Diabetic nephropathy （DKD）， as a common microvascular complication of diabetes mellitus （DM）， is a major cause of end-stage renal disease （ESRD）. Its clinical manifestations include increased urinary protein excretion， thickening of the glomerular basement membrane， and renal tubulointerstitial fibrosis. The pathogenesis of DKD is complex and involves multiple factors， including disordered glucose metabolism， hemodynamic alterations， and oxidative stress. Although modern medical approaches can alleviate certain symptoms， they still have limitations such as insufficient therapeutic targeting and prominent adverse effects. The transforming growth factor-β/Smad （TGF-β/Smad） signaling pathway is not only a tissue fibrosis pathway that has attracted considerable attention in recent years， but also regulates multiple protein molecules， including the glomerular podocyte slit diaphragm protein Podocin， interleukin-1β （IL-1β）， and superoxide dismutase （SOD）， thereby participating in various pathological processes and ultimately mediating renal injury. Flavonoid compounds， owing to their sustained pharmacological effects， broad spectrum of action， and high safety profile， have become ideal candidates for targeted therapy research in DKD. Existing studies have shown that these compounds can exert inhibitory effects on renal fibrosis， alleviate inflammatory responses， protect podocytes， and reduce oxidative stress by regulating the interactions between the TGF-β/Smad signaling pathway and the aforementioned protein molecules， thereby maintaining renal structure and function， reducing proteinuria， and significantly improving DKD lesions. This review briefly outlines the composition and functions of the TGF-β/Smad signaling pathway， elucidates the mechanisms by which this pathway regulates DKD， and focuses on summarizing major studies from the past decade on flavonoid-based interventions in DKD through targeted inhibition of the TGF-β/Smad signaling pathway. Furthermore， it discusses the considerable therapeutic potential of flavonoids in the treatment of this disease， aiming to provide a scientific basis for future clinical prevention and treatment of DKD and to promote the development of targeted drugs.

Objective:To investigate the role of Fem-1 homolog C(FEM1C)in breast cancer progression and elucidate its underlying regulat-ory mechanism.Methods:The expression of FEM1C in breast cancer tissues and cells were detected with qPCR.The binding of FEM1C to ELAVL1 protein was predicted with an online database and validated by CoIP analysis;and the binding of ELAVL1 protein to OPA1 mRNA was predicted by using the starBase database and validated by RIP analysis.Next,breast cancer cell MDA-MB-231 was transfected with FEM1C shRNA(sh-FEM1C)or overexpression vector(FEM1C)or/and ELAVL1 overexpression vector(ELAVL1)or/and OPA1 overexpression vector(OPA1),or treated with 100 μM Mdivi-1,an DRP1 inhibitor,or MYLS22,an OPA1 inhibitor.Finally,nude mice were injected with sh-FEM1C lentiviral vectors to construct xenograft tumor models,and tumor growth was monitored.Results:The expression of FEM1C was upregu-lated in breast cancer tissues(P<0.01).Silencing FEM1C inhibited the proliferation,induced apoptosis,promoted the expression of auto-phagy protein LC3 Ⅱ/Ⅰ,inhibited p62 protein expression,upregulated the protein level of PINK1 in mitochondrial,promoted the expres-sion of mitochondrial fission proteins DRP1 and MIEF2,and inhibited the expression of fusion proteins OPA1 and MFN1 in MDA-MB-231 cells(P<0.01).Mdivi-1 treatment inhibited DRP1 expression(P<0.01),but had no effect on cell viability(P>0.05);MYLS22 treatment inhibited OPA1 expression and counteracted the effect of FEM1C overexpression on MDA-MB-231 cells(P<0.01).Mechanistic studies revealed that FEM1C binds to ELAVL1 protein and promotes its expression(P<0.01);ELAVL1 protein stabilizes OPA1 mRNA by binding to it and upregu-lates OPA1 protein levels(P<0.01).Overexpression of OPA1 reversed the effect of FEM1C silencing on MDA-MB-231 cells(P<0.01).In vivo results showed that knockdown of FEM1C inhibited tumor growth in vivo(P<0.01).Conclusions:FEM1C promotes the stability of OPA1 mRNA by upregulation of ELAVL1 protein to promote mitochondrial fusion and inhibit autophagy,thereby promoting breast cancer progression.

Objective To investigate the levels of gross α and gross β activities in different water types within a 40-kilometer radius around the Zhangzhou Nuclear Power Plant prior to its operation. Methods In 2018, drinking water samples were collected from the area surrounding the nuclear power plant during both the wet and dry seasons, including source water, treated water, tap water, and well water. The gross α and gross β activity concentrations were measured using a low-background α/β counter, followed by statistical analysis. Results A total of 80 water samples from different sources around the Zhangzhou Nuclear Power Plant were collected. The average gross α and gross β activity concentrations during the wet season were (0.110 ± 0.036) Bq/L and (0.643 ± 0.028) Bq/L, respectively, while those during the dry season were (0.124 ± 0.032) Bq/L and (0.624 ± 0.026) Bq/L, respectively. There were no significant differences in the gross α and gross β activity concentrations between the wet and dry seasons for the overall sample set (P > 0.05). However, there were statistically significant differences in the gross α and gross β activity concentrations between the wet and dry seasons for source water and well water (Z_wet = −2.005, −2.123; Z_dry = −1.943, −3.090; P < 0.05). Conclusion The radioactivity levels in different water types within various ranges around the Zhangzhou Nuclear Power Plant before its operation were determined. The measured activity concentrations were at the same level as those from previous investigations in other regions of Fujian Province.

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

OBJECTIVE To analyze the diagnosis of latent tuberculosis infection(LTBI)in hospitalized patients of a tertiary general hospital and investigate the current status of related comorbidities.METHODS The clinical data were collected from the 14 448 hospitalized patients who received tuberculin skin test(TST)or interferon-gamma release assay(IGRA)in China-Japan Friendship Hospital from Jan.1,2022 to Dec.31,2023,and the results were assessed.RESULTS The detection rate of LTBI was 23.62％(3413/14448)among the hospitalized patients who received the tests,and the rate of definite diagnosis was only 4.22％(144/3413).88.40％(3017/3413)of the hospitalized patients with LTBI had at least one type of comorbidity,and the top 5 comorbidities were in turn as follows:high blood pressure,hyperlipidemia,diabetes mellitus,malignant tumors and rheumatic immune disea-ses;the number of comorbidities was increased with the age(x2=291.199,P＜0.001).The rheumatic immune disease(73/144,50.69％)was the most common type of comorbidity among the hospitalized patients with definite diagnosis of LTBI,and less than half of the patients(66/144,45.83％)were treated in rheumatology and immu-nology department.CONCLUSION The two-way screening of LTBI and comorbidities is the core premise for the standardized management of LTBI.

Objective To explore the value of improved ResNet18 lightweight deep learning(DL)models for automatically detecting gouty arthritis(GA)based on ultrasonogram of the first metatarsophalangeal joint(MTP1).Methods A total of 2 401 ultrasonograms obtained from 260 patients with suspected gout who underwent MTP1 ultrasound examination were included and divided into training set(1 910 ultrasonograms from 209 cases)and test set(491 ultrasonograms from 51 cases)at the ratio of 4∶1.GA lesions on ultrasonograms were manually labeled.After preprocessing,ResNet18 lightweight network was used to construct DL models for identifying the ultrasonogram category was normal or abnormal(with any manifestation of GA).Five-fold cross-validation method was adopted to evaluate the efficacy of the DL models constructed with 2,3,4 or 6 residual blocks,i.e.model 1,2,3 and 4,respectively,and the computational cost and the amount of parameters of each model were recorded.The efficacy of the models were verified using test set,and the best DL model was screened.Results The computational cost of model 1,2,3 and 4 was 7 558.27,2 963.73,4 012.33 and 6 093.39 M,respectively,while the amount of parameters was 4.61,4.91,4.91 and 5.28 M,respectively.Model 2 had the least computational cost with parameters only slightly more than model 1.In test set,no significant difference of accuracy nor the area under the curve was found among 4 models(all P＞0.05).The sensitivity of model 2 was higher than that of model 3,while its specificity was lower only than that of model 3(both P＜0.05),hence model 2 was the best DL model.Conclusion Improved ResNet18 lightweight DL models could be used for automatically detecting GA based on ultrasonogram of MTP1,among which model 2 was the best one.