Ferroptosis, an iron-dependent form of regulated cell death, is mechanistically characterized by disrupted iron homeostasis, lipid peroxidation, and compromised antioxidant defense systems. Recent studies have demonstrated that artemisinin and its derivatives, such as dihydroartemisinin and artesunate, exhibit therapeutic potential against lymphatic system malignancies through ferroptosis induction. These compounds exert their antitumor effects by modulating critical regulatory proteins including SLC7A11, GPX4, and STAT3, as well as activating pivotal signaling pathways such as ATF4-CHOP and SREBP2-IPP-GPX4 axes. Notably, synergistic therapeutic effects have been observed when artemisinin derivatives are combined with conventional chemotherapeutic agents or targeted therapies, demonstrating enhanced tumor-suppressive activity and circumvention of drug resistance mechanisms. This review systematically summarizes recent advancements in understanding the ferroptosis-mediated antitumor mechanisms of artemisinin compounds in lymphoid malignancies, with particular emphasis on their molecular targets and clinical translational potential.
Humans ; Ferroptosis/drug effects* ; Artemisinins/therapeutic use* ; Signal Transduction

The aim of the present study was to investigate the effects of short-term ketogenic diet on the low temperature tolerance of mice and the involvement of peroxisome proliferator-activated receptor α (PPARα). C57BL/6J mice were divided into two groups: normal diet (WT+ND) group and ketogenic diet (WT+KD) group. After being fed with normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The changes in core temperature, blood glucose, blood pressure of mice under low temperature condition were detected, and the protein expression levels of PPARα and mitochondrial uncoupling protein 1 (UCP1) were detected by Western blot. PPARα knockout mice were divided into normal diet (PPARα^-/-+ND) group and ketogenic diet (PPARα^-/-+KD) group. After being fed with the normal or ketogenic diet at room temperature for 2 d, the mice were exposed to 4 °C low temperature for 12 h. The above indicators were also detected. The results showed that, at room temperature, the protein expression levels of PPARα and UCP1 in liver and brown adipose tissue of WT+KD group were significantly up-regulated, compared with those of WT+ND group. Under low temperature condition, compared with WT+ND, the core temperature and blood glucose of WT+KD group were increased, while mean arterial pressure was decreased; The ketogenic diet up-regulated PPARα protein expression in brown adipose tissue, as well as UCP1 protein expression in liver and brown adipose tissue of WT+KD group. Under low temperature condition, compared to WT+ND group, PPARα^-/-+ND group exhibited decreased core temperature and down-regulated PPARα and UCP1 protein expression levels in liver, skeletal muscle, white and brown adipose tissue. Compared to the PPARα^-/-+ND group, the PPARα^-/-+KD group exhibited decreased core temperature and did not show any difference in the protein expression of UCP1 in liver, skeletal muscle, white and brown adipose tissue. These results suggest that the ketogenic diet promotes UCP1 expression by up-regulating PPARα, thus improving low temperature tolerance of mice. Therefore, short-term ketogenic diet can be used as a potential intervention to improve the low temperature tolerance.
Animals ; Mice ; Adipose Tissue, Brown/metabolism* ; PPAR alpha/pharmacology* ; Diet, Ketogenic ; Uncoupling Protein 1/metabolism* ; Blood Glucose/metabolism* ; Temperature ; Mice, Inbred C57BL ; Liver ; Adipose Tissue/metabolism*

The present study was aimed to investigate the role and mechanism of glutaminolysis of cardiac fibroblasts (CFs) in hypertension-induced myocardial fibrosis. C57BL/6J mice were administered with a chronic infusion of angiotensin II (Ang II, 1.6 mg/kg per d) with a micro-osmotic pump to induce myocardial fibrosis. Masson staining was used to evaluate myocardial fibrosis. The mice were intraperitoneally injected with BPTES (12.5 mg/kg), a glutaminase 1 (GLS1)-specific inhibitor, to inhibit glutaminolysis simultaneously. Immunohistochemistry and Western blot were used to detect protein expression levels of GLS1, Collagen I and Collagen III in cardiac tissue. Neonatal Sprague-Dawley (SD) rat CFs were treated with 4 mmol/L glutamine (Gln) or BPTES (5 μmol/L) with or without Ang II (0.4 μmol/L) stimulation. The CFs were also treated with 2 mmol/L α-ketoglutarate (α-KG) under the stimulation of Ang II and BPTES. Wound healing test and CCK-8 were used to detect CFs migration and proliferation respectively. RT-qPCR and Western blot were used to detect mRNA and protein expression levels of GLS1, Collagen I and Collagen III. The results showed that blood pressure, heart weight and myocardial fibrosis were increased in Ang II-treated mice, and GLS1 expression in cardiac tissue was also significantly up-regulated. Gln significantly promoted the proliferation, migration, mRNA and protein expression of GLS1, Collagen I and Collagen III in the CFs with or without Ang II stimulation, whereas BPTES significantly decreased the above indices in the CFs. α-KG supplementation reversed the inhibitory effect of BPTES on the CFs under Ang II stimulation. Furthermore, in vivo intraperitoneal injection of BPTES alleviated cardiac fibrosis of Ang II-treated mice. In conclusion, glutaminolysis plays an important role in the process of cardiac fibrosis induced by Ang II. Targeted inhibition of glutaminolysis may be a new strategy for the treatment of myocardial fibrosis.
Rats ; Mice ; Animals ; Rats, Sprague-Dawley ; Angiotensin II/pharmacology* ; Fibroblasts ; Mice, Inbred C57BL ; Fibrosis ; Collagen/pharmacology* ; Collagen Type I/metabolism* ; RNA, Messenger/metabolism* ; Myocardium/pathology*

Selective dorsal neurotomy (SDN) is a surgical treatment for primary premature ejaculation (PE), but there is still no standard surgical procedure for selecting the branches of the dorsal penile nerves to be removed. We performed this study to explore the value of intraoperative neurophysiological monitoring (IONM) of the penile sensory-evoked potential (PSEP) for standard surgical procedures in SDN. One hundred and twenty primary PE patients undergoing SDN were selected as the PE group and 120 non-PE patients were selected as the normal group. The PSEP was monitored and compared between the two groups under both natural and general anesthesia (GA) states. In addition, patients in the PE group were randomly divided into the IONM group and the non-IONM group. During SDN surgery, PSEP parameters of the IONM group were recorded and analyzed. The differences in PE-related outcome measurements between the perioperative period and 3 months' postoperation were compared for the PE patients, and the differences in effectiveness and complications between the IONM group and the non-IONM group were compared. The results showed that the average latency of the PSEP in the PE group was shorter than that in the normal group under both natural and GA states (P < 0.001). Three months after surgery, the significant effective rates in the IONM and non-IONM groups were 63.6% and 34.0%, respectively (P < 0.01), and the difference in complications between the two groups was significant (P < 0.05). IONM might be useful in improving the short-term therapeutic effectiveness and reducing the complications of SDN.
Male ; Humans ; Premature Ejaculation/surgery* ; Intraoperative Neurophysiological Monitoring/methods* ; Prospective Studies ; Neurosurgical Procedures/methods* ; Penis/surgery* ; Retrospective Studies

Objective: To investigate the association between gene polymorphism of vesicular monoamine transporter type 2(VMAT2) and schizophrenia in Han Chinese population. Methods: 430 patients with schizophrenia and 470 age-sex matched controls were recruited from four mental health centers. All patients were diagnosed by two psychiatrists based on the Structured Clinical Interview for DSM Disorders (SCID). The ligase detection reactions (LDR) method was used to assess the polymorphism of the two SNPs (rs363371 and rs363324) of VMAT2. Results: No associations of two SNPs with schizophrenia was found. When we stratified males and females for the analysis, we found that that in the recessive model of rs363371, there was an obvious significant association between rs363371 and schizophrenia in males (OR=0.564, 95% CI=0.357–0.892, p=0.014) but not females. For the association between rs363324 and schizophrenia, no association was found in either males or females. No association was found when stratifying early-onset schizophrenia and late-onset schizophrenia. Conclusion Our findings indicate that both rs363371 and rs363324 were not associated with schizophrenia, while it seemed that the AA genotype of rs363371 plays a protective effect in male Chinese in developing schizophrenia.

Coronary Artery Bypass ; adverse effects ; Female ; Humans ; Male ; Mammary Arteries ; injuries

Objective: To investigate the significance of endoplasmic reticulum stress-associated gene tri-bbles pseudokinase 3 (TRIB3) in the long-term brain injury in rats with developing epilepy. Methods: Thirty male SD rats aged 21 days were randomly divided into the control group and the epilepsy group, 15 rats in each group.The rats in the epilepsy group were intraperitoneally injected with kainic acid (10 mg/kg) to induce seizures, while the rats in the control group were injected with the equal volume of 9 g/L saline.The rats in two groups were euthanized at 30 d after kainic acid administration.The damage to the ultrastructure of the cortex were observed by using transmission electron microscopy.Neuronal apoptosis in the cortex of rats was detected by terminal-deoxynucleoitidyl transferase mediated nick end labeling (TUNEL) assay.The expression and localization of glucose regulated protein 78 (GRP78), CCAAT/enhancer binding protein-homologous protein (CHOP), TRIB3, and the activation of protein kinase B (AKT) in the cortex were examined by using Western blot analysis and immunohistochemistry. Results: Compared with the control group, the different ultrastructural changes were observed in the cortex in the epilepsy group rats.TUNEL assay indicated that the number of apoptosis cells of cortex in the epilepsy group was increased.The protein levels of GRP78 and TRIB3 were upregulated in the cortex of the epileptic rats (1.280±0.272, 1.725±0.570), compared with the control group (1.000±0.000, 1.000±0.000), and the differences were statistically significant (all P<0.05). There was no significant change in CHOP protein between the control group and the epilepsy group.The level of phosphorylated AKT(p-AKT) was decreased in the cortex of the epilepsy group (0.150±0.047), compared with the control group (1.000±0.000), and the difference was statistically significant (P<0.05). Conclusions The brain injury caused by epilepsy in the developing rats can sustain to the stage of mature rats, and the endoplasmic reti-culum stress-associated gene TRIB3 is involved in the pathogenesis of long-term brain damage in the rats with deve-loping epilepsy.

Objective To explore the changes of Beclin-1,P62/SQSTM1,microtubule-associated protein 1 light chain 3 (LC3)and unc-51 like autophagy activating kinase 1 (ULK-1)in the brains of the rats in the deve-lopmental stage with epilepsy. Methods Seventy-two male Sprague Dawley (SD)rats aged 21 days were randomly divided into the control group and the epilepsy group. The rats in 2 groups were randomly subdivided into 4 groups according to the time intervals (3 h,6 h,12 h and 48 h),respectively,with 9 rats in each group. The rats in the epilep-sy group were injected with kainic acid (12 mg/kg)to induce epilepsy,and the rats in the control group were injected with equal volume of saline. The rats in 2 groups were anaesthetized and sacrificed. Then,the brain tissues of the rats were quickly removed according to the time intervals. The brain damages were determined by adopting Nissl staining method. The apoptotic cells were detected by Terminal - deoxynucleoitidyl transferase mediated nick end labeling (TUNEL)assays. The expressions of Beclin-1,P62/SQSTM1,LC3 and ULK-1 mRNA levels in cortex were mea-sured by using real-time quantitative polymerase chain reaction (qPCR)analysis. Results Nissl staining indicated that many neurons were damaged performing vague outline,irregularly aligned,pyknotic nuclei and shrunken somata in the epilepsy 48 h group. In addition,there was a huge loss of neurons in cortex in the epilepsy 48 h group [(82 ± 8)num-bers],compared with the control group [(122 ± 8)numbers],and the difference was statistically significant (F＝3. 768, P＝0. 01). The apoptotic cells tremendously increased in the epilepsy 48 h group [(13 ± 7)numbers],compared with the control group [(2 ± 1)numbers]by TUNEL analysis,and the diffe-rence was statistically significant (t＝ -3. 821, P＝0. 003). qPCR showed the mRNA levels of Beclin-1,P62/SQSTM1,LC3 and ULK-1 were upregulated in the epi-lepsy 12 h group (1. 70 ± 0. 75,1. 75 ± 0. 77,1. 52 ± 0. 43,7. 48 ± 6. 12)and the epilepsy 48 h group (1. 63 ± 0. 43, 1. 48 ± 0. 74,1. 74 ± 0. 55,7. 69 ± 5. 65),compared with the control group (1. 00,1. 00,1. 00,1. 00),and the differences were statistically significant (F＝2. 820,3. 452,5. 811,5. 002,all P＜0. 05). Conclusion The autophagy activates be-fore apoptosis occurs,and autophagy-related genes probably are involved in epilepsy-induced brain damage.

The medical management department of individual hospitals varies with their organizational structure and operational mechanism, instead of following a general pattern. Inspired by the"super-ministry" system of government,the hospital has integrated successively the Medical Affairs Office, Patient Safety Office,Medical Quality Control Office,Hospital-acquired Infection Control Office and Medical insurance office. Through integration and innovation of duties, regulations, culture, decision-making progress,coordination and talent training mechanism, the " Five-in-One" super-ministry model of medical management came into being,achieving collaborative and efficient medical management as a result.

INTRODUCTIONStreptococcus agalactiae (Group B Streptococcus, GBS) is an uncommon cause of septic arthritis in the adult population. In recent years, there has been an increase in the incidence of GBS septic arthritis. This study aims to compare the clinical presentation, investigations, microbiology and outcome of management in patients with GBS and non-GBS septic arthritis.

METHODSRetrospective review of hospital surgical records was done to identify all patients treated surgically at our institution from January 2011 to January 2016 for primary septic arthritis. Patients were categorised into two groups: those with culture-proven GBS septic arthritis and those with causative pathogens that were not GBS. Patients who were medically unfit for surgical intervention as well as those who declined interventional procedures were excluded from the study.

RESULTSA total of 83 patients were included in the study: 62 (74.7%) had non-GBS septic arthritis and 21 (25.3%) had GBS septic arthritis. Patients with GBS septic arthritis were more likely to have polyarticular involvement (p < 0.001) and involvement of less common sites such as the elbow joint. They were also more likely to have elevated inflammatory markers (C-reactive protein > 150 mg/L; p = 0.017) and positive blood cultures (p = 0.02), and were typically healthy adults with no medical comorbidities (p = 0.012).

CONCLUSIONPatients with GBS septic arthritis were more likely to present with polyarticular involvement, positive blood cultures and higher levels of C-reactive protein on admission, and tended to be healthier individuals with no medical comorbidities.