to a greater extent through motor imagery and neural feedback technology, promote functional connectivity between brain regions, and ameliorate cognitive impairment after stroke.This paper summarized the mechanisms involved in BCI promoting cognitive rehabilitation and current applications of BCI in post-stroke cognitive impairment, and identifies the shortcomings of BCI in the treatment of post-stroke cognitive impairment, in order to provide insight for the research and clinical practice of BCI in post-stroke cognitive rehabilitation.

OBJECTIVE To study the preparation technology based on quality by design (QbD) concept of Erdong decoction particles, and to control its quality. METHODS Design L9(34) orthogonal test method, and the extraction process of Erdong decoction was optimized by AHP-CRITIC mixed weighted method with the extract rate, index component transfer rate and total polysaccharide as evaluation indexes. Taking ratio of briquetting, dissolution rate, angle of repose and moisture absorption rate as indexes, the central composite design-response surface methodology method combined with entropy weight method was used to optimize the forming process of Erdong decoction granules. The relative homogeneity index, bulk density, vibration density, moisture, hygroscopicity, angle of reposition and Hausner ratio were used as indicators to establish a physical fingerprint to evaluate particle quality consistency. RESULTS The optimal extraction process of Erdong decoction was to add 12 times of water without soaking and extract it 3 times for 30 min each time. The mean comprehensive score of the three batches of repeated validation tests was 54.24, and the RSD was 1.09%. The optimum molding process of Erdong decoction granules was as follows: the ratio of dry paste powder to auxiliary material was 1∶0.6, the volume fraction of wetting agent was 87%, the amount of wetting agent was 16%, and it was dried at 80 ℃ for 30 min. The similarity of physical fingerprints of 5 batches of particles was>0.99. CONCLUSION The method is stable and feasible, which can provide direction for the industrial production of Erdong decoction granules and the further research of this preparation.

Objective:To discuss the effect of NOD-like receptor protein 3(NLRP3)inflammasome on the renal interstitial fibrosis in the unilateral ureteral obstruction(UUO)model rats,and to clarify its potential mechanism.Methods:Thirty healthy male Wistar rats were randomly divided into sham operation group(n=6)and UUO group(n=24).The rats in sham operation group underwent the dissection of the ureter without ligation,while the rats in UUO group were sacrificed on the 3rd,7th,and 14th days after operation,and based on the treatment duration,the rats were divided into UUO 3 d group(n=8),UUO 7 d group(n=8),and UUO 14 d group(n=8).HE staining and Masson staining were used to observe the pathomorphology of kidney tissue of the rats in various groups;reagent kits were used to detect the levels of malondialdehyde(MDA),activities of superoxide dismutase(SOD),and levels of hydroxyproline(HYP)in kidney tissue of the rats in various groups;immunohistochemistry method was used to detect the expression levels of α-smooth muscle actin(α-SMA)and transforming growth factor-β1(TGF-β1)proteins in kidney tissue of the rats in various groups;Western blotting method was used to detect the expression levels of NLRP3 protein in kidney tissue of the rats in various groups.Results:The HE staining results showed significant tubular dilation,interstitial edema,and widening,with increased infiltration of inflammatory cells,and shedding of epithelial cells was seen in parts of the tubular lumina of the rats in UUO group.Compared with sham operation group,the interstitial fibrosis scores of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were significantly increased(P<0.05);compared with UUO 3 d group and UUO 7 d group,the interstitial fibrosis score of the rats in UUO 14 d group was significantly decreased(P<0.05).The Masson staining results showed that in UUO group,there was evident infiltration of inflammatory cells in the renal interstitium and a noticeable increase in fibrotic tissue proliferation;with the increasing of duration of UUO,some tubular structures disappeared,and the interstitial widened further with gradually increasing collagen deposition,particularly at the corticomedullary junction.Compared with sham operation group,the interstitial fibrosis scores of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were significantly increased(P<0.05);and compared with UUO 3 d and UUO 7 d groups,the interstitial fibrosis score of the rats in UUO 14 d group was significantly decreased(P<0.05).Compared with sham operation group,the levels of MDA in obstructed kidney tissue of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were significantly increased(P<0.05),and the SOD activities were significantly decreased(P<0.05).Compared with sham operation group,the levels of HYP in obstructed kidney tissue of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were also significantly increased(P<0.05);compared with UUO 3 d group,the level of HYP in obstructed kidney tissue of the rats in UUO 14 d group was significantly increased(P<0.05).The immunohistochemistry results showed that compared with sham operation group,the expression levels of α-SMA protein in kidney tissue of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were significant increased(P<0.05);compared with UUO 3 d and UUO 7 d groups,the expression levels of α-SMA protein in kidney tissue of the rats in UUO 14 d group was significantly increased(P<0.05);compared with sham operation group,the expression levels of TGF-β1 protein in renal tubular epithelial cells and renal tubule interstitial tissue of the rats in UUO 3 d,UUO 7 d,and UUO 14 d groups were also significantly increased(P<0.05);compared with UUO 3 d group,the expression levels of TGF-β1 protein in the tubular epithelial cells and renal tubule interstitial tissue of the rats in UUO 14 d group were significantly decreased(P<0.05).The Western blotting results showed that compared with sham operation group,the expression levels of NLRP3 protein in kidney tissue of the rats in UUO 7 d and UUO 14 d groups were significantly increased(P<0.05).Conclusion:The NLRP3 inflammasome plays a critical role in renal fibrosis of the UUO rats,and its mechanism may be related to the increasing of oxidative stress and the increasing of expression level of TGF-β1 protein.

Objective:To analyze the types and functions of CD34 + cells in full-thickness skin defect wounds of normal mice and diabetic mice by single-cell RNA sequencing. Methods:This study was an experimental study. The CD34 + cell lineage tracing mouse was produced, and the visualization of CD34 + cells under the fluorescent condition was realized. Six male CD34 + cell lineage tracing mice aged 7-8 weeks (designated as diabetic group) were intraperitoneally injected with streptozotocin to establish a diabetic model, and full-thickness skin defect wounds were prepared on their backs when they reached 13 weeks old. Another 6 male CD34 + cell lineage tracing mice aged 13 weeks (designated as control group) were also subjected to full-thickness skin defect wounds on their backs. On post-injury day (PID) 4, wound tissue was collected from 3 mice in control group and 2 mice in diabetic group, and digested to prepare single-cell suspensions. CD34 + cells were screened using fluorescence-activated cell sorting, followed by single-cell RNA sequencing. The Seurat 4.0.2 program in the R programming language was utilized for dimensionality reduction, visualization, and cell clustering analysis of CD34 + cell types, and to screen and annotate the marker genes for each CD34 + cell subpopulation. Kyoto encyclopedia of genes and genomes (KEGG) and gene ontology (GO) enrichment analysis was performed to analyze the differentially expressed genes (DEGs) of CD34 + fibroblasts (Fbs), smooth muscle cells (SMCs), keratinocytes (KCs), and chondrocyte-like cells (CLCs) in the wound tissue of two groups of mice for exploring cellular functions. Results:On PID 4, CD34 + cells in the wound tissue of both groups of mice were consisted of 7 cell types, specifically endothelial cells, Fbs, KCs, macrophages, T cells, SMCs, and CLCs. Among these, Fbs were further classified into 5 subpopulations. Compared with those in control group, the proportions of CD34 + endothelial cells, Fbs subpopulation 1, Fbs subpopulation 4, KCs, and CLCs in the wound tissue of mice were increased in diabetic group, while the proportions of CD34 + Fbs subpopulation 2, Fbs subpopulation 3, and SMCs were decreased. The marker genes for annotating CD34 + CLCs, endothelial cells, Fbs subpopulation 1, Fbs subpopulation 2, Fbs subpopulation 3, Fbs subpopulation 4, Fbs subpopulation 5, KCs, macrophages, SMCs, and T cells were respectively metastasis-associated lung adenocarcinoma transcript 1, fatty acid binding protein 4, Gremlin 1, complement component 4B, H19 imprinted maternally expressed transcript, Dickkopf Wnt signaling pathway inhibitor 2, fibromodulin, keratin 5, CD74 molecule, regulator of G protein signaling 5, and inducible T-cell co-stimulator molecule. KEGG and GO enrichment analysis revealed that, compared with those in control group, DEGs with significant differential expression (SDE) in CD34 + Fbs from the wound tissue of mice in diabetic group on PID 4 were significantly enriched in terms related to inflammatory response, extracellular matrix (ECM) organization, regulation of cell proliferation, and aging (with Pvalues all <0.05), DEGs with SDE in CD34 + SMCs were significantly enriched in terms related to cell migration, apoptotic process, positive regulation of transcription, and phagosome (with P values all <0.05), DEGs with SDE in CD34 + KCs were significantly enriched in terms related to mitochondrial function, transcription, and neurodegenerative diseases (with P values all <0.05), and DEGs with SDE in CD34 + CLCs were significantly enriched in terms related to rhythm regulation, ECM, and viral infection (with P values all <0.05). Conclusions:CD34 + cells display high heterogeneity in the healing process of full-thickness skin defect wounds in both normal mice and diabetic mice. The significantly enriched functions of DEGs with SDE in CD34 + cell subpopulations in the wound tissue of the two mouse groups are closely related to the wound healing process.

Objective To investigate how maternal MTR gene polymorphisms and their interactions with periconceptional folic acid supplementation are associated with the incidence of ventricular septal defects(VSD)in offspring.Methods A case-control study was conducted,recruiting 426 mothers of infants with VSD under one year old and 740 mothers of age-matched healthy infants.A questionnaire survey collected data on maternal exposures,and blood samples were analyzed for genetic polymorphisms.Multivariable logistic regression analysis and inverse probability of treatment weighting were used to analyze the associations between genetic loci and VSD.Crossover analysis and logistic regression were utilized to examine the additive and multiplicative interactions between the loci and folic acid intake.Results The CT and TT genotypes of the maternal MTR gene at rs6668344 increased the susceptibility of offspring to VSD(P<0.05).The GC and CC genotypes at rs3768139,AG and GG at rs1050993,AT and TT at rs4659743,GG at rs3768142,and GT and TT at rs3820571 were associated with a decreased risk of VSD(P<0.05).The variations at rs6668344 demonstrated an antagonistic multiplicative interaction with folic acid supplementation in relation to VSD(P<0.05).Conclusions Maternal MTR gene polymorphisms significantly correlate with the incidence of VSD in offspring.Mothers with variations at rs6668344 can decrease the susceptibility to VSD in their offspring by supplementing with folic acid during the periconceptional period,suggesting the importance of periconceptional folic acid supplementation in genetically at-risk populations to prevent VSD in offspring.