1.Extracellular vesicles deliver thioredoxin to rescue stem cells from senescence and intervertebral disc degeneration via a feed-forward circuit of the NRF2/AP-1 composite pathway.
Xuanzuo CHEN ; Sheng LIU ; Huiwen WANG ; Yiran LIU ; Yan XIAO ; Kanglu LI ; Feifei NI ; Wei WU ; Hui LIN ; Xiangcheng QING ; Feifei PU ; Baichuan WANG ; Zengwu SHAO ; Yizhong PENG
Acta Pharmaceutica Sinica B 2025;15(2):1007-1022
Intervertebral disc degeneration (IDD) is largely attributed to impaired endogenous repair. Nucleus pulposus-derived stem cells (NPSCs) senescence leads to endogenous repair failure. Small extracellular vesicles/exosomes derived from mesenchymal stem cells (mExo) have shown great therapeutic potential in IDD, while whether mExo could alleviate NPSCs senescence and its mechanisms remained unknown. We established a compression-induced NPSCs senescence model and rat IDD models to evaluate the therapeutic efficiency of mExo and investigate the mechanisms. We found that mExo significantly alleviated NPSCs senescence and promoted disc regeneration while knocking down thioredoxin (TXN) impaired the protective effects of mExo. TXN was bound to various endosomal sorting complex required for transport (ESCRT) proteins. Autocrine motility factor receptor (AMFR) mediated TXN K63 ubiquitination to promote the binding of TXN on ESCRT proteins and sorting of TXN into mExo. Knocking down exosomal TXN inhibited the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2) and activator protein 1 (AP-1). NRF2 and AP-1 inhibition reduced endogenous TXN production that was promoted by exosomal TXN. Inhibition of NRF2 in vivo diminished the anti-senescence and regenerative effects of mExo. Conclusively, AMFR-mediated TXN ubiquitination promoted the sorting of TXN into mExo, allowing exosomal TXN to promote endogenous TXN production in NPSCs via TXN/NRF2/AP-1 feed-forward circuit to alleviate NPSCs senescence and disc degeneration.
2.Clinical efficacy of extended abdominal wall resection combined with reconstruction for abdo-minal wall aggressive fibromatosis
Zhen REN ; Lisheng WU ; Wenxiu HAN ; Bo HAO ; Xiaohan WEI ; Hu LIU ; Shuhan WANG ; Chen PAN ; Pengfei JI ; Baichuan ZHOU
Chinese Journal of Digestive Surgery 2025;24(9):1186-1190
Objective:To investigate the clinical efficacy of extended abdominal wall resec-tion combined with reconstruction for abdominal wall aggressive fibromatosis (AF).Methods:The retrospective and descriptive study was conducted. The clinical data of 70 patients with abdominal wall AF who were admitted to 3 medical centers, including The First Affiliated Hospital of the University of Science and Technology of China, between January 2009 and July 2024 were collected. There were 6 males and 64 females, aged (36±13)years. All patients underwent extended abdominal wall resection combined with abdominal wall reconstruction. Observation indicators: (1) surgical situations; (2) tumor recurrence and postoperative complications. Comparisons 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. Results:(1)Surgical situations. All 70 patients underwent extended abdominal wall resection combined with abdominal wall recons-truction. The operation time was 90(91)minutes and duration of postoperative hospital stay was 10(6)days. Of the 70 patients, 41 patients underwent abdominal wall AF resection plus polypropylene mesh abdominal wall reconstruction, with a defect area of 60(54)cm2. The mesh placement method was uniformly Sublay repair. The remaining 29 patients underwent abdominal wall AF resection plus direct suture repair, with a defect area of 34(31)cm2. There was a significant difference in the abdominal wall defect area between the two groups ( U=291.00, P<0.05). All 70 patients achieved R 0 resection. The distance from surgical margin to tumor edge was 2-3 cm in 39 cases and >3 cm in 31 cases. (2) Tumor recurrence and postoperative complications. All 70 patients were followed up for 78(90)months. During follow-up, 10 patients developed tumor recurrence (5 cases with mesh reinforced abdominal wall reconstruction and 5 cases with direct suture repair). Among them, one case was monitored, one case underwent radiotherapy, and neither received further surgical treatment. The remaining 8 patients underwent repeat R 0 resection, and no further recurrence occurred. There was no significant difference in recurrence rate between the patients with mesh reconstruction and patients with direct suture repair ( χ2=0.06, P>0.05). The postoperative recurrence rate was 9.7%(3/31) in patients with the distance from surgical margin to tumor edge >3 cm, versus 17.9%(7/39) in patients with the distance from surgical margin to tumor edge of 2-3 cm, showing no significant difference between them ( χ2=0.97, P>0.05). Sixty patients had no tumor recurrence. During follow-up, none of the 70 patients developed incisional hernia. Two patients experienced postoperative wound infection, and 6 cases developed postoperative chronic pain. Conclusion:Extended abdominal wall resection combined with reconstruction is safe and feasible for abdominal wall AF.
3.Clinical efficacy of extended abdominal wall resection combined with reconstruction for abdo-minal wall aggressive fibromatosis
Zhen REN ; Lisheng WU ; Wenxiu HAN ; Bo HAO ; Xiaohan WEI ; Hu LIU ; Shuhan WANG ; Chen PAN ; Pengfei JI ; Baichuan ZHOU
Chinese Journal of Digestive Surgery 2025;24(9):1186-1190
Objective:To investigate the clinical efficacy of extended abdominal wall resec-tion combined with reconstruction for abdominal wall aggressive fibromatosis (AF).Methods:The retrospective and descriptive study was conducted. The clinical data of 70 patients with abdominal wall AF who were admitted to 3 medical centers, including The First Affiliated Hospital of the University of Science and Technology of China, between January 2009 and July 2024 were collected. There were 6 males and 64 females, aged (36±13)years. All patients underwent extended abdominal wall resection combined with abdominal wall reconstruction. Observation indicators: (1) surgical situations; (2) tumor recurrence and postoperative complications. Comparisons 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. Results:(1)Surgical situations. All 70 patients underwent extended abdominal wall resection combined with abdominal wall recons-truction. The operation time was 90(91)minutes and duration of postoperative hospital stay was 10(6)days. Of the 70 patients, 41 patients underwent abdominal wall AF resection plus polypropylene mesh abdominal wall reconstruction, with a defect area of 60(54)cm2. The mesh placement method was uniformly Sublay repair. The remaining 29 patients underwent abdominal wall AF resection plus direct suture repair, with a defect area of 34(31)cm2. There was a significant difference in the abdominal wall defect area between the two groups ( U=291.00, P<0.05). All 70 patients achieved R 0 resection. The distance from surgical margin to tumor edge was 2-3 cm in 39 cases and >3 cm in 31 cases. (2) Tumor recurrence and postoperative complications. All 70 patients were followed up for 78(90)months. During follow-up, 10 patients developed tumor recurrence (5 cases with mesh reinforced abdominal wall reconstruction and 5 cases with direct suture repair). Among them, one case was monitored, one case underwent radiotherapy, and neither received further surgical treatment. The remaining 8 patients underwent repeat R 0 resection, and no further recurrence occurred. There was no significant difference in recurrence rate between the patients with mesh reconstruction and patients with direct suture repair ( χ2=0.06, P>0.05). The postoperative recurrence rate was 9.7%(3/31) in patients with the distance from surgical margin to tumor edge >3 cm, versus 17.9%(7/39) in patients with the distance from surgical margin to tumor edge of 2-3 cm, showing no significant difference between them ( χ2=0.97, P>0.05). Sixty patients had no tumor recurrence. During follow-up, none of the 70 patients developed incisional hernia. Two patients experienced postoperative wound infection, and 6 cases developed postoperative chronic pain. Conclusion:Extended abdominal wall resection combined with reconstruction is safe and feasible for abdominal wall AF.
4.Evaluation of circadian rhythms in depression by using actigraphy:a systematic review and meta-analysis
Chenyin SUN ; Baichuan WU ; Huifeng ZHANG ; Yiru FANG ; Daihui PENG
Journal of Shanghai Jiaotong University(Medical Science) 2024;44(5):606-616
Objective·To systematically review the effectiveness of actigraphy on the evaluation of circadian rhythm characteristics in patients with depression.Methods·A systematic literature search was conducted in PubMed,Embase,Web of Science,Cochrane Library,PsycINFO,CNKI,WanFang Data,and Chinese biomedical literature database(CBM),from the inception of each database to May 5th,2023.Case control studies that used actigraphy to evaluate circadian rhythms in patients with depression and compared them with healthy controls were collected.Literature was screened according to the inclusion and exclusion criteria,and the quality of the included literature was evaluated by using the Newcastle-Ottawa Scale.The meta-analysis was performed by using RevMan 5.4 software.Results·A total of 9 articles were included,including 390 patients with depression and 288 healthy controls.The meta-analysis showed that the MESOR(midline statistic of rhythm)(SMD=-0.29,95%CI-0.51 ?-0.07,P=0.009)of the circadian cosine function in patients with depression was lower than that in healthy controls;sleep onset(MD=33.06,95%CI 14.90 ? 51.23,P=0.000)and sleep offset(MD=53.80,95%CI 22.38 ? 85.23,P=0.000)were later in patients with depression than those in healthy controls;no statistical difference was found in the activity level of the most active 10 hours(SMD=-0.26,95%CI-0.52 ? 0.01,P=0.060)between patients with depression and healthy controls,although there was a trend for lower activity in patients with depression;no statistical difference was found in the acrophase(MD=25.33,95%CI-12.41 ? 63.06,P=0.190)of the circadian cosine function between patients with depression and healthy controls;no clear statistical significance of the difference was found in the amplitude(SMD=-0.14,95%CI-0.42 ? 0.14,P=0.340)and the activity level of the least active 5 hours(SMD=0.31,95%CI-0.10 ? 0.71,P=0.140)between patients with depression and healthy controls.Conclusion·Actigraphy can reflect circadian rhythm disruption in patients with depression to some extent,but the limited number of included studies and inconsistencies in the study populations and methodologies have affected the quality and results of the analyses.More high-quality clinical trials are needed to provide evidence.
5.Attaching importance to the value of inflammatory cytokine research in the clinical practice of adolescent depression
Baichuan WU ; Chenyin SUN ; Huifeng ZHANG ; Daihui PENG
Chinese Journal of Psychiatry 2024;57(1):8-11
Adolescent depression has a high prevalence, atypical symptoms, and poor prognosis. Cytokines, as related to the inflammation hypothesis, which is one of the potential pathogenesis of depressive disorder and thus crucial in adolescent patients who are in the early stage of the disease, have received widespread attention. Based on the current research status, this commentary briefly discusses the research on cytokines related to adolescent depression to elucidate the value of cytokines in the clinical practice of adolescent depression.
6.Study of kynurenine pathway metabolites and their dynamic association with clinical symptoms in depressed patients with suicidal ideation
Baichuan WU ; Jiaye CHEN ; Dongmei ZHAO ; Feng JIN ; Hua LI ; Yiyun CAI ; Huifeng ZHANG ; Daihui PENG ; Ting SHEN
Chinese Journal of Psychiatry 2024;57(5):290-297
Objective:This study aimed to explore whether there are abnormalities in the kynurenine pathway in patients with depression and suicidal ideation, and their dynamic relationship with clinical symptoms.Methods:According to the DSM-5 diagnostic criteria, a total of 68 patients with depression were prospectively enrolled, including 28 males and 40 females, aged( M ( Q1, Q3)) 22.0 (17.3, 47.8) years, who were the inpatients in the Division of Mood Disorders of Shanghai Mental Health Center from July 2019 to July 2022. The depressed patients were divided into groups with ( n=41) or without suicidal ideation ( n=27) based on whether they chose "weak" or "moderate to strong" suicidal ideation in questions 4 and 5 of the Beck Scale for Suicide Ideation (BSI). And 72 gender-matched healthy controls were also enrolled, including 29 males and 43 females, aged 25.5 (24.0, 36.8) years. Hamilton Depression Rating Scale-24 (HAMD 24), Hamilton Anxiety Rating Scale (HAMA), and BSI were used to evaluate the depression symptoms, anxiety symptoms, and suicidal ideation of depressed patients. All the participants received fasting venous blood collection to measure the levels of kynurenine metabolites in plasma. Among them, depressed patients with suicidal ideation were followed up, and the assessment s of depression symptoms, anxiety symptoms, and suicidal ideation, as well as kynurenine metabolites measurements, were repeated at the end of the 2nd and 4th weeks. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry was used to measure the levels of kynurenine metabolites in plasma. The hematological indicators were log-transformed, Z-score standardized, and false discovery rate correction was used for multiple comparisons of different metabolites. The relationship between baseline kynurenine metabolites and scale scores was analyzed. The relationship between kynurenine metabolites and scale scores during the follow-up process was analyzed by a linear mixed-effects model. Results:The peripheral picolinic acid (0.39±0.87 vs -0.23±1.09, t=3.89), 3-hydroxykynurenine/kynurenine (3-HK/KYN) (0.38±0.85 vs -0.09±1.01, t=2.98) and 3-HK (0.31±0.81 vs 0.14±1.04, t=2.78) of patients with depression were lower than those of healthy controls (both P<0.05). No statistically significant difference was found between patients with depression with or without suicidal ideation in kynurenine metabolites. In patients with depression and suicidal ideation, baseline HAMD 24 and HAMA scores were positively correlated with plasma 3-HK (HAMD 24: r=0.38; HAMA: r=0.39) and 3-HK/KYN (HAMD 24: r=0.34; HAMA: r=0.37) levels (all P<0.05). After adjusting for age and gender factors, a linear mixed-effects model was established for the follow-up scale scores, and kynurenine metabolite levels of this group of patients, and the results showed that the positive effect of HAMA score on 3-HK/KYN during follow-up was statistically significant ( B=0.04, t=2.46, P<0.05). Conclusion:There are abnormalities in the kynurenine pathway of tryptophan metabolism in patients with depression. 3-HK and 3-HK/KYN are related to the severity of depression and anxiety in patients with depression and suicidal ideation, among which 3-HK/KYN, representing the activity of kynurenine-3-monooxygenase, is dynamically associated with anxiety level.
7.Attaching importance to the value of inflammatory cytokine research in the clinical practice of adolescent depression
Baichuan WU ; Chenyin SUN ; Huifeng ZHANG ; Daihui PENG
Chinese Journal of Psychiatry 2024;57(1):8-11
Adolescent depression has a high prevalence, atypical symptoms, and poor prognosis. Cytokines, as related to the inflammation hypothesis, which is one of the potential pathogenesis of depressive disorder and thus crucial in adolescent patients who are in the early stage of the disease, have received widespread attention. Based on the current research status, this commentary briefly discusses the research on cytokines related to adolescent depression to elucidate the value of cytokines in the clinical practice of adolescent depression.
8.Study of kynurenine pathway metabolites and their dynamic association with clinical symptoms in depressed patients with suicidal ideation
Baichuan WU ; Jiaye CHEN ; Dongmei ZHAO ; Feng JIN ; Hua LI ; Yiyun CAI ; Huifeng ZHANG ; Daihui PENG ; Ting SHEN
Chinese Journal of Psychiatry 2024;57(5):290-297
Objective:This study aimed to explore whether there are abnormalities in the kynurenine pathway in patients with depression and suicidal ideation, and their dynamic relationship with clinical symptoms.Methods:According to the DSM-5 diagnostic criteria, a total of 68 patients with depression were prospectively enrolled, including 28 males and 40 females, aged( M ( Q1, Q3)) 22.0 (17.3, 47.8) years, who were the inpatients in the Division of Mood Disorders of Shanghai Mental Health Center from July 2019 to July 2022. The depressed patients were divided into groups with ( n=41) or without suicidal ideation ( n=27) based on whether they chose "weak" or "moderate to strong" suicidal ideation in questions 4 and 5 of the Beck Scale for Suicide Ideation (BSI). And 72 gender-matched healthy controls were also enrolled, including 29 males and 43 females, aged 25.5 (24.0, 36.8) years. Hamilton Depression Rating Scale-24 (HAMD 24), Hamilton Anxiety Rating Scale (HAMA), and BSI were used to evaluate the depression symptoms, anxiety symptoms, and suicidal ideation of depressed patients. All the participants received fasting venous blood collection to measure the levels of kynurenine metabolites in plasma. Among them, depressed patients with suicidal ideation were followed up, and the assessment s of depression symptoms, anxiety symptoms, and suicidal ideation, as well as kynurenine metabolites measurements, were repeated at the end of the 2nd and 4th weeks. Ultra-high performance liquid chromatography-triple quadrupole mass spectrometry was used to measure the levels of kynurenine metabolites in plasma. The hematological indicators were log-transformed, Z-score standardized, and false discovery rate correction was used for multiple comparisons of different metabolites. The relationship between baseline kynurenine metabolites and scale scores was analyzed. The relationship between kynurenine metabolites and scale scores during the follow-up process was analyzed by a linear mixed-effects model. Results:The peripheral picolinic acid (0.39±0.87 vs -0.23±1.09, t=3.89), 3-hydroxykynurenine/kynurenine (3-HK/KYN) (0.38±0.85 vs -0.09±1.01, t=2.98) and 3-HK (0.31±0.81 vs 0.14±1.04, t=2.78) of patients with depression were lower than those of healthy controls (both P<0.05). No statistically significant difference was found between patients with depression with or without suicidal ideation in kynurenine metabolites. In patients with depression and suicidal ideation, baseline HAMD 24 and HAMA scores were positively correlated with plasma 3-HK (HAMD 24: r=0.38; HAMA: r=0.39) and 3-HK/KYN (HAMD 24: r=0.34; HAMA: r=0.37) levels (all P<0.05). After adjusting for age and gender factors, a linear mixed-effects model was established for the follow-up scale scores, and kynurenine metabolite levels of this group of patients, and the results showed that the positive effect of HAMA score on 3-HK/KYN during follow-up was statistically significant ( B=0.04, t=2.46, P<0.05). Conclusion:There are abnormalities in the kynurenine pathway of tryptophan metabolism in patients with depression. 3-HK and 3-HK/KYN are related to the severity of depression and anxiety in patients with depression and suicidal ideation, among which 3-HK/KYN, representing the activity of kynurenine-3-monooxygenase, is dynamically associated with anxiety level.
9.Posterior axillary approach for treatment of some scapular fractures
Ziyan ZHANG ; Yong XING ; Jian DING ; Hua CHEN ; Yan GUO ; Baichuan HE ; Chuangang PENG ; Guangkai REN ; Dankai WU ; Yun TIAN
Chinese Journal of Orthopaedic Trauma 2022;24(5):414-420
Objective:To investigate the efficacy of the posterior axillary approach in the treatment of some scapular fractures.Methods:Retrospectively analyzed were the data of 41 patients with scapular fracture who had been treated through the posterior axillary approach at Department of Traumatology, The Second Hospital of Jilin University from April 2018 to July 2021. There were 32 males and 9 females, aged from 24 to 83 years (average, 52.4 years). Of them, 7 were complicated with multiple injuries, 16 with other fractures, and 4 with brachial plexus injury. Recorded were length of surgical incision, intraoperative blood loss, operation time, and range of shoulder motion, Disability of Arm Shoulder and Hand (DASH) score, Constant shoulder score and postoperative complications at the last follow-up.Results:In this cohort, length of incision ranged from 7 to 12 cm (average, 9.3 cm), intraoperative blood loss from 80 to 150 mL (average, 110.5 mL), exposure time of the posterior axillary approach from 5 to 10 min (average, 7.9 min), and fracture operation time from 85 to 140 min (average, 110.8 min). The 41 patients were followed up for 6 to 36 months (mean, 14.3 months) after surgery. At the last follow-up, the average ranges of shoulder motion were 177° (from 150° to 180°) in flexion, 175° (from 140° to 180°) in abduction and 47° (from 30° to 50°) in extension, the average DASH score was 36.4 points (from 34 to 46 points), and the average Constant score 96.0 points (from 84 to 100 points). There were no complications like loss of fracture reduction, loosening or breakage of plate or screw during follow-up. Incision healing was delayed in 2 patients and mild heterotopic ossification occurred in 2 patients.Conclusion:As a new surgical approach for some scapular fractures, the posterior axillary approach allows internal fixation of the fractures of the scapular glenoid, neck and body under direct vision, leading to good-looking postoperative wound and reliable curative effects.
10.Train of thought for specialty construction in primary care institutions based on experience of rehabilitation service development in Shanghai Fenglin community
Peng ZHOU ; Bin XUE ; Lan YANG ; Yangyang WEI ; Yinghua WU ; Jiankang HU ; Yuanfei SHAN ; Jie QIN ; Baichuan WEI ; Haijiao LIU ; Wenqin GU
Chinese Journal of General Practitioners 2021;20(3):366-369
Community health institutions have entered a new development stage of featured specialty construction. After 12 years of development, rehabilitation medicine now is the featured specialty of Fenglin Community Health Service Center. This article presents the train of thought and key points of specialty construction in primary care institutions based on the Fenglin′s experience. The positioning of featured specialty should be based on the community. The construction process should include 7 elements, namely, the standard operation procedure(SOP)of service system construction, the detailed publicity and implementation of the collaboration of specialists, prevention and control knowledge promotion for general practitioners, prevention and control knowledge education for community residents, service list, clinical efficacy evaluation, and clinical database. In the later iterations, the head of the department should always focus on the service system construction SOP and clinical database construction, and the rest parts can be assigned to the relevant team members.

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