BACKGROUND:Gradient artificial bone repair scaffolds can mimic unique anatomical features in musculoskeletal tissues,showing great potential for repairing injured musculoskeletal tissues. OBJECTIVE:To review the latest research advances in gradient artificial bone repair scaffolds for tissue engineering in the musculoskeletal system and describe their advantages and fabrication strategies. METHODS:The first author of the article searched the Web of Science and PubMed databases for articles published from 2000 to 2023 with search terms"gradient,bone regeneration,scaffold".Finally,76 papers were analyzed and summarized after the screening. RESULTS AND CONCLUSION:(1)As an important means of efficient and high-quality repair of skeletal system tissues,gradient artificial bone repair scaffolds are currently designed bionically for the natural gradient characteristics of bone tissue,bone-cartilage,and tendon-bone tissue.These scaffolds can mimic the extracellular matrix of native tissues to a certain extent in terms of structure and composition,thus promoting cell adhesion,migration,proliferation,differentiation,and regenerative recovery of damaged tissues to their native state.(2)Advanced manufacturing technology provides more possibilities for gradient artificial bone repair scaffold preparation:Gradient electrospun fiber scaffolds constructed by spatially differentiated fiber arrangement and loading of biologically active substances have been developed;gradient 3D printed scaffolds fabricated by layered stacking,graded porosity,and bio-3D printing technology;gradient hydrogel scaffolds fabricated by in-situ layered injections,simple layer-by-layer stacking,and freeze-drying method;and in addition,there are also scaffolds made by other modalities or multi-method coupling.These scaffolds have demonstrated good biocompatibility in vitro experiments,were able to accelerate tissue regeneration in small animal tests,and were observed to have significantly improved histological structure.(3)The currently developed gradient artificial bone repair scaffolds have problems such as mismatch of gradient scales,unclear material-tissue interactions,and side effects caused by degradation products,which need to be further optimized by combining the strengths of related disciplines and clinical needs in the future.

Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

ObjectiveTo investigate the effects of Scutellariae Radix combined with epidermal growth factor receptor-tyrosine kinase inhibitors （EGFR-TKIs） on cell proliferation， apoptosis， cancer stem cell （CSC） marker expression， and metabolism in non-small cell lung cancer （NSCLC） cells. MethodsThe anti-tumor effects of Scutellariae Radix and EGFR-TKIs （gefitinib or osimertinib） in NSCLC cells were evaluated using the cell counting kit-8 （CCK-8） and Annexin V-FITC/propidium iodide （PI） double staining apoptosis assay. The activity of Scutellariae Radix and EGFR-TKIs in three-dimensional （3D） cultures of NSCLC cells was assessed using the CellTiter-Glo® 3D cell viability assay. The mRNA and protein expression levels of CSC markers， sex determining region y box protein 2 （SOX2） and aldehyde dehydrogenase 1 family member A1 （ALDH1A1）， were detected by quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot， respectively. Changes in intracellular reactive oxygen species （ROS） levels were detected by ROS staining， and the redox ratio was detected by femtosecond laser labeling free imaging （FLI）. ResultsUnder both two-dimensional （2D） and 3D culture conditions， compared with the blank group and EGFR-TKI group， the combination group showed significantly reduced cell viability and increased apoptosis rate （P<0.05）. Compared with the EGFR-TKI group， the mRNA and protein levels of CSC markers were significantly downregulated in the combination group （P<0.05）. Additionally， the redox ratio was significantly elevated （P<0.05）， and ROS levels were also increased in the combination group compared with the EGFR-TKI group. ConclusionIn NSCLC cells， Scutellariae Radix enhances the redox ratio and increases ROS levels， thereby inhibiting the expression of CSC markers and strengthening the anti-tumor effects of EGFR-TKIs. This provides a novel molecular mechanism by which Scutellariae Radix may enhance the sensitivity of targeted therapies.

This study aims to explore the mechanism of Huanglian Jiedu Decoction(HJD) in treating acute liver injury(ALI) in the mouse model of sepsis induced by lipopolysaccharide(LPS). Fifty-four male C57BL/6 mice were randomized into six groups: blank group, model group, low-, medium-, and high-dose group HJD, and dexamethasone group. The mouse model of sepsis was established by intraperitoneal injection of LPS after 7 days of gavage with HJD, and dexamethasone(0.2 mL) was injected intraperitoneally 1.5 h after modeling. The murine sepsis score(MSS) was recorded 12 h after modeling. The levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) in the liver tissue and tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) in the serum were measured by ELISA. Hematoxylin-eosin(HE) staining was used to observe the pathological changes of the mouse liver. The content of light chain 3 of microtubule-associated protein 1(LC3) was detected by immunofluorescence, and that of sirtuin 1(SIRT1) was detected by immunohistochemistry. The mRNA levels of adenosine 5'-monophosphate-activated protein kinase(AMPK), LC3, and P62 were detected by RT-PCR. Western blot was employed to determine the protein levels of AMPK, p-AMPK, and SIRT1 in the liver tissue. The results showed that compared with model group, drug interventions decreased the MSS and liver injury indicators, lowered the levels of inflammatory cytokines, improved the liver tissue structure, upregulated the protein levels of of p-AMPK/AMPK and SIRT1 and the mRNA levels of AMPK and LC3, and downregulated the mRNA level of P62. To sum up, HJD can regulate the autophagy level and reduce inflammation to ameliorate acute liver injury in septic mice by activating the AMPK/SIRT1 autophagy pathway.
Animals ; Drugs, Chinese Herbal/administration & dosage* ; Sirtuin 1/genetics* ; Male ; Mice ; Sepsis/metabolism* ; Mice, Inbred C57BL ; Autophagy/drug effects* ; AMP-Activated Protein Kinases/genetics* ; Liver/metabolism* ; Humans ; Signal Transduction/drug effects* ; Disease Models, Animal ; Tumor Necrosis Factor-alpha/genetics*

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*

Background Staff in biosafety laboratories (BSL) are more likely to experience occupational burnout and other psychological issues due to their unique working environment and high job demands. However, current research in this field tends to focus on overall analyses, overlooking the internal differences within this group. Objective To explore latent profiles of occupational burnout among BSL workers and their influencing factors, providing a reference for targeted burnout interventions. Methods In 2022, cluster random sampling was used to select 8023 BSL workers in Xinjiang. Data were collected via a questionnaire survey, including a self-designed general information questionnaire, the Maslach Burnout Inventory-General Survey (MBI-GS), and the Effort-Reward Imbalance (ERI) scale, to analyze demographic characteristics, occupational burnout, and job stress status. After data cleaning, latent profile analysis (LPA) was applied to identify burnout profiles, followed by K-means clustering for verification. Logistic regression was used to analyze influencing factors with burnout profiles as the dependent variable. Results After excluding invalid questionnaires, 7924 valid questionnaires were retained, with an recovery rate of 98.77%. The LPA results indicated that occupational burnout among BSL staff was categorized into three latent profiles: a low burnout profile (2208 individuals, 27.86%), a moderate burnout profile (4636 individuals, 58.51%), and a high burnout profile (1080 individuals, 13.63%). A similar grouping was derived from K-means clustering analysis (28.71%, 53.37%, and 17.92%), and a Sankey diagram demonstrated significant overlap between the two classification results. Statistically significant differences were observed across the three latent profiles in all three dimensions of burnout: emotional exhaustion, cynicism, and reduced personal accomplishment. The final logistic regression model revealed that the influencing factors exhibited characteristics of partial overlap and partial differentiation. Among the common influencing factors, the shared protective factors included: age ≥50 years (OR_{moderate burnout}=0.42, OR_{high burnout}=0.45), monthly income of 4000-6000 RMB (OR_{moderate burnout}=0.83, OR_{high burnout}=0.71), good sleep quality (OR_{moderate burnout}=0.70, OR_{high burnout}=0.13) and very good sleep quality (OR_{moderate burnout}=0.51, OR_{high burnout}=0.12), and engaging in physical exercise ≥5 times per week (OR_{moderate burnout}=0.74, OR_{high burnout}=0.48). The protective effects were more pronounced for the high burnout profile. The common risk factors included: 21–30 years of service (OR_{moderate burnout}=1.38, OR_{high burnout}=3.00), ≥31 years of service (OR_{moderate burnout}=1.47, OR_{high burnout}=3.39), working in "other positions" (OR_{moderate burnout}=1.46, OR_{high burnout}=1.56), and occupational stress (ERI>1) (OR_{moderate burnout}=2.62, OR_{high burnout}=3.25), with the risk effects being more significant for the high burnout profile. Regarding differentiated influencing factors, protective factors exclusively associated with the moderate burnout profile included having an associate degree (OR=0.70) and engaging in physical exercise 3-4 times per week (OR=0.74). For the high burnout profile, exclusive protective factors included age 40-50 years (OR=0.56), while exclusive risk factors included having a senior professional title (OR=1.85), holding a managerial role (OR=1.78), a high number of night shifts per month (OR=2.66), and a very high number of night shifts per month (OR=3.93). Conclusion BSL workers exhibit three distinct latent burnout profiles. Occupational burnout requires greater attention, and targeted prevention and intervention strategies should be developed based on worker subtypes.

Objective To discuss the accuracy and effectiveness of digital subtraction angiography(DSA)in determining the cause of limb ischemia after extra corporeal membrane oxygenation(ECMO.Methods The clinical data of 3 child patients,who developed 4 times of acute limb ischemia during perioperative period of ECMO at the Affiliated Children's Hospital of Zhengzhou University of China from July to October of 2023,were retrospectively analyzed.In all the child patients,emergency angiography was carried out to quickly identify the cause,then,appropriate treatment plan was adopted to open the blood vessels of the right lower limb.Results After the child patients entered the operating room and received DSA examination,the causes of the limb ischemia were quickly identified.After treatment,the blood supply to the lower limbs was restored.Except for one child who experienced irreversible necrosis of the distal limb due to repeated ischemia-reperfusion injury and required amputation,the other two child patients recovered well.Conclusion It is of great significance to perform DSA examination as soon as possible when the child patients develop limb ischemic manifestations after ECMO so as to quickly identify the cause,promptly restore blood supply to ischemic limbs and increase limb preservation rate,besides,DSA examination can also be used as a preventive measure for child patients after ECMO.

Objective To explore the safety and efficacy of semiconductor laser combined with sclerotherapy in the treatment of venous malformations(VM)in child patients.Methods The clinical data of 68 child patients with VM,who were admitted to the Affiliated Children's Hospital of Zhengzhou University of China from April 2023 to April 2024,were retrospectively analyzed.The child patients were divided into semiconductor laser combined with sclerotherapy group(laser+sclerotherapy group)and simple sclerotherapy group(sclerotherapy group),with 34 child patients in each group.The reduction rate of lesion size and the incidence of complications were compared between the two groups.Results The total effective rate and significant effective rate in the laser+sclerotherapy group were 100％ and 79.41％(27/34)respectively,which were higher than 82.35％(28/34)and 29.41％(10/34)respectively in the sclerotherapy group.The incidences of blister and pigmentation complications in the laser+sclerotherapy group were 11.76％(4/34)and 14.71％(5/34)respectively,which were lower than 41.18％(14/34)and 38.24％(13/34)respectively in the sclerotherapy group,and the differences between the two groups were statistically significant(all P＜0.05).Conclusion In treating child patients with VM,the combination use of semiconductor laser and sclerotherapy has higher clinical safety and effectiveness.

Objective To discuss the application value of intracavitary semiconductor laser therapy in improving facial appearance for child patients with facial venous malformations(VM)after receiving sclerotherapy.Methods The clinical data of 12 child patients with facial VM after receiving sclerotherapy,for whom the improvement of their facial appearance was difficult and who were admitted to the Affiliated Children's Hospital of Zhengzhou University of China from February 2023 to February 2024,were retrospectively analyzed.Intracavitary semiconductor laser treatment was adopted in all the 12 child patients.All the child patients were followed up to check the degree of appearance improvement and lesion volume reduction,and the curative effect was evaluated.Results Three months after intracavitary semiconductor laser treatment,obvious improvement of facial appearance was obtained in all the 12 child patients.The mean postoperative PAC-QOL psychological discomfort score was(10.4±3.9)points,when compared with the preoperative(23.7±4.3)points the difference was statistically significant(P＜0.05).MRI examination showed that after treatment no obvious improvement of the lesion was seen in 0 case,moderate improvement in one case,significant improvement in 4 cases,and cure in 7 cases.Conclusion Intracavitary semiconductor laser therapy has significant therapeutic effect in improving facial appearance for child patients with facial VM after receiving sclerotherapy,for whom the improvement of their facial appearance is difficult,therefore,this therapy has high clinical application value.

Objective To explore the effect of Polysaccharides of Panax notoginseng(PPN)on anti-exercise fatigue in mice.Methods One hundred male KM mice were randomly divided into negative control group,positive control group and experimental-L,-M,-H groups,with 20 cases per group.Experimental-L,-M,-H groups was given 100,200,400 mg·kg-1 PPN,respectively;positive control group was given 200 mg·kg-1 vitamin C;negative control group was given 0.1 mL·10 g-1 0.9％NaCl.Five groups were gavaged once a day for 28 days.After the last administration,the loaded swimming time was measured;after 90 minutes of the unloaded swimming test,the mice were allowed to rest for 30 minutes,the levels of lactic acid(LD),blood urea nitrogen(BUN),glycogen,and malondialdehyde(MDA)were measured,the safety of PPN with organ indices and histopathology.Results LD levels in negative control group,positive control group and experimental-L,-M,-Hgroupswere(4.76±0.84),(2.86±0.34),(3.00±0.69),(2.35±0.65)and(1.39±0.48)mg·kg-1;BUN contents were(13.65±1.25),(12.55±0.91),(12.12±1.24),(11.06±1.30)and(9.85±1.05)mmol·L-1;liver glycogen contents were(3.24±0.56),(11.11±2.16),(5.61±1.41),(6.60±1.49)and(12.05±2.25)mg·g-1;MDA levels were(2.36±0.21),(1.23±0.41),(1.93±0.23),(1.73±0.21)and(1.04±0.18)mg prot·mL-1.Compared with negative control group,the differences of above indexes in the positive control group and experimental-L,-M,-H groups were statistically significant(P＜0.05,P＜0.01,P＜0.001).Conclusion PPN can increase exercise endurance in mice and has an anti-fatigue effect.This study provides a theoretical basis for the application of PPN in the field of anti-fatigue research.