Elevated glucose metabolism is a prominent characteristic of fibroblast-like synoviocytes (FLS) in rheumatoid arthritis (RA). However, the efficacy of inhibiting a single target of glucose metabolism in FLS using small molecular inhibitors is limited for RA treatment. Herein, the synergistic inhibition of FLS' survival, proliferation, and activation by combining two glucose metabolism inhibitors, diclofenac (DC) and lonidamine (LND) was first verified. Subsequently, DC and LND were individually conjugated to cystamine-modified hyaluronic acid (HA) to prepare two polymer-prodrug conjugates. A HAP-1 peptide-modified dual polymer-prodrug conjugates-assembled nanoparticles system (^HAP-1NP_DC+LND) was further tailored in the optimal synergistic ratio for targeted and synergistic metabolic modulation of FLS to alleviate RA symptoms. Upon targeted uptake by FLS in inflamed joints, ^HAP-1NP_DC+LND released DC and LND within the intracellular reductive microenvironment, where DC hinders glucose uptake and LND suppresses glycolytic enzymes to eliminate FLS synergistically. Additionally, the secretion of lactic acid and pro-inflammatory factors from FLS were reduced, thereby disrupting the crosstalk between FLS and pro-inflammatory macrophages. Finally, ^HAP-1NP_DC+LND demonstrated promising efficacy in a mouse model of collagen-induced arthritis (CIA). Overall, this research provides valuable insights into novel therapeutic strategies for the safe and effective of treatment RA through targeted and synergistic metabolic modulation of FLS.

Hypoxia-inducible factor (HIF-1α), a core transcription factor responding to changes in cellular oxygen levels, is closely associated with a wide range of physiological and pathological conditions. However, its differential impacts on vascular cell types and molecular programs modulating human vascular homeostasis and regeneration remain largely elusive. Here, we applied CRISPR/Cas9-mediated gene editing of human embryonic stem cells and directed differentiation to generate HIF-1α-deficient human vascular cells including vascular endothelial cells, vascular smooth muscle cells, and mesenchymal stem cells (MSCs), as a platform for discovering cell type-specific hypoxia-induced response mechanisms. Through comparative molecular profiling across cell types under normoxic and hypoxic conditions, we provide insight into the indispensable role of HIF-1α in the promotion of ischemic vascular regeneration. We found human MSCs to be the vascular cell type most susceptible to HIF-1α deficiency, and that transcriptional inactivation of ANKZF1, an effector of HIF-1α, impaired pro-angiogenic processes. Altogether, our findings deepen the understanding of HIF-1α in human angiogenesis and support further explorations of novel therapeutic strategies of vascular regeneration against ischemic damage.
Humans ; Vascular Endothelial Growth Factor A/metabolism* ; Endothelial Cells/metabolism* ; Transcription Factors/metabolism* ; Gene Expression Regulation ; Hypoxia/metabolism* ; Cell Hypoxia/physiology*

Logistics informatization is importantfor promoting the high-quality development of public hospitals.It is a driving force for innovating hospital logistics management and an important practice of"green hospitals"and"smart hospitals".The logistics information system can effectively integrate people,machines,materials,and events of hospitals to achieve data-driven scientific management and improve service and management efficiency.By analyzing the current status of logistics manage-ment in the Sun Yat-sen University Cancer Center,this article proposes a transformation path to and management ideas for hospi-tal refined logistics management based on the information system,expecting to provide an insight into future information construc-tion and hospital logistics management development.

As public hospitals continue to expand,buildings continue to age,sporadic renovation projects are increas-ing,and expenditures are increasing.In order to ensure the safe,stable and efficient operation of the hospital,the piecemeal re-pair project has become an important basic guarantee for the hospital.There are many kinds of sporadic repair projects,and the projects are trivial and scattered.The contradictions among the needs,cost control,management ability and service quality of sporadic repair projects are becoming increasingly prominent,which has become the difficulty and pain point of logistics service management.In the practice of hospital sporadic repair project management,the traditional project management mode is broken,the whole process of fine management system is established,the level of management personnel and the whole process of the pro-ject are effectively integrated,and the management ability and service quality of sporadic maintenance projects are comprehensive-ly improved.

Objective To compare the clinical outcomes and retinal volume changes in patients with ischemic and non-ischemic macular edema secondary to branch retinal vein occlusion(BRVO-ME)using optical coherence tomography angiography(OCTA).Methods The clinical data of 34 ischemic BRVO-ME patients(34 eyes,ischemic group)and 21 non-ischemic BRVO-ME patients(21 eyes,non-ischemic group)were retrospectively analyzed.Patients in both groups re-ceived intravitreal injections of ranibizumab.The best corrected visual acuity(BCVA)and retinal volume of the macular ar-ea were assessed before,1 day,1 week,1 month,3 months and 6 months after the treatment.Results The BCVA(log-MAR)at 1 day after the treatment was 0.63±0.37 in the ischemic group and 0.44±0.22 in the non-ischemic group,and the difference was statistically significant(P=0.017).The retinal volumes of the outer retina,the full retina,and the Farafovea and Perifovea subdivisions of the full retina before the treatment were(6.42±1.90)mm3,(8.75±1.82)mm3,(3.20±0.87)mm3 and(5.10±0.89)mm3 in the ischemic group and(5.52±1.57)mm3,(7.83±1.56)mm3,(2.80± 0.71)mm3,and(4.66±0.77)mm3 in the non-ischemic group,respectively;1 day after treatment,they were(4.97± 1.18)mm3,(7.46±1.47)mm3,(2.62±0.60)mm3 and(4.53±0.80)mm3 in the ischemic group and(4.25±0.48)mm3,(6.58±0.56)mm3,(2.26±0.26)mm3 and(4.06±0.40)mm3 in the non-ischemic group,respectively;at 1 week after the treatment,they were(4.40±0.82)mm3,(6.90±0.85)mm3,(2.38±0.36)mm3 and(4.24±0.49)mm3 in the ischemic group and(4.04±0.35)mm3,(6.33±0.49)mm3,(2.15±0.19)mm3 and(3.95±0.35)mm3 in the non-ische-mic group,respectively,and the differences between the two groups were statistically significant(all P＜0.05).The a-mount of retinal volume change from baseline in the outer retina and the full retina was(-2.48±2.38)mm3 and(-2.54±2.38)mm3 in the ischemic group,and(-1.31±1.58)mm3 and(-1.38±1.58)mm3 in the non-ischemic group at 1 month after treatment,respectively,and the differences between the two groups were statistically significant(both P＜0.05).Conclusion Ranibizumab is effective in treating both ischemic and non-ischemic BRVO-ME.The short-term visu-al prognosis is better in the non-ischemic group than the ischemic group,and the retinal volume is higher in the ischemic group than the non-ischemic group.However,no significant difference is observed in the visual prognosis or retinal volume between the two groups after long-term treatment.

OBJECTIVE To improve the quality evaluation method of Platycodonis Radix, to study the differences in the quality of three-years-old Platycodonis Radix under different harvesting periods, and to determine the optimal harvesting period of Platycodonis Radix. METHODS The leachate, ash, moisture, refractive index and the content of six saponins were used as the quality evaluation indexes. The differences between the herbs of Platycodonis Radix at different harvesting periods were characterized with the help of mathematical and statistical methods. And link the entropy weight method, gray correlation analysis and TOPSIS method were combined to obtain the statistical analysis of the relevant indexes and the quality ranking information of the herbs in different harvesting periods. RESULTS There were significant differences between the quality evaluation indexes of three-years-old Platycodonis Radix at different harvesting periods. The added multi-indicator testing had improved the quality evaluation system of Platycodonis Radix and enhanced the "Drug properties-Effectiveness" linkage of the herbs. And the results of the comprehensive quality evaluation model showed that the herbs harvested around October 21 (Frost’s Descent) were ranked best in terms of comprehensive index. CONCLUSION In order to ensure the quality of Platycodonis Radix, the best harvesting period for three-years-old Platycodonis Radix is determined around the "Frost’s Descent" season, taking into account the characteristics of the herbs' appearance and the material basis of herbs.

Objective To observe the value of anatomical characteristics of femoral intercondylar notch of knee joint for predicting non-contact anterior cruciate ligament tear(NC-ACLT).Methods MRI data of knee joint of 55 patients with NC-ACLT(NC-ACLT group)and 55 controls(control group)were retrospectively analyzed.The parameters of intercondylar notch,including depth,width,depth/width ratio,opening width,opening width index,area and width of the femoral condyle's outer edge at the same level were measured between groups,and the types of intercondylar notch(type A,U and W)were recorded.Univariate and multivariate logistic regression analysis were used to screen the independent impact factors of NC-ACLT.Receiver operating characteristic curves were drawn,and the area under the curves(AUC)were calculated to evaluate the efficacy of each intercondylar notch parameter for predicting NC-ACLT.Results The depth and depth/width ratio of intercondylar notch in NC-ACLT group were both higher,while the opening width and opening width index of intercondylar notch in NC-ACLT group were both lower than those in control group(all P＜0.05).Multivariate logistic regression analysis revealed that the depth of intercondylar notch was an independent impact factors of NC-ACLT(P＜0.05).Taken 29.55 mm in depth of intercondylar notch,1.45 in depth/width ratio of intercondylar notch,21.15 mm in opening width of intercondylar notch and 0.29 in opening width index as the optimal cut-off value,respectively,the sensitivity of the above parameters for predicting NC-ACLT was 74.55％,58.18％,67.27％and 67.27％,the specificity was 69.09％,80.00％,61.82％and 78.18％,and the AUC was 0.720,0.713,0.652 and 0.710,respectively.Conclusion The anatomical characteristics of femoral intercondylar notch of knee joint could be used to predict NC-ACLT.The depth,depth/width ratio,opening width and opening width index of intercondylar notch could be used as predictive indicators.

Objective:To explore the effect of sinomenine(SIN)on LPS-induced apoptosis and autophagy of lung epithelial cells through the JNK/c-Jun signaling pathway.Methods:MLE-12 lung epithelial cells were cultured,and the toxicity of SIN was detected by CCK-8.Apoptosis was detected by flow cytometry,the number of autophagosomes was detected by immunofluorescence,and the expression levels of apoptosis,autophagy and JNK/c-Jun signaling pathway-related proteins were detected by Western blot.Results:After LPS modeling,apoptosis rate and the number of autophagosomes were increased,the protein levels of Cleaved caspase-3,Bax,and Beclin-1,and LC3Ⅱ/LC3Ⅰ,p-JNK/JNK and p-c-Jun/c-Jun were increased(P<0.05);Bcl-2 and P62 protein levels were decreased(P<0.05).SIN treatment can significantly improve the effects of LPS on apoptosis and autophagy,as well as the regulation of the JNK/c-Jun signaling pathway(P<0.05).Treatment with the autophagy inhibitor 3-MA or the JNK agonist ANISO could partially reverse the protective effect of SIN on LPS-induced lung epithelial cells(P<0.05).Conclusion:SIN may increase autophagy and pro-tect lung epithelial cells damaged by LPS by regulating proteins related to the JNK/c-Jun signaling pathway.

Hair loss affects millions of people at some time in their life, and safe and efficient treatments for hair loss are a significant unmet medical need. We report that topical delivery of quercetin (Que) stimulates resting hair follicles to grow with rapid follicular keratinocyte proliferation and replenishes perifollicular microvasculature in mice. We construct dynamic single-cell transcriptome landscape over the course of hair regrowth and find that Que treatment stimulates the differentiation trajectory in the hair follicles and induces an angiogenic signature in dermal endothelial cells by activating HIF-1α in endothelial cells. Skin administration of a HIF-1α agonist partially recapitulates the pro-angiogenesis and hair-growing effects of Que. Together, these findings provide a molecular understanding for the efficacy of Que in hair regrowth, which underscores the translational potential of targeting the hair follicle niche as a strategy for regenerative medicine, and suggest a route of pharmacological intervention that may promote hair regrowth.
Mice ; Animals ; Quercetin/pharmacology* ; Endothelial Cells ; Hair ; Hair Follicle ; Alopecia

Objective:To investigate the value of visceral fat index (VAI) and lipid accumulation product (LAP) on predicting metabolic associated fatty liver disease (MAFLD) in the population without overweight/obesity.Methods:This study is a cross-sectional study. The physical examination data derived from International Physical Examination and Health Center of the Second Affiliated Hospital of Harbin Medical University from January to December 2021 were collected. According to the inclusion and exclusion criteria, a total of 4 304 subjects without overweight/obesity aged from 18-75 were included in this study. The subjects were divided into two groups with MAFLD or without MAFLD, according to the diagnostic criteria of MAFLD provided by The Asian Pacific Association for the Study of the liver clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease. Comparison of the clinical parameters (blood pressure, lipid, glucose) and obesity measurement indexes (BMI, VAI, LAP) between the two groups was analyzed. All subjects were respectively divided into four groups according to BMI, VAI and LAP quartile, which were defined as A, B, C, D. The prevalence of MAFLD in the population without overweight/obesity in quartile area groups of different obesity measurement indexes was calculated. Spearman′s rank correlation was used to evaluate the correlation between BMI, LAP, VAI and MAFLD in the population without overweight/obesity, respectively. Meanwhile, receiver operating characteristics (ROC) curves were used to calculate area under the curve (AUC) and evaluate the accuracy of BMI, VAI and LAP on predicting for MAFLD in the population without overweight/obesity.Results:The prevalence of MAFLD in the population without overweight/obesity was 10.87%. In the population without overweight/obesity, the clinical data blood pressure, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), triglyceride (TG) and fasting plasma glucose (FPG) in the group with MAFLD were significantly higher than those of the group without MAFLD (131/80 vs 113/70 mmHg, 5.29 vs 4.65 mmol/L, 3.21 vs 2.75 mmol/L, 1.87 vs 0.89 mmol/L, 5.60 vs 4.95 mmol/L; P<0.001), but high density lipoprotein cholesterol (HDL-C) of the group with MAFLD was significantly lower than that of the group without MAFLD (1.19 vs 1.49 mmol/L; P<0.001). The obesity measurement indexes (BMI, VAI, LAP) in the group with MAFLD were significantly higher than those of the group without MAFLD (22.10 vs 20.70 kg/m 2, 2.64 vs 1.00, 36.27 vs 12.48; all P<0.001). In the population without overweight/obesity, the prevalence of MAFLD was increased with the increase of BMI, VAI and LAP quartile area, and there was a linear correlation between MAFLD and obesity measurement indexes above. Spearman′s rank correlation analysis showed that correlation coefficient between obesity measurement indexes and MAFLD in the population without overweight/obesity was respectively LAP (0.427)>VAI (0.406)>BMI (0.282). ROC curve analysis showed that in the population without overweight/obesity, LAP had the highest accuracy on predicting MAFLD, with the AUC value of 0.896 (0.886-0.905), the optional cut-off value was 20.75, sensitivity and specificity was 85.9% and 79.0%, respectively. VAI (0.876) took the second place and BMI (0.761) located lastly. Conclusions:Both VAI and LAP have good prediction ability for MAFLD in the population without overweight/obesity. However, compared with VAI, LAP has higher accuracy on predicting MAFLD in the population without overweight/obesity.