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.

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.

Metabolic disorders,characterized by a complex pathogenesis,are experiencing a rising prevalence globally and a trend toward younger populations,making them a significant public health concern.Olfaction,a crucial sensory function,plays a pivotal role in an individual's nutrition and quality of life.There is a bidirectional relationship between obesity and olfactory function.Olfaction is influenced by nutritional status;simultaneously,it plays a vital role in the regulation of food intake,energy expenditure,and lipid metabolism.Moreover,individuals with metabolic disorders such as type 2 diabetes and obstructive sleep apnea syndrome exhibit olfactory dysfunction.Mechanisms underlying olfactory changes in metabolic disorders involve alterations in metabolic states such as hyperglycemia and insulin resistance.These changes can lead to dysregulation of peptide hormones,adipocyte factors,and neurotransmitters,which may potentially act as mediators between metabolic disorders and olfactory dysfunction.Vascular and neural alterations resulting from metabolic disorders can directly damage olfactory nerves or induce abnormal neural transmission.Furthermore,dysbiosis in the gut microbiota induced by metabolic disorders is a potential mechanism for olfactory dysfunction.Cognitive dysfunction is a significant complication of metabolic disorders.Olfactory dysfunction can serve as an early clinical manifestation of cognitive impairment and contributes to early identification and assessment of diseases.This article reviews recent researches on the relationship between metabolic diseases and olfactory changes and the potential mechanisms.

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.

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.

Objective To explore epidemic characteristics of the coexistence of common chronic diseases among community residents in Jiading District, Shanghai, and to provide a basis for comprehensive prevention and control of chronic diseases in the community. Methods A multi-stage stratified cluster random sampling method was adopted in the present study, and residents over 20 years old in three selected streets (towns) were investigated. SPSS statistical software was used to analyze the data, and χ² test was used to compare the difference between groups. Results Among the respondents, 24.80% had no chronic diseases and 75.20% had various chronic diseases. The top ten most common diseases were hypertension (37.82%), fatty liver (30.10%), chronic gastritis (18.11%), hyperlipidemia (14.51%), thyroid disease (8.85%), diabetes mellitus (8.65%), renal cyst (8.12%), chronic bronchitis (7.62%), kidney stone (6.97%) and gout (5.75%). The prevalence increased with age. Chronic diseases existed in the form of multiple diseases, and the prevalence rates of two, three, four, five, six and more chronic diseases at the same time were respectively 19.78%, 13.07%, 7.90%, 4.11% and 4.09%. The most common comorbid diseases were hypertension, hyperlipidemia and diabetes combined with other chronic diseases. Conclusion The prevalence of chronic diseases in residents in Jiading District was very high. Most of the residents suffered from multiple chronic diseases in which hypertension, hyperlipidemia and diabetes were the common basis. The comprehensive prevention and control of chronic diseases in the community should be strengthened.

Objective:To analyze the epidemiological, clinical characteristics and treatment of coronavirus disease 2019 (COVID-19) in Northeastern Sichuan, and summarize experience in time to provide reference for clinical diagnosis and treatment.Methods:A retrospective study was conducted. Fifty-nine patients with COVID-19 admitted to Bazhong Central Hospital and Dazhou Central Hospital from January 27th to February 9th, 2020 were selected as the subjects. The data of demography, epidemiology, laboratory examination, chest CT and related clinical treatment were collected. According to the severity of the disease, the patients were divided into three types: mild, general and severe types, and the differences of the above indices among different clinical types were compared.Results:① General information and epidemiology: 31 cases (52.5%) were male, 28 cases (47.5%) were female, the average age was (42.0±16.4) years old, and the patients over 40 years old accounted for the largest proportion (35 cases, 59.3%). The proportion of clinical type was 72.9% (43 cases) in general type, and 62.7% (37 cases) were imported type. With the increase of disease severity, the average age of patients also showed a significant increase trend [the age of the mild, general and severe patients were (30.9±13.6), (42.7±15.3), (55.8±18.9) years old, P < 0.01]. The proportion of patients with more than one basic disease in severe patients was significantly higher than those in mild and general patients [66.7% (4/6) vs. 20.0% (2/10), 9.3% (4/43), both P < 0.05]. In the distribution of clinical symptoms, the proportion of severe patients with chest distress/dyspnea was significantly higher than those in mild and general patients [66.7% (4/6) vs. 10.0% (1/10), 11.6% (5/43), both P < 0.05]. ② Laboratory examination index: the total number of white blood cell count (WBC), neutrophils count (NEU), C-reactive protein (CRP) in severe patients were higher than those in mild patients and general patients [WBC (×10 9/L): 7.21±4.35 vs. 5.85±1.69, 5.43±2.04; NEU (×10 9/L): 6.09±4.43 vs. 3.95±1.45, 3.54±1.83; CRP (mg/L): 16.00 (8.20, 46.43) vs. 5.00 (0.00, 16.13), 15.00 (3.13, 28.58)], the albumin (Alb) level in severe patients was lower than those in mild and general patients (g/L: 38.00±5.35 vs. 49.23±5.27, 39.81±2.15, both P < 0.05), while the hemoglobin (Hb) level in mild patients was higher than that in severe and general patients (g/L:155.2±12.1 vs. 141.3±6.8, 131.1±11.7, both P < 0.05). ③ Chest imaging: the CT manifestations of typical cases were single or multiple ground glass shadows. With the progress of the disease, the focus gradually increased, the scope gradually expanded, and multiple solid shadows of lung lobes were involved. ④ Treatment: all patients received at least 2 kinds of antiviral therapy, and the application rate of Interferon and Ribavirin in severe patients were higher than those in mild and general patients [100.0% (6/6) vs. 80.0% (8/10), 97.7% (42/43); 83.3% (5/6) vs. 0% (0/10), 20.9% (9/43); all P < 0.05]. ⑤ Prognosis: until March 6th 2020, 50 patients (84.8%) were discharged from the hospital after rehabilitation, and the remaining 9 patients were still under treatment, none deaths. Conclusions:The proportion of severe patients with chest distress/dyspnea is higher, the older the patients are and the more basic diseases are, the more likely they are to develop into severe type. High resolution chest CT could be considered for suspected cases or even fever patients, which may show the progress of the disease.