BACKGROUND:Cell-free therapy is a research hotspot in the field of medical cosmetic anti-aging.It is still unknown for paracellular secretion of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles loaded with the antiaging drug α-ketoglutaric acid to delay skin aging.OBJECTIVE:To investigate the effect of the anti-aging agent α-ketoglutarate engineered human umbilical cord mesenchymal stem cell-derived small extracellular vesicles in a D-galactose-induced model of dermal fibroblast senescence.METHODS:(1)Biological characteristics of primary human umbilical cord mesenchymal stem cells were identified by osteogenic-lipogenic differentiation staining and flow cytometry.(2)The small extracellular vesicles derived from human umbilical cord mesenchymal stem cell were obtained by using differential-ultracentrifugation.α-Ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles were constructed by electroporation,and biologically characterized by transmission electron microscopy and nanoparticle tracking analyzer,while the encapsulation rate was assessed using high-performance liquid chromatography.(3)The effect of α-ketoglutarate on the proliferative capacity of dermal fibroblasts was assessed by CCK-8 and Edu cell proliferation assay kits.(4)The effect of α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles on delaying the senescence of dermal fibroblasts was evaluated by reactive oxygen species detection kit,western blot assay,and cellular immunofluorescence.RESULTS AND CONCLUSION:(1)The obtained human umbilical cord mesenchymal stem cell and human umbilical cord mesenchymal stem cell-small extracellular vesicles were biologically compatible.(2)There was no toxic effect on dermal fibroblasts when α-ketoglutarate was used in the concentration range of 0.5-8 mmol/L.(3)D-gal induced senescence in dermal fibroblasts,while α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles treatment reduced the level of oxidative stress,DNA damage,and collagen loss,which was further verified that α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles could effectively slow down the skin aging process.

BACKGROUND:Cell-free therapy is a research hotspot in the field of medical cosmetic anti-aging.It is still unknown for paracellular secretion of human umbilical cord mesenchymal stem cell-derived small extracellular vesicles loaded with the antiaging drug α-ketoglutaric acid to delay skin aging.OBJECTIVE:To investigate the effect of the anti-aging agent α-ketoglutarate engineered human umbilical cord mesenchymal stem cell-derived small extracellular vesicles in a D-galactose-induced model of dermal fibroblast senescence.METHODS:(1)Biological characteristics of primary human umbilical cord mesenchymal stem cells were identified by osteogenic-lipogenic differentiation staining and flow cytometry.(2)The small extracellular vesicles derived from human umbilical cord mesenchymal stem cell were obtained by using differential-ultracentrifugation.α-Ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles were constructed by electroporation,and biologically characterized by transmission electron microscopy and nanoparticle tracking analyzer,while the encapsulation rate was assessed using high-performance liquid chromatography.(3)The effect of α-ketoglutarate on the proliferative capacity of dermal fibroblasts was assessed by CCK-8 and Edu cell proliferation assay kits.(4)The effect of α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles on delaying the senescence of dermal fibroblasts was evaluated by reactive oxygen species detection kit,western blot assay,and cellular immunofluorescence.RESULTS AND CONCLUSION:(1)The obtained human umbilical cord mesenchymal stem cell and human umbilical cord mesenchymal stem cell-small extracellular vesicles were biologically compatible.(2)There was no toxic effect on dermal fibroblasts when α-ketoglutarate was used in the concentration range of 0.5-8 mmol/L.(3)D-gal induced senescence in dermal fibroblasts,while α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles treatment reduced the level of oxidative stress,DNA damage,and collagen loss,which was further verified that α-ketoglutarate-engineered human umbilical cord mesenchymal stem cell-small extracellular vesicles could effectively slow down the skin aging process.

Objective:To investigate the efficacy of virtual simulation-guided unilateral locking plate combined with Jail screw technique for double column tibial plateau fractures involving the posterolateral plateau.Methods:A retrospective case series study was conducted to analyze the clinical data of 32 patients with double column tibial plateau fractures involving the posterolateral plateau admitted to Nanjing Drum Tower Hospital Group Suqian Hospital from March 2018 to March 2022, including 20 males and 12 females, aged 37-69 years [(47.5±6.9)years]. According to AO/OTA classification, the fractures were classified as type 41B in 17 patients and type 41C in 15. According to the three-column classification, the fractures were classified as lateral column+posterior column in 17 patients and medial column+posterior column in 15. Virtual simulation technique was used to simulate surgical operation before surgery. After reduction, the patients′ tibial plateau mirror models of the healthy side were used to simulate the implantation of internal fixators on the affected side. The position data of the placed internal fixators were obtained to guide the personalized treatment with unilateral locking plate combined with Jail screw technique. The total number of Jail screws, average number of Jail screws, distribution and accuracy of screw placement, operative duration, intraoperative blood loss, and fracture healing status were recorded. The posterior tibial plateau angle (PTSA), proximal medial tibial angle (MPTA) and Rasmussen anatomical score were compared before operation, at 1, 3, 6, 12 months after operation and at the last follow-up. The Lysholm scores at 6, 12 months after operation and at the last follow-up were used to evaluate the knee function. At the last follow-up, the knee range of motion was measured. Postoperative complications were observed.Results:All the patients were followed up for 28-36 months [(30.7±2.3)months]. The total number of Jail screws inserted was 48, with an average of (1.5±0.5) screws. In the sagittal direction, 1-2 Jail screws were inserted in each patient, with an accuracy rate of 88% (42/48). The operative duration was 78-116 minutes [(98.7±10.5)minutes]. The intraoperative blood loss was 70-120 ml [(96.6±15.6)ml]. All the fractures had healing of stage I, with a healing time of 4-7 months [(5.4±0.9)months]. At 1, 3, 6, 12 months after operation and at last follow-up, the PTSA, MPTA, and Rasmussen anatomical scores were significantly improved when compared with those before operation ( P<0.05), while there was no statistically significant difference between those at various postoperative time points ( P>0.05). The Lysholm knee scores were (83.6±3.9)points, (88.5±3.6)points, and (93.7±2.6)points at 6, 12 months after operation, and at the last follow-up, respectively, which were gradually increased with the passage of the follow-up time ( P<0.05). The range of motion was (121.4±4.6)° in flexion and was 0.0(0.0, 3.0)° in extension at the last follow-up. Two patients had superficial wound infection and 1 had wound dehiscence after operation, which recovered with dressing change or debridement and suturing. No deep infection, vascular injury or nerve damage occurred. Conclusions:The virtual simulation-guided unilateral locking plate combined with Jail screw technique has the advantages of high accuracy of screw placement, shorter operative duration, less intraoperative blood loss, satisfactory fracture reduction, favorable recovery of knee function and range of motion, and fewer postoperative complications in the treatment of double column tibial plateau fractures involving the posterolateral plateau.

Objective:To explore the association between childhood trauma and prefrontal cortex functional networks in early adulthood using functional near-infrared spectroscopy(fNIRS).Methods:Twenty-eight individu-als with childhood trauma comprised the trauma group,while 32 without trauma formed the control group.The Childhood Trauma Questionnaire(CTQ)assessed abuse and neglect,the Ruminative Responses Scale(RRS)meas-ured repetitive thinking about negative events,and the Iowa Gambling Task(IGT)evaluated decision-making tend-encies.fNIRS data collected during the IGT were used to calculate degree centrality(DC),betweenness centrality(BC),and local efficiency(LE)in prefrontal networks.Mediation analysis explored relationships among childhood trauma,brain function(DC,BC,LE),and ruminative thinking.Results:Compared to controls,the trauma group had decreased DC in bilateral dorsolateral prefrontal cortices,increased DC,BC,and LE in the right inferior frontal gy-rus,and elevated LE in the bilateral frontal poles.BC and LE in the right inferior frontal gyrus partially mediated the relationship between CTQ sexual abuse and RRS scores(48.57％and 41.43％,respectively).Conclusion:Child-hood trauma is significantly associated with changes in prefrontal network properties in early adulthood.Sexual a-buse,in particular,may influence emotional regulation and cognitive functions by altering the network attributes of the right inferior frontal gyrus.

Objective To systematically evaluate the differences in clinicopathologic features and prog-nosis of colorectal cancer(CRC)between youth and middle-aged and elderly people.Methods The relevant literatures in Chinese and English databases before June 2024 were retrieved.The Stata 18 and RevMan5.3 softwares were used to perform the heterogeneity and sensitivity analyses as well as publication bias tests for the relevant outcome indicators.Results A total of 17 case-control studies were included,including a total of 6 817 patients with pathologically diagnosed CRC,among them 1 939 cases in the young group and 4 878 cases in the middle-aged and elderly group.The results of meta analysis showed that the proportion of family histo-ry in the young adult group(OR=3.09,95%CI:2.33-4.09),misdiagnosis rate(OR=4.40,95%CI:3.30-5.86),proportion of poorly differentiated carcinomas(OR=3.57,95%CI:2.73-4.67),proportion of mucin-ous adenocarcinomas and imprinted cell carcinomas(OR=3.41,95%CI:2.79-4.18),and proportion of TNM stage at diagnosis(stage Ⅲ-Ⅳ,OR=1.71,95%CI:1.44-2.02),incidence rate of lymph node metas-tasis(OR=1.92,95%CI:1.61-2.28),incidence rate of distant metastasis(OR=2.09,95%CI:1.53-2.86)were higher than those in the middle-aged and elderly group(all P<0.05);the CEA-positive rate at diagnosis(OR=0.68,95%CI:0.57-0.80)and 5-year survival rate(OR=0.24,95%CI:0.16-0.36)in the young group were lower than those in the middle-aged and elderly group(all P<0.05).The difference in the tumor diameter size(OR=1.32,95%CI:0.98-1.77)between the two groups was not statistically significant(P=0.07).Conclusion Compared with middle-aged and elderly CRC,young patients with CRC has a closer famil-ial correlation,may be more easily misdiagnosed clinically,its malignant degree would be higher,and the TNM stage in diagnosis is relatively late;in clinic the young population with CRC high risk could be appropriately relaxed in the age limit for screening.

Objective To analyze the current situation of quality control and regulation of centralized decoction of Chinese materia medica in Hangzhou through a mixed study combining quantitative research and qualitative research;To provide references for its standardization.Methods A self-designed questionnaire was distributed from July 20,2023 to August 10,2023 in institutions providing centralized decoction services of Chinese materia medica in different regions of Hangzhou.Using the stratified sampling method,the institutional personnel who completed the questionnaire survey were selected as the interviewees,and the semi-structured interview was used to refine the theme according to the Colaizzi seven step method.Results Totally 98 questionnaires were distributed and 96 valid questionnaires were recovered,with a valid recovery rate of 97.96%.There were significant differences in soaking time,concentration degree,and special decoction method such as decocted earlier or later of decoction pieces of Chinese materia medica among different types of institutions(P<0.05).The centralized decoction of Chinese materia medica in Hangzhou mainly involves two themes and seven sub themes:the supervision and management of the whole process of centralized decoction of Chinese materia medica(optimizing distribution of medical resources,strengthening of supervision,demanding guidance of standards),the operation of centralized decoction of Chinese materia medica(soaking time of decoction pieces of Chinese materia medica,the pretreatment operation of"decocted earlier and decocted later",the concentration treatment of Chinese materia medica decoction,and the quality control of Chinese materia medica decoction).Conclusion At present,centralized decoction of Chinese materia medica in Hangzhou still needs to be further standardized.It is recommended to strengthen the construction of shared Chinese materia medica pharmacy in the region,establish and improve the standard system of centralized decoction of Chinese materia medica decoction,and strengthen the construction of digital full chain traceability to improve the service quality and management level of centralized decoction of Chinese materia medica in Hangzhou.

Sonodynamic therapy（SDT）has garnered significant attention in cancer treatment modalities due to its superior tissue penetration capabilities，non-invasive approach，and controllability. SDT operates by utilizing sonosensitizers and ultrasound-responsive devices to induce the production of reactive oxygen species（ROS）under ultrasound stimulation，thereby eliciting immunogenic cell death（ICD）in tumor cells and the release of damage-associated molecular patterns，which in turn trigger an immune response against the tumor.However，the tumor microenvironment often results in a relatively weak immune response post-cancer treatment. To address this issue，extensive research is being conducted on combining SDT with immunotherapy，particularly focusing on immune checkpoint blockade（ICB）therapies. This review synthesizes the mechanisms of SDT，its integration with immunotherapy，especially ICB therapies，and the current state of research，with the objective of providing strategic guidance for the advancement of sonodynamic immunotherapy.

Objective:To investigate the influencing factors and prognosis of early recurrence after gastrectomy for gastric cancer.Methods:The retrospective cohort study was conducted. The clinicopathological data of 2 078 patients who underwent gastrectomy for gastric cancer at six medical centers across China, including Fudan University Shanghai Cancer Center et al, between January 2012 and June 2023 were collected. There were 1 449 males and 629 females, aged (59±11) years. Patients were classified as early recurrence and late recurrence based on the time of post-operative recurrence. Observation indicators: (1) comparison of clinicopathological characteristics between gastric cancer patients with different recurrence types; (2) recurrence and metastasis of tumor; (3) survival of patients after postoperative recurrence of gastric cancer; (4) analysis of influencing factors for early recurrence after gastrectomy for gastric cancer. Comparison of measurement data with normal distribution between groups was conducted using the independent sample t test. Comparison of measurement data with skewed distribution between groups was conducted using the Mann-Whitney U test. Comparison of count data between groups was conducted using the chi-square test. Comparison of ordinal data between groups was conducted using the rank sum test. Multivariate analysis was conducted using the Logistic regression model. Kaplan-Meier method was used to calculate survival rate and plot survival curve, and Log-rank test was used for survival analysis. Results:(1) Comparison of clinicopathological characteristics between gastric cancer patients with different recurrence types. Among the 2 078 patients, 1 452 cases had early recurrence and 626 cases had late recurrence. There were significant differences in preoperative carcinoembryonic antigen, preoperative CA19-9, preoperative CA72-4, preoperative albumin, tumor diameter, neoadjuvant therapy, R 0 resection, combined organ resection, scope of gastric resection, nerve and vessel infiltration, degree of tumor differentiation, pathological N staging, pathological TNM staging between early and late recurrence patients ( P<0.05). (2) Recurrence and metastasis of tumor. Among the 2 078 patients, 200 cases had local recurrence, 1 213 cases had hematogenous metastases, 392 cases had distant lymph node metastases, and 731 cases had peritoneal metastases. Among the 1 452 early recurrence patients, 142 cases had local recurrence, 834 cases had hematogenous metastases, 289 cases had distant lymph node metastases, and 507 cases had peritoneal metastases. Among the 626 late recurrence patients, 58 cases had local recurrence, 379 cases had hematogenous metastases, 103 cases had distant lymph node metastases, and 224 cases had peritoneal metastases. One patient may have multiple forms of recurrence and metastasis. There was no significant difference in the above indica-tors between early and late recurrence patients ( χ2=0.13, 1.74, 3.40, 0.14, P>0.05). (3) Survival of patients after postoperative recurrence of gastric cancer. All 2 078 patients were followed up until death after recurrence, with a follow-up time of 31(range, 9?147)months. The 1-, 2-, 3-, and 5-year overall survival rates after recurrence were 33.5%, 17.2%, 10.1%, and 3.3% in early recurrence patients, versus 44.2%, 21.6%, 12.8%, and 5.8% in late recurrence patients, respectively, showing a significant difference in overall survival after recurrence between the two groups ( hazard ratio=0.84, 95% confidence interval as 0.76?0.92, P<0.05). (4) Analysis of influencing factors for early recurrence after gastrectomy for gastric cancer. Results of multivariate analysis showed that combined organ resection, total gastrectomy, pathological TNM staging as stage Ⅲ were independent risk factors for early recurrence after gastrectomy for gastric cancer ( odds ratio=1.31, 1.32, 1.34, 95% confidence interval as 1.01?1.70, 1.06?1.65, 1.05?1.71, P<0.05) and normal preoperative tumor markers, neoadjuvant therapy, R 0 resection were independent protective factors for early recurrence ( odds ratio=0.61, 0.50, 0.38, 95% confidence interval as 0.49?0.76, 0.35?0.72, 0.25?0.58, P<0.05). Conclusions:Compared with patients with late recurrence after gastric cancer surgery, patients with early recurrence have a poor prognosis, in which liver metastases is more common. Combine organ resection, total gastrectomy, pathological TNM staging as stage Ⅲ are independent risk factors for early recurrence, and normal preoperative tumor markers, neoadjuvant therapy, R 0 resection are independent protective factors for early recurrence after gastrectomy for gastric cancer.

Objective:To explore the association between childhood trauma and prefrontal cortex functional networks in early adulthood using functional near-infrared spectroscopy(fNIRS).Methods:Twenty-eight individu-als with childhood trauma comprised the trauma group,while 32 without trauma formed the control group.The Childhood Trauma Questionnaire(CTQ)assessed abuse and neglect,the Ruminative Responses Scale(RRS)meas-ured repetitive thinking about negative events,and the Iowa Gambling Task(IGT)evaluated decision-making tend-encies.fNIRS data collected during the IGT were used to calculate degree centrality(DC),betweenness centrality(BC),and local efficiency(LE)in prefrontal networks.Mediation analysis explored relationships among childhood trauma,brain function(DC,BC,LE),and ruminative thinking.Results:Compared to controls,the trauma group had decreased DC in bilateral dorsolateral prefrontal cortices,increased DC,BC,and LE in the right inferior frontal gy-rus,and elevated LE in the bilateral frontal poles.BC and LE in the right inferior frontal gyrus partially mediated the relationship between CTQ sexual abuse and RRS scores(48.57％and 41.43％,respectively).Conclusion:Child-hood trauma is significantly associated with changes in prefrontal network properties in early adulthood.Sexual a-buse,in particular,may influence emotional regulation and cognitive functions by altering the network attributes of the right inferior frontal gyrus.

Objective To analyze the current situation of quality control and regulation of centralized decoction of Chinese materia medica in Hangzhou through a mixed study combining quantitative research and qualitative research;To provide references for its standardization.Methods A self-designed questionnaire was distributed from July 20,2023 to August 10,2023 in institutions providing centralized decoction services of Chinese materia medica in different regions of Hangzhou.Using the stratified sampling method,the institutional personnel who completed the questionnaire survey were selected as the interviewees,and the semi-structured interview was used to refine the theme according to the Colaizzi seven step method.Results Totally 98 questionnaires were distributed and 96 valid questionnaires were recovered,with a valid recovery rate of 97.96%.There were significant differences in soaking time,concentration degree,and special decoction method such as decocted earlier or later of decoction pieces of Chinese materia medica among different types of institutions(P<0.05).The centralized decoction of Chinese materia medica in Hangzhou mainly involves two themes and seven sub themes:the supervision and management of the whole process of centralized decoction of Chinese materia medica(optimizing distribution of medical resources,strengthening of supervision,demanding guidance of standards),the operation of centralized decoction of Chinese materia medica(soaking time of decoction pieces of Chinese materia medica,the pretreatment operation of"decocted earlier and decocted later",the concentration treatment of Chinese materia medica decoction,and the quality control of Chinese materia medica decoction).Conclusion At present,centralized decoction of Chinese materia medica in Hangzhou still needs to be further standardized.It is recommended to strengthen the construction of shared Chinese materia medica pharmacy in the region,establish and improve the standard system of centralized decoction of Chinese materia medica decoction,and strengthen the construction of digital full chain traceability to improve the service quality and management level of centralized decoction of Chinese materia medica in Hangzhou.