In this report, the protective effect and molecular mechanism of Chaihu Shugan San-containing serum on corticosterone(CORT)-induced mitochondrial damage in pheochromocytoma(PC12) cells was studied based on CORT-induced rat PC12 cell model. The cultured cells were divided into five groups: blank control group, CORT group(400 μmol·L~(-1) CORT), Chaihu Shugan San-containing serum group(400 μmol·L~(-1) CORT + 10% Chaihu Shugan San-containing serum), control serum group(400 μmol·L~(-1) CORT + 10% control serum), and fluoxetine group(400 μmol·L~(-1) CORT + 10% fluoxetine-containing serum). The study was carried out by cell activity detection, mitochondrial morphology observation, membrane potential measurement, energy metabolism analysis, and mitochondrial dynamics-related protein detection. The results showed that CORT treatment significantly reduced the survival rate of PC12 cells, altered mitochondrial morphology, and decreased mitochondrial membrane potential and adenosine triphosphate(ATP) synthetic rate. Both Chaihu Shugan San-and fluoxetine-containing serum significantly increased the survival rate of CORT-treated PC12 cells and the ATP synthetic rate in the mitochondria. Unlike fluoxetine, Chaihu Shugan San-containing serum significantly inhibited the decrease in mitochondrial membrane potential caused by CORT and increased the oxygen consumption rate(OCR) values of both mitochondrial maximum respiration and reserve respiration capacity. Western blot analysis showed that CORT induced upregulated protein expressions of dynamin-related protein 1(Drp1) and peroxisome proliferator-activated receptor gamma co-activator 1α(PGC-1α) in PC12 cells and specific protein expression of optic atrophy protein 1(OPA1), yet it repressed the protein expressions of silent information regulator 1(SIRT1) and mitochondrial fusion protein 1(Mfn1) in PC12 cells. Both Chaihu Shugan San-and fluoxetine-containing serum significantly inhibited the protein expression of Drp1. However, only Chaihu Shugan San-containing serum could significantly inhibit the CORT-induced upregulation protein of PGC-1α. RESULTS:: herein suggest that Chaihu Shugan San-containing serum can alleviate CORT-induced damage in PC12 cells, which may be related to the mitochondrial fragmentation/lipid peroxidation protection by Drp1 inhibition, as well as mitochondrial dynamics and energy metabolism mediated by PGC-1α/SIRT1 signaling pathway.
Animals ; PC12 Cells ; Rats ; Mitochondrial Dynamics/drug effects* ; Mitochondria/metabolism* ; Corticosterone/adverse effects* ; Membrane Potential, Mitochondrial/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Protective Agents/pharmacology* ; Cell Survival/drug effects*

Glutamine provides carbon and nitrogen to support the proliferation of cancer cells. However, the precise reason why cancer cells are particularly dependent on glutamine remains unclear. In this study, we report that glutamine modulates the tumor suppressor F-box and WD repeat domain-containing 7 (FBW7) to promote cancer cell proliferation and survival. Specifically, lysine 604 (K604) in the sixth of the 7 substrate-recruiting WD repeats of FBW7 undergoes glutaminylation (Gln-K604) by glutaminyl tRNA synthetase. Gln-K604 inhibits SCFFBW7-mediated degradation of c-Myc and Mcl-1, enhances glutamine utilization, and stimulates nucleotide and DNA biosynthesis through the activation of c-Myc. Additionally, Gln-K604 promotes resistance to apoptosis by activating Mcl-1. In contrast, SIRT1 deglutaminylates Gln-K604, thereby reversing its effects. Cancer cells lacking Gln-K604 exhibit overexpression of c-Myc and Mcl-1 and display resistance to chemotherapy-induced apoptosis. Silencing both c-MYC and MCL-1 in these cells sensitizes them to chemotherapy. These findings indicate that the glutamine-mediated signal via Gln-K604 is a key driver of cancer progression and suggest potential strategies for targeted cancer therapies based on varying Gln-K604 status.
Glutamine/metabolism* ; Myeloid Cell Leukemia Sequence 1 Protein/genetics* ; Humans ; Proto-Oncogene Proteins c-myc/genetics* ; Cell Proliferation ; Signal Transduction ; Neoplasms/pathology* ; F-Box-WD Repeat-Containing Protein 7/genetics* ; Cell Survival ; Cell Line, Tumor ; Apoptosis

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

A mounting body of research suggests that circRNAs significantly contribute to the develop-ment of myocardial fibrosis.The microarray results of human circular RNA expression profile indicated that circHERC4_041 expression increased in the myocardium of patients with heart failure,RT-qPCR a-nalysis confirmed that the myocardial expression level of circHERC4_041 in individuals with heart failure were considerably elevated compared to that in healthy organ donors.Fluorescence in situ hybridization(FISH)confirmed that circHERC4_041 was abundant in the cytoplasm of human cardiomyocyte AC16.Overexpression of circHERC4_041 in mouse myocardial fibroblasts(mCFs)mediated by adenovirus in-hibited the expression of fibrosis-related proteins in mCFs.Experiments involving cell proliferation,wound healing,and Transwell assays demonstrated that overexpression of circHERC4_041 suppressed the growth and mobility of mCFs(P＜0.001).Sequence analysis results suggested that circHERC4_041 con-tains potential ribosome entry sequence(IRES)and open reading frame(ORF).Western blot confirmed that circHERC4_041 could translate the 516 amino acid HERC4-516aa protein,which was mainly located in the cytoplasm of the cell.Cell functional experiments confirmed that circHERC4_041 inhibited the fi-brotic phenotype of mCFs by specifically translating HERC4-516aa(P＜0.05).The specific interaction between HERC4-516aa and transglutaminase 2(TGM2)was confirmed by IP-MS screening and Co-IP i-dentification.Further results found that the degradation of TGM2 was promoted through proteasome path-way.The overexpression of TGM2 in mCFs facilitated by adenoviral vectors could counteract the suppres-sive effects of HERC4-516aa on the fibrotic phenotype of mCFs.Therefore,this study confirmed that the HERC4-516aa protein translated by circHERC4_041 can specifically bind to TGM2 to inhibit the fibrotic phenotype of myocardial fibroblasts.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

With the rapid development of generative artificial intelligence(GAI)technologies,their widespread application in academic research and writing is continuously expanding the boundaries of sci-entific inquiry.However,this trend has also raised a series of ethical and regulatory challenges,inclu-ding issues related to authorship,content authenticity,citation accuracy,and accountability.In light of the growing involvement of AI in generating academic content,establishing an open,controllable,and trustworthy ethical governance framework has become a key task for safeguarding research integrity and maintaining trust within the academic community.This expert consensus outlines ethical requirements across key stages of AI-assisted academic writing-including topic selection,data management,citation practices,and authorship attribution.It aims to clarify the boundaries and ethical obligations surrounding AI use in academic writing,ensuring that technological tools enhance efficiency without compromising in-tegrity.The goal is to provide guidance and institutional support for building a responsible and sustainable research ecosystem.

OBJECTIVE: To explore the effectiveness of the combined anteversion angle technique in total hip arthroplasty (THA) for treating ankylosing spondylitis (AS) affecting the hip joint. METHODS: A retrospective analysis was conducted on the clinical data of 73 patients with AS affecting the hip joint who underwent THA between August 2018 and August 2021. According to whether the combined anteversion angle technique was used in THA, the patients were divided into study group (37 cases, combined anteversion angle technique was used in THA) and control group (36 cases, traditional THA). There was no significant difference in baseline data such as gender, age, body mass index, disease duration, preoperative Harris score, range of motion (ROM), acetabular anteversion angle, acetabular abduction angle, femoral anteversion angle, and combined anteversion angle between the two groups ( P>0.05). The operation time, hospital stay, and complications of the two groups were recorded and compared. The Harris score and hip ROM were compared between the two groups before operation, at 1, 3, 6, 12 months after operation, and at last follow-up. The acetabular component anteversion angle, femoral component anteversion angle, acetabular component abduction angle, and component combined anteversion angle were measured postoperatively. RESULTS: The operation time in the study group was significantly shorter than that in the control group ( P<0.05), and there was no significant difference in hospital stay between the two groups ( P>0.05). There was no intraoperative complication such as acetabular and proximal femoral fractures, neurovascular injuries in both groups, and the incisions healed by first intention. All patients were followed up 2-3 years, with an average of 2.4 years; there was no significant difference in the follow-up time between the two groups ( P>0.05). During the follow-up period, there was no complication such as hip dislocation, wound infection, delayed wound healing, deep venous thrombosis, and hip dislocation in both groups. The hip Harris score and ROM of the two groups gradually increased with time after operation, and the differences were significant when compared with those before operation ( P<0.05); the above two indicators of the study group were significantly better than those of the control group at each time point after operation ( P<0.05). Extensive bone ingrowth on the surface of the components could be observed in the anteroposterior X-ray films of the hip joint of the two groups at 12 months after operation, and the acetabular components was stable without femoral stem subsidence, osteolysis around the components, and heterotopic ossification. At last follow-up, the acetabular component anteversion angle, femoral component anteversion angle, and component combined anteversion angle in the study group were significantly superior to those in the control group ( P<0.05), except that there was no significant difference in the acetabular component abduction angle between the two groups ( P>0.05). CONCLUSION For patients with AS affecting the hip joint, the use of the combined anteversion angle technique during THA effectively promotes the recovery of hip joint function and enhances the postoperative quality of life of patients when compared to traditional THA.
Humans ; Arthroplasty, Replacement, Hip/methods* ; Hip Dislocation/surgery* ; Spondylitis, Ankylosing/surgery* ; Retrospective Studies ; Quality of Life ; Treatment Outcome ; Hip Joint/surgery* ; Hip Prosthesis

BACKGROUND:With the further development of minimally invasive concepts,unicompartmental knee arthroplasty has become an important treatment for osteoarthritis of the knee;however,early postoperative pain adversely affects the recovery process,so effective analgesic measures are necessary.Femoral nerve block and cocktail therapy are common analgesic methods for unicompartmental knee arthroplasty,but there is a lack of studies confirming the analgesic effect and safety of their combined application. OBJECTIVE:To investigate the analgesic effect of cocktail therapy combined with femoral nerve block in unicompartmental knee arthroplasty. METHODS:One hundred patients who received unicompartmental knee arthroplasty from October 2021 to January 2023 were selected as the study subjects.They were divided into a control group(n=50)and a study group(n=50)using a random number table method.The femoral nerve block was used in the control group,while cocktail therapy combined with femoral nerve block was used in the study group during unicompartmental knee arthroplasty.Postoperative analgesia effect,analgesic frequency of dezocine injection within 2 days after surgery,motion range of affected knee joint,KSS function scores,and the occurrence of postoperative adverse reactions were compared between the two groups. RESULTS AND CONCLUSION:(1)Visual analog scale scores in the study group were lower than those in the control group at 12,24,and 48 hours after surgery(P<0.05).(2)The analgesic frequency of dezocine in the study group was less than that in the control group within 2 days after surgery(P<0.05).(3)The motion range in the study group was higher than that in the control group 1 and 3 days after surgery(P<0.05).On day 14 after surgery,there was no significant difference in motion range between the two groups(P>0.05).(4)The knee KSS score in the study group was higher than that in the control group at 2 weeks after surgery(P<0.05).There was no statistically significant difference in knee KSS scores between the two groups from 6 weeks to 6 months after surgery(P>0.05).(5)The difference in the occurrence of adverse reactions within 14 days after surgery was not significant between the two groups(P>0.05).(6)These results show that the use of cocktail therapy combined with femoral nerve block in unicompartmental knee arthroplasty can effectively reduce postoperative pain,improve the analgesic effect,reduce the frequency of analgesic drugs,and improve motion range of the early affected knee joint of patients.