1.Facilitation of mucosal healing by estrogen receptor β in ulcerative colitis through suppression of branched-chain amino acid transport and subsequent triggering of autophagy in colonic epithelial cells.
Yilei GUO ; Yanrong ZHU ; Jing ZHANG ; Yue HE ; Mianjiang ZHAO ; Haochang LIN ; Zhifeng WEI ; Yufeng XIA ; Yue DAI
Acta Pharmaceutica Sinica B 2025;15(1):168-187
Colonic mucosal healing is the ultimate goal of ulcerative colitis (UC) treatment, but it remains difficult to realize. Given the higher incidence of UC in males and the beneficial effect of estrogen on UC, we conducted this study to examine the therapeutic potential of estrogen receptor β (ERβ), the primary ER subtype in colon, on mucosal healing in UC. Our study is the first to report that ERβ activation degree was positively correlated with mucosal healing in patients with UC. Furthermore, ERβ activation enhanced mucosal healing in mice with dextran sulfate sodium-induced and biopsy-induced colonic injuries. Mechanistically, ERβ activation promoted autophagy of colonic epithelial cells by inhibiting branched-chain amino acid transport, leading to focal adhesion kinase (FAK) activation. Activated FAK promoted focal adhesion turnover and colonic epithelial cell migration, ultimately facilitating mucosal healing. ERβ -/- colitis mice exhibited impaired mucosal healing compared to wild-type littermates, highlighting the crucial effect of ERβ. Importantly, combination with ERβ-agonist diarylpropionitrile enhanced the amelioration of 5-aminosalicylic acid, a standard UC treatment agent, against mouse colitis. These findings attest to the crucial role of ERβ activation in colonic mucosal healing and may further inform the development of novel strategies for UC treatment.
2.Study on the current status and influencing factors of maximum tongue pressure in cardiac surgery inpatients based on a random forest model
Aimin SHAO ; Yilei ZHU ; Haiou XIA ; Jun ZHONG ; Run HUANG
Chinese Journal of Practical Nursing 2025;41(8):620-627
Objective:To investigate the current status of maximum tongue pressure (MTP) in cardiac surgery inpatients and analyze its influencing factors, providing a basis for developing personalized nursing measures for high-risk groups.Methods:This cross-sectional study used a convenience sampling method to select cardiac surgery inpatients at Zhongshan Hospital, Fudan University, from January 2022 to April 2023. General and clinical data questionnaires, a swallowing tongue muscle evaluation training device, and a hand dynamometer were used for data collection. The random forest model and Lasso regression were employed to identify key influencing factors, and multiple linear regression was used to analyze the factors affecting MTP.Results:A total of 501 cardiac surgery inpatients meeting the inclusion and exclusion criteria were enrolled, including 308 males and 193 females, with a mean age of (56.94 ± 14.02) years. The mean MTP was (45.92 ± 9.57) kPa. When the lambda (λ) value was 0.181, the model achieved the best fit, identifying 10 key influencing factors in descending order of importance: age, handgrip strength, gender, BMI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), glomerular filtration rate, cardiac function grade, hemoglobin, history of stroke, and history of atrial fibrillation. Age, handgrip strength, low-level BMI, NT-proBNP, and history of stroke were determined as significant factors influencing MTP in cardiac surgery inpatients ( R2 = 0.324, F = 24.92, P<0.05). Conclusions:Nurses should pay close attention to the tongue muscle strength of cardiac surgery inpatients. Early assessment of MTP is essential for older patients, those with low handgrip strength, low BMI, elevated NT-proBNP, or a history of stroke. Targeted early identification and pre-rehabilitation measures should be implemented for patients with weakened tongue muscle strength.
3.Construction and implementation of a blood glucose chain management model for critically ill patients after cardiac surgery
Haibo ZHANG ; Yilei ZHU ; Min XU ; Jiacheng DUAN ; Jingjing TANG ; Yujie ZHANG ; Run HUANG
Chinese Journal of Practical Nursing 2025;41(33):2585-2591
Objective:To establish a chain management model for blood glucose in critically ill patients after cardiac surgery and analyze its clinical effectiveness, and to provide a reference for related clinical nursing practices.Methods:A quasi-experimental study design was adopted. Using convenience sampling, 120 critically ill patients after cardiac surgery admitted to Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were selected as study subjects. They were divided into groups based on the time of admission to the intensive care unit after surgery. Sixty patients admitted from March to May 2024 were assigned to the control group and received conventional blood glucose management. Another 60 patients admitted from June to August 2024 were assigned to the observation group and received the chain management model for blood glucose control in addition to the conventional approach. Blood glucose levels and quality indicators of blood glucose management (including maximum blood glucose fluctuation, time in target glucose range, duration of insulin use, incidence of hypoglycemia, etc.) were compared between the two groups.Results:The control group included 27 males and 33 females, with an age of 63.00(59.00, 69.25) years; the observation group included 28 males and 32 females, with an age of 66.00(60.00, 70.00) years. The blood glucose levels of the observation group on postoperative days 2, 3, 4 were 9.10(8.68, 9.90), 8.90(8.40, 10.00), 8.75(7.38, 9.03) mmol/L, respectively, which were lower than those of the control group [10.30(9.80, 11.00), 9.95(9.40, 11.05), 9.30(8.10, 10.02) mmol/L], with a statistically significant difference ( Z=-5.85, -4.95, -3.50, all P<0.05). The maximum blood glucose fluctuation in the observation group was (4.09 ± 2.45) mmol/L, lower than that of the control group [(5.19 ± 2.47) mmol/L], with a statistically significant difference ( t=2.46, P<0.05). The time in the target glucose range was 67.00(60.00, 75.00)% in the observation group, higher than that of the control group 52.00(45.00, 60.00)%, with a statistically significant difference ( Z=-6.57, P<0.05). The duration of insulin use was 6.00(5.00, 7.00) h in the observation group, shorter than that of the control group [13.00(9.75, 15.32) h], with a statistically significant difference ( Z=-8.68, P<0.05). The incidence of hypoglycemia was 3.33%(2/60) in the observation group and 15.00%(9/60) in the control group, with a statistically significant difference ( χ2=4.90, P<0.05). The mechanical ventilation time, ICU stay, and total hospital stay in the observation group were 42.00(37.00, 89.25) h, 6.00(5.00, 7.00) d, and 12.00(11.75, 13.00) d, respectively, which were shorter than those of the control group [96.00(86.25, 98.00) h, 7.00(7.00, 10.00) d, and 13.00(11.75, 15.00) d], with a statistically significant difference ( Z=8.67, 17.57, 4.73, all P<0.05). Conclusions:The implemented chain management model for blood glucose control meets the comprehensive requirements of blood glucose management. It not only reduces blood glucose fluctuations and decreases the incidence of hypoglycemia but also effectively improves the quality of blood glucose management in critically ill patients after cardiac surgery, enhances the safety of blood glucose control, and promotes patient recovery.
4.Construction and implementation of a blood glucose chain management model for critically ill patients after cardiac surgery
Haibo ZHANG ; Yilei ZHU ; Min XU ; Jiacheng DUAN ; Jingjing TANG ; Yujie ZHANG ; Run HUANG
Chinese Journal of Practical Nursing 2025;41(33):2585-2591
Objective:To establish a chain management model for blood glucose in critically ill patients after cardiac surgery and analyze its clinical effectiveness, and to provide a reference for related clinical nursing practices.Methods:A quasi-experimental study design was adopted. Using convenience sampling, 120 critically ill patients after cardiac surgery admitted to Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine were selected as study subjects. They were divided into groups based on the time of admission to the intensive care unit after surgery. Sixty patients admitted from March to May 2024 were assigned to the control group and received conventional blood glucose management. Another 60 patients admitted from June to August 2024 were assigned to the observation group and received the chain management model for blood glucose control in addition to the conventional approach. Blood glucose levels and quality indicators of blood glucose management (including maximum blood glucose fluctuation, time in target glucose range, duration of insulin use, incidence of hypoglycemia, etc.) were compared between the two groups.Results:The control group included 27 males and 33 females, with an age of 63.00(59.00, 69.25) years; the observation group included 28 males and 32 females, with an age of 66.00(60.00, 70.00) years. The blood glucose levels of the observation group on postoperative days 2, 3, 4 were 9.10(8.68, 9.90), 8.90(8.40, 10.00), 8.75(7.38, 9.03) mmol/L, respectively, which were lower than those of the control group [10.30(9.80, 11.00), 9.95(9.40, 11.05), 9.30(8.10, 10.02) mmol/L], with a statistically significant difference ( Z=-5.85, -4.95, -3.50, all P<0.05). The maximum blood glucose fluctuation in the observation group was (4.09 ± 2.45) mmol/L, lower than that of the control group [(5.19 ± 2.47) mmol/L], with a statistically significant difference ( t=2.46, P<0.05). The time in the target glucose range was 67.00(60.00, 75.00)% in the observation group, higher than that of the control group 52.00(45.00, 60.00)%, with a statistically significant difference ( Z=-6.57, P<0.05). The duration of insulin use was 6.00(5.00, 7.00) h in the observation group, shorter than that of the control group [13.00(9.75, 15.32) h], with a statistically significant difference ( Z=-8.68, P<0.05). The incidence of hypoglycemia was 3.33%(2/60) in the observation group and 15.00%(9/60) in the control group, with a statistically significant difference ( χ2=4.90, P<0.05). The mechanical ventilation time, ICU stay, and total hospital stay in the observation group were 42.00(37.00, 89.25) h, 6.00(5.00, 7.00) d, and 12.00(11.75, 13.00) d, respectively, which were shorter than those of the control group [96.00(86.25, 98.00) h, 7.00(7.00, 10.00) d, and 13.00(11.75, 15.00) d], with a statistically significant difference ( Z=8.67, 17.57, 4.73, all P<0.05). Conclusions:The implemented chain management model for blood glucose control meets the comprehensive requirements of blood glucose management. It not only reduces blood glucose fluctuations and decreases the incidence of hypoglycemia but also effectively improves the quality of blood glucose management in critically ill patients after cardiac surgery, enhances the safety of blood glucose control, and promotes patient recovery.
5.Study on the current status and influencing factors of maximum tongue pressure in cardiac surgery inpatients based on a random forest model
Aimin SHAO ; Yilei ZHU ; Haiou XIA ; Jun ZHONG ; Run HUANG
Chinese Journal of Practical Nursing 2025;41(8):620-627
Objective:To investigate the current status of maximum tongue pressure (MTP) in cardiac surgery inpatients and analyze its influencing factors, providing a basis for developing personalized nursing measures for high-risk groups.Methods:This cross-sectional study used a convenience sampling method to select cardiac surgery inpatients at Zhongshan Hospital, Fudan University, from January 2022 to April 2023. General and clinical data questionnaires, a swallowing tongue muscle evaluation training device, and a hand dynamometer were used for data collection. The random forest model and Lasso regression were employed to identify key influencing factors, and multiple linear regression was used to analyze the factors affecting MTP.Results:A total of 501 cardiac surgery inpatients meeting the inclusion and exclusion criteria were enrolled, including 308 males and 193 females, with a mean age of (56.94 ± 14.02) years. The mean MTP was (45.92 ± 9.57) kPa. When the lambda (λ) value was 0.181, the model achieved the best fit, identifying 10 key influencing factors in descending order of importance: age, handgrip strength, gender, BMI, N-terminal pro-B-type natriuretic peptide (NT-proBNP), glomerular filtration rate, cardiac function grade, hemoglobin, history of stroke, and history of atrial fibrillation. Age, handgrip strength, low-level BMI, NT-proBNP, and history of stroke were determined as significant factors influencing MTP in cardiac surgery inpatients ( R2 = 0.324, F = 24.92, P<0.05). Conclusions:Nurses should pay close attention to the tongue muscle strength of cardiac surgery inpatients. Early assessment of MTP is essential for older patients, those with low handgrip strength, low BMI, elevated NT-proBNP, or a history of stroke. Targeted early identification and pre-rehabilitation measures should be implemented for patients with weakened tongue muscle strength.
6.Cholinergic dysfunction-induced insufficient activation of alpha7 nicotinic acetylcholine receptor drives the development of rheumatoid arthritis through promoting protein citrullination via the SP3/PAD4 pathway.
Changjun LV ; Minghui SUN ; Yilei GUO ; Wenxin XIA ; Simiao QIAO ; Yu TAO ; Yulai FANG ; Qin ZHANG ; Yanrong ZHU ; Yusufu YALIKUN ; Yufeng XIA ; Zhifeng WEI ; Yue DAI
Acta Pharmaceutica Sinica B 2023;13(4):1600-1615
Both cholinergic dysfunction and protein citrullination are the hallmarks of rheumatoid arthritis (RA), but the relationship between the two phenomena remains unclear. We explored whether and how cholinergic dysfunction accelerates protein citrullination and consequently drives the development of RA. Cholinergic function and protein citrullination levels in patients with RA and collagen-induced arthritis (CIA) mice were collected. In both neuron-macrophage coculture system and CIA mice, the effect of cholinergic dysfunction on protein citrullination and expression of peptidylarginine deiminases (PADs) was assessed by immunofluorescence. The key transcription factors for PAD4 expression were predicted and validated. Cholinergic dysfunction in the patients with RA and CIA mice negatively correlated with the degree of protein citrullination in synovial tissues. The cholinergic or alpha7 nicotinic acetylcholine receptor (α7nAChR) deactivation and activation resulted in the promotion and reduction of protein citrullination in vitro and in vivo, respectively. Especially, the activation deficiency of α7nAChR induced the earlier onset and aggravation of CIA. Furthermore, deactivation of α7nAChR increased the expression of PAD4 and specificity protein-3 (SP3) in vitro and in vivo. Our results suggest that cholinergic dysfunction-induced deficient α7nAChR activation, which induces the expression of SP3 and its downstream molecule PAD4, accelerating protein citrullination and the development of RA.
7.Clinical characteristics and diagnosis and treatment experiences of Langerhans cell histocytosis in skull
Guoyang YIN ; Cuicui LIU ; Yilei XIAO ; Haitao JIANG ; Chongfu XU ; Zhiyu GAO ; Zipeng ZHU ; Fenghai YANG ; Qiang FU
Chinese Journal of Neuromedicine 2021;20(5):495-500
Objective:To analyze the clinical characteristics and diagnosis and treatment experiences of Langerhans cell histocytosis (LCH) in skull.Methods:Sixteen patients with cranial LCH admitted to our hospital from January 2015 to December 2019 were chosen in our study. Their clinical data, diagnosis and treatment procedures and prognoses were retrospectively analyzed.Results:Among the 16 patients, there were 13 males and 3 females, aged from 1 to 31 years. The clinical manifestations included space-occupying lesions of the skull; and imaging showed bone destruction of the skull, with or without involvement of other bones or organs. All patients were pathologically confirmed to have LCH after surgical total resection of the lesions. Routine whole-body bone scanning was performed after surgery: one was found to have local abnormal metabolic activity and received local radiotherapy; 8 were combined with other bone or organ involvement, and received chemotherapy. All the patients were followed up for 1-5 years, and no recurrence was found, and no one died.Conclusion:Good prognosis can be achieved in cranial LCH patients accepted resection by giving additional treatment according to the results of postoperative reexamination and combination use of standardized radiotherapy and chemotherapy.
8.Bortezomib and obatoclax for dual blockade of protein degradation pathways show synergistic anti-tumor effect in human acute T lymphoblastic leukemia cells.
Dan ZHOU ; Lixia DAI ; Xiaolian LIU ; Fuchang QUE ; Yuyan XU ; Xin LUO ; Yaolu ZHU ; Shuwen LIU ; Yilei LI ; Le YU
Journal of Southern Medical University 2019;39(4):401-408
OBJECTIVE:
To explore whether bortezomib and a Bcl-2 inhibitor exhibit synergistic anti-tumor effect in human acute T lymphoblastic leukemia cells.
METHODS:
MTT assay was used to determine the cytotoxicity of bortezomib in the absence or presence of Bcl-2 inhibitors (obatoclax, AT-101 and ABT-199) in Jurkat cells. The effects of drug treatment on the expression of Bcl-2 family proteins, LC3B, p62, ubiquitin, BiP/Grp78, p-JNK, p-p38 and CHOP proteins were examined by Western blotting. Flow cytometry was used to determine the effects of bortezomib and Bcl-2 inhibitors (obatoclax, AT-101 and ABT-199) on cell apoptosis. Quantitative real-time PCR was used to measure the mRNA expression levels of the key regulatory factors of unfolded protein reaction (UPR). A zebrafish xenograft model was used to study the anti-tumor effect of bortezomib, obatoclax and their combination in vivo.
RESULTS:
Bortezomib or Bcl-2 inhibitors alone inhibited the cell viability of Jurkat cells, but only obatoclax and bortezomib showed synergistic cytotoxicity and pro-apoptotic effect. Obatoclax, rather than AT-101 and ABT- 199, blocked autophagic flux in the cells evidenced by concomitant accumulation of LC3B-Ⅱ and p62. Both bortezomib and obatoclax alone caused accumulation of polyubiquinated proteins, and their combination showed a synergistic effect, which was consistent with their synergistic cytotoxicity. The dual blockade of proteasome and autophagy by the combination of bortezomib and obatoclax triggered unfolded protein response followed by cell apoptosis. Preventing UPS dysfunction by tauroursodeoxycholic acid (TUDCA) significantly attenuated the cytotoxicity and pro-apoptotic effect of bortezomib in combination with obatoclax. In zebrafish xenograft models, bortezomib combined with obatoclax significantly decreased tumor foci formation.
CONCLUSIONS
Bortezomib and obatoclax for dual blockade of protein degradation pathways show synergistic anti-tumor effect in human acute T lymphoblastic leukemia cells.
Antineoplastic Agents
;
Apoptosis
;
Bortezomib
;
Cell Line, Tumor
;
Drug Synergism
;
Humans
;
Precursor Cell Lymphoblastic Leukemia-Lymphoma
;
Proteolysis
;
Proto-Oncogene Proteins c-bcl-2
;
Pyrroles
9.Changes in relative pituitary hormones following severe traumatic brain injury in children and mild hypothermia treatment
Jianxin ZHU ; Zonglei CHONG ; Yilei XIAO ; Li LI ; Fuhua YU ; Wei LIU ; Ming SUN ; Qingju ZHAO
Chinese Journal of Neuromedicine 2018;17(6):582-587
Objective To observe changes in relative pituitary hormones after severe traumatic brain injury (STBI) in children and to investigate the short-and long-term effects of mild hypothermia on pituitary function.Methods Included for this study were 81 children who had been admitted to the Brain Hospital of Liaocheng People's Hospital from June 2011 to January 2015 for STBI and abnormal secretion of pituitary-related hormones.They were divided by the wishes of patients and their families into 2 groups,subjected to mild hypothermia treatment (n=42) or conventional treatment (n=41).The levels were examined of growth hormone (GH),prolactin (PRL),adrenocorticotropic hormone (ACTH),free triiodothyronine (FT3),free thyroxine (FT4) and thyroid stimulating hormone (TSH) for both groups unpon admission and in the moming of 1,3,5,7 and 14 days after injury.At 6 months after injury the patients were followed up for Glasgow Outcome Score (GOS) and levels of pituitary-related hormones.Results Of the 83 patients,disturbance of one single hormone was found in 31 (30.10%) and disturbance of 2 or more hormones in 52 (50.48%).The top 3 hormones disturbed were PRL,ACTH and GH.On days 3,5 and 7 after injury,the levels of PRL and ACTH in the mild hypothermia treatment group were significantly lower than in the conventional treatment group (P<0.05).On day 3 after injury,the level of FT3 in the mild hypothermia treatment group was significantly lower than in the conventional treatment group (P<0.05).At 6 months after injury,the GOS score for the conventional treatment group was 3.04±0.38,significantly lower than that for the mild hypothermia treatment group (4.56±0.62) (P<0.05).The incidence of hypopituitarism in the hypothermia treatment group (16.67%) was significantly lower than in the conventional treatment group (46.88%) (P<0.05).Conclusions Incidence of pituitary dysfunction is high in children following severe traumatic brain injury.Mild hypothermia treatment can effectively alleviate early-stage parasecretion of pituitary hormones,and decrease the incidence of later pituitary dysfunction.
10.Construction and effect evaluation of platform for evidence dissemination
Zheng ZHU ; Weijie XING ; Yan HU ; Yingfeng ZHOU ; Ying GU ; Lei CHENG ; Chunqing WANG ; Rui ZHAO ; Yilei WANG
Chinese Journal of Nursing 2017;52(3):271-274
Objective To establish WeChat official account-based platform for evidence dissemination,and to evaluate the effects of the platform.Methods The WeChat official account-based platform for evidence dissemination was established,and big data analysis and sampling survey were adopted to analyze information and its communication effects published from December,2014 to September,2016.Results Totally 22 369 followers used the platform and conducted 404 232 hits on its pages in total.The most frequent searches were Evidence and Knowledge of evidence-based nursing.The WeChat Communication Index was 433.07.The overall evaluation score was 4.34± 0.67.Conclusion WeChat official account-based platform for evidence dissemination can promote the accessibility of evidence and receives high evaluation score from followers.

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