Lumbar disc (LD) herniation and aging are prevalent conditions that can result in substantial morbidity. This study aimed to clarify the mechanisms connecting the LD aging and herniation, particularly focusing on cellular senescence and molecular alterations in the nucleus pulposus (NP). We performed a detailed analysis of NP samples from a diverse cohort, including individuals of varying ages and those with diagnosed LD herniation. Our methodology combined histological assessments with single-nucleus RNA sequencing to identify phenotypic and molecular changes related to NP aging and herniation. We discovered that cellular senescence and a decrease in nucleus pulposus progenitor cells (NPPCs) are central to both processes. Additionally, we found an age-related increase in NFAT1 expression that promotes NPPC senescence and contributes to both aging and herniation of LD. This research offers fresh insights into LD aging and its associated pathologies, potentially guiding the development of new therapeutic strategies to target the root causes of LD herniation and aging.
Intervertebral Disc Displacement/metabolism* ; Humans ; Aging/pathology* ; Nucleus Pulposus/pathology* ; Male ; Female ; Transcriptome ; Middle Aged ; Lumbar Vertebrae/pathology* ; Adult ; Cellular Senescence ; Stem Cells/pathology* ; Aged ; Intervertebral Disc Degeneration/metabolism*

Objective To explore and construct the clinical questions and outcome indicators of the Clinical Practice Guideline of Acupuncture and Moxibustion Treatment for Irritable Bowel Syndrome;To provide a basis for the subsequent preparation of this guide to form recommendations.Methods First,by searching the databases of seven major Chinese and English journals,including CNKI,the preliminary list of clinical problems and outcome indicators in the Clinical Practice Guideline of Acupuncture and Moxibustion Treatment for Irritable Bowel Syndrome were sorted out,and then the clinical questions and outcome indicators that formed the recommendations of the guide were finally determined based on the modified Delphi method in the form of three rounds of online.The first two rounds were conducted in the form of online questionnaires filled out by experts,and the importance ratings of clinical issues and outcome indicators were imported into the SPSS 27.0 software for statistical analysis.The first and second rounds of clinical questions and outcome indicators were rated as the average score≥4,full score frequency≥30%,and the coefficient of variation≤25%,respectively;the inclusion criteria for entering the second round of evaluation were an average score of≥7 and an average score of≤25%.The third round would be further discussed and voted on by experts in an online consensus meeting,with a voting rate of≥80%as the standard to determine the final items to be included in the guidelines.Results A total of 109 questionnaires were distributed nationwide in the first round of inquiry,and 107 were collected;a total of 20 questionnaires were distributed for the second round of expert research,and 20 were collected.The positive coefficients of the first and second rounds of experts were 98.17%and 100%;the Cronbach coefficients of clinical questions were 0.937 and 0.943,respectively;the Cronbach coefficients of the outcome indicators were 0.970 and 0.940,respectively.In the third round,a total of 22 experts participated in the meeting and all voted,resulting in a positive coefficient of 100%and an authority coefficient of 0.88.13 clinical questions and 17 outcome indicators were finally included in Clinical Practice Guideline of Acupuncture and Moxibustion Treatment for Irritable Bowel Syndrome.Conclusion According to the results of the above three rounds of modified Delphi method,it indicates that the questionnaire survey in the process of formulating the guidelines is highly reliable,which can provide a reliable basis for the writing of this guide,and to provide a reference for the development of acupuncture guidelines in related fields.

Surgery can solve many medical problems, but it also brings scar problems. Excessive hypertrophy or contracture scar not only affect appearance and function, but also affect mental health. With the continuous deepening of scar research and the continuous progress of technical means, scholars have realized the importance of early intervention of scars after surgery, and have achieved certain clinical result. This review introduced the concept of early intervention for postoperative scarring, and reviewd the treatment method related to early intervention.

Objective:The aim of this study was to explore the risk factors that affect implementation of the innovative technique of single-incision laparoscopic appendectomy (solo-SLA) without assistance in patients with complicated appendicitis, the goal being improving surgical success rates and reducing the incidence of complications.Methods:This was an observational study. Indications for solo-SLA surgery were as follows: (1) computed tomography or ultrasound findings suggestive of acute appendicitis, accompanied by a high white blood cell count and C-reactive protein concentration; (2) disease course exceeding 72 hours, standard anti-infection treatment ineffective, inflammatory reaction not localized, surgery mainly aimed at abscess drainage, and the appendix removed if indicated intraoperatively; (3) acute onset stabilized for more than 3 months after conservative treatment; and (4) recurrent chronic appendicitis. Relative contraindications comprised: (1) cardiopulmonary insufficiency, extremely high risk for general anesthesia for laparoscopic surgery; (2) severe coagulation dysfunction; and (3) imaging findings suggestive of formation of a peri-appendiceal abscess, stable after anti-infection treatment, and a tendency for the inflammatory reaction to localize. We retrospectively collected clinical data of 106 patients with complicated appendicitis who had undergone solo-SLA in the Department of Emergency Surgery, Peking University People's Hospital from February to October 2023. Preoperative computed tomography showed appendiceal fecaliths, blurring of the tissue surrounding fat, intra- and extra-luminal gas and exudate, peri-appendiceal abscess, ascites, and intestinal obstruction by appendicitis. The study cohort comprised 53 male and 53 female patients aged (41.4±17.4) years. The median body mass index was (24.2±3.6) kg/m 2 and median preoperative body temperature (37.3±0.9)℃ Appendicitis had been present for >3 days in 21 of the patients (19.8%) and the maximum diameter of the appendix was (12.4±3.8) mm. The efficacy of the surgery was assessed and logistic regression analysis used to explore the factors affecting the duration of the procedure. The relationship between the maximum diameter of the appendix and duration of surgery was non-linear and was explored using a logistic regression model with restricted cubic spline (RCS). Results:Only one patient required conversion to open surgery; all the other patients successfully completed solo-SLA with a median intraoperative blood loss of 10 (1-100) ml and a surgical time of (65.4±31.7) minutes. Pain scores on postoperative Day 1 and 7 were (3.4±3.2) points and (1.5±1.7) points, respectively. There were no significant postoperative complications .The postoperative hospital stay was (3.5±1.5) days and the interval to resuming normal activities 14 (2-40) days. According to univariate and multivariate analyses, disease course >3 days (OR=5.19, 95%CI: 1.59-16.98, P=0.006) and C-reactive protein >10 mg/L (OR=1.01,95%CI: 1.00-1.02, P=0.003) were independent risk factors for surgical duration >60 minutes, whereas the maximum diameter of the appendix was not independently associated with duration of surgery (OR=1.10, 95%CI: 0.97-1.25, P=0.119). RCS analysis results showed a "U-shaped" association between the maximum diameter of the appendix and duration of surgery, the inflection point of the RCS curve being at a diameter of 10 mm. When the maximum diameter of the appendix was <10 mm, increases in diameter were not associated with longer duration of surgery (OR=1.15,95%CI: 0.55-2.58, P=0.710); whereas when the diameter was ≥10 mm, the maximum diameter of the appendix was associated with increased duration of surgery (OR=1.20, 95% CI: 1.04-1.42, P=0.022). Conclusion:The solo-SLA procedure can be performed to treat complicated appendicitis. A disease course >3 days, C-reactive protein concentration >10 mg/L, and maximum diameter of the appendix ≥10 mm are all associated with greater difficulty of solo-SLA surgery.

Objective To investigate the effects of Icariin(ICA)on the proliferation,angiogenesis,and migration of human retinal pigment epithelial(RPE)cells in a high-glucose environment and its mechanism.Methods ARPE-19 cells in good growth state were selected and divided into five groups:control group(Control group),high glucose group(HG group),high glucose+low-dose Icariin group(HG+ICA-L group),high glucose+medium-dose Icariin group(HG+ICA-M group),and high glucose+high-dose Icariin group(HG+ICA-H group).The cells in the control group were cul-tured in a medium containing 5.5 mmol·L-1 glucose.Cells in the HG group were cultured in a medium containing 30.0 mmol·L-1 glucose.The cells in each ICA intervention group were first cultured in a medium containing 30.0 mmol·L-1 glucose,and then 10.0 μmol·L-1,20.0 μmol·L-1 and 40.0 μmol·L-1 ICA were added for culture,respectively.The CCK-8 assay was used to detect cell proliferation activity,the EdU assay was used to detect cell proliferation,the Transwell assay was used to detect cell migration ability,and the Matrigel assay was used to detect in vitro tube formation ability.The expression levels of α-smooth muscle actin(α-SMA),matrix metalloproteinase-2(MMP-2),vascular endothelial growth factor A(VEGFA),epidermal growth factor receptor(EGFR),and proteins related to the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway were detected by Western blot.Results The cell viability and EdU-positive rate of ARPE-19 cells in the HG group were higher than those in the Control group(all P＜0.05).The cell viability and EdU-positive rate in the HG+ICA-L,HG+ICA-M,and HG+ICA-H groups were lower than those in the HG group(all P＜0.05).The number of migrated cells and tubes formed in the HG+ICA-L,HG+ICA-M,and HG+ICA-H groups were less than those in the HG group,and the expression levels of α-SMA,MMP-2,VEGFA,and EGFR proteins were lower than those in the HG group(all P＜0.05).The levels of p-PI3K and p-Akt in the HG+ICA-L,HG+ICA-M,and HG+ICA-H groups were lower than those in the HG group(all P＜0.05).Conclusion ICA inhibits the proliferation,migration,and angiogenesis of ARPE-19 cells stimulated by high glucose by suppressing the activation of the PI3K/Akt pathway.

Objective:The aim of this study was to explore the risk factors that affect implementation of the innovative technique of single-incision laparoscopic appendectomy (solo-SLA) without assistance in patients with complicated appendicitis, the goal being improving surgical success rates and reducing the incidence of complications.Methods:This was an observational study. Indications for solo-SLA surgery were as follows: (1) computed tomography or ultrasound findings suggestive of acute appendicitis, accompanied by a high white blood cell count and C-reactive protein concentration; (2) disease course exceeding 72 hours, standard anti-infection treatment ineffective, inflammatory reaction not localized, surgery mainly aimed at abscess drainage, and the appendix removed if indicated intraoperatively; (3) acute onset stabilized for more than 3 months after conservative treatment; and (4) recurrent chronic appendicitis. Relative contraindications comprised: (1) cardiopulmonary insufficiency, extremely high risk for general anesthesia for laparoscopic surgery; (2) severe coagulation dysfunction; and (3) imaging findings suggestive of formation of a peri-appendiceal abscess, stable after anti-infection treatment, and a tendency for the inflammatory reaction to localize. We retrospectively collected clinical data of 106 patients with complicated appendicitis who had undergone solo-SLA in the Department of Emergency Surgery, Peking University People's Hospital from February to October 2023. Preoperative computed tomography showed appendiceal fecaliths, blurring of the tissue surrounding fat, intra- and extra-luminal gas and exudate, peri-appendiceal abscess, ascites, and intestinal obstruction by appendicitis. The study cohort comprised 53 male and 53 female patients aged (41.4±17.4) years. The median body mass index was (24.2±3.6) kg/m 2 and median preoperative body temperature (37.3±0.9)℃ Appendicitis had been present for >3 days in 21 of the patients (19.8%) and the maximum diameter of the appendix was (12.4±3.8) mm. The efficacy of the surgery was assessed and logistic regression analysis used to explore the factors affecting the duration of the procedure. The relationship between the maximum diameter of the appendix and duration of surgery was non-linear and was explored using a logistic regression model with restricted cubic spline (RCS). Results:Only one patient required conversion to open surgery; all the other patients successfully completed solo-SLA with a median intraoperative blood loss of 10 (1-100) ml and a surgical time of (65.4±31.7) minutes. Pain scores on postoperative Day 1 and 7 were (3.4±3.2) points and (1.5±1.7) points, respectively. There were no significant postoperative complications .The postoperative hospital stay was (3.5±1.5) days and the interval to resuming normal activities 14 (2-40) days. According to univariate and multivariate analyses, disease course >3 days (OR=5.19, 95%CI: 1.59-16.98, P=0.006) and C-reactive protein >10 mg/L (OR=1.01,95%CI: 1.00-1.02, P=0.003) were independent risk factors for surgical duration >60 minutes, whereas the maximum diameter of the appendix was not independently associated with duration of surgery (OR=1.10, 95%CI: 0.97-1.25, P=0.119). RCS analysis results showed a "U-shaped" association between the maximum diameter of the appendix and duration of surgery, the inflection point of the RCS curve being at a diameter of 10 mm. When the maximum diameter of the appendix was <10 mm, increases in diameter were not associated with longer duration of surgery (OR=1.15,95%CI: 0.55-2.58, P=0.710); whereas when the diameter was ≥10 mm, the maximum diameter of the appendix was associated with increased duration of surgery (OR=1.20, 95% CI: 1.04-1.42, P=0.022). Conclusion:The solo-SLA procedure can be performed to treat complicated appendicitis. A disease course >3 days, C-reactive protein concentration >10 mg/L, and maximum diameter of the appendix ≥10 mm are all associated with greater difficulty of solo-SLA surgery.

Objective To investigate the effects of Icariin(ICA)on the proliferation,angiogenesis,and migration of human retinal pigment epithelial(RPE)cells in a high-glucose environment and its mechanism.Methods ARPE-19 cells in good growth state were selected and divided into five groups:control group(Control group),high glucose group(HG group),high glucose+low-dose Icariin group(HG+ICA-L group),high glucose+medium-dose Icariin group(HG+ICA-M group),and high glucose+high-dose Icariin group(HG+ICA-H group).The cells in the control group were cul-tured in a medium containing 5.5 mmol·L-1 glucose.Cells in the HG group were cultured in a medium containing 30.0 mmol·L-1 glucose.The cells in each ICA intervention group were first cultured in a medium containing 30.0 mmol·L-1 glucose,and then 10.0 μmol·L-1,20.0 μmol·L-1 and 40.0 μmol·L-1 ICA were added for culture,respectively.The CCK-8 assay was used to detect cell proliferation activity,the EdU assay was used to detect cell proliferation,the Transwell assay was used to detect cell migration ability,and the Matrigel assay was used to detect in vitro tube formation ability.The expression levels of α-smooth muscle actin(α-SMA),matrix metalloproteinase-2(MMP-2),vascular endothelial growth factor A(VEGFA),epidermal growth factor receptor(EGFR),and proteins related to the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)pathway were detected by Western blot.Results The cell viability and EdU-positive rate of ARPE-19 cells in the HG group were higher than those in the Control group(all P＜0.05).The cell viability and EdU-positive rate in the HG+ICA-L,HG+ICA-M,and HG+ICA-H groups were lower than those in the HG group(all P＜0.05).The number of migrated cells and tubes formed in the HG+ICA-L,HG+ICA-M,and HG+ICA-H groups were less than those in the HG group,and the expression levels of α-SMA,MMP-2,VEGFA,and EGFR proteins were lower than those in the HG group(all P＜0.05).The levels of p-PI3K and p-Akt in the HG+ICA-L,HG+ICA-M,and HG+ICA-H groups were lower than those in the HG group(all P＜0.05).Conclusion ICA inhibits the proliferation,migration,and angiogenesis of ARPE-19 cells stimulated by high glucose by suppressing the activation of the PI3K/Akt pathway.

Surgery can solve many medical problems, but it also brings scar problems. Excessive hypertrophy or contracture scar not only affect appearance and function, but also affect mental health. With the continuous deepening of scar research and the continuous progress of technical means, scholars have realized the importance of early intervention of scars after surgery, and have achieved certain clinical result. This review introduced the concept of early intervention for postoperative scarring, and reviewd the treatment method related to early intervention.

Objective To explore and construct the clinical questions and outcome indicators of the Clinical Practice Guideline of Acupuncture and Moxibustion Treatment for Irritable Bowel Syndrome;To provide a basis for the subsequent preparation of this guide to form recommendations.Methods First,by searching the databases of seven major Chinese and English journals,including CNKI,the preliminary list of clinical problems and outcome indicators in the Clinical Practice Guideline of Acupuncture and Moxibustion Treatment for Irritable Bowel Syndrome were sorted out,and then the clinical questions and outcome indicators that formed the recommendations of the guide were finally determined based on the modified Delphi method in the form of three rounds of online.The first two rounds were conducted in the form of online questionnaires filled out by experts,and the importance ratings of clinical issues and outcome indicators were imported into the SPSS 27.0 software for statistical analysis.The first and second rounds of clinical questions and outcome indicators were rated as the average score≥4,full score frequency≥30%,and the coefficient of variation≤25%,respectively;the inclusion criteria for entering the second round of evaluation were an average score of≥7 and an average score of≤25%.The third round would be further discussed and voted on by experts in an online consensus meeting,with a voting rate of≥80%as the standard to determine the final items to be included in the guidelines.Results A total of 109 questionnaires were distributed nationwide in the first round of inquiry,and 107 were collected;a total of 20 questionnaires were distributed for the second round of expert research,and 20 were collected.The positive coefficients of the first and second rounds of experts were 98.17%and 100%;the Cronbach coefficients of clinical questions were 0.937 and 0.943,respectively;the Cronbach coefficients of the outcome indicators were 0.970 and 0.940,respectively.In the third round,a total of 22 experts participated in the meeting and all voted,resulting in a positive coefficient of 100%and an authority coefficient of 0.88.13 clinical questions and 17 outcome indicators were finally included in Clinical Practice Guideline of Acupuncture and Moxibustion Treatment for Irritable Bowel Syndrome.Conclusion According to the results of the above three rounds of modified Delphi method,it indicates that the questionnaire survey in the process of formulating the guidelines is highly reliable,which can provide a reliable basis for the writing of this guide,and to provide a reference for the development of acupuncture guidelines in related fields.