1.Obesity-driven oleoylcarnitine accumulation in tumor microenvironment promotes breast cancer metastasis-like phenotype.
Chao CHEN ; Hongxia ZHANG ; Lingling QI ; Haoqi LEI ; Xuefei FENG ; Yingjie CHEN ; Yuanyuan CHENG ; Defeng PANG ; Jufeng WAN ; Haiying XU ; Shifeng CAO ; Baofeng YANG ; Yan ZHANG ; Xin ZHAO
Acta Pharmaceutica Sinica B 2025;15(4):1974-1990
Obesity is a significant risk factor for cancer and is associated with breast cancer metastasis. Nevertheless, the mechanism by which alterations in systemic metabolism affect tumor microenvironment (TME) and consequently influence tumor metastasis remains inadequately understood. Herein, we found that perturbations in circulating metabolites induced by obesity promote metastasis-like phenotypes in breast cancer. Oleoylcarnitine (OLCarn) concentrations were elevated in the serum of obese mice and humans. Administration of exogenous OLCarn induces metastasis-like characteristics in breast cancer cells. Mechanistically, OLCarn directly interacts with the Arg176 site of adenylate cyclase 10 (ADCY10), leading to the activation of ADCY10 and enhancement of cAMP production. Mutations at Arg176 prevent OLCarn from binding to ADCY10, disrupting the ADCY10-mediated activation of cyclic adenosine monophosphate (cAMP) signaling pathway. This activation promotes transcription factor 4 (TCF4)-dependent kinesin family member C1 (KIFC1) transcription, thereby driving breast cancer metastasis. Conversely, the neutralization of both ADCY10 and KIFC1 through knockdown or pharmacological inhibition abrogates the oncogenic effects mediated by OLCarn. Hence, obesity-induced systemic environmental changes lead to the aberrant accumulation of OLCarn within the TME, making it a potential therapeutic target and biomarker for breast cancer.
2.Live combined Bacillus subtilis and Enterococcus faecium improves glucose and lipid metabolism in type 2 diabetic mice with circadian rhythm disruption via the SCFAs/GPR43/GLP-1 pathway.
Ruimin HAN ; Manke ZHAO ; Junfang YUAN ; Zhenhong SHI ; Zhen WANG ; Defeng WANG
Journal of Southern Medical University 2025;45(7):1490-1497
OBJECTIVES:
To investigate the effects of live combined Bacillus subtilis and Enterococcus faecium (LCBE) on glucose and lipid metabolism in mice with type 2 diabetes mellitus (T2DM) and circadian rhythm disorder (CRD) and explore the possible mechanisms.
METHODS:
KM mice were randomized into normal diet (ND) group (n=8), high-fat diet (HFD) group (n=8), and rhythm-intervention with HFD group (n=16). After 8 weeks of feeding, the mice were given an intraperitoneal injection of streptozotocin (100 mg/kg) to induce T2DM. The mice in CRD-T2DM group were further randomized into two equal groups for treatment with LCBE (225 mg/kg) or saline by gavage; the mice in ND and HFD groups also received saline gavage for 8 weeks. Blood glucose level of the mice was measured using a glucometer, and serum levels of Bmal1, PER2, insulin, C-peptide and lipids were determined with ELISA. Colon morphology and hepatic lipid metabolism of the mice were examined using HE staining and Oil Red O staining, respectively, and fecal short-chain fatty acids (SCFAs) was detected using LC-MS; GPR43 and GLP-1 expression levels were analyzed using RT-qPCR and Western blotting.
RESULTS:
Compared with those in CRD-T2DM group, the LCBE-treated mice exhibited significant body weight loss, lowered levels of PER2, insulin, C-peptide, total cholesterol (TC) and LDL-C, and increased levels of Bmal1 and HDL-C levels. LCBE treatment significantly increased SCFAs, upregulated GPR43 and GLP-1 expressions at both the mRNA and protein levels, and improved hepatic steatosis and colon histology.
CONCLUSIONS
LCBE ameliorates lipid metabolism disorder in CRD-T2DM mice by reducing body weight and improving lipid profiles and circadian regulators possibly via the SCFAs/GPR43/GLP-1 pathway.
Animals
;
Mice
;
Lipid Metabolism
;
Diabetes Mellitus, Type 2/metabolism*
;
Enterococcus faecium
;
Glucagon-Like Peptide 1/metabolism*
;
Bacillus subtilis
;
Diabetes Mellitus, Experimental/metabolism*
;
Circadian Rhythm
;
Blood Glucose/metabolism*
;
Receptors, G-Protein-Coupled/metabolism*
;
Fatty Acids, Volatile/metabolism*
;
Male
;
Chronobiology Disorders/metabolism*
3.Reconstruction of soft tissue defects of multiple fingers in one hand with free posterior interosseous artery perforator flap
Hongjie XU ; Xiaohang ZHAO ; Jian'an MA ; Defeng HU ; Zhenye HU ; Yongsong CHENG ; Haonan CHEN ; Peigao GUO
Chinese Journal of Microsurgery 2024;47(5):520-524
Objective:To investigate the clinical effects of free posterior interosseous artery perforator flap on reconstruction of the soft tissue defects of multiple fingers in one hand.Methods:Clinical data of 9 patients with soft tissue defect of multiple fingers in one hand admitted to the Department of Hand Surgery, Yongkang Orthopedic Hospital between January 2021 and August 2023 were retrospectively studied. The patients were 7 males and 2 females, aged between 19 and 55 years old. The soft tissue defects of 2 patients with 3 fingers injury and 7 patients with 2 fingers injury were reconstructed with free posterior interosseous artery perforator flaps. The size of defects in single finger was 1.5 cm×2.5 cm-3.0 cm×4.5 cm. The size of flap was 2.5 cm×7.0 cm-3.5 cm×13.0 cm. The posterior cutaneous nerve of the forearm were sutured to the intrinsic nerve of palmar side of the 14 fingers. Donor sites in forearm were directly sutured. After discharge, regular follow-up at outpatient clinic and through WeChat interviews were conducted to observe the appearance and texture of the flaps, finger fullness, donor site function and appearance, as well as patient satisfaction. For the flaps with anastomosis of cutaneous nerve, the recovery of TPD of the flap was tested. Sensory recovery was assessed according to the British Medical Research Council (BMRC) sensory function assessment criteria. Hand functions were evaluated using the Total Active Movement (TAM) of fingers of the Hand Surgery of the Chinese Medical Association.Results:All of the 20 flaps survived and were evaluated through follow-up visits, which ranged from 6 to 25 months with an average of 13 months. The flaps were soft, unbloated and without obvious pigmentation. The protective sensations were recovered with an average static TPD of 14 flaps anastomosed with cutaneous nerve was of 9.7 (7-13) mm. Among them, S 3+ 10 fingers, S 3 4 fingers; 6 fingers of flap without sutured cutaneous nerve, S 2 5 fingers, S 1 1 finger. According to the TAM of Hand Surgery of Chinese Medical Association, the results were excellent for 15 fingers and good for 5 fingers. There was no scar contracture in the forearm donor sites and motor function was not affected. Conclusion:Posterior interosseous artery perforator flap has the advantages of thin flap, similar texture to the hand, good recovery in sensory, and minimal damage to the donor site. Therefore, it is a good option in reconstruction of soft tissue defects of multiple fingers in one hand.
4.Relationship between serum reproductive hormones and sperm parameters and surgical outcomes in Micro-TESE
Chenyao DENG ; Defeng LIU ; Wenhao TANG ; Lianming ZHAO ; Haocheng LIN ; Jiaming MAO ; Zhe ZHANG ; Yuzhuo YANG ; Haitao ZHANG ; Hui JIANG ; Kai HONG
Journal of Modern Urology 2023;28(12):1032-1037
【Objective】 To investigate the relationship between serum reproductive hormones and sperm parameters and outcomes of micro-testicular sperm extraction (Micro-TESE). 【Methods】 Clinical data of 1 091 patients treated in our hospital during Jan. and Dec.2021 were retrospectively analyzed. According to the sperm concentration,the patients were divided into non-obstructive azoospermia (NOA) group (group A,n=418),normal sperm concentration group (group B,n=615),mild to moderate oligospermia group (group C,n=18),severe oligospermia group (group D,n=18),and obstructive azoospermia group (group E,n=22). In group A,244 cases treated with Micro-TESE were grouped into the sperm-acquired group (Micro-TESE positive group,n=82) and non-sperm-acquired group (Micro-TESE negative group,n=162),and according to the pathological types of testicular tissue,the patients were divided into normal testicular tissue with hypospermatogenesis group (HYPO group,n=129),maturation arrest group (MA group,n=10),and support-only cell syndrome group (SCO group,n=122). Differences in semen parameters and reproductive hormone levels were compared,and relationship between reproductive hormones and sperm parameters and Micro-TESE outcomes was determined with Pearson correlation analysis. 【Results】 In the sperm concentration subgroup,the testicular volume of group A was lower than that of group B and group E (P<0.05); the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in group A were the highest (P<0.05),but the level of testosterone (T) was the lowest (P<0.05); the levels of anti-mullerian hormone (AMH) and serum inhibin B (INHB) in group A were lower than those in group B and group E (P<0.05),the normal sperm morphology rate in group B was higher than that in group A and group E (P<0.05); the percentage of forward moving sperm in group B was the highest (P<0.05). Pearson correlation analysis revealed that sperm concentration,normal sperm morphology rate,and percentage of forward moving sperm were negatively correlated with age,FSH,LH (P<0.05),and positively correlated with testicular volume,T,AMH,and INHB (P<0.05). NOA patients were grouped according to testicular histology and pathology. The INHB in the SCO group was the smallest of the three groups (P<0.05); the FSH and LH levels in the SCO group were higher than those in the MA group (P<0.05),while the 17β-estradiol (E
5.Transfer of anteriolateral thigh flap with partial iliotibial tract in reconstruction of composite tissue defect in dorsal wrist and hand
Jian'an MA ; Defeng HU ; Hongjie XU ; Zhenye HU ; Hongyu YE ; Yi SUN ; Yongsong CHENG ; Shunjiang ZHENG ; Xiaohang ZHAO ; Maochao DING
Chinese Journal of Microsurgery 2023;46(6):661-665
Objective:To investigate the curative effect of transfer of free anteriolateral thigh flap (ALTF) with partial iliotibial tract on reconstruction of composite tissue defects in dorsal wrist/hand.Methods:Ten patients who were admitted in the Department of Hand Surgery of Yongkang Orthopaedic Hospital from March 2018 to August 2022 were entered in the study due to extensive composite tissue defects in dorsal wrists and hands. The patients were 24-48 (37 in average) years old. All patients had tendon defects in 3 or more digits with 35 digits in total. The length of the tendon defects were 5.0-11.0 cm in various digits. The soft tissue defects ranged from 6.0 cm×8.0 cm to 11.0 cm×21.0 cm in size. Six patients had defects accompanied with metacarpal and phalangeal bone fracture and joint capsule. In emergency surgery, all patients received thorough debridement and VSD coverage after internal fixation for combined fractures. At 3-5 days after the primary surgery, free ALTF transfer with partial iliotibial tract was employed to reconstruct the defects on dorsal wrists and hands and the digit extension function. The size of flap was 6.0 cm×9.0 cm-9.0 cm×17.0 cm, and the rest of defect wound was covered by skin graft. All the donor sites were sutured directly, except 1 that received abdominal skin graft. Patients had the follow-ups in outpatient clinics, or via telephone or Wechat, to observe the sensation and appearance of the flap, and the healing of the donor site. The recovery of the extension function of the hand was evaluated according to the totle active motion (TAM) system.Results:All flaps survived except one that had vascular compromise after the surgery and it survived after two explorations and a vascular transfer. Postoperative follow-ups lasted for 6 to 24 months, with 13 months in average. At the last follow-up, a all the flaps were found soft in texture and slightly swollen in appearance. There was no obvious pigmentation or rupture of skin and extensor tendon. Sensory recovery achieved to S 2 in 7 patients and S 3 in 3 patients. The hand function was evaluated according to TAM system and rated as excellent for 3 digits, good for 18 digits, fair for 9 digits and poor for 5 digits. There were linear scars in the donor sites. Conclusion:Free ALTF transfer with partial iliotibial tract in the reconstruction of composite tissue defect of dorsal wrists and hands can not only reconstruct the wound surface, but also the extension of digits, which cuts short the course of treatment.
6.A survey of current situation of nurses in 52 hospitals in China on mastery of knowledge about skin injury in the elderly based on the background of mixed-mode homogenization training
Qixia JIANG ; Dongmei ZHU ; Wei WEI ; Yuxuan BAI ; Ying LI ; Yingying ZHAN ; Jing WANG ; Yajuan WENG ; Yumei LI ; Guangyang WANG ; Zujing WANG ; Haihua GUO ; Defeng CHEN ; Ping YU ; Wei DOU ; Suling SHI ; Jianxi PANG ; Rui CHEN ; Qiuying HAN ; Yue'e ZHOU ; Lianqun WANG ; Fangfang XU ; Haiyan YANG ; Fang MA ; Huijuan SUO ; Xiangyun LIU ; Xiujuan YU ; Yunxia LUO ; Min WANG ; Huilian ZHAO ; Ying SUN ; Kaiwen WANG
Chinese Journal of Modern Nursing 2022;28(10):1337-1341
Objective:To understand the current situation of nurses in 52 hospitals in China on mastery of knowledge about skin injury in the elderly based on the background of mixed-mode homogenization training.Methods:Using the convenient sampling method, a total of 1 067 nurses from 52 hospitals in China were selected as the research objects in January 2021. A self-designed questionnaire on knowledge of skin injury in the elderly was used to investigate the nurses through the questionnaire star and univariate analysis was used to analyze the influencing factors. A total of 1 067 questionnaires were distributed and 1 067 valid questionnaires were recovered, and the effective recovery rate was 100%.Results:The knowledge scores of pressure injury, incontinence-associated dermatitis, skin tear and xerosis cutis among 1067 nurses were (95.66±7.37) , (95.65±9.15) , (91.37±15.45) and (87.67±15.91) , respectively. The results of univariate analysis showed that hospital grade was the influencing factor of nurses' knowledge score of pressure injury, skin tear and incontinence-associated dermatitis ( P<0.05) , educational background was the influencing factor of nurses' knowledge score of skin tear ( P<0.05) , professional title was the influencing factor of nurses' knowledge scores of pressure injury, incontinence-associated dermatitis and xerosis cutis ( P<0.05) . Conclusions:Hospitals at all levels need to strengthen the theoretical and practical knowledge training for nurses on skin xerosis and skin tear in the elderly, especially for nurses with primary titles and lower education in grassroots hospitals.
7.LINC00612 targeted Bcl-2 to inhibit the apoptosis of neurons incubated with Aβ1-42
Qian PENG ; Defeng ZHAO ; Jian ZHANG
Journal of Apoplexy and Nervous Diseases 2021;38(9):810-812
Objective To investigate the effect of LINC00612 on apoptosis of SH-SY5Y cells incubated with Aβ1-42.Methods Neuronal injury model of Alzheimer’s disease were established by SH-SY5Y cells incubated with Aβ1-42.The expression of LINC00612 in SH-SY5Y cells incubated with Aβ1-42 was detected by qRTPCR. The LINC00612 overexpressed plasmid was transfected into SH-SY5Y cells incubated with Aβ1-42,and the expression of Bcl-2 was detected by Western blot. Apoptosis was detected by Annexin V-FITC /PI staining. RNA-pulldown and RIP experiments were performed to detect the binding effect of LINC00612 and Bcl-2.Results LINC00612 was low expressed in SH-SY5Y cells incubated with Aβ1-42.Overexpression of LINC00612 significantly increased Bcl-2 expression and decreased apoptosis. RNA pulldown and RIP results showed that LINC00612 could bind to Bcl-2.Conclusion Overexpression of LINC00612 can up-regulate Bcl-2 expression and inhibit the apoptosis of SH-SY5Y cells incubated with Aβ1-42.
8.Investigation on colonization status of Streptococcus pneumoniae and Haemophilus influenzae in healthy infants in Wuhan
Defeng ZHAO ; Fang WANG ; Jian CHEN ; Li CAI ; Li WEN ; Yan XIONG
Journal of Public Health and Preventive Medicine 2020;31(2):74-77
Objective To understand the colonization status of Streptococcus pneumoniae and Haemophilus influenzae in nasopharynx of healthy infants in Wuhan. Methods Six vaccination clinics were randomly selected, and the nasopharyngeal specimens of healthy infants were collected and cultured for Streptococcus pneumoniae and Haemophilus influenza. Results The carrying rate of Streptococcus pneumoniae and Haemophilus influenzae in 998 healthy infants was 18.84% and 17.54%, respectively. The carrying rate of Streptococcus pneumoniae and Haemophilus influenzae within 6 months of age was 15.79% and 14.39%, and the carrying rate of Streptococcus pneumoniae and Haemophilus influenzae at 7-12 months old was 22.90% and 21.73%, respectively. The difference was statistically significant (Sp: χ2=5.60 P=0.02; Hi:χ2=8.98 P=0.00); The carrying rate of Streptococcus pneumoniae in urban and suburban areas was 18.08% and 19.78%, respectively, and the Haemophilus influenzae carrying rate was 17.18% and 17.98%, respectively. The differences were not statistically significant (Sp:χ2=0.47 P=0.50; Hi:χ2=0.11 P=0.74). The correlation coefficient (r value) of the age of the month and the carrying rate of sp and hi was 0.98 and 0.96, respectively. Conclusion The age of healthy infants in Wuhan was highly linearly and positively correlated with the carrying rate of Streptococcus pneumoniae and Haemophilus influenza.
9.Clinical analysis of different cases with pachymeningeal enhancement on magnetic resonance imaging
Jirui WANG ; Defeng ZHAO ; Meiqing LIN
Journal of Apoplexy and Nervous Diseases 2020;37(5):413-418
Objective To investigate the clinical manifestations and diagnosis of the diseases with the imaging characteristics of pachymeningeal enhancement on magnetic resonance imaging (MRI),in order to improve the understanding of the diseases with pachymeningeal enhancement on MRI. Methods The clinical data and auxiliary examination results of 5 patients with pachymeningeal enhancement on MRI from February 2017 to October 2019 were analyzed retrospectively,and the characteristics of each patient were analyzed. Results MRI was similar in all five patients. All of them showed pachymeningeal enhancement,but the clinical diagnosis was different:1 case was idiopathic hypertrophic pachymeningitis;1 case was IgG4-related hypertrophic pachymeningitis;1 case was intracranial hypotension syndrome;1 case was cerebral venous sinus thrombosis;1 case was meningoma. Conclusions The etiology,treatment and prognosis of diseases with pachymeningeal enhancement on MRI are complex,history and other auxiliary examination should be combined carefully to identify the diagnosis,avoiding misdiagnosis.
10.Repair of distal thumb degloving injury with B-shaped first palmar dorsal neurocutaneous vascular flap
Hongjie XU ; Xiaohang ZHAO ; Defeng HU ; Yi SUN ; Jian’an MA ; Zhenye HU ; Shunjiang ZHENG ; Yongsong CHENG
Chinese Journal of Plastic Surgery 2020;36(6):660-663
Objective:To explore the clinical effect of repair of distal thumb degloving injury with B-shaped first palmar dorsal neurocutaneous vascular flap.Methods:The clinical data included 15 patients with distal thumb degloving injury received in Yongkang Orthopedic Hospital from March 2015 to June 2018. These patients included 10 males and 5 females, aged between 24 and 61 years. For the injury, 7 cases were beyond the interphalangeal joint, 8 cases were beyond the nail root. The length of the distal segment of degloving finger was 1.8 to 2.3 cm, and the skin and soft tissue defect ranged from 1.8 cm × 4.6 cm to 2.3 cm × 5.6 cm. The distal thumb degloving injury was repaired with B-shaped first palmar dorsal neurocutaneous vascular flap. The radial dorsal metacarpal nerve of the first metacarpal was anastomosed with the ulnar proper digital nerve stump. And full-thickness skin graft transplantation was performed in donor area. After the operation, the shape and function of the thumb were followed up. The sensory function of the skin was determined by British Medical Research Association Sensory Function Evaluation Standard, and the function of the thumb was evaluated with reference to the total active movement (TAM) of fingers of the Chinese Medical Association Hand Surgery Branch.Results:The flap area was 2.0 cm × 5.0 cm-2.5 cm × 6.0 cm, and all the flaps were survived. Follow-up period was 5-18 months after the operation, with an average of 10 months. The flap at the thumb repair site was soft, wear-resistant, non-bloated, no obvious pigmentation. Its protective sensation was restored. The two-point discrimination of the flap reached 8-11 mm, with an average of 9.3 mm, basically restoring the original shape and function of the thumb. There were 13 cases reaching the S3 + flap sensory function, 2 cases reaching S3. The thumb function was evaluated as excellent for 9 cases, and good for 6 cases. There were no complications such as scar contracture and hypersensitivity in the donor area. Conclusions:The repair of distal thumb degloving injury with B-shaped first palmar dorsal neurocutaneous vascular flap can complete skin coverage and sensory reconstruction, with satisfactory postoperative effect.


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