ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

ObjectiveTo explore the role of cucurbitacin B （CuB） in inducing ferroptosis in 4T1 cells and its mechanism. MethodsThe effects of CuB（0.2， 0.4， 0.8 μmol·L^-1）on the proliferation ability of 4T1 cells in vitro were detected using the methyl thiazolyl tetrazolium （MTT） assay. The clonogenic ability of 4T1 cells was detected by the plate cloning assay， and the levels of lactate dehydrogenase （LDH） in 4T1 cells were detected by the use of a kit. The mitochondrial membrane potential and reactive oxygen species （ROS） levels in 4T1 cells were detected by flow cytometry， and the mitochondrial ultrastructure of 4T1 cells was observed by transmission electron microscopy. The western blot was used to detect the expression of ferroptosis-related protein p53 in 4T1 cells， solute carrier family 7 member 11 （SCL7A11）， glutathione peroxidase 4 （GPX4）， long-chain acyl-CoA synthetase 4 （ACSL4）， transferrin receptor protein 1 （TFR1）， and ferritin heavy chain 1 （FTH1）. ResultsCompared with that in the blank group， the survival rate of 4T1 cells in CuB groups was significantly decreased （P<0.05）， and the number of cell clones in CuB groups was significantly reduced （P<0.01）. In addition， compared with that in the blank group， the leakage of LDH in cells in CuB groups was significantly increased （P<0.01）， and the mitochondrial membrane potential of cells in CuB groups decreased significantly （P<0.01）. Cellular ROS levels were significantly elevated in CuB groups （P<0.01）. The mitochondria of cells in CuB groups were obviously wrinkled， and the mitochondrial cristae were reduced or even disappeared. Compared with that in the blank group， the protein expression of p53， ACSL4， and TFR1 were significantly up-regulated in CuB groups （P<0.05）， and that of SLC7A11， GPX4， and FTH1 were significantly down-regulated （P<0.05）. ConclusionCuB may inhibit SLC7A11 and GPX4 expression by up-regulating the expression of p53， which in turn regulates the p53/SLC7A11/GPX4 signaling pathway axis and accelerates the generation of lipid peroxidation substrate by up-regulating the expression of ACSL4. It up-regulates TFR1 expression to promote cellular uptake of Fe³⁺ and down-regulates the expression of FTH1 to reduce the ability of iron storage， resulting in an elevated free Fe²⁺ level. It catalyzes the Fenton reaction， generates excess ROS， imbalances the antioxidant system and iron metabolism， and then induces ferroptosis in 4T1 cells.

Ferroptosis， a new form of programmed cell death different from apoptosis， necrosis， and autophagy， is closely associated with a variety of physiological and pathological processes. Iron-mediated accumulation of reactive oxygen species is the main inducement of ferroptosis， the mechanism of which is related to intracellular lipid metabolism， iron metabolism， and antioxidant defense pathways. Multiple signaling axes and regulators jointly regulate the occurrence and disruption of ferroptosis. Studies have demonstrated that ferroptosis regulates the growth and proliferation of tumor cells. Inducing ferroptosis in tumor cells can control the growth， metastasis， and multi-drug resistance of tumors. Therefore， the effect and mechanism of ferroptosis on tumor cells have become a hot topic in anti-cancer research. As the research advances， a variety of ferroptosis inducers has been used in the clinical chemotherapy for cancers and demonstrate significant efficacy. Accordingly， the development of ferroptosis-inducing anticancer drugs has become a new research direction for tumor treatment. Some active ingredients such as lycorine， oleanolic acid， dihydroartemisinin， pseudolaric acid B， and ophiopogonin B of Chinese medicines can induce ferroptosis in tumor cells via lipid metabolism， iron metabolism， system X_c^-， and GPX4/GSH to regulate the development of tumors， demonstrating a promising prospect in clinical treatment. Based on the theory of the mechanism of ferroptosis， this paper reviews the research progress in ferroptosis induced by active ingredients of Chinese medicines in tumor cells and describes the metabolic regulatory network of ferroptosis from signaling pathways and regulatory factors， providing new strategies for applying active ingredients of Chinese medicines in the treatment of tumors.

Objective·To evaluate the changes in cognitive function in overweight and obese adolescents,and explore the association between cognitive function and fibroblast growth factor 21(FGF21).Methods·A total of 175 adolescents from a senior high school in Shanghai were divided into normal weight group(n=50),overweight group(n=50)and obese group(n=75)based on their body mass index(BMI).General information,anthropometric data and laboratory testing indicators of the adolescents were collected and compared.The cognitive function of the three groups of adolescents was assessed by using the accuracy(ACC)and reaction time of Flanker task and n-back task.Enzyme-linked immunosorbent assay(ELISA)was used to detect the serum FGF21 level of the three groups of adolescents.Partial correlation analysis and multiple linear regression model were used to evaluate the correlation between cognitive task performance and anthropometric data and laboratory testing indicators.Results·Compared with the normal weight group,systolic blood pressure,diastolic blood pressure,and the levels of fasting plasma glucose,glycosylated hemoglobin and triacylglycerol in the obese group were higher(all P<0.05).Under congruent or incongruent stimulus conditions in the Flanker task,there was no significant difference in ACC between any two groups;compared with the normal weight and overweight groups,the reaction time of the adolescents in the obese group was prolonged(all P<0.05).In the n-back task,there were no significant differences in ACC between any two groups,while the obese group had longer reaction time in the 1-back and 2-back tasks compared to the normal weight and overweight groups(all P<0.05).Compared with the normal weight group,serum FGF21 levels of the adolescents in the obese group were higher(P=0.000).Partial correlation analysis showed that the reaction time of the adolescents in Flanker and n-back tasks was correlated with their BMI,body fat mass,waist circumference,waist-to-hip ratio and FGF21 level(all P<0.05).Multiple linear regression analysis further confirmed that BMI was associated with prolonged reaction time in cognitive-related behavioral tasks in the adolescents(all P<0.05),and FGF21 level was associated with ACC in the 2-back task(P=0.000)and reaction time in the incongruent stimulus condition(P=0.048).Conclusion·Overweight and obese adolescents have cognitive impairments,and BMI and serum FGF21 levels are associated with changes in their cognitive function.

In recent years,the global prevalence of obesity has continued to rise,with a preference for high-sugar and high-fat foods being one of the primary contributors to this condition.Food preference refers to the degree of individual liking for specific foods,and its formation is closely related to the physiological effects such as satiety,satisfaction and reward that occur after food digestion in the gastrointestinal tract.With the continuous advancement of technologies such as neuroimaging and chemogenetics,the underlying neural and physiological mechanisms of food preference behavior are gradually being elucidated.Studies have shown that the digestion and absorption of food in the gastrointestinal tract can release chemical or electrical signals,which are transmitted to the central nervous system via neural pathways,humoral pathways and the gut-brain axis mediated by gut microbiota.Subsequently,these signals regulate feeding behavior by activating or inhibiting neurons in the nucleus of the solitary tract,the dopaminergic reward pathways and relevant neural circuits in the hypothalamus.Based on this,the article introduces the definition,evaluation methods and mechanisms of food preference,and reviews the pathways of food information transmission within the gut-brain axis,the reward circuits that modulate food preference and the application of food preference behavior to the treatment of obesity,in order to provide reference for research in the field of food preference and obesity treatment.

Mitochondrial DNA depletion syndrome (MDS) is a group of genetic diseases in which the number of mitochondrial DNA copies is severely decreased due to mutations in nuclear genes and affects energy metabolism in several tissues and organs. Renal involvement of MDS is often manifested as proximal renal tubular disease, while MDS combined with nephrotic syndrome is rare. This paper report a case of child with mitochondrial DNA depletion syndrome 8A (MTDPS8A) complicated with nephrotic syndrome due to compound heterozygous variants of RRM2B gene. The child mainly presented with epilepsy, auditory dysfunction, and nephrotic syndrome as clinical manifestations. The histopathological findings indicated focal segmental glomerulosclerosis (collapsing variant). The child was treated with glucocorticoid combined with immunosuppressant, energy support and symptomatic treatment, while the effect was not significant. He continued to experience progressive deterioration of renal function during the six-month follow-up period and had a long-term peritoneal dialysis for maintenance therapy.

Objective:To analyze the clinicopathological features and prognosis of idiopathic membranous nephropathy (IMN) in children, and to investigate the factors influencing their prognosis.Methods:The clinical and pathological data of 128 children with IMN hospitalized in the First Affiliated Hospital of Zhengzhou University from January 2012 to December 2019 were retrospectively analyzed.They were divided into 2 groups according to the pathological manifestations: group A[typical membranous nephropathy(MN) group] and group B (atypical MN group), and the clinicopathological characteristics of the 2 groups were compared.Different treatment regimens and their efficacy were summarized, and the prognosis and its influencing factors were analyzed.The primary endpoint event at follow-up was the occurrence of end stage renal disease (ESRD), and the secondary endpoint event was the occurrence of renal insufficiency.Children with IMN were further divided into endpoint event group and non-endpoint event group according to the presence or absence of endpoint events at the last follow-up.Survival analysis was performed using the Kaplan-Meier survival curve method.The Cox proportional risk model method was used to analyze the factors influencing the prognosis of poor kidney outcomes in children with IMN. Results:(1)A total of 128 children were included, with the male-to-female ratio of 1.13∶1.00.The median age of onset and peak age of onset were 13.0 (10.3, 15.0) years, and 12-16 years (68.8%), respectively.Massive proteinuria was detected in 119 cases (93.0%), including 103 cases (80.5%) with massive proteinuria and hematuria, 4 cases(3.1%) with simple hematuria, and 5 cases (3.9%) with non-renal proteinuria.There were 29 cases (22.7%) in group A and 99 cases (77.3%) in group B. (2)Blood triacylglycerol level was significantly higher in group B than that of group A[2.1 (1.5, 3.0) mmol/L vs.1.7(1.1, 2.5) mmol/L], while high-density lipoprotein[1.5(1.1, 1.8) mmol/L vs.1.8(1.4, 2.1) mmol/L], serum albumin[22.0(17.0, 27.3) g/L vs.25.5 (21.0, 32.5) g/L] and complement C3[(1.1±0.2) g/L vs.(1.2±0.2) g/L] were significantly lower in group B than those of group A (all P<0.05). (3)Complete clinical data during hospitalization and follow-up data were obtained from 91 children with IMN, with a median follow-up time of 87.0 (49.0, 104.5) months.Among them, 5 cases (5.5%) progressed to ESRD, involving 3 cases received renal transplantation, and 9 cases (9.9%) had secondary endpoints.Cumulative renal survival rate for ESRD at 5 and 10 years were 96.2% and 92.9%, respectively, which, for the secondary endpoints at 5 and 10 years were 95.2% and 84.8%, respectively.(4)Kaplan-Meier survival analysis showed no significant difference in the cumulative renal survival between group A and group B ( P>0.05). Multifactorial Cox regression analysis showed that tubular atrophy/interstitial fibrosis was an independent risk factor for renal insufficiency in children with IMN ( HR=0.102, 95% CI: 0.011-0.940, P<0.05). Conclusions:Massive proteinuria combined with hematuria is the major clinical manifestation of IMN in children, and atypical MN is the major pathological manifestation.Tubular atrophy/interstitial fibrosis is an independent risk factor for renal insufficiency in children with IMN.

BackgroundDepression， anxiety， impulse control disorders， insomnia are prevalent non-motor symptoms of Parkinson's disease， severely impairing the quality of life of patients. Cognitive behavioral therapy （CBT） is a common psychological intervention for various clinical psychological conditions， which can improve anxiety， insomnia and depression in patients with Parkinson's disease. However， the current research evidence on the effects of CBT in improving quality of life in patients with Parkinson's disease remains inconsistent. ObjectiveTo assess the effects of CBT on the quality of life among patients with Parkinson's disease， so as to provide references for the clinical application of CBT in this population. MethodsOn May 25， 2023， a systematic search was conducted across PubMed， PsycINFO， Embase， CNKI， Wanfang Database and VIP Database to identify randomized controlled trials investigating the impact of CBT on the quality of life in patients with Parkinson's disease. Literature screening， quality evaluation and data extraction were performed， focusing on variables related to quality of life， anxiety， and depression. Meta-analysis was performed using Stata 13.0 and RevMan 5.3. ResultsA total of 11 studies with 456 participants were included， comprising 241 in the CBT group and 215 in the control group. The CBT group exhibited significantly higher quality of life compared with the control group （SMD=0.47， 95% CI： 0.27~0.67， P<0.01）. Anxiety and depression scores in CBT group were significantly lower than those in the control group （SMD=-0.63，95% CI：-0.84~-0.43， P<0.01； SMD=-0.83， 95% CI： -1.15~-0.51， P<0.01）. Among the 11 studies， 6 studies delivered CBT remotely and 5 studies implemented CBT face-to-face. Meta-analysis results revealed that remote CBT group yielded significantly higher quality of life （SMD=0.43， 95% CI： 0.17~0.70， P<0.01）， and lower anxiety and depression scores （SMD=-0.62， 95% CI： -0.91~-0.34， P<0.01； SMD=-0.78， 95% CI： -1.34~-0.21， P<0.01） compared with the control group. Similarly， face-to-face CBT group showed better outcomes than the control group in terms of quality of life， anxiety and depression （SMD=0.51， 95% CI： 0.22~0.81， P<0.01； SMD=-0.64， 95% CI： -0.93~-0.35， P<0.01； SMD=-0.90， 95% CI： -1.20~-0.60， P<0.01）. ConclusionCBT may contribute to alleviating anxiety and depression levels of patients with Parkinson's disease， and improving their quality of life.｛Funded by Shanghai 13th Five-Year Key Specialty Construction Project （number， shslczdzk04901）； Nature Fund Project of Shanghai Science and Technology Commission （number， 22ZR1459300）； Shanghai Municipal Health Commission Traditional Chinese Medical Science Non-drug Therapy Demonstration Center Project ［number， ZY（2021-2023） -0204-03］｝

OBJECTIVE Parkinson's disease(PD)is a progressive neurodegenerative disease clinically char-acterized by dyskinesia,tremor,rigidity,abnormal gait,whereas 90%of patients with PD suffer from defects of the sense of smell before the appearance of the motor dysfunctions.However,the mechanism of olfactory disor-der is still not clear.METHODS We utilized olfaction based delayed paired association task in head-fixed mice.We focused on functional role of neural circuit using opto-genetic techniques.In addition,we viewed the synaptic transmission by slice physiological recording and count-ed the cell number of targeted circuits.RESULTS AND CONCLUSION In our experiments,olfactory working memory impairments were found in the PD mice,and the working memory impairment appeared before motor dys-functions.Furthermore,we also investigated the functional role of neural circuit for olfactory working memory in PD mice.Meanwhile,the excitatory post synaptic currents were decreased as a result of presynaptic release proba-bility suppression in PD mice.However cell loss wasn't found in working memory related circuit recently.These will provide a new idea of clinic diagnosis for PD.

Objective:To systematically analyze and integrate the real experience of puerpera in free delivery positions.Methods:Qualitative or mixed method studies on attitudes and emotional experiences of puerpera towards free delivery positions were retrieved through computer on PubMed, ScienceDirect, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, and WanFang Data. The search period was from database establishment to November 30, 2022. The quality of literature was evaluated using the quality evaluation criteria for qualitative research of the Joanna Briggs Institute Evidence-Based Health Care Center in Australia. The aggregation integration method was used to integrate the results.Results:A total of 5 articles were included and 28 results were extracted. The results were summarized into 10 categories, and 3 integrated results were formed, including factors that affected the choice of delivery position, the complex delivery experience of the puerpera, and the hope for much support.Conclusions:Hospitals, communities, and families should fully understand women's emotional experiences and needs for free delivery positions, provide sufficient support and guidance, and provide a reference basis for developing a reasonable delivery position plan and promoting a positive delivery experience.