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 standardize the main processes and related technical links of the clinical comprehensive evaluation of drugs， and provide guidance and reference for improving the quality of comprehensive evaluation evidence and its transformation and application value. METHODS The construction of Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs was based on the standard guideline formulation method of the World Health Organization （WHO）， strictly followed the latest definition of guidelines by the Institute of Medicine of the National Academy of Sciences of the United States， and conformed to the six major areas of the Guideline Research and Evaluation Tool Ⅱ. Delphi method was adopted to construct the research questions； research evidence was established by applying the research methods of evidence-based medicine. The evidence quality classification system of the Chinese Evidence-Based Medicine Center was adopted for evidence classification and evaluation. The recommendation strength was determined by the recommendation strength classification standard formulated by the Oxford University Evidence-Based Medicine Center， and the recommendation opinions were formed through the expert consensus method. RESULTS & CONCLUSIONS The Guideline for the Workflow of Clinical Comprehensive Evaluation of Drugs covers 4 major categories of research questions， including topic selection， evaluation implementation， evidence evaluation， and application and transformation of results. The formulation of this guideline has standardized the technical links of the entire process of clinical comprehensive evaluation of drugs， which can effectively guide the high-quality and high-efficient development of this work， enhance the standardized output and transformation application value of evaluation evidence， and provide high-quality evidence support for the scientific decision-making of health and the rationalization of clinical medication.

Aim To investigate the effect of Xuefu Zhuyu decoction on transforming growth factor-β1(TGF-β1 ) -induced endothelial-to-mesenchymal transition (EndMT) of pulmonary microvascular endothelial cells ( PMVEC), and further analyze the mechanism related to the TGF-β1/Smad signaling pathway. Method To construct an EndMT cell model, PMVEC was treated with TGF-β1 (5 μg · L

Hydrogel is a kind of material with high water content,good biocompatibility and extracellular matrix-like property,among which polypyrrole(PPy)conductive hydrogels have both physical characteristics and excellent conductivity of hydrogels themselves.Its conductivity can be used to detect electrical signals generated in biological systems and provide electrical stimulation to regulate the activities and functions of cells and tissues.These characteristics make it widely used in the biomedical field.The recent progress of PPy conductive hydrogels in biomedical field was reviewed in this paper.In terms of classification,according to the cross-linking mechanism of PPy and hydrogel matrix,the non-covalent cross-linked PPy conductive hydrogels and covalent cross-linked PPy conductive hydrogels were divided.The applications of PPy conductive hydrogels in the biomedical field(Skin damage repair,nerve repair,myocardial repair and flexible sensing,etc.)were mainly introduced,and the development trend and challenges of PPy conductive hydrogels in the biomedical field were discussed.

The adulteration and counterfeiting of herbal ingredients in medicinal and food homology (MFH) have a serious impact on the quality of herbal materials, thereby endangering human health. Compared to pharmaceutical drugs, health products derived from traditional Chinese medicine (TCM) are more easily accessible and closely integrated into consumers' daily life. However, the authentication of the authenticity of TCM ingredients in MFH has not received sufficient attention. The lack of clear standards emphasizes the necessity of conducting systematic research in this area. This study utilized DNA barcoding technology, combining ITS2, psbA-trnH, matK as universal barcode sequences, and DX, HH, JYH as specific barcode sequences, to identify the authenticity of commercial medicinal and food homology scented herbal teas. The aim was to investigate the authenticity of scented herbal tea products circulating in the market. The research results revealed that among 180 scented herbal tea samples, DNA barcodes were successfully obtained from 164 samples, while the remaining samples either lacked the target components or suffered severe DNA degradation, resulting in failed amplification. Combined with morphological identification studies, it was found that out of the 180 samples, 141 were authentic, accounting for 78.33% of the total samples, while 31 samples showed adulteration and 8 samples lacked the target components, accounting for 21.67% of the total samples. Additionally, water testing revealed that 5 samples of Carthamus tinctorius herbal tea exhibited the phenomenon of weight adulteration. This study exposed the presence of adulteration and weight adulteration in scented herbal tea products, highlighting the need for regulatory authorities to expedite the establishment of quality standards in scented herbal tea industry. These findings provide valuable insights for the rapid development of the scented herbal tea industry.

AIM:To study the expression of glucose transporters(GLUTs)and silent information regulators(SIRTs/sirtuins)in the liver of diabetic rats and human hepatocytes(LO2 cells)treated with high glucose.METHODS:(1)Twenty male SD rats were randomly divided into normal control(NC)group and diabetes mellitus(DM)group.The rats in DM group were given single intraperitoneal injection of streptozotocin(STZ,60 mg/kg)to establish the DM model,while the rats in NC group were intraperitoneally injected with equal volume of solvent once.Fasting blood glucose(FBG)and body mass were measured every 2 weeks.After 12 weeks of rearing,the blood and liver tissues of the rats were ob-tained after anesthesia with 1%sodium pentobarbitone,the biochemical indicators of blood were detected,and the liver in-dex was calculated.Hematoxylin-eosin(HE)staining and periodic acid-Schiff(PAS)staining were used to observe liver histopathological changes.Lipid accumulation in liver tissues was detected by oil red O staining.The expression levels of GLUTs and SIRTs family member proteins were detected in rat liver tissues.(2)The LO2 cells were treated with different concentrations of glucose for 48 h.The viability of the cells in each group was measured by CCK-8 assay,and Western blot was used to detected the protein expression levels of GLUTs and SIRTs in the cells.RESULTS:(1)Compared with NC group,the rats in DM group were depressed,lost weight,and the FBG and liver index were significantly increased(P＜0.05).The results of HE staining showed that the hepatic sinuses were dilatated and congested near the central vein in DM rats,and mild edema and scattered infiltration of inflammatory cells were found in liver cells.The results of oil red O staining showed the red fat droplets were diffusely scattered within liver cells in DM group.The results of PAS staining showed that there were numerous diffuse light purple circular droplets in the cytoplasm of the liver cells in the central ve-nous area of the DM rats.Western blot showed that the protein levels of GLUTs were higher and the protein levels of SIRTs were lower than those in NC group(P＜0.01).(2)The results of CCK-8 assay showed that the viability of LO2 cells was increased in 50 mmol/L glucose group(P＜0.01),without significant difference in 75,100 and 125 mmol/L glucose groups(all P＞0.05),and decreased in 150,175 and 200 mmol/L glucose groups(all P＜0.01).Later,150 mmol/L glu-cose was used as the high-glucose intervention condition.Western blot showed that the protein levels of GLUTs and SIRTs in LO2 cells under high glucose intervention were consistented with the results in animal experiments.CONCLUSION:High concentration of glucose can cause liver damage in SD rats and reduce the viability of human hepatocytes(LO2 cells).It can also increase the expression of GLUTs and decrease the expression of SIRTs in rat liver tissues and LO2 cells.Therefore,GLUTs and SIRTs family members may be the target proteins of diabetes-induced liver injury.

Objective This study explored the effects of Epimedium koreanum Nakai(EK)on liver function in normal,kidney yang deficiency(KYANGDS),and kidney yin deficiency(KYINDS)rats based on the theory of"You Gu Wu Yun."The study also investigated the connection between EK-induced liver injury and symptoms.Methods Seventy-two male SD rats were divided into normal,KYANGDS,and KYINDS groups using the random number table method.The KYANGDS model was established through intramuscular injection of 20 mg/kg of hydrocortisone,whereas the KYINDS model was established through daily gavage of 160 mg/kg of thyroid tablet suspension for 14 consecutive days.After successful modeling,the rats were divided into the normal,EK low-dose,EK high-dose,KYANGDS,KYANGDS+EK low-dose,KYANGDS+EK high-dose,KYINDS,KYINDS+EK low-dose,and KYINDS+EK high-dose groups using the random number table method.Animals in the drug groups were administered low(0.26 g/kg)and high(0.77 g/kg)EK extract doses through continuous gavage.The other groups received drinking water once a day for 28 consecutive days.Changes in body mass were monitored during the administration period,and serum alkaline phosphatase(ALP),alanine transaminase(ALT),aspartate transaminase(AST),direct bilirubin,indirect bilirubin(IBil),and total bilirubin(TBil)were measured at the end of administration using biochemical analyzers.The liver weight,visceral body ratio,and visceral brain ratio were measured.Hematoxylin and eosin staining were performed to observe the pathological changes in the liver.Results Compared with the normal group,the EK high-dose group showed a decrease in body weight on the 21st day during the drug administration period and an increase in IBil(P<0.05);the KYANGDS group had lower body weight at each measurement time point from the third to the 28th day,higher ALP,and lower liver weight(P<0.05).Compared with the KYANGDS group,the KYANGDS+EK high-dose group had decreased ALP levels(P<0.05).The pathological damage of liver tissue in each KYANGDS administration group improved,the presence of fat vacuoles were reduced,and pathological scores show a decreasing trend.Compared with the KYINDS group,KYINDS+EK high-dose group exhibited a higher IBil level and a lower visceral brain ratio(P<0.05).Conclusion EK has a small effect on the liver function of rats with KYANGDS within the dose range;however,it has a specific hepatogenic impact on normal and KYINDS rats,and EK-induced liver injury and the symptoms may be associated with each other.

Objective This study explored the effects of Epimedium koreanum Nakai(EK)on liver function in normal,kidney yang deficiency(KYANGDS),and kidney yin deficiency(KYINDS)rats based on the theory of"You Gu Wu Yun."The study also investigated the connection between EK-induced liver injury and symptoms.Methods Seventy-two male SD rats were divided into normal,KYANGDS,and KYINDS groups using the random number table method.The KYANGDS model was established through intramuscular injection of 20 mg/kg of hydrocortisone,whereas the KYINDS model was established through daily gavage of 160 mg/kg of thyroid tablet suspension for 14 consecutive days.After successful modeling,the rats were divided into the normal,EK low-dose,EK high-dose,KYANGDS,KYANGDS+EK low-dose,KYANGDS+EK high-dose,KYINDS,KYINDS+EK low-dose,and KYINDS+EK high-dose groups using the random number table method.Animals in the drug groups were administered low(0.26 g/kg)and high(0.77 g/kg)EK extract doses through continuous gavage.The other groups received drinking water once a day for 28 consecutive days.Changes in body mass were monitored during the administration period,and serum alkaline phosphatase(ALP),alanine transaminase(ALT),aspartate transaminase(AST),direct bilirubin,indirect bilirubin(IBil),and total bilirubin(TBil)were measured at the end of administration using biochemical analyzers.The liver weight,visceral body ratio,and visceral brain ratio were measured.Hematoxylin and eosin staining were performed to observe the pathological changes in the liver.Results Compared with the normal group,the EK high-dose group showed a decrease in body weight on the 21st day during the drug administration period and an increase in IBil(P<0.05);the KYANGDS group had lower body weight at each measurement time point from the third to the 28th day,higher ALP,and lower liver weight(P<0.05).Compared with the KYANGDS group,the KYANGDS+EK high-dose group had decreased ALP levels(P<0.05).The pathological damage of liver tissue in each KYANGDS administration group improved,the presence of fat vacuoles were reduced,and pathological scores show a decreasing trend.Compared with the KYINDS group,KYINDS+EK high-dose group exhibited a higher IBil level and a lower visceral brain ratio(P<0.05).Conclusion EK has a small effect on the liver function of rats with KYANGDS within the dose range;however,it has a specific hepatogenic impact on normal and KYINDS rats,and EK-induced liver injury and the symptoms may be associated with each other.

Objective:To investigate the molecular mechanism of autophagy and apoptosis induced by ultrafine carbon black in human bronchial epithelial cells (BEAS-2B cells), and to study the intervention effect and mechanism of N-acetylcysteine (NAC) on ultrafine carbon black-induced oxidative damage in BEAS-2B cells.Methods:In March 2023, BEAS-2B cells were used as research object, an in vitro airway model exposed to ultrafine carbon black was constructed. A control group and three carbon black exposure groups (50, 100, 200 μg/ml) were set up, and the cells were treated with corresponding concentrations of ultrafine carbon black for 24 hours. In addition, the experiment was divided into control group, NAC+ control group, 100 μg/ml carbon black exposure group and NAC+ exposure group. The corresponding groups were treated with 2 mmol/L NAC for 1 h and 100 μg/ml ultrafine carbon black for 24 h, respectively. Cell viability was measured by CCK-8 assay. Intracellular reactive oxygen species (ROS) level was detected by chemical fluorescence method. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT), as well as the content of malondialdehyde (MDA) were detected by colorimetry. The mRNA and protein expressions of autophagy-related genes[Atg5, Atg7, Beclin1, microtubule-associated protein light chain 3B (LC3B), p62 and lysosome-associated membrane protein 2 (LAMP2) ] and apoptosis-related genes [B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), Caspase3, Caspase9 and poly (ADP-ribose) polymerase 1 (PARP1) ] were determined by fluorescence quantitative PCR and Western blot. Cell apoptosis was determined by flow cytometry.Results:Compared with the control group, the relative survival rates of BEAS-2B cells in 50, 100, 200 μg/ml carbon black exposure groups were significantly decreased, the levels of ROS and MDA were significantly increased, and the activities of SOD, GSH-Px and CAT were significantly decreased ( P<0.05). The relative survival rate, ROS and MDA levels, SOD, GSH-Px and CAT activities were significantly correlated with the exposure dose of ultrafine carbon black ( rs=-0.755, 0.826, 0.934, -0.810, -0.880, -0.840, P<0.05). Compared with the control group, the relative expression levels of Atg5, Atg7, Beclin1, LC3B, p62, LAMP2, Bax, Caspase3, Caspase9, PARP1 mRNA and Atg5, Atg7, Beclin1, LC3BⅡ, p62, LAMP2, Bax, cleaved Caspase3 (C-Caspase3), cleaved Caspase9 (C-Caspase9), cleaved PARP1 (C-PARP1) protein and the ratio of LC3BⅡ/LC3BⅠ in 50, 100 and 200 μg/ml carbon black exposure groups were significantly increased, while the relative expression levels of Bcl-2 mRNA and protein were significantly decreased ( P<0.05). The changes of the above indexes were significantly correlated with the exposure dose of carbon black ( rs=0.892, 0.879, 0.944, 0.892, 0.828, 0.880, 0.814, 0.794, 0.931, 0.918, 0.813, 0.866, 0.774, 0.695, 0.918, 0.761, 0.794, 0.944, 0.833, 0.866, 0.905, -0.886, -0.748, P<0.05). Compared with 100 μg/ml carbon black exposure group, the relative survival rate, the activities of SOD, GSH-Px and CAT in NAC+exposure group were significantly increased, while the levels of ROS and MDA were significantly decreased, and the relative expression levels of LC3B, p62 and Caspase3 mRNA and protein as well as the ratio of LC3BⅡ/LC3BⅠ were significantly decreased, and the differences were statistically significant ( P<0.05). Compared with the control group, the apoptosis rates of BEAS-2B cells in 50, 100, 200 μg/ml carbon black exposure groups were significantly increased ( P<0.05), and there was a significant positive correlation between ultrafine carbon black exposure dose and cell apoptosis rate ( rs=0.944, P<0.05). While compared with 100 μg/ml carbon black exposure group, the apoptosis rate of NAC+exposure group was significantly decreased, and the difference was statistically significant ( P<0.05) . Conclusion:Cell autophagy and apoptosis may be important pathophysiological mechanisms of ultrafine carbon black-induced oxidative damage in BEAS-2B cells. NAC can alleviate the occurrence of BEAS-2B cell damage caused by ultrafine carbon black by regulating oxidative stress and the cascading autophagy and apoptosis pathways.

BackgroundPatients with depressive disorder commonly experience sleep disturbances. Previous studies have indicated that group exercise therapy is beneficial in alleviating depressive symptom among patients with depressive disorder. However， there is a lack of research on the impact of group exercise therapy on improving sleep quality in patients with depressive disorder. ObjectiveTo explore the impact of group exercise therapy on sleep quality in patients with acute mild-to-moderate depression during the acute phase， so as to provide references for clinically improving the sleep quality of patients with mild to moderate depressive disorder during the acute phase. MethodsFrom December 2018 to July 2021， patients with mild-to-moderate depressive disorder during the acute phase （n=40）， who met the diagnostic criteria for depressive disorder according to International Classification of Diseases， tenth edition （ICD-10） ，were recruited from the outpatient clinic of Beijing Anding Hospital， Capital Medical University. All participants underwent an 8-week moderate-intensity group exercise therapy program comprising three sessions per week， each lasting 60 minutes. Assessments were conducted at baseline and after 2， 4， 6 and 8 weeks of intervention using Visual Analogue Scale （VAS）， Hamilton Depression Scale-17 item （HAMD-17） and Pittsburgh Sleep Quality Index （PSQI）. The reduction scores at each time point relative to baseline treated as the dependent variables， time as the independent variable， baseline scores as covariates， with time as a fixed effect and baseline values as random effects. Data were analyzed using a linear mixed-effects model. ResultsThe PSQI scores of patients at baseline， 2， 4 ， 6 and 8 weeks after the intervention were （10.62±5.12）， （9.07±3.58）， （7.39±3.66）， （6.54±3.84） and （5.50±3.41）， respectively. The results of linear mixed effect model analysis showed that after 2， 4， 6 and 8 weeks of intervention， patients scored lower than baseline， with statistically significant differences observed in all cases （P<0.01）. The HAMD-17 sleep fcctor scores at baseline， 2， 4， 6 and 8 weeks were （2.25±1.56）， （2.06±1.49）， （1.36±1.27）， （1.22±1.46） and （0.97±1.34）， respectively. The results of linear mixed effects model analysis showed that the HAMD-17 sleep factor scores of 4， 6 and 8 weeks of intervention were lower than that of baseline， and the difference was statistically significant （P<0.05 or 0.01）. The VAS scores at baseline， 2， 4， 6 and 8 weeks after the intervention were （3.18±2.17）， （4.74±2.22）， （6.01±2.31）， （6.54±2.16） and （7.90±1.64）， respectively. The results of linear mixed effect model analysis showed that VAS scores of 2， 4， 6 and 8 weeks of intervention were higher than baseline，and the difference was statistically significant （P<0.01）. ConclusionGroup exercise therapy may improve sleep quality and alleviate depressive symptoms in patients with mild-to-moderate depressive disorder during the acute phase. ［Funded by National Key Research and Development Plan Project （number， 2016YFC1307200）； Beijing Municipal Hospital Scientific Research and Cultivation Plan Project （number， PX2024070）］