ObjectiveTo investigate the effect of Yuejuwan on lipid metabolism in serum， prefrontal cortex and hippocampus of depressed mice based on lipidomics， and to explore the potential pathways for improving lipid metabolism to prevent depression. MethodsSeven-week-old C57BL/6 mice were randomly divided into blank group， model group， Yuejuwan group（3.6 g·kg^-1） and fluoxetine group（10 mg·kg^-1）， and chronic unpredictable mild stress（CUMS） was used to establish the depression model. After 3 weeks of modeling， each administration group was gavaged with the corresponding drug solution according to the dose， and mice in the blank and model groups were given an equal volume of deionised water by gavage， one time/d for 2 weeks. After administration， the antidepressant effect of Yuejuwan was evaluated by neurobehavioral indices such as sucrose preference test， open field test， tail suspension test and forced swimming test. An automatic biochemical analyzer was used to measure contents of total cholesterol（TC）， triglyceride（TG）， low-density lipoprotein cholesterol（LDL-C）， high-density lipoprotein cholesterol（HDL-C）， aspartate aminotransferase（AST） and alanine aminotransferase（ALT） in mouse serum. Lipidomic analysis of mouse serum， prefrontal cortex and hippocampus was performed based on ultra-performance liquid chromatography-linear ion trap-electrostatic field orbitrap mass spectrometry（UPLC-LTQ-Orbitrap-MS）， and the expression of mammalian target of rapamycin（mTOR）， ribosomal protein S6 kinase（S6K）， phosphorylation（p）-mTOR， p-S6K in gastric tissues of mice was detected by Western blot. ResultsCompared with the blank group， mice in the model group exhibited significantly reduced sucrose preference rate and center movement time in the open field test（P<0.01）， the immobility times in the tail suspension test and forced swimming test were significantly increased（P<0.01）， and serum levels of TC， TG， LDL-C， HDL-C， AST and ALT were significantly elevated（P<0.05， P<0.01）. Compared with the model group， the Yuejuwan group showed a significant increase in the sucrose preference rate and center movement time in the open field test（P<0.01）， the immobility times in the tail suspension test and forced swimming test were significantly reduced（P<0.01）， and the serum levels of TC， TG， LDL-C， AST and ALT were significantly decreased（P<0.05， P<0.01）. Lipidomic analysis revealed that Yuejuwan had a significant effect on lipid metabolism in serum， prefrontal cortex and hippocampus of depressed mice， and The differential lipid metabolites were mainly enriched in the metabolic pathways of glycerophospholipid metabolism， sphingolipid signaling， and glycosylphosphatidylinositol-anchored protein biosynthesis， among which the glycerophospholipid metabolic pathway was the most significant. Western blot results showed that compared with the blank group， the relative expression levels of p-mTOR/mTOR and p-S6K/S6K in the gastric tissues of mice in the model group were significantly increased（P<0.01）. In comparison with the model group， the relative expression levels of p-mTOR/mTOR and p-S6K/S6K in the gastric tissues of mice in the Yuejuwan group were significantly decreased（P<0.01）. ConclusionThe intervention of Yuejuwan on lipid metabolism is one of the potential pathways for its antidepressant effect， which may be related to the regulation of mTOR/S6K signaling pathway upstream of lipid metabolism in the gastric tissues.

Background Air pollution exposure has a significant impact on maternal and child health. However, the research on the association between ambient ozone (O₃) exposure during pregnancy and the risk of premature birth in newborns is limited, and the conclusions are inconsistent. Objective To investigate the association of ambient O₃ exposure during pregnancy with the risk of preterm birth in Guangdong Province. Methods Data of pregnant women in Guangzhou from 2013 to 2019 and Foshan from 2018 to 2023 were collected, and O₃ concentrations during different trimesters were assessed according to maternal residential addresses. Bilinear interpolation was used to evaluate the concentrations of air pollution. A cohort study design was adopted in our study. Restricted cubic spline curves were used to evaluate the exposure-response relationship between O₃ exposure and preterm birth risk and explore potential exposure threshold of O₃. Logistic regression models were used to evaluate the association of O₃ exposure with preterm birth. Results A total of 702 924 pregnant women were included in this study, of whom 43 051 (6.12%) were preterm. The average O₃ exposure concentrations of pregnant women during the first, second, third, and whole trimesters were 95.51, 97.51, 100.60, and 97.87 μg·m⁻³, respectively. We observed J-shaped associations between O₃ exposure and preterm birth risk during the second, third, and whole trimesters of pregnancy using restricted cubic spline curves. This study found that there were threshold concentrations between O₃ exposure and preterm birth risk during different gestational periods, and the threshold concentrations in the first, second, third, and whole trimesters were 112.32, 99.83, 111.74, and 112.46 μg·m⁻³, respectively. During the second, third, and whole trimesters of pregnancy, after adjusting for maternal age, baby sex, pre-pregnancy body mass index, mode of delivery, baby birth weight, gestational diabetes, and gestational hypertension, the odds ratios (OR) of preterm birth were 1.02 (95%CI: 1.01, 1.04), 1.02 (95%CI: 1.00, 1.03), and 1.17 (95%CI: 1.13, 1.21) for each 10 μg·m⁻³ increase in O₃ concentration above the O₃ threshold. No significant association was found between O₃ exposure and the risk of preterm birth during the first trimester. Conclusion There is a nonlinear association between the risk of preterm birth and O₃ exposure during pregnancy, and higher concentrations of O₃ exposure during pregnancy are associated with the risk of preterm birth. Above the O₃ threshold concentration during pregnancy, especially during the second, third, and whole trimesters, the risk of preterm birth elevates with the increase of O₃ exposure concentrations.

Objective To investigate the epidemiological status of toxic diffuse goiter hyperthyroidism (abbreviated as hyperthyroidism) in Xining area and analyze its influencing factors. Methods Patients with toxic diffuse goiter and hyperthyroidism who were hospitalized in Class ⅲ Grade A hospitals in Xining from January 2020 to January 2023 were collected as the experimental group by random cluster sampling method. During the same period, 500 healthy people in each hospital were selected as the control group. The general data of the patients were collected and the levels of thyroid function indexes of the two groups were detected. Multivariate logistic regression was used to analyze the influencing factors of diffuse goiter with hyperthyroidism. Results A total of 718 questionnaires were collected in this study, and 705 questionnaires were collected after excluding invalid questionnaires. There were 234 males and 471 females in 705 patients with diffuse goiter and hyperthyroidism. The most common age was 41-50 years, followed by 51-60 years and 31-40 years. The serum TSH level of the experimental group was lower than that of the control group, and the levels of FT3 and FT4 were higher than those of the control group ( P < 0.05 ) . There was no significant difference in family history, thyroid texture and thyroid imaging between the two groups ( P > 0.05 ). There were significant differences in exophthalmos and thyroid weight between the two groups (P<0.05). Multivariate Logistic regression analysis showed that exophthalmos, thyroid weight ≥30g , TSH , FT3 and FT4 were independent risk factors for the experimental group ( P < 0.05) . Conclusion Gender, age, exophthalmos, thyroid weight and thyroid related hormone levels are the influencing factors of diffuse goiter and hyperthyroidism in Xining area . Thyroid function should be monitored for early prevention and treatment of the disease.

AIM: To analyze the abnormal refractive status of infants and young children aged 6 to 48 months, and to provide basis for the correction of ametropia and the early prevention and treatment of amblyopia.METHODS: Infants and young children aged 6 to 48 months were examined for refraction by Spot vision screener for natural optometry. Clinical data of infants and young children with refractive abnormalities were collected, Ciliary muscle paralysis agent was used for retinoscopy and optometry, and the results were statistically analyzed.RESULTS: A total of 168 cases(336 eyes)with abnormal Spot refractive outcomes were collected, with a high proportion of hyperopia and astigmatism abnormalities, 38.4% and 28.6%, respectively, while the proportion of myopia was low(12.2%). There were 90 cases of anisometropia(≥1.00 D), among which 41 cases(45.6%)were astigmatic anisometropia, 33 cases(36.7%)were hyperopic anisometropia, and 16 cases(17.8%)were myopic anisometropia, accounting for the least proportion. A total of 109 infants and young children with Spot refractive abnormalities completed ciliary muscle paralysis retinal optometry. The analysis of the difference and correlation between Spot diopter and post ciliary muscle paralysis optometry results showed that the difference in astigmatism was 0.34±0.64 D(P<0.001), the difference in hyperopia was -2.10±1.27 D(P<0.001), and the difference in myopia was -0.43±0.91 D(P=0.023). Although there was a statistical difference between the two results, astigmatism, hyperopia, and myopia were highly positively correlated, respectively(r=0.694, 0.762, 0.909).CONCLUSION: The main refractive abnormalities in infants and young children aged 6 to 48 months are astigmatism, hyperopia, and anisometropia, with fewer abnormalities in myopia. For screening abnormalities, further ciliary muscle paralysis agent retinoscopy and optometry should be performed, and glasses correction should be given to effectively prevent refractive amblyopia in infants and young children.

Objective To investigate the effects of MCSO on physiological behavior and antioxidant index in D.melanogaster.Methods One-day-old wild type D.melanogaster was divided into control group,0.25％,0.5％,1％,2％and 4％dose groups,as well as male and female groups.The control group was exposed to the base medium,and each dose group was exposed to the MCSO medium added with 0.25％,0.5％,1％,2％and 4％concentrations,respectively.The optimal dosage concentration and time of administration were investigated by climbing experiment.Then the flies were divided into control group,model group and MCSO group.The model group was established by depriving the flies of sleep through repeated nocturnal light stimulation.Period of drug treatment,appetite test,negative geotaxis ability test,stress test,olfactory memory test,and sleep-wake rhythm detection were used to explore the effects of MCSO on their physiological behavior.The activities of super oxidase dismutase(SOD),catalase(CAT),and malondialdehyde(MDA)were detected by enzyme-linked immunosorbent assay.Results MCSO enhanced the locomotory ability of 30-day-old D.melanogaster(P＜0.01),increased the activity of SOD and CAT(P＜0.01),and decreased the concentration of MDA(P＜0.01).Improve olfactory memory of senile fruit flies.After sleep deprivation,the night sleep time of female Drosophila model group was reduced(P＜0.05),and that of male Drosophila model group was reduced(P＜0.01).After feeding MCSO,the night sleep time of female drosophila model group was extended(P＜0.05),and that of male drosophila model group was extended(P＜0.01).Conclusions MCSO had a certain antioxidant effect,prolonging the sleep time and improving the olfactory memory of sleep-deprived Drosophila.

Objective:Using the established epilepsy patient database to validate the efficacy of the web-based epilepsy diagnosis and anti-seizure medications (ASM) selection tool, EpiPick, for domestic epilepsy patients.Methods:The retrospective collection of clinical data was conducted on patients aged 10 and above who were diagnosed with epilepsy at the Comprehensive Epilepsy Center of the First Affiliated Hospital of Kunming Medical University from January 2017 to December 2020, with regular follow-up and complete information. According to the first ASM recommended by the EpiPick tool and whether they are consistent with the actual ASM used by patients, patients were divided into EpiPick group and clinical group to verify the effectiveness of the EpiPick tool in selecting ASM. The drug retention rate, Engel score, and cumulative probability of no consecutive episodes within 30 months after using the first ASM were compared between the 2 groups, and Kaplan-Meier survival curves were drawn. Finally, the diagnostic results provided by the EpiPick tool were compared with the actual types of epileptic seizures diagnosed clinically, and consistency tests were performed.Results:A total of 364 epilepsy patients were included, including 237 in the EpiPick group and 127 in the clinical group. The ASM retention rates of patients in the EpiPick group and clinical group were 67.9%(161/237) and 56.7%(72/127), respectively, with statistically significant differences (χ2=4.534, P=0.039). Grades Ⅰ, Ⅱ, Ⅲ and Ⅳ according to the Engel scores in the EpiPick group patients who took the first ASM after diagnosis accounted for 47.3%(112/237), 14.8%(35/237), 12.7%(30/237), and 25.3%(60/237), respectively, compared to the clinical group of 32.3%(41/127), 11.8%(15/127), 11.0%(14/127), and 44.9%(57/127), respectively. There was a statistically significant difference in Engel scores between the 2 groups (χ2=14.968, P=0.002). The cumulative seizure-free rates in the EpiPick group at the 1st, 6th, 12th, 30th month and above after starting the first ASM were 73.8%, 61.2%, 53.2%, and 50.6%, respectively, which in the clinical group were 52.0%, 44.1%, 40.2%, and 33.5%, respectively. The logrank test showed a statistically significant difference in the cumulative probability of consecutive seizure freedom between the 2 groups ( HR=0.644 ,95% CI 0.476-0.871 ,P<0.001). After grouping by seizure type [focal seizures (196 cases) and generalized seizures (168 cases)], the cumulative seizure-free rates at the 1st, 6th, 12th, 30th month and above after starting ASM were significantly higher in the EpiPick group than in the clinical group (comparison between the 2 groups in patients with focal seizures: HR=0.654, 95%CI 0.443-0.964, P=0.004; comparison between the 2 groups in patients with generalised seizures: HR=0.586, 95%CI 0.361-0.954, P=0.014). Among 364 patients, 293 cases were clinically diagnosed with seizure classification consistent with the classification results of EpiPick tool. Agreement between the algorithm and the experts in classifying generalized seizures was 83.9%(104/124), which in classifying focal seizures was 78.8%(189/240; Kappa=0.591, P<0.001). Conclusion:Web-based EpiPick tool is suitable to be used to select the first ASM, and is portable for Chinese non-epilepsy specialists to choose ASM for epilepsy patients.

Objective : This study aimed to assess the incidence ，etiological characteristic ，potential risk factors and clinical outcomes of multidrug-resistant (MDR) infection in patients with peritoneal dialysis associated peritoni- tis (PDAP) ． Methods : The data of PDAP patients admitted in recent 3 years in our center were collected retro- spectively to analyze the distribution of pathogenic bacteria and drug resistance．According to whether the pathogen- ic bacteria were MDR or not，they were divided into MDR group and non-MDR group．The data of the two groups were compared，and the risk factors and clinical outcomes of MDR infection were analyzed. Results : PDAP pa- tients were mainly infected with gram-positive bacteria． Staphylococcus was the most common pathogen isolated from the peritoneal fluid in the MDR group，accounting for 60. 6% (43 /71) ，and streptococcus was the most com- mon pathogen isolated in the non-MDR group，accounting for 42. 0% (21 /50) ．Multivariate analysis showed that the use of wide-spectrum antibiotics for more than 5 days within 3 months before the onset of PDAP ( OR = 3. 634， P = 0. 033) ，gram-positive bacterial infection ( OR = 3. 741，P = 0. 031 ) ，higher lipoprotein ( a) level ( OR = 1. 003，P = 0. 003) ，and higher platelet-to-albumin ratio ( OR = 1. 198，P = 0. 038) were independent risk factors for MDR infection in PDAP patients．The incidence of refractory peritonitis in MDR group (29. 6% ) was higher than that in non-MDR group ( 12. 0% ) ( χ2 = 5. 229 ，P = 0. 022 ) ． The incidence of recurrent peritonitis ( 16. 9% ) was also higher than that in the non-MDR group (4. 0% ) ( χ2 = 4. 773，P = 0. 029) ． Conclusion The main pathogen of MDR infection is staphylococcus in PDAP patients． Compared with the non-MDR group ，the MDR group has a higher proportion of wide-spectrum antibiotics used for more than 5 days within 3 months before the onset of PDAP，a higher proportion of gram-positive bacterial infection，higher lipoprotein ( a) level，higher platelet-to-albumin ratio，and an increased risk of refractory peritonitis and recurrent peritonitis.

Objective : To investigate the effects of carnosine (CAR) on streptozotocin (STZ) induced renal feroptosis and inflammation in diabetic mice . Methods : Type 1 diabetes mice model were induced by STZ , and normal C57 mice were used as normal control group . The C57 mice were divided into 5 groups (6 - 8 mice in each group) : normal control group (NC) , normal control + carnosine group (NC + CAR) , STZ model group (STZ) ,STZ model + carnosine group (STZ + CAR) , STZ model + ferroptosis inhibitor group (STZ + Fer⁃1) . After feeding the mice for 16 weeks , serum samples were collected to detect blood creatinine ( CRE) and urea nitrogen ( BUN) levels . The urine of mice was collected to detect the 24 - hour urinary albumin level . HE staining and PAS staining were performed to observe the degree of renal pathological injury . Real⁃time PCR was used to detect the expression of interleukin (IL) Ⅳ1β , IL⁃6 , monocyte chemotactic protein 1(MCP⁃1) and tumor necrosis factor⁃α (TNF⁃α ) in mouse kidney tissue . The expression of reactive oxygen species(ROS) in mouse kidney was detected by immunofluorescence . Morphology of renal mitochondria was observed by transmission electron microscopy . The protein expression levels of glutathione peroxidase 4(GPX 4) and long⁃chain lipoacyl⁃CoA synthetase 4( ACSL4) , which are ferroptosis indexes , were detected by Western blot . The contents of malondialdehyde ( MDA) , glutathione ( GSH) and Fe2 + in mouse kidney tissue were determined . Results : Compared with NC group , CRE and BUN levels in STZ group increased (P < 0. 001) ; and ompared with STZ group , these indexes decreased in STZ + CAR group (P < 0. 001 , P < 0. 01) . Renal histopathological examination showed that compared with NC group , renal tubule dilatation , inflammatory cell infiltration and glycogen deposition significantly increased in STZ group ; and compared with STZ group , tubule dilatation , inflammatory cell infiltration and glycogen deposition decreased in STZ + CAR group . Electron microscope results showed that the renal mitochondria in STZ group were swollen , membrane density increased , mitochondrial ridges decreased or absent , renal tubule dilation was improved significantly in the STZ + CAR group and STZ + Fer⁃1 group , and inflammatory cell infiltration was reduced . Real⁃time PCR test results showed that compared with NC group , mRNA expression levels of inflammatory factor (IL⁃1β , IL⁃6 , MCP⁃1 and TNF⁃α ) increased in STZ group (P < 0. 001 or P < 0. 01) ; and mRNA expressions of IL⁃1β , IL⁃6 , MCP⁃1 and TNF⁃α were decreased in STZ + CAR group compared with STZ group (P < 0. 01 or P < 0. 05) . Immunofluorescence results showed that compared with NC group , ROS level in kidney tissue of mice in STZ group increased (P < 0. 001) ; and compared with STZ group , the expression of ROS in kidney tissue of STZ + CAR group decreased while ROS expression in STZ + CAR group decreased ( P < 0. 01) . Compared with NC group , GPX4 expression and GSH content in kidney of STZ group decreased ( P < 0. 001) , and ACSL4 protein expression and MDA and Fe2 + contents increased (P < 0. 01 or P < 0. 001) , GPX4 expression and GSH content increased (P < 0. 01) , ACSL4 protein expression and MDA and Fe2 + content decreased in STZ + CAR group (P < 0. 01 or P < 0. 001) . Conclusion CAR inhibits ferroptosis and inflammation in the kidney in diabetic mice induced by STZ , and improved renal pathological injury in diabetic mice .

[摘 要] 近年来，以T淋巴细胞为主的免疫细胞疗法在血液系统肿瘤和部分实体瘤中取得了一定的进展。然而，其对大部分实体瘤治疗的有效性和安全性仍面临着诸多挑战，如肿瘤抗原异质性和免疫逃逸、免疫细胞浸润能力差、免疫抑制微环境、代谢微环境阻碍和T细胞耗竭等，这些问题限制了免疫细胞对实体瘤治疗的疗效进一步的提升。通过寻找新抗原、设计多靶点CAR、过表达趋化因子受体及细胞因子、敲除抑制性信号分子、增强T细胞代谢能力、联合免疫检查点抑制剂，以及表观遗传修饰等手段能够有效改善免疫细胞在实体瘤治疗中的效果。本文系统性地对TIL、TCR-T细胞和CAR-T细胞为代表的免疫细胞对实体瘤治疗的研究现状、面临的挑战和解决策略进行评述。

ObjectiveTo explore the compatibility advantage of Scutellariae Radix-Coptidis Rhizoma in the prevention and treatment of neuroinflammation， and to elucidate the action characteristics and mechanism of the compatibility advantage based on Toll like receptor （TLR4）/myeloid differentiation factor 88 （MyD88）/nuclear factor kappaB （NF-κB） pathway. MethodRepresentative mouse microglia cells （BV2） in vitro were selected and divided into 8 groups： control group， model group， Scutellariae Radix-Coptidis Rhizoma group， Piracetam group， Scutellariae Radix group and Coptidis Rhizoma group. The BV2 cell inflammatory model was established by lipopolysaccharide （LPS）， and the cell activity was detected by cell counting kit-8 （CCK-8）. Cell morphology was observed under bright field. The production and release of pro-inflammatory factors in BV2 cells were determined by enzyme-linked immunosorbent assay （ELISA） and immunofluorescence assay， and the mRNA expressions of TLR4， MyD88 and NF-κB were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR）. The nuclear translocation of NF-κB p65 was detected by immunofluorescence， and TLR4 signal transduction inhibitor （CLI-095） and NF-κB inhibitor （PDTC） were used to confirm the anti-neuroinflammation targets of Scutellariae Radix-Coptidis Rhizoma. ResultCompared with the conditions in the control group， most cells in LPS-induced model group were activated， and the contents of IL-6， TNF-α and IL-1β in culture medium and cells and the mRNA expressions of TLR4， MyD88， NF-κB p50 and NF-κB p65 were increased （P<0.01）， with obvious nuclear entry of NF-κB p65. Compared with the conditions in the model group， BV2 cell morphology was mostly recovered after pretreatment in Scutellariae Radix-Coptidis Rhizoma and Piracetam groups， and the levels of IL-6， TNF-α and IL-1β and the mRNA expressions of TLR4， MyD88， NF-κB p50 and NF-κB p65 were decreased （P<0.05， P<0.01）， with NF-κB p65 mostly observed in cytoplasm. Compared with the conditions in the model group， cell morphology was slightly recovered in Scutellariae Radix group and Coptidis Rhizoma group， and the levels of pro-inflammatory factors and mRNA expressions of TLR4， MyD88， NF-κB p50 and NF-κB p65 were reduced. In terms of inhibitory effect on pro-inflammatory factors， Scutellariae Radix group and Coptidis Rhizoma group were lower than Scutellariae Radix-Coptidis Rhizoma group （P<0.05）. Compared with the model group， the "Scutellariae Radix-Coptidis Rhizoma+CLI-095" group and "Scutellariae Radix-Coptidis Rhizoma+PDTC" group had lowered mRNA expressions of TLR4， MyD88， NF-κB p50 and NF-κB p65 （P<0.05， P<0.01）， and the transfer of NF-κB p65 into nucleus was obviously inhibited. ConclusionThe anti-neuroinflammation effect of Scutellariae Radix-Coptidis Rhizoma was significantly better than Scutellariae Radix or Coptidis Rhizom alone， and the anti-neuroinflammation advantage was closely related to the inhibition of activation of TLR4/MyD88/NF-κB signaling pathway in microglial cells. It was confirmed that TLR4， MyD88 and NF-κB were potential targets for Scutellariae Radix-Coptidis Rhizoma to exert the compatibility advantage.