ObjectiveTo systematically evaluate the efficacy and safety of Qi-reinforcing and blood-activating/stasis-expelling Chinese patent medicines in the treatment of coronary microvascular disease （CMD）. MethodsPubMed， Cochrane Library， CNKI， Wanfang Data， and VIP were searched for the randomized controlled trials （RCTs） on the treatment of CMD with Chinese patent medicines for reinforcing Qi and activating blood/expelling stasis with the time interval from inception to December 31， 2023. The primary outcome indicators included the index of microcirculatory resistance （IMR）， coronary flow reserve （CFR）， and corrected TIMI flow frame count （cTFC）. The secondary outcome indicators included symptomatic efficacy， left ventricular ejection fraction （LVEF）， hypersensitive C-reactive protein （hs-CRP）， nitric oxide （NO）， and adverse events. Cochrane risk-of-bias assessment tool 2.0 （RoB 2.0） and Stata 17.0 were used for literature quality evaluation and meta-analysis of the included RCTs. The Grading of Recommendations， Assessment， Development and Evaluation （GRADE） was used to evaluate the quality of evidence. ResultsA total of 36 RCTs were included in this study， involving 3 029 patients. Compared with conventional Western medicine alone， the combined use of Chinese patent medicines for reinforcing Qi and activating blood/expelling stasis and Western medicine reduced the IMR ［mean difference （MD）=-5.93， 95% confidence interval （95%CI） ［-8.73，-3.14］， n=382， P<0.01］， cTFC （MD=-9.35， 95%CI ［-13.94，-4.76］， n=618， P<0.01）， and hs-CRP ［standard mean difference （SMD）=-1.50， 95%CI ［-1.90，-1.11］， n=1 483， P<0.01］， improved the CFR （SMD=1.14， 95%CI ［0.08，2.19］， n=304， P=0.03）， symptomatic efficacy ［relative risk （RR）=1.36， 95%CI ［1.21，1.53］， n=756， P<0.01］， LVEF （MD=4.39， 95%CI ［2.31，6.47］， n=533， P<0.01）， and NO （SMD=3.16， 95%CI ［2.07，4.25］， n=946， P<0.01） of CMD patients. In terms of safety， the combined therapy reduced the occurrence of adverse events in CMD patients （RR=0.49， 95%CI ［0.29，0.82］， n=591， P=0.01）. GRADE showed moderate quality evidence for adverse events， low quality evidence for cTFC， symptomatic efficacy， LVEF， and NO， and very low quality evidence for IMR， CFR， and hs-CRP. ConclusionBased on microcirculatory function indicators， the combined use of Qi-reinforcing and blood-activating/stasis-expelling Chinese patent medicines and Western medicine may further improve the coronary microvascular function in CMD patients with good safety. The above conclusions remain to be verified with high-quality clinical trials.

“Stasis generating deficiency” is considered to be an important pathogenesis of recurrence after catheter ablation of atrial fibrillation （AF）. Blood stasis is commonly seen after ablation together with various pathogens such as phlegm-fire， qi stagnation and retained fluid， and will lead to depletion of zang-fu （脏腑） organs and then the failure of the nourishment of the heart. Therefore， it is advised to emphasize on the importance of considering zang-fu organs depletion caused by blood stasis and various excess pathogens in dealing with the recurrence after catheter ablation. The method of dissolving stasis and supplementing deficiency simultaneously has been proposed before catheter ablation， and it is critical to calm heart and dissolve stasis， regulate and supplement internal deficiency so as to prevent the postoperative recurrence of AF. For recurrence of AF after ablation， attention should be paid to dissolving stasis and dispelling pathogens， regulating vessels and supplementing deficiency， as well as the excess pathogens such as stasis binding and phlegm fire， stasis binding and qi stagnation， stasis binding and retained fluid， and the depletion of zang-fu organs should be considered. Accordingly， the method of dissolving stasis and dispelling phlegm， subduing fire and unblocking vessels， regulating and supplementing heart and spleen； dissolving stasis and move stagnation， unblocking qi and blood， supplementing lung and boosting qi； dispelling stasis and dissolving rheum， warming yang and activating blood， consolidating the root and nourishing heart can be used respectively， so as to treat both the root and the branch simultaneously.

OBJECTIVE To investigate the role of the complement C3/C3aR signaling pathway in the prefrontal cortex and colon neuroglia cell interactions during meth-amphetamine(METH)addiction,to observe the effects of TLR4 inhibitors as well as complement C3 elimination on METH reward and relapse behavior,and to explore the neuroinflammatory mechanisms of complement C3 acti-vation in METH addiction.METHODS ①A 14 d and 28 d rat METH addiction model was established to observe the effects of TLR4 antagonist ibudilast 3 mg·kg-1 and 10 mg·kg-1 on self-administration,reward motivation,relapse,and natural reward behavior in METH-trained 14 d rats and the effects of 0.02 mg·kg-1 complement C3 antago-nist on self-administration behavior in METH-trained 28 d rats.② Differences in the expression of TLR4,NF-κB,GRP94,C3,cathepsin L,CD68,and GFAP in the pre-frontal cortex of each group were examined using West-ern blotting.③ In addition,the expression of ATF6 in the prefrontal cortex of each group and the effects on neuro-nal and microglia/macrophage INOS,CD206 GRP94,and complement C3/C3aR.RESULTS ① Endoplasmic reticulum stress occurred in neurons and microglia after METH exposure depending on GRP94 and unfolded pro-tein responses to the ATF6 pathway.In addition,it acti-vates the TLR4-NF-κB pathway.② Microglia with high complement C3/C3aR expression in the prefrontal cortex were recruited to synaptic pruning and phagocytic responses around neurons with high GRP94,comple-ment C3/C3aR expression and these effects were blocked by complement C3 antagonists.③ In the rec-tum,GRP94 functions as a molecular chaperone for com-plement C3 and cathepsin L.Crosstalk occurs between enteric neurons high in GRP94,complement C3,and macrophages high in C3aR,located in the submucosa,lamina propria,and muscular,respectively,and all of these effects are blocked by complement C3 antago-nists.④ Treatment with the TLR4 antagonist ibudilast inhibits self-administration,reward motivation,and cue-or METH-priming in METH-trained 14 d rats,but fails to affect natural reward behavior.Ibudilast treatment attenu-ates the TLR4-NF-κB inflammatory pathway and comple-ments C3/C3aR pathway in the prefrontal cortex.CON-CLUSION Activation of the complement C3/C3aR signal-ing pathway by TLR4-NF-κB inflammatory signaling in the prefrontal cortex mediates the METH addiction pro-cess,providing an experimental basis for the clinical treatment of METH addiction,and targeting TLR4/NF-κB inflammatory signaling and complement C3/C3aR may be a new way to intervene in METH addiction.

The gummy smile means excessive gingival display, which impairs patients’ appearance, psychological status, and social relationships. With the development of orthodontics, orthognathics, periodontics, and plastic surgeries, the treatment of the gummy smile turned into comprehensive multidisciplinary approaches. The etiology and recently developed approaches will be reviewed in this article.

The gummy smile means excessive gingival display, which impairs patients’ appearance, psychological status, and social relationships. With the development of orthodontics, orthognathics, periodontics, and plastic surgeries, the treatment of the gummy smile turned into comprehensive multidisciplinary approaches. The etiology and recently developed approaches will be reviewed in this article.

The gummy smile means excessive gingival display, which impairs patients’ appearance, psychological status, and social relationships. With the development of orthodontics, orthognathics, periodontics, and plastic surgeries, the treatment of the gummy smile turned into comprehensive multidisciplinary approaches. The etiology and recently developed approaches will be reviewed in this article.

The gummy smile means excessive gingival display, which impairs patients’ appearance, psychological status, and social relationships. With the development of orthodontics, orthognathics, periodontics, and plastic surgeries, the treatment of the gummy smile turned into comprehensive multidisciplinary approaches. The etiology and recently developed approaches will be reviewed in this article.

Objective:The differentially expressed genes were screened from microarray data in the patients with non-syndromic craniosynostosis, and a protein interaction network was established to screen and predict hub genes related to the disease.Methods:The data set of GSE50796 were downloaded from the GEO database, which included seven samples of the closed cranial suture tissues from the non-syndromic craniosynostosis patients, and seven samples of the unclosed cranial suture tissues from the non-syndromic craniosynostosis patients. Analyze the differentially expressed genes were collected and analyzed with GEO2R, a GEO database online tool. P<0.05 and |logFC|> 2 were set as filter criteria. The ggplot2 of R package was applied for GO enrichment analysis, and the KEGG pathway analysis was completed with Enrichr. Gene set enrichment analysis (GSEA) was performed via GSEA 3.0 to analyze the correlation between gene sets and phenotypes. Secondly, the STRING database was used to analyze the interaction relationships between differentially expressed proteins in different tissues, and then Cytoscape and related plug-ins were used to establish the differentially expressed protein interaction network and screen the hub genes. Meanwhile, the key modules, important biological processes, and multiple co-expression relationships were analyzed. Results:A total of 255 differentially expressed genes based on the above screening conditions were obtained. The regulation of neural development screened by GO enrichment analysis, the PI3K-Akt signaling pathway screened by KEGG enrichment analysis, the important biological pathways (DNA replication, cell cycle, cytokine and receptor interaction) screened by GSEA enrichment analysis, and the positive regulation of osteoblast differentiation screened by ClueGO analysis, might be closely related to the etiology of non-syndromic craniosynostosis. The up-regulated hub genes such as CLEC12A, MS4A3 and DNTT in the group with closed sutures were screened by protein-protein interaction network and literature analysis, which might play a vital role in the pathogenic processes of non-syndromic craniosynostosis.Conclusions:With the multi-dimensional enrichment analysis of the differentially expressed genes and the establishment of protein interaction networks, we have deepened our understanding of differentially expressed genes, important biological processes and signaling pathways involved in the pathogenesis of non-syndromic craniosynostosis. The selected hub genes may become early diagnostic markers and potential molecular therapeutic targets.

To use dermal scaffolds to cover the wound can accelerate the wound repair and healing. Rapid vascularization is the basis for dermal scaffolds to function and a necessary condition for these implants to survive in vivo. This review summarizes the latest research on vascularization of dermal scaffolds in recent years. Through explaining the process of angiogenesis, the cytokines regulating angiogenesis and the latest research on the vascularization of various materials and 3D-printed materials, we explore the ideas and method to solve the deficiency of dermal scaffold vascularization.

Objective:The differentially expressed genes were screened from microarray data in the patients with non-syndromic craniosynostosis, and a protein interaction network was established to screen and predict hub genes related to the disease.Methods:The data set of GSE50796 were downloaded from the GEO database, which included seven samples of the closed cranial suture tissues from the non-syndromic craniosynostosis patients, and seven samples of the unclosed cranial suture tissues from the non-syndromic craniosynostosis patients. Analyze the differentially expressed genes were collected and analyzed with GEO2R, a GEO database online tool. P<0.05 and |logFC|> 2 were set as filter criteria. The ggplot2 of R package was applied for GO enrichment analysis, and the KEGG pathway analysis was completed with Enrichr. Gene set enrichment analysis (GSEA) was performed via GSEA 3.0 to analyze the correlation between gene sets and phenotypes. Secondly, the STRING database was used to analyze the interaction relationships between differentially expressed proteins in different tissues, and then Cytoscape and related plug-ins were used to establish the differentially expressed protein interaction network and screen the hub genes. Meanwhile, the key modules, important biological processes, and multiple co-expression relationships were analyzed. Results:A total of 255 differentially expressed genes based on the above screening conditions were obtained. The regulation of neural development screened by GO enrichment analysis, the PI3K-Akt signaling pathway screened by KEGG enrichment analysis, the important biological pathways (DNA replication, cell cycle, cytokine and receptor interaction) screened by GSEA enrichment analysis, and the positive regulation of osteoblast differentiation screened by ClueGO analysis, might be closely related to the etiology of non-syndromic craniosynostosis. The up-regulated hub genes such as CLEC12A, MS4A3 and DNTT in the group with closed sutures were screened by protein-protein interaction network and literature analysis, which might play a vital role in the pathogenic processes of non-syndromic craniosynostosis.Conclusions:With the multi-dimensional enrichment analysis of the differentially expressed genes and the establishment of protein interaction networks, we have deepened our understanding of differentially expressed genes, important biological processes and signaling pathways involved in the pathogenesis of non-syndromic craniosynostosis. The selected hub genes may become early diagnostic markers and potential molecular therapeutic targets.