A portion of patients undergoing implant restoration require bone augmentation procedures to ensure that there is sufficient bone volume around the implant. For the patients with horizontal bone ridge defects at edentulous sites, with or without mild to moderate vertical bone defects, the shell technique serves as a reliable and minimally invasive bone augmentation method with effective space maintenance. The shell technique involves fixating 1 mm cortical bone blocks to the recipient site, using retention screws and filling the gap between the bone block and recipient bed with particulate bone substitute materials, and covering the barrier membrane to achieve bone augmentation. The overlying tension-free soft tissue closure seals the surgical site while local peripheral blood releases osteoclasts and cytokines that gradually degrade the bone block. The rigid fixation of the bone block ensures a stable internal environment for osteogenesis and a new bone regeneration cycle. Although this technique demonstrates favorable bone augmentation outcomes, it is highly technique-sensitive. There are certain differences in the application scenarios and osteogenic processes for autologous and allogeneic bone shells. The selection of bone blocks and particulate bone substitute materials significantly influences the osteogenic biological process and the predictability of bone augmentation results. Complications associated with the shell technique possess distinct characteristics, such as the immunogenicity of allogeneic bone fragments, soft tissue cracking, and bone fragment loosening. Their prevention and subsequent management substantially impact the success rate of osteogenesis. This article delves into the biological mechanisms of osteogenesis in the bone block technique, summarizing the indications, clinical outcomes, classification of bone blocks, and surgical workflow management, as well as complication prevention and management, aiming to provide a reference for the future application and development of the bone shell technique.

ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris （SAP） of coronary heart disease （CHD）. MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome， 125 cases of qi deficiency-accompanied syndrome， 38 cases of qi stagnation-accompanied syndrome， and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine （TCM） patterns. Data of patients with different TCM patterns were collected， including general condition， TCM symptoms， blood lipids， coagulation function， immune indicators， and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection （VIP） ≥1 and fold change （FC） ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group， with a relatively high proportion of males. Regarding TCM symptoms， patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse， chest pain， and chest tightness； in patients with qi deficiency-accompanied syndrome， fatigue， chest pain， and weak pulse were most common； in patients with qi stagnation-accompanied sydnrome， wiry-choppy or wiry-slippery pulse， chest pain， and symptoms that increase or decrease with emotional changes， belching， or flatulence were most common； in patients with toxin accumulation-accompanied syndrome， bitter taste in the mouth， chest tightness， irritability， restlessness or manic delirium， and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters （P＜0.05）， whereas no statistically significant difference was found in blood lipid levels and immune indicators （P＞0.05）.Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine， leucine， and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin （FC = 3.58） and oxypurinol （FC = 124.50）. Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine （FC = 2.62） and D-mannosamine （FC = 2.99）. Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine （FC = 7.83） and canrenone （FC = 8.94）. ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders， amino acid metabolism abnormalities， and multiple immune indicators activation， which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.

ObjectiveTo explore the clinical and phenomics characteristics of patients with phlegm-stasis binding syndrome and its accompanied patterns in stable angina pectoris （SAP） of coronary heart disease （CHD）. MethodsA multicenter cross-sectional study design was adopted. A total of 300 patients with SAP of CHD were enrolled and classified into 120 cases of phlegm-stasis binding syndrome， 125 cases of qi deficiency-accompanied syndrome， 38 cases of qi stagnation-accompanied syndrome， and 17 cases of toxin accumulation-accompanied syndrome according to traditional Chinese medicine （TCM） patterns. Data of patients with different TCM patterns were collected， including general condition， TCM symptoms， blood lipids， coagulation function， immune indicators， and serum metabolomics. Metabolic pathway enrichment analysis was used to compare differences in phenomics characteristics among groups. Metabolites with variable importance in projection （VIP） ≥1 and fold change （FC） ≥2 were considered as representative differential metabolites. ResultsPatients in each TCM pattern type were most commonly in the 60-75 years age group， with a relatively high proportion of males. Regarding TCM symptoms， patients with phlegm-stasis binding syndrome most commonly presented with wiry-choppy or wiry-slippery pulse， chest pain， and chest tightness； in patients with qi deficiency-accompanied syndrome， fatigue， chest pain， and weak pulse were most common； in patients with qi stagnation-accompanied sydnrome， wiry-choppy or wiry-slippery pulse， chest pain， and symptoms that increase or decrease with emotional changes， belching， or flatulence were most common； in patients with toxin accumulation-accompanied syndrome， bitter taste in the mouth， chest tightness， irritability， restlessness or manic delirium， and dry and hard stools or foul-smelling diarrhea were most common. Comparisons among the different TCM patterns showed statistically significant differences in coagulation parameters （P＜0.05）， whereas no statistically significant difference was found in blood lipid levels and immune indicators （P＞0.05）.Metabolomics analysis suggested that disorders of glycerophosphate metabolism and valine， leucine， and isoleucine metabolism are characteristic features of phlegm-stasis binding syndrome and its accompanied patterns. The representative differential metabolites between phlegm-stasis binding syndrome and qi deficiency-accompanied syndrome were 7,8-dihydrobiopterin （FC = 3.58） and oxypurinol （FC = 124.50）. Those between phlegm-stasis binding syndrome and qi stagnation-accompanied syndrome were cytidine 5′-diphosphocholine （FC = 2.62） and D-mannosamine （FC = 2.99）. Those between phlegm-stasis binding syndrome and toxin accumulation-accompanied syndrome were anserine （FC = 7.83） and canrenone （FC = 8.94）. ConclusionThere are certain differences in the clinical characteristics and phenomics characteristics among patients with SAP due to CHD exhibiting phlegm-stasis binding syndrome and its accompanied patterns. The phenomics characteristics mainly involve biological alterations such as lipid metabolism disorders， amino acid metabolism abnormalities， and multiple immune indicators activation， which may provide a reference for precise differentiation and treatment of SAP of CHD in TCM clinical practice.

Objective To explore the immediate,long-term,and delayed effects of spiral stabilizing muscle chain technique compared to static distraction and Proprioceptive Neuromuscular Facilitation(PNF)stretching techniques on the flexibility of hip flexors.Methods Ninety subjects were randomly divided intothree groups of 30 each.Group 1 underwent the static stretching of the hip joint.Group 2 received PNF stretching,and Group 3 participated in SPS training.All participants were measured for hip extension angle to assess hip flexor flexibility before training,immediately after the first training session,at the end of 4 weeks of training,and 2 weeks after training cessation.Results Within-group comparisons showed significant increases in hip extension angles after one training session,after 4 weeks of training,and after 2 weeks of cessation compared to pre-training(P＜0.05).Between-group comparisons indicated no statistically significant differences in hip extension angle improvements among the three groups after one training session,after 4 weeks of training,and after 2 weeks of cessation(P＞0.05).Conclusion SPS training,static stretching,and PNF stretching all demonstrate good immediate,long-term,and delayed effects on improving hip extension angles,with consistent stretching outcomes.

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.

Objective To explore the correlation of MET status in patients with advanced prostatic acinar adenocarcinoma with the clinical pathological parameters and prognosis. Methods The specimen from 135 patients with advanced prostatic acinar adenocarcinoma was included. The expression of c-MET protein was detected via immunohistochemistry, and MET gene amplification was assessed by fluorescence in situ hybridization. The relationships of c-MET expression and gene amplification with clinicopathological features and prognosis were analyzed. Results The positive expression rate of c-MET was 52.60% (71/135). Compared with the c-MET expression in adjacent tissues, that in tumor tissues showed lower heterogeneous expression. Among the cases, 1.71% (2/117) exhibited MET gene polyploidy, but no gene amplification was detected. Positive c-MET expression was significantly correlated with high Gleason scores and grade groups (P=0.0073). However, no significant relationship was found between c-MET expression and progression-free survival or post-treatment t-PSA levels. Conclusion c-MET protein is expressed at a relatively low level in advanced prostatic acinar adenocarcinoma, suggesting that c-MET may not be a viable target for ADC drug development in prostatic acinar adenocarcinoma.

The Split-Cre system consists of two inactive polypeptides: NCre and CCre, which can be recombined into an active full-length Cre under certain conditions. This system is typically used with LoxP. To develop an efficient Split-Cre system, this study used Rma intein from Rhodothermus marinus to split Cre and screened out the split site S102 which could efficiently mediate the recombination of Cre in the "Traffic Light" reporter cell line. Moreover, the S102 Split-Cre system was delivered to mice by dual-adeno-associated virus (AAV), and it was demonstrated that the efficiency of the Rma intein-mediated S102 Split-Cre system was comparable to the full-length Cre in mice. This system lays a foundation for both basic and applied research on Split-Cre.
Inteins/genetics* ; Animals ; Integrases/biosynthesis* ; Mice ; Dependovirus/metabolism* ; Bacterial Proteins/genetics* ; Recombination, Genetic ; Humans

To investigate the molecular mechanisms underlying the mechanosensitive ion channel PI-EZO2 in osteoarthritis(OA),we developed a lentiviral vector for endogenous PIEZO2 overexpression and established a stable PIEZO2-high-expressing immortalized human primary chondrocyte line.By map-ping the open reading frame of the PIEZO2 locus and designing sequence-specific sgRNA,we employed the CRISPR/Cas9 synergistic activation mediator(SAM)system to precisely integrate transcriptional ac-tivation elements into the PIEZO2 promoter region.Lentiviral-mediated targeted genomic integration en-sured endogenous PIEZO2 overexpression,confirmed by mCherry fluorescence tracing coupled with flow cytometric sorting,which revealed membrane-specific localization of PIEZO2 protein(localization effi-ciency:78.49％).Quantitative PCR demonstrated a 17-fold upregulation of PIEZO2 mRNA,while Western blotting validated enhanced membrane-localized protein expression.Strikingly,PIEZO2-overex-pressing chondrocytes exhibited hallmark OA metabolic phenotypes compared to wild-type controls:typeⅡ collagen mRNA expression decreased to 50％of baseline levels,whereas matrix metalloproteinase 13(MMP13)mRNA surged by 20-fold.These alterations recapitulated the pathological matrix metabolic phenotype observed in biomechanical OA models induced by cyclic mechanical stress(10％strain,0.5 Hz,8 h/day for 2 consecutive days).Collectively,we successfully generated a human chondrocyte model with stable PIEZO2 overexpression,which faithfully mirrors mechanotransduction-driven OA progression.This engineered cellular system provides a robust platform for dissecting PIEZO2-mediated mechanosig-naling networks and advancing targeted therapeutic discovery.

Thyroid cancer is the most prevalent malignant tumor of the endocrine system,and its incidence has shown a significant upward trend in recent years.Acetylation,an important post-translational protein modification,is involved in regulating gene transcription,cell cycle progression,and invasion ability in various types of thyroid cancers.Additionally,histone deacetylase(HDAC)inhibitors have shown potential in the treatment of thyroid cancer.This article systematically reviews the biological functions and regulatory mechanisms of acetylation in the development and progression of thyroid cancer based on recent literature.Furthermore,it discusses the clinical application prospects of HDAC inhibitors,providing a solid theoretical basis and feasible therapeutic strategies for targeted therapy of thyroid cancer.

This study selected 6 529 plant-based Chinese materia medica(PCMM) from Chinese Materia Medica as research subjects and applied a random permutation test to explore the overall correlation characteristics between nature and flavor, as well as the correlation characteristics after distinguishing different medicinal parts and harvest seasons. The results showed that the overall correlation characteristics between nature and flavor in PCMM were significantly associated in the following pairs: cold and bitter, cool and bitter, cool and astringent, cool and light, neutral and sweet, neutral and astringent, neutral and light, neutral and sour, hot and pungent, and warm and pungent. When analyzing the data by distinguishing medicinal parts and/or harvest seasons, new correlation patterns emerged, characterized by the disappearance of some significant correlations and the emergence of new ones. When analyzing by medicinal parts alone, significant correlations were found in the following cases: cold and light in leaves, cold and salty in barks, cool and sweet in fruits and seeds, neutral and pungent in whole herbs, neutral and salty in stems, and warm and salty in flowers. However, no significant correlations were found between cool and bitter in stems and other types of herbs, cool and astringent in fruits, seeds, flowers, and other types of herbs, cool and light in leaves, fruits, seeds, barks, flowers and other types of herbs, neutral and sweet in barks, neutral and astringent in whole herbs and stems, neutral and light in leaves, fruits, seeds, and flowers, neutral and sour in whole herbs, stems, barks, flowers, and other types of herbs, and hot and pungent in whole herbs, stems, flowers, and other types of herbs. When analyzing by harvest season alone, significant correlations were found in the following cases: cold and salty, and cool and sour in herbs harvested in winter, and neutral and salty in herbs harvested year-round. However, no significant correlation was found between cool and light in herbs harvested in winter. When considering both medicinal parts and harvest seasons, compared to the independent influence of medicinal parts, 14 new significant correlations emerged(e.g., the correlation between cool and bitter in stems harvested in spring), while 53 previously significant correlations disappeared(e.g., the correlation between cool and bitter in barks harvested in summer). Compared to the independent influence of harvest seasons, 11 new significant correlations appeared(e.g., the correlation between cold and light in barks harvested in autumn), while 50 previously significant correlations disappeared(e.g., the correlation between hot and pungent in leaves harvested in winter). This study is the first to reveal the influence of medicinal parts and harvest seasons on the correlation between nature and flavor in PCMM, which highlights that these two factors can interact and jointly affect nature-flavor correlations. Further research is needed to explore the underlying mechanisms. This study provides a deeper understanding of the inherent scientific connotations of herbal properties and offers a theoretical foundation for the cultivation and harvesting of PCMM.
Seasons ; Plants, Medicinal/growth & development* ; Drugs, Chinese Herbal/chemistry* ; Taste