1.α-ketoglutarate ameliorated arsenic-induced hepatic lipid deposition in offspring via PI3K/AKT signaling pathway
Shuangrui BAO ; Hongyan WU ; Ying SUN ; Tong ZHAN ; Qian YANG ; Xinru LIANG ; Zhiyan WAN ; Wenyi CHEN ; Cheng ZHANG
Acta Universitatis Medicinalis Anhui 2026;61(2):225-231
ObjectiveTo investigate the protective effect of α-ketoglutarate (α-KG) on hepatic lipid deposition in offspring caused by arsenic exposure during pregnancy. Methods8-week-old institute of cancer research (ICR) mice were mated in a ratio of 2∶1 between females and males, and the detection of vaginal plugs confirmed pregnant. A total of 32 pregnant mice were randomly divided into four groups: control group, arsenic group, α-KG group, arsenic+α-KG group. On gestational day 0-16 (GD0-GD16), the arsenic and arsenic+α-KG groups were exposed to sodium arsenite (NaAsO2 ,15 mg/L) in drinking water everyday, and the α-KG and arsenic+α-KG groups were gavaged with α-KG (2 g/kg) everyday. On GD16, pregnant mice were euthanized to collect fetal liver, and fetal body weight and crown-rump length were measured. Gene expression differences between the control group and the arsenic group were analyzed by transcriptome. The total triglycerides (TGs) and subtypes in fetal liver were detected by liquid chromatography tandem mass spectrometry (LC-MS/MS). Oil red O staining was used to observe the histopathological changes in the liver. Quantitative polymerase chain reaction (qPCR) was used to detect the expression level of genes related to lipid synthesis, transport, and degradation, and phosphatidylinositol 3' -kinase/ protein kinase B (PI3K/AKT) in the liver of fetus. ResultsTranscriptomics analysis showed that 2 144 genes were downregulated and 1 675 genes were upregulated in the arsenic exposed fetal liver; body weight and crown-rump length were reduced (PTuKey<0.05); the level of hepatic TGs was elevated in arsenic group (PTuKey<0.05); oil-red O staining showed a significant increase in lipid droplets in arsenic group (PTuKey<0.01); the expression of lipid synthesis-related genes were significantly upregulated (PTuKey<0.05); the expression of β-oxidation-related genes and lipid degradation-related genes were downregulated (PTuKey<0.05); the expression of PI3K, AKT decreased(PTuKey<0.05). Compared with the arsenic group, the body weight and crown-rump length of fetus increased in the arsenic+α-KG group (PTuKey<0.05); the level of hepatic TGs decreased in the arsenic+α-KG group (PTuKey<0.05); oil red O staining showed lipid droplets significantly decreased (PTuKey<0.01); the expression of lipid synthesis-related genes were downregulated (PTuKey<0.05), the expression of β-oxidation-related genes and lipid degradation-related genes were upregulated (PTuKey<0.05); the expression levels of PI3K and AKT increased (PTuKey<0.05). Conclusionα-KG alleviated hepatic lipid deposition in offspring exposed to arsenic during pregnancy through activating PI3K/AKT signaling pathway.
2.Establishment of a LC-MS/MS method for detecting gamma-aminobutyric acid in plasma and its clinical application
Jia-qian QIN ; Lei CAO ; Ying-fei PENG ; Fang-jun CHEN ; Bai-shen PAN ; Bei-li WANG ; Wei GUO
Fudan University Journal of Medical Sciences 2025;52(5):708-716
Objective To establish a stable liquid chromatography-tandem mass spectrometry(LC-MS/MS)method for detecting gamma-aminobutyric acid(GABA)in plasma,and to evaluate the value of GABA detection in the diagnosis of sleep disorders.Methods GABA was detected using a UPLC Xevo TQs system.The method was pre-validated and its performance was verified to establish a reference range for healthy individuals.The difference in plasma GABA levels between apparently healthy individuals and patients with sleep disorders was compared.Results We employed deuterated compounds as isotopic internal standards and utilized an Amide chromatographic column for separation.The mobile phase was 0.050%formic acid in water and 90%acetonitrile in water containing 0.175%formic acid and 5 mmol/L ammonium acetate with gradient elution in the column temperature of 35℃.The linear range for the detection of GABA by LC-MS/MS was 0.05-10.00 μmol/L,with a lower limit of quantification of 0.02 μmol/L,the inter-day CV<3.00%and intra assay CV<4.00%,respectively,and the recovery rate was 101.06%-109.02%.The reference ranges for plasma GABA were established by analyzing 300 healthy controls stratified by age:18-34 years(0.08-0.15 μmol/L),35-49 years(0.10-0.20 μmol/L),and≥50 years(0.12-0.23 μmol/L).Then plasma GABA was used as a biomarker for auxiliary diagnosis of sleep disorders in analyzing 221 patients and 300 healthy controls,which revealed that AUC values were 0.510(P=0.850),0.686(P=0.002),and 0.890(P<0.001)in the groups of 18-34 years,35-49 years,and≥50 years,respectively,with optimal cut-off values of 0.09,0.10 and 0.11 μmol/L.Conclusion A reliable LC-MS/MS method for detecting GABA has been established,which can detect plasma GABA levels sensitively and accurately and can be used in assisting the clinical diagnosis of sleep disorders.
3.Clinicopathologic characteristics,gene mutation profile,and prognostic analysis of patients with adrenal diffuse large B-cell lymphoma
Jiayin HE ; Siyuan CHEN ; Qing SHI ; Muchen ZHANG ; Hongmei YI ; Lei DONG ; Ying QIAN ; Li WANG ; Shu CHENG ; Pengpeng XU ; Weili ZHAO
Journal of Shanghai Jiaotong University(Medical Science) 2025;45(9):1194-1201
Objective·To analyze the clinicopathologic characteristics,gene mutation profile,and prognostic factors of patients with adrenal diffuse large B-cell lymphoma(DLBCL).Methods·From March 2002 to December 2022,a total of 105 patients with adrenal DLBCL admitted to Ruijin Hospital,Shanghai Jiao Tong University School of Medicine were retrospectively analyzed for their clinicopathological data,survival outcomes,and prognostic factors.Patients'gene mutation profiles were evaluated by targeted sequencing of 152 lymphoma-related genes.Results·The median age of the patients was 62(15?82)years and the male-to-female ratio was 2.3∶1.Among them,63 patients(60.0%)were over 60 years old,22 patients(21.0%)had an Eastern Cooperative Oncology Group(ECOG)performance status of two or higher,87 patients(82.9%)were staged Ann Arbor Ⅲ?Ⅳ,92 patients(87.6%)had elevated serum lactate dehydrogenase(LDH)levels(above the upper limit of reference),84 patients(80.0%)had extranodal invasion in at least two organs,67 patients(63.8%)were of non-germinal center B-cell(non-GCB)origin,and 95 patients(90.5%)had an international prognosis index(IPI)scored over 2.With a median follow-up of 28.3(0.7?191.9)months,the estimated 2-year overall survival(OS)rate and progression-free survival(PFS)rate were 68.3%and 53.1%,respectively.The estimated 5-year OS rate and PFS rate were 52.6%and 44.0%,respectively.Among 93 patients who could be evaluated for clinical outcomes,62(66.7%)got a complete response(CR).Univariate analysis and multivariate Cox analysis revealed that age over 60 years was an adverse prognostic factor for PFS,and ECOG performance status of two or higher was an adverse prognostic factor for both OS and PFS.Targeted gene sequencing in 46 adrenal diffuse DLBCL patients showed high mutation frequencies in lysine methyltransferase 2D(KMT2D;n=17,37%),Pim-1 proto-oncogene,serine/threonine kinase(PIM1;n=17,37%),MYD88 innate immune signal transduction adaptor(MYD88;n=15,33%),CD79b molecule(CD79B;n=13,28%),and BTG anti-proliferation factor 2(BTG2;n=10,22%).Conclusion·Age over 60 years is an adverse prognostic factor for PFS,and ECOG performance status of two or higher is an adverse prognostic factor for both OS and PFS in patients with adrenal DLBCL.Patients exhibited high frequencies of KMT2D,PIM1,MYD88,CD79B,and BTG2 mutations,as well as an increased proportion of the MCD-like subtype.
4.Effect of adjusting timing of nebulization and analgesic usage on the pain and exercise self-efficacy during early postoperative respiratory function exercise of lung cancer surgery patients
Ying LIU ; Yaqing ZHOU ; Qian CHEN ; Rui ZHOU ; Yun CAO ; Yanan REN ; Lanying LIU
Chinese Journal of Practical Nursing 2025;41(30):2360-2365
Objective:To explore applications of adjusting timing of nebulization and analgesic usage in patients after lung cancer surgery, to provide reference for postoperative rehabilitation of lung cancer.Methods:Adopting a prospective randomized controlled study design, a total of 84 patients with lung cancer who underwent surgery in affiliated hospital of Jining Medical University from September 2020 to June 2023 were enrolled by a convenience sampling method, they were randomly divided into experimental group and control group according to random number table method. Two groups was given routine perioperative care, on this basis, the control group received lip and abdomen contraction breathing training according to the conventional process, and the experimental group adjusted timing of nebulization and analgesic usage and received respiratory function training when nebulization and analgesics were at the peak of blood drug concentration. Pain level and exercise self-efficacy of two groups were compared.Results:There were 27 males and 15 females in the control group, aged (54.52 ± 14.06) years; and 24 males and 18 females in the experimental group, aged (53.33 ± 12.02) years. At one day, two days and three days after operation, the scores of Numerical Rating Scale (NRS) were (5.07 ± 0.84), (3.40 ± 0.49), (2.93 ± 0.87) in the experimental group, lower than (5.86 ± 1.05), (4.09 ± 0.88), (3.33 ± 0.65) in the control group, the differences were statistically significant ( t=3.79, 4.44.2.42, all P<0.05), and for both groups, the differences in the time effect, between-group effect, and the interaction effect were all statistically significant ( F=582.92, 44.65, 3.82, all P<0.05). Three days after operation, the dimensions of efficacy expectation, outcome expectation and total self-efficacy scores were (28.62 ± 6.75), (33.71 ± 7.04) and (62.33 ± 9.07) in the experimental group, and (25.52 ± 6.66), (30.43 ± 6.80) and (55.95 ± 9.34) in the control group, the differences were statically significant ( t=2.12, 2.18, 3.18, all P<0.05). Conclusions:Adjusting timing of nebulization and analgesic usage and giving respiratory function training for lung cancer surgery when nebulization and analgesics at the peak of blood drug concentration can effectively alleviate the pain caused by respiratory exercise and improve training self-efficacy of patients after lung cancer surgery.
5.Effect of joint management of type 2 diabetes mellitus between specialty department and community health under National Diabetes Prevention and Control Center (DPCC) model
Ying HUANG ; Yi QIAN ; Xuchi WU ; Zhongyu ZHOU ; Cong WANG ; Lin WANG ; Caiyan HUANG ; Zhuangsen CHEN ; Yanrong ZHANG ; Shanshan WANG ; Lu WANG ; Jie WAN ; Ruihong YANG ; Huiya WANG ; Yan CHEN ; Cheng HE ; Kun FENG ; Dewen YAN
Journal of Chinese Physician 2025;27(3):338-342
Objective:To analyze the effect of joint management of type 2 diabetes mellitus (T2DM) between specialty and community under the model of National Diabetes Prevention and Control Center (DPCC).Methods:A total of 2 527 T2DM patients managed by DPCC Pingshan Center of Shenzhen from January 1, 2022 to December 31, 2024 were retrospectively included. After management, the rate of downturn, reexamination rate, blood pressure compliance rate, metabolic indicators (waist circumference, body mass index, fasting blood glucose, glycosylated hemoglobin, blood lipids) and screening rate of chronic complications of diabetes (atherosclerotic cardiovascular disease, microvascular disease, diabetic peripheral neuropathy) were analyzed. Those included 2022 ( n=564), 2023 ( n=1 477), and 2024 ( n=2 527). Results:The downturn rate in 2022, 2023 and 2024 increased year by year (22.8% vs 67.2% vs 89.9%, P<0.01), and the review rate (41.1% vs 62.2% vs 52.7%, P<0.01), complication screening rate (51.6% vs 85.3% vs 62.2%, P<0.01), blood pressure compliance rate (53.1% vs 78.0% vs 67.2%, P<0.01), body mass index compliance rate (13.2% vs 17.3% vs 28.6%, P<0.01), fasting blood glucose meeting rate (46.4% vs 60.2% vs 68.5%, P<0.01), glycated hemoglobin meeting rate (58.4% vs 63.2% vs 45.6%, P<0.01) were relatively improved. Waist circumference compliance rate (30.6% vs 27.7% vs 21.6%) and blood lipid compliance rate (33.6% vs 35.5% vs 31.9%) were not significantly improved, and the review rate, blood pressure compliance rate and complication screening rate in 2024 were lower than those in 2023 and higher than those in 2022. Conclusions:The combined management of type 2 diabetes under the DPCC model has significant effects on improving the down-conversion rate, rediagnosis rate, blood pressure compliance rate, metabolic index compliance rate and the screening rate of diabetes-related chronic complications in patients with diabetes. At the same time, it was also found that with the progress of hierarchical diagnosis and treatment, the review rate, complication screening rate, blood pressure, waist circumference, blood lipid and glycosylated hemoglobin reached the standard of patients decreased compared with the previous situation, which needs to be further analyzed and improved.
6.Effects of Focused Solution Model Nursing on quality of life and negative emotions of prostate cancer patients
Lei YU ; Ting-ling ZHANG ; Wen-fang CHEN ; Xiu-qin YE ; Jie LIU ; Qian MENG ; Ying-chun HUANG ; Song XU
National Journal of Andrology 2025;31(8):723-727
Objective:To analyze the effects of the Focused Solution Model Nursing intervention on quality of life,negative emotions of the patients with prostate cancer.Methods:A total of 82 prostate cancer patients who were diagnosed and treated at the General Hospital of Eastern Theater Command between September 2022 and September 2024 were included and randomly divided into study group and control group by the method of random number table,with 41 patients in each group.The patients in the study group were treated with Focused Solution Model Nursing intervention.And the routine care was used in the control group The quality of life and negative emotions were compared between the two groups by using the scales of World Health Organization Quality of Life-Brief(WHOQOL-BREF),HAMA and HAMD.Results:Compared to the control group,the patients in the study group exhibited signifi-cantly higher scores in the physiological,psychological,environmental,and social relationship domains of the WHOQOL-BREF scale(P<0.05).The scores of HAMA and HAMD in study group were lower than those of the control group(P<0.05).Additionally,all subscales of the Social Impact Scale including social exclusion,internalized shame,social isolation and economic discrimination were significantly lower than those of the study group(P<0.05).Conclusion:Focused Solution Model Nursing intervention can effec-tively improve the quality of life and negative emotions of the prostate cancer patients in the clinical treatment.
7.Effect of the axial position of posterior chamber phakic intraocular lens on the early postoperative vault changes
Yi-lin XU ; Qian JIAN ; Xun CHEN ; Yin-jie JIANG ; Ling-ling NIU ; Xiao-ying WANG
Fudan University Journal of Medical Sciences 2025;52(1):83-90
Objective To observe the early changes of vault after implantation of posterior chamber phakic intraocular lens implantable collamer lens(ICL),and investigate the effect of different implantation axes on the early vault changes.Methods A prospective,parallel cohort study was performed,enrolling a total of 124 eyes of who underwent ICL(V4c)implantation in the refractive clinic.The changes of vault were observed by scheimpflug tomography(Pentacam)and anterior segment optical coherence tomography(CASIA2)at 1 day,1 week and 1 month after surgery.Results The ICL vault declined significantly by approximately(108.2±82.4)μm 1 week after surgery with the proportion of 16.6%±12.1%compared with the values 1 day after surgery(P<0.001),and then remained stable.Within 1 month after surgery,excluding the difference in vault baseline at 1 day after surgery,the proportion of vault decline in the middle vault group(250-749 μm)and the high vault group(≥750 μm)was similar,and there was no statistically significant difference.We analyzed the relationship between ICL axial directions and vault and found that the vault decline of the horizontal ICL group stabilized quickly at 1 week after surgery,and the vault decline of the vertical ICL group was more significant within 1 month after surgery(P<0.05).Conclusion The vault of the ICL shows a downward trend in the early stage after implantation.The middle vault group and ICL in the horizontal position stabilizes faster,and the downward trend of the high vault group or ICL in the vertical position is more obvious.
8.Mechanism of action of D-limonene on steatosis in primary hepatocytes based on AMPK/ACC/CPT1A signaling pathway
Qian-jun REN ; Su LI ; Yu-qing CHEN ; Yin-ying LIAO ; Chun-ni LIANG ; Rui-chao FANG ; Xu-dong LIU ; Xiao-fang ZHAO
Chinese Pharmacological Bulletin 2025;41(9):1665-1672
Aim To explore the effects of D-limonene on the steatosis of primary mouse hepatocytes and its potential mechanism of action.Methods Oleic acid-induced steatosis in primary mouse hepatocytes was used as a model to observe the effects of D-limonene on cell viability,cellular lipid content,and intracellular expression of proteins such as AMP-activated protein kinase(AMPK),acetyl-coenzyme A carboxylase 1(ACC1),and carnitine palmitoyl transferase 1A(CPT1A).Results It was found that a low dose of D-limonene could effectively enhance the viability of primary mouse hepatocytes.When oleic acid at a con-centration of 300 μmol·L-1 successfully induced steatosis in primary mouse hepatocytes,D-limonene re-duced the lipid content of the cells,and D-limonene up-regulated the cellular AMPK expression level,down-regulated the cellular ACC1 and fatty acid synthetase(FAS)expression levels,which in turn promoted the overexpression of CPT1A.Conclusions D-limonene has the effect of reducing lipid deposition in primary mouse hepatocytes,and the mechanisms may be related to the activation of AMPK,the inhibitions of ACC1 and FAS,and the up-regulation of CPT1A protein expres-sion level.
9.Clinical Study of Modified Cangfu Daotan Decoction Combined with Ethinylestradiol and Cyproterone Acetate,Metformin in Patients with Spleen Deficiency Phlegm-Dampness Type Polycystic Ovary Syndrome Accompanied by Insulin Resistance
Jing LIN ; Fan CHEN ; Yan-hua CHEN ; Ying XU ; Lin-lin WANG ; Hong WANG ; Xi-na LIAN ; Rong-qian XU
Progress in Modern Biomedicine 2025;25(17):2768-2775,2739
Objective:To observe the clinical effect of Cangfu Daotan Decoction combined with ethinylestradiol and cyproterone acetate,metformin in patients with spleen deficiency phlegm-dampness type polycystic ovary syndrome(PCOS)accompanied by insulin resistance.Methods:80 patients with PCOS accompanied by insulin resistance who were admitted to our hospital from June 2023 to June 2024 were included.The patients were divided into control group(treated with ethinylestradiol and cyproterone acetate,metformin)and study group(treated with modified Cangfu Daotan Decoction combine with ethinylestradiol and cyproterone acetate,metformin)by the random number table method,with 40 cases in each group.The total clinical effective rate,TCM syndrome score,sex hormone levels[prolactin(PRL),estradiol(E2),follicle-stimulating hormone(FSH),testosterone(T),and luteinizing hormone(LH)],insulin resistance indicators[fasting insulin(FINS),fasting blood glucose(FBG),homeostatic model assessment of insulin resistance(HOMA-IR)],and endometrial receptivity[pulsatile index(PI),resistance index(RI),endometrial thickness(ET),ovulation rate]and the occurrence of adverse reactions were compared between the two groups.Results:Compared with the control group after treatment,the total clinical effective rate,PRL,E2,FSH level,ET and the ovulation ratein the study group were higher,while the main symptoms,secondary symptoms,total score,T,LH levels,FBG,FINS levels,HOMA-IR,PI and RI were lower(P<0.05).There was no difference in the incidence of adverse reactions between the two groups(P>0.05).Conclusion:Cangfu Daotan Decoction combined with ethinylestradiol and cyproterone acetate,metformin in patients with spleen deficiency phlegm-dampness type PCOS accompanied by insulin resistance,can improve the clinical symptoms,increase the total clinical effective rate,it may be related to the regulation of insulin resistance,sex hormone levels,and endometrial receptivity,it is safe and reliable.
10.Recent advance in NLRP3 inflammatome in neuropathic pain after spinal cord injury
Simin CHEN ; Hongyu QUAN ; Mai LI ; Qian CHEN ; Ying WU ; Yongmei LI
Chinese Journal of Neuromedicine 2025;24(1):94-99
The mechanism of neuropathic pain after spinal cord injury is still unclear, which might be closely related to ion channel changes, central sensitization and decreased function of descending inhibitory system after injury. Existing studies have shown that the nucleotide-binding domain leucine-rich repeat and pyrin domain-containing receptor 3 (NLRP3) inflammasome play a key role in neuropathic pain after spinal cord injury; therefore, targeting NLRP3 inflammasome is a promising therapeutic strategy. This review analyzes the molecular mechanism and treatment of NLRP3 inflammasome in neuropathic pain after spinal cord injury, aiming to provide references for pathogenesis and treatment of neuropathic pain after spinal cord injury.

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