BACKGROUND:Cell derivative is cell-derived bioactive components,including decellularized extracellular matrix,exosome,apoptotic extracellular vesicle,and conditioned medium,has the effects on immune regulation,promoting angiogenesis,bone regeneration,ligament remodeling,and is capable of promoting stem cell chemotherapy,migration,proliferation,and adhesion.Its excellent characteristics make it a promising biomaterial for application and clinical translation in the field of periodontal tissue engineering. OBJECTIVE:To review the characteristics of cell derivatives(decellularized extracellular matrix,exosome,apoptotic extracellular vesicle,and conditioned medium)and its effect and the latest progress in the field of regenerative restoration of periodontal complex tissue structures. METHODS:We searched the articles on CNKI and PubMed databases with the search terms"regeneration,periodontal tissue,tissue engineering,decellularized matrix,exosome,apoptotic extracellular vesicle,condition medium"in Chinese and English,respectively.Finally,76 articles were included for analysis and discussion. RESULTS AND CONCLUSION:(1)Among those four cell derivatives,the decellularized extracellular matrix has the best mechanical properties and fibrous structure,serving as a biomimetic scaffold to provide physiochemical signals and participate in mechanical signaling in periodontal tissue engineering,providing supporting effect suitable for periodontal regeneration.Recently,the development of soluble decellularized extracellular matrix bioinks has enabled the fabrication of regenerative scaffolds for personalized periodontal defects.(2)Exosomes are the simplest cell derivatives that have immunomodulatory capacity,promoting cell migration and differentiation.As a carrier,they can be used to carry target molecules to regulate periodontal regeneration,promote ligament remodeling and bone regeneration,and are suitable for periodontal tissue engineering.(3)Apoptotic vesicles generated from apoptotic cells have a strong immunomodulatory effect and can recruit stem cells and macrophages,which determine the fate of stem cells through signal transduction and can enhance immunomodulation to promote periodontal regeneration.Engineered extracellular vesicle is considered to have the potential to initiate targeted internal immunomodulation.(4)The extraction of conditioned medium is simple and completely noninvasive,which provides essential nutrients and growth factors for tissue regeneration.These components are crucial for successful periodontal regeneration.Therefore,the conditioned medium is especially suitable for studying the interactions between cells in vitro and has an important role in high-throughput detection in the future.

BACKGROUND:De novo adipose regeneration induced by small extracellular vesicles has become a promising method for repairing soft tissue defects.However,due to different animal models and small extracellular vesicle application dosages,it is difficult to quantitatively compare the therapeutic effect of small extracellular vesicles from various sources on adipose regeneration. OBJECTIVE:To compare the regenerative effects of small extracellular vesicles derived from stem cells and small extracellular vesicles from tissue. METHODS:Small extracellular vesicles derived from adipose-derived stem cells and from adipose tissue were isolated by ultracentrifugation.The particle number,particle size,morphology,and protein expression of small extracellular vesicles were identified by nanoparticle tracking analysis,transmission electron microscopy and western blot assay.A quantitative and evaluative subcutaneous model for adipose regeneration in C57 mice was established using a customized silicone tube.The regenerative effects of induced de novo adipose were compared by cell counting and hematoxylin-eosin staining. RESULTS AND CONCLUSION:(1)Small extracellular vesicles derived from adipose-derived stem cells and from adipose tissue were isolated by ultracentrifugation.Both small extracellular vesicles were round-shape in transmission electron microscopy with particle size between 50-200 nm,and abundant with the small extracellular vesicles marker protein CD81,CD63 and TSG101.(2)An equal number of small extracellular vesicles were mixed with matrigel in customized silicone tubes,implanted subcutaneously in the back of mice to establish a cell-free and quantifiable adipose regeneration model.(3)On days 3 and 7 after implantation,the results of cell counting and hematoxylin-eosin staining showed that both small extracellular vesicle groups recruited more host cells than the blank group,and the small extracellular vesicles derived from adipose tissue group were superior to the small extracellular vesicles derived from adipose-derived stem cell group.(4)4 weeks after implantation,hematoxylin-eosin staining of the contents in silicone tubes showed that small extracellular vesicles induced de novo adipose regeneration in vivo,and the small extracellular vesicles derived from adipose tissue group were superior to the small extracellular vesicles derived from adipose-derived stem cell group.The above results indicated that small extracellular vesicles derived from tissues have a superior effect on inducing de novo adipose regeneration compared to small extracellular vesicles derived from stem cells.

Objective:To investigate the impact of intermittent senescent cell clearance on the proliferation and differentiation of dental pulp stem cells (DPSC) in long-term, large-scale expansion, and to explore strategies for maintaining the youthful state of DPSC in vitro. Methods:Human-derived dental pulp stem cells were isolated from healthy permanent teeth extracted for orthodontic or impeding eruption reasons, provided by the Department of Oral and Maxillofacial Surgery at West China Hospital of Stomatology, Sichuan University. Long-term, large-scale in vitro expansion of DPSC was conducted. The study compared young DPSC (passage 5) with aged DPSC (passage 25) using cellular senescence-associated β-galactosidase staining, colony formation assay, and Alizarin Red S staining for osteogenic differentiation induction. To assess the differences between the two cell populations in terms of senescence and amplification and differentiation ability. Medicine screening for the most effective senolytic was compared among 5 common senolytics [Navitoclax (ABT-263), curcumin, dasatinib, fisetin, and quercetin]. The clearance efficacy was compared using cellular senescence-associated β-galactosidase staining to reflect the changes in senescent cell ratio. The senolytic with the highest efficacy was chosen for further experiments. The passage at which the proportion of senescent cells significantly increased was identified, and the selected senolytic was administered three times at three-generation intervals from that passage to remove senescent cells. Both the control and senolytic-treated groups were estimated by fluorescence cellular senescence-associated β-galactosidase staining, real-time fluorescence quantitative PCR (RT-qPCR), colony formation assay, wound healing assay, and Alizarin Red S staining for osteogenic differentiation induction. Subcutaneous heterotopic osteogenesis was performed in nude mice and the grafts were analyzed by HE staining and alkaline phosphatase (ALP) immunohistochemical staining. Results:The proportion of senescent cells increased as the expansion extended, leading to decreased proliferation and osteogenic differentiation ability of senescent DPSC compared to young DPSC ( P<0.05). Senescent DPSC exhibited altered mRNA expression levels of senescence-related genes, including p21, p16INK4a, IL-6, and Ki67 ( P<0.001). Among the five senolytics, ABT-263 had the biggest decreases in the proportion of senescent cells. After intermittent ABT-263 treatment during expansion, the proportion of senescent cells in the senolytic-treated group [(6.72±2.34)%] was significantly lower than that in the control group [(31.82±0.57)%] ( P<0.001). RT-qPCR confirmed that compared with the control group, mRNA expressions of p21, p16 INK4a, and IL-6 in the senolytic-treated group were significantly decreased ( P<0.05), while mRNA expressions of Ki67 were significantly increased ( P<0.01). Furthermore, the cell healing ability and osteogenic differentiation ability of the senolytic-treated group were higher than those of the control group ( P<0.05). In vivo experimental results indicated that the relative new bone area [(2.36±0.48)%] after DPSC transplantation in the senolytic-treated group was greater than that in the control group [(1.00±0.46)%] ( P<0.05), and the expression of ALP was higher than that in the control group ( P<0.01). Conclusions:ABT-263 can effectively eliminate senescent cells in long-term large-scale DPSC expansion. Continuous treatment with ABT-263 during cultivation can maintain the proliferation and differentiation ability of DPSC both in vivo and in vitro.

Objective:To compare the short- and mid-term clinical outcomes of robotic versus laparoscopic radical resection of right- and left-sided colon cancer.Methods:In this retrospective cohort study, clinical data on patients who had undergone robotic or laparoscopic radical resection of right and left sided-colon cancer performed by two senior physicians in the Department of Gastro-Colorectal and Anal Surgery, Daping Hospital, Army Medical University between January 2015 and December 2023 were collected. The patients were allocated to robotic ( n=117) or laparoscopic groups ( n=267). Propensity score matching in a ratio of 1∶1 was implemented to minimize the impact of imbalances in baseline information between the two groups. Propensity score matching left 228 patients in the study cohort, with 114 in each group. The participants were aged (60.8±12.1) and (60.3±13.1) years and the body mass indices were (23.1±3.0) kg/m 2 and (23.1±2.8) kg/m 2 in the robotic and laparoscopic groups respectively. After matching, relevant perioperative indicators, postoperative complications, and 3-year survival outcomes were compared between the two groups. Results:After propensity score matching, the differences in baseline information between the two groups were not statistically significant ( P>0.05). After matching, in the robotic surgery group, radical resection of right- versus left-sided colon cancer had been performed on 80 and 34 patients, respectively; compared with 78 and 36, respectively, in the laparoscopic surgery group. Compared with the laparoscopic group, the robotic group had a longer operative time ( [209.8±48.4] minutes vs. [186.7±46.9] minutes, t=3.665, P<0.001), higher hospitalization cost ( [88657.8±18548.1] yuan vs. [61179.5±13822.7] yuan, t=12.683, P<0.001), and lower rate of postoperative complications (7.9% [9/114] vs. 17.5% [20/114], χ 2=4.780, P=0.029); these differences are statistically significant. The robotic group tended to have a lower conversion rate than the laparoscopic group (0 vs. 4.4% [5/114]); however, this difference between the two groups was not statistically significant (χ 2=3.272, P=0.070). The amount of intraoperative bleeding, time to first passage of flatus, postoperative hospital stay, postoperative complications (Clavien-Dindo grade), number of resected lymph nodes, and number of positive lymph nodes did not differ significantly between the two groups (all P>0.05). Furthermore, the differences between the robotic and laparoscopic groups in 3-year disease-free survival (81.4% vs. 82.8%, P=0.863) and overall survival (83.1% vs. 86.5%, P=0.921) were not statistically significant ( P>0.05). Conclusion:Robotic radical resection of right and left-sided colon cancer is safe and feasible and an effective alternative to laparoscopic surgery. Although robotic surgery has a longer operative time and higher hospitalization costs than laparoscopic surgery, it has a lower rate of postoperative complications, and a 3-year survival outcome comparable to that of laparoscopic surgery.

Objective:To compare the short- and mid-term clinical outcomes of robotic versus laparoscopic radical resection of right- and left-sided colon cancer.Methods:In this retrospective cohort study, clinical data on patients who had undergone robotic or laparoscopic radical resection of right and left sided-colon cancer performed by two senior physicians in the Department of Gastro-Colorectal and Anal Surgery, Daping Hospital, Army Medical University between January 2015 and December 2023 were collected. The patients were allocated to robotic ( n=117) or laparoscopic groups ( n=267). Propensity score matching in a ratio of 1∶1 was implemented to minimize the impact of imbalances in baseline information between the two groups. Propensity score matching left 228 patients in the study cohort, with 114 in each group. The participants were aged (60.8±12.1) and (60.3±13.1) years and the body mass indices were (23.1±3.0) kg/m 2 and (23.1±2.8) kg/m 2 in the robotic and laparoscopic groups respectively. After matching, relevant perioperative indicators, postoperative complications, and 3-year survival outcomes were compared between the two groups. Results:After propensity score matching, the differences in baseline information between the two groups were not statistically significant ( P>0.05). After matching, in the robotic surgery group, radical resection of right- versus left-sided colon cancer had been performed on 80 and 34 patients, respectively; compared with 78 and 36, respectively, in the laparoscopic surgery group. Compared with the laparoscopic group, the robotic group had a longer operative time ( [209.8±48.4] minutes vs. [186.7±46.9] minutes, t=3.665, P<0.001), higher hospitalization cost ( [88657.8±18548.1] yuan vs. [61179.5±13822.7] yuan, t=12.683, P<0.001), and lower rate of postoperative complications (7.9% [9/114] vs. 17.5% [20/114], χ 2=4.780, P=0.029); these differences are statistically significant. The robotic group tended to have a lower conversion rate than the laparoscopic group (0 vs. 4.4% [5/114]); however, this difference between the two groups was not statistically significant (χ 2=3.272, P=0.070). The amount of intraoperative bleeding, time to first passage of flatus, postoperative hospital stay, postoperative complications (Clavien-Dindo grade), number of resected lymph nodes, and number of positive lymph nodes did not differ significantly between the two groups (all P>0.05). Furthermore, the differences between the robotic and laparoscopic groups in 3-year disease-free survival (81.4% vs. 82.8%, P=0.863) and overall survival (83.1% vs. 86.5%, P=0.921) were not statistically significant ( P>0.05). Conclusion:Robotic radical resection of right and left-sided colon cancer is safe and feasible and an effective alternative to laparoscopic surgery. Although robotic surgery has a longer operative time and higher hospitalization costs than laparoscopic surgery, it has a lower rate of postoperative complications, and a 3-year survival outcome comparable to that of laparoscopic surgery.

Periodontitis is a chronic inflammatory and destructive disease in which plaque acts as an initiator.Recruitment of host im-mune cells and production of multiple inflammatory mediators leads to periodontal tissue damage.Programmed cell death(PCD)is a self-destructive process that is actively initiated by cells under specific conditions and can be mainly categorized into apoptosis,necrop-tosis,autophagy,pyroptosis,ferroptosis,cuproptosis,etc.Different types of programmed cell death have their own distinctive roles in periodontitis.In this review,we summarizes the characteristics of different types of PCD and their role in the progression of periodonti-tis,in order to provide new research ideas on the pathogenic mechanism of periodontitis and more references for the precise treatment of periodontitis.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective:The study aimed to analyze the clinical and endoscopic characteristics of adult celiac disease (CD) to provide a scientific basis for more effective CD diagnosis and treatment.Methods:In this cross-sectional study, the clinical and endoscopic data of 96 adult CD patients treated in the Department of Gastroenterology of the People′s Hospital of Xinjiang Uygur Autonomous Region from March 2016 to December 2021 were retrospectively collected and analyzed.Results:A total of 96 CD patients were diagnosed, including 33 men and 63 women. The average age was 47±14 years (range, 18-81 years). The disease occurred mainly in the age group of 31-60 years. The median course of the disease was 2.0 (0.2-40.0) years. There were 41 (42.7%) classical and 55 (57.3%) non-classical CD patients. All patients with classical CD showed chronic diarrhea, often accompanied by abdominal pain (46.3%, 19/41), abdominal distension (17.1%, 7/41), anemia (65.9%, 27/41), and chronic fatigue (48.8%, 20/41). The main manifestations of non-classical CD were chronic abdominal pain (58.2%, 32/55), abdominal distension (32.7%, 18/55), anemia (40.0%, 22/55), and osteopenia/osteoporosis (38.2%, 21/55). Compared with non-classical CD, anemia developed more frequently in classical CD, and the difference was statistically significant ( P = 0.012). The incidence of complications in CD patients was 36.5% (35/96), and the main complications were thyroid disease (19.8%, 19/96), connective tissue disease (6.2%, 6/96), and kidney disease (6.2%, 6/96). There was no significant difference between classical and non-classical CD ( P>0.05). The frequency of endoscopic manifestations in CD patients was 84.4% (81/96). Duodenal bulb endoscopy showed nodular changes (72.9%, 70/96), grooved changes (10.4%, 10/96), and focal villous atrophy (9.4%, 9/96). The main manifestations of descending endoscopy were the decrease, flattening, or disappearance of duodenal folds (43.8%, 42/96), scallop-like changes (38.5%, 37/96), and nodular changes (34.4%, 33/96). Conclusions:Adult CD patients are mostly female. CD occurred mainly in the age group of 31-60 years. The clinical manifestations were mainly those of non-classical CD. Some patients often had other autoimmune diseases. Patients with characteristic endoscopic manifestations should be warned about the possibility of developing CD. Clinicians should strengthen the understanding of CD and reduce the related rates of missed diagnosis.

Objective:To investigate the predictive value of systemic immune-inflammatory index (SII) for hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) after intravenous thrombolysis in patients with acute ischemic stroke (AIS).Methods:Patients with AIS received intravenous thrombolysis in the Department of Neurology, Huai’an First People’s Hospital from July 2019 to July 2022 were included retrospectively. The head CT was performed at 24 h after intravenous thrombolysis and determined whether HT existed. sICH was defined as brain parenchymal hematoma, and the National Institutes of Health Stroke Scale (NIHSS) scores increased by ≥4 compared with the baseline, or the patient died within 36 h after onset. Multivariate logistic regression analysis was used to determine the independent correlation between SII and HT and sICH after intravenous thrombolysis. The receiver operating characteristics (ROC) curve was used to evaluate the predictive value of SII for HT and sICH after intravenous thrombolysis. Results:A total of 352 patients with AIS received intravenous thrombolysis were enrolled, including 240 males (68.1%), aged 66.46±12.00 years. The median baseline NIHSS score was 8 (interquartile range, 5-13), and the median SII is 531.91×10 9/L (interquartile range, 351.20-896.91×10 9/L). HT occurred in 62 patients (17.6%) and sICH occurred in 27 patients (7.7%). Univariate analysis showed that the SII of the HT group was significantly higher than that of the non-HT group ( Z=–2.731, P=0.006), and the SII of the sICH group was significantly higher than that of non-sICH group ( Z=–4.125, P<0.01). Multivariate logistic regression analysis showed that the increased SII was the independent risk factor for HT (odds ratio [ OR] 1.001, 95% confidence interval [ CI] 1.000-1.001; P=0.004) and sICH ( OR 1.001, 95% CI 1.001-1.002; P<0.01). ROC curve analysis shows that the area under curve of SII predicting HT was 0.610 (95% CI 0.535-0.686; P=0.006), and the best cutoff value was 488.48×10 9/L. The corresponding sensitivity and specificity were 69% and 47% respectively. The area under the curve of SII predicting sICH was 0.739 (95% CI 0.636-0.842; P<0.01), and the best cutoff value was 846.56×10 9/L, the corresponding sensitivity and specificity were 70% and 77% respectively. Conclusion:The increased SII at admission can predict the risks of HT and sICH in patients with AIS after intravenous thrombolysis.

Objective:To investigate the predicting value of eosinophil-to-neutrophil ratio (ENR) for outcomes at 3 months after intravenous thrombolysis in patients with acute ischemic stroke (AIS).Methods:Patients with AIS received intravenous thrombolysis in the Department of Neurology, Huai'an First People's Hospital from July 2019 to July 2022 were included retrospectively. Multivariate logistic regression model was used to determine the independent correlation between ENR and outcomes at 3 months after intravenous thrombolysis. The receiver operating characteristics (ROC) curve was used to evaluate the predictive value of ENR levels for poor outcomes at 3 months after intravenous thrombolysis. Results:A total of 352 patients with AIS receiving intravenous thrombolysis were enrolled, including 240 men (68.1%), age 66.46±12.00 years old. The median National Institutes of Health Stroke Scale score was 8 (interquartile range, 5-13). At 3 months after onset, 215 patients (61.0%) had good outcomes, 137 (38.9%) had poor outcomes. Univariate analysis showed that the median ENR×10 2 level of the poor outcome group was significantly lower than that of the good outcome group ( Z= –7.305, P<0.01). Multivariate logistic regression analysis showed that lower ENR×10 2 was an independent risk factor for poor outcomes at 3 months after intravenous thrombolysis (odds ratio 0.619, 95% confidence interval 0.514-0.745; P<0.01). ROC curve analysis showed that the area under the curve for ENR×10 2 predicting the poor outcomes after intravenous thrombolysis was 0.731 (95% confidence interval 0.678-0.784; P<0.01). The optimal cutoff value was 0.625 and the corresponding sensitivity and specificity were 94% and 40%, respectively. Conclusion:Lower ENR before intravenous thrombolysis in patients with AIS is independently associated with the poor outcomes at 3 months.