Lipotoxicity is a pivotal factor that initiates and exacerbates liver injury and is involved in the development of metabolic-associated fatty liver disease (MAFLD). However, there are few reported lipotoxicity inhibitors. Here, we identified a natural anti-lipotoxicity candidate, HN-001, from the marine fungus Aspergillus sp. C1. HN-001 dose- and time- dependently reversed palmitic acid (PA)-induced hepatocyte death. This protection was associated with IRE-1α-mediated XBP-1 splicing inhibition, which resulted in suppression of XBP-1s nuclear translocation and transcriptional regulation. Knockdown of XBP-1s attenuated lipotoxicity, but no additional ameliorative effect of HN-001 on lipotoxicity was observed in XBP-1s knockdown hepatocytes. Notably, the ER stress and lipotoxicity amelioration was associated with PLA2. Both HN-001 and the PLA2 inhibitor MAFP inhibited PLA2 activity, reduced lysophosphatidylcholine (LPC) level, subsequently ameliorated lipotoxicity. In contrast, overexpression of PLA2 caused exacerbation of lipotoxicity and weakened the anti-lipotoxic effects of HN-001. Additionally, HN-001 treatment suppressed the downstream pro-apoptotic JNK pathway. In vivo, chronic administration of HN-001 (i.p.) in mice alleviated all manifestations of MAFLD, including hepatic steatosis, liver injury, inflammation, and fibrogenesis. These effects were correlated with PLA2/IRE-1α/XBP-1s axis and JNK signaling suppression. These data indicate that HN-001 has therapeutic potential for MAFLD because it suppresses lipotoxicity, and provide a natural structural basis for developing anti-MAFLD candidates.

Objective To analyze the characteristics of adult anomalous aortic origin of coronary artery(AAOCA)and the causes of missed diagnosis by transthoracic echocardiography(TTE)so as to facilitate TTE in diagnosing adult AAOCA.Methods A total of 37 adult patients with AAOCA diagnosed by non-invasive coronary CT angiography(CCTA)and/or invasive coronary angiography(ICA)were selected as research samples at some hospital from January 2019 to December 2022,and their clinical symptoms and the findings of 12-lead electrocardiogram,cardiac enzymes and TTE were summarized;the patients were typed according to the site of origin of coronary artery anomalies,and the causes for the missed diagnosis of TTE were eplored.Chi-square test was used to compare the differences in TTE missed diagnoses.Results Of the 37 patients,31 ones had no or only mild symptoms;most ones had negative results in terms of 12-lead electrocardiography,cardiac enzymes,changes in the size of the cardiac chambers,segmental ventricular wall motion abnormalities and left ventricular systolic function.The patients with anomalous origin of the right coronary artery from left sinus(ARCA-L)gained the largest proportion of 59.45％(22/37);21 patients were diagnosed with anomalous origin of coronary artery arising from the opposite sinus(ACAOS)in the two examinations of TTE,of whom there were 19 cases of ARCA-L,and the detection rate of ACAOS by TTE was 87.5％;all the 13 patients origins in branches and high-grade openings were missed by TTE.The detection rate of ACAOS by TTE was significantly higher than that of coronary artery anomalies originating in branches and in high openings,and the difference was statistically significant(21/24 vs 0/13,P＜0.001).Conclusion Most adult AAOCA patients lack specificity in symptoms and related examination results.TTE has a high detection rate of ACAOS,while it is easy to miss the diagnosis of coronary artery anomalies originating from branches and high openings.Ultrasonographers have to identify false negative AAOCA by multi-section and multi-angle scanning and color Doppler flow imaging in order to reduce the rate of missed diagnosis.[Chinese Medical Equipment Journal,2024,45(1):71-75]

This paper collects questionnaires from graduates and graduate students of clinical-related majors through economic experiments,and discusses the impact of different payment modes on the quantity and quality of medical services provided by doctors by simulating the decision of medical students to provide medical and health services to patients with different health conditions and disease types under two medical insurance payment methods:Fee-for-service(FFS)and Ambulatory Patient Groups(APG).The results showed that there were significant differences in the number of health services provided by doctors to patients with different health conditions and patients with different disease types under two different payment models.Physicians are motivated by the FFS model to provide too many medical and health services to patients,and APG can restrain doctors from providing excessive medical services,and the number of optimal health care service decisions made by doctors in the APG model is significantly higher than that of the FFS model.Compared with APG,the FFS model can better protect the medical needs of cases with poor health and complex conditions,and provide more comprehensive medical and health services.Finally,the paper puts forward suggestions such as using the APG payment mode as much as possible for routine outpatient clinics and common cases,and promoting FFS payment as a supplementary payment method for complex and severe cases.

Objective To observe the intervention effect and mechanism of Chinese herbal compound(Zhenyuan Granules)on overweight in mice caused by estrogen deficiency.Methods An ovariectomized female mouse model was established to observe the effects of intragastric 14 week administration of Zhenyuan Granules on body mass and fat accumulation in mice.The 3T3-L1 mouse preadipocyte model was constructed to observe the effect of Zhenyuan Granules intervention on adipogenic differentiation.The expressions of key genes/proteins regulating adipocyte formation and fat synthesis in mouse adipose tissue and 3T3-L1 cells was detected to explore the mechanism of lipid-lowering effect of Zhenyuan Granules in vivo and in vitro.Results Zhenyuan Granules significantly decreased the body mass gain(P＜0.01),perigonadal and inguinal fat indexes(P＜0.05),significantly inhibited the differentiation of 3T3-L1 preadipocytes into mature adipocytes(P＜0.01),significantly downregulated the expression levels of transcription factors peroxisome proliferators activated receptor γ(PPARγ)and sterol-regulatory element binding protein 1c(SREBP-1c)and enzymes acetyl-CoA carboxylase 1(ACC1)and fatty acid synthase(FAS)in adipose tissue and 3T3-L1 preadipocytes(P＜0.05),significantly enhanced the phosphorylation of AMP-activated protein kinase(AMPK)and ACC1(P＜0.05).Conclusion Zhenyuan Granules can inhibit the formation of adipocytes and improve the overweight of female mice caused by estrogen deficiency.The mechanism is related to the activation of AMPK signaling pathway.It is suggested that Bushen Jianpi Chinese herbal compound Zhenyuan Granules is helpful for body mass control in postmenopausal women.

Aim To screen and study the effects of Tao Hong Si Wu decoction(THSWD)-mediated treat-ment on circular RNA(circRNA)expression profiles in rats with middle cerebral artery occlusion(MCAO),and investigate the possible roles and molecular mecha-nisms of THSWD.Methods Next-generation RNA sequencing was conducted to identify circRNA expres-sion profiles in MCAO rats after treatment with THSWD and compared with the MCAO model group and control group.Bioinformatics analysis was performed to predict the potential target microRNAs and mRNAs.Gene On-tology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses for the potential target mRNAs were applied to explore the potential roles of differentially expressed circRNAs.RT-qPCR was performed to verify circRNAs with significant differences in expression.Results We identified 87 significantly differentially expressed circRNAs between the MCAO group versus the control group,and 86 sig-nificantly differentially expressed circRNAs between the MCAO group versus the THSWD group.respective-ly.Among them,17 circRNAs induced by the MCAO model were reversed via treatment with THSWD.To demonstrate the roles of mRNAs targeted by DECs,the GO and KEGG databases were used.Further analysis revealed that five circRNAs may play important roles in the development of MCAO.Conclusions The com-prehensive expression profile of circRNAs in rats with middle cerebral artery occlusion after THSWD treat-ment is determined for the first time,suggesting that the therapeutic effect of THSWD on MCAO may be a-chieved by regulating the expression of circRNAs.

Aim To explore the mechanism of the effect of rosiglitazone(Rsg)on the pancreatic cancer in diabetic mice based on the impact of PPARγ on glu-cose transport and metabolism.Methods A high-fat and high sugar diet combined with STZ was used to construct T2DM model;T2DM mice and normal mice were subcutaneously injected with PANC02 cells to construct a transplanted tumor model.T2DM trans-planted tumor mice and normal transplanted tumor mice were divided into the following groups:Rsg,PPARy inhibitor(PIN-2),rosiglitazone+PPARγ in-hibitor(Rsg+PIN-2),and normal transplanted tumor mice(NDM)and T2DM transplanted tumor mice(DM)were used as control groups,respectively.Tis-sue samples were collected after intervention.Tissue pathological changes were observed by HE staining.The expressions of Ki67 and PCNA proteins were de-tected by immunohistochemistry.Cell apoptosis was detected by TUNEL assay.The expression of PPARγwas detected by immunofluorescence.The expressions of Glucokinase,GLUT2,Nkx6.1,PDX-1RT-PCR were determined by Western blot.Results Rsg could significantly reduce the tumor mass,pathological chan-ges,Ki67 and PCNA expression of transplanted tumors(P＜0.05),increase cell apoptosis and the expression of PPARγ,Glucokinase,GLUT2,Nkx6.1,PDX-1 proteins in NDM and DM mice(P＜0.05).PIN-2 could reverse the indicator changes caused by Rsg in NDM and DM mice.However,compared with NDM mice,the above related indicators of the DM group mice were more sensitive to Rsg and PIN-2.Conclu-sions Compared to non-diabetic pancreatic cancer,rosiglitazone can more sensitively inhibit the prolifera-tion of pancreatic cancer with T2DM,induce apopto-sis,and reprogram the metabolism of pancreatic cancer with T2DM by activating PPA Rγ and altering the ex-pression of glucose and lipid metabolism genes,there-by exerting an anti-cancer effect.

Aim To study the resistance of SIRT3 ex-pression in dopaminergic neurons against the inflamma-tory damage caused by microglia activation and its re-lated mechanism.Methods Dopaminergic neurons(MN9D cells)and microglia(BV-2 cells)were co-cultured to establish an inflammatory injury model in vitro.MN9D cells were divided into the control group,model group,SIRT3 group and SIRT3+PJ34 group.mRNA levels were analyzed by real-time quantitative polymerase chain reaction,cell apoptosis rate was de-tected by flow cytometry,changes in mitochondrial membrane potential were tested by JC-1 method,and the opening of mitochondrial permeability transport pore(mPTP)was analyzed by co-incubation of calce-in-AM and CoCl2.The protein expression was detected by Western blot.Results Compared to the model group,overexpression of SIRT3 in the SIRT3 group significantly reduced the apoptosis rate of MN9D cells.It also led to a significant increase in the expression of SIRT3 and SOD2 genes,as well as a notable decrease in PARP-1,tumor necrosis factor-α,and interleukin 1β(IL-1β)protein expressions.Moreover,it resulted in a substantial reduction in the p-NF-κB p65/NF-κB p65 ratio.There was an improvement observed in mito-chondrial membrane potential along with decreased mPTP opening and ROS production in the SIRT3 group.These differences among these groups were sta-tistically significant(all P＜0.05).After inhibiting PARP-1 activity of MN9D cells in the SIRT3+PJ34 group,except for the insignificant changes in SIRT3 and IL-1 β protein expression,the changing trend of other indicators was further enhanced on the basis of SIRT3 group.The differences between two groups re-mained statistically significant(all P＜0.05).Con-clusions SIRT3 expression can attenuate the inflam-matory damage of dopaminergic neurons induced by microglia activation,and the mechanism may be relat-ed to improving mitochondrial function,inhibiting PARP-1 activity and NF-κB signaling pathway caused by the reduction of ROS production.

Polygoni multiflori radix praeparata is a processed product of Polygoni multiflori radix(Polygonum multiflorum Thunb.),and its main components include stilbene glycosides,anthraquinones,flavonoids,alkaloids,phenolic acids,etc.It has antioxidant,antianemic,anti-tumor,hypoglycemic,anti-inflammatory effects,etc,and is widely used in clinical practice.The processing technology is mainly stewinging with black bean juice,steaming,processing for 9 times and braising and simmering.After processing,the color deepens and the content of composition changes.By consulting domestic and foreign literature,the research on Polygoni multiflori radix praeparata is not comprehensive enough compared with Polygoni multiflori radix.Therefore,this paper mainly summarizes the processing technology,chemical composition and pharmacological activity of Polygoni multiflori radix preparata reported in the past 20 years,and provides a reference for further development of Polygoni multiflori radix preparata.

Objective:To explore the relationship between heart rate variability, severity, and prognosis in patients with acute cerebral infarction (ACI).Methods:A prospective study was conducted on 80 patients with acute cerebral infarction (ACI) admitted to Qinhuangdao Workers′ Hospital from February 2021 to March 2023. The severity of ACI patients was evaluated based on their National Institutes of Health Stroke Scale (NIHSS) scores, and they were divided into mild group (26 cases, NIHSS scores 0-15), moderate group (32 cases, NIHSS scores 16-30), and severe group (22 cases, NIHSS scores 31-45); And 30 healthy individuals who underwent physical examinations during the same period were selected as the control group. The improved Rankin Scale (MRS) was used to evaluate the prognosis of patients, who were divided into a good prognosis group (59 cases) and a poor prognosis group (21 cases) based on the scoring results. All patients underwent dynamic electrocardiogram examination, and the heart rate variability parameters of each group were compared [standard deviation of R-R interval for all sinus beats at 24 hours (SDNN), mean standard deviation of R-R interval for 5 consecutive minutes at 24 hours (SDNN Index), standard deviation of R-R interval mean every 5 minutes (SDANN), root mean square of all adjacent R-R interval differences (rMSSD), and the proportion of adjacent NN interval differences greater than 50 ms (PNN50%)]. The predictive value of heart rate variability parameters on the severity and prognosis of ACI patients was analyzed using receiver operating characteristic (ROC) curves. Logistic regression analysis was used to identify the risk factors for the severity and prognosis of ACI patients.Results:The SDNN, SDANN, SDNN Index, rMSSD, and PNN50% of the mild, moderate, and severe groups were significantly lower than those of the control group ( F=59.382, 11.859, 12.376, 11.699, 47.703, all P<0.01), and the severe group was less than the moderate group and less than the mild group (all P<0.05). The SDNN, SDANN, SDNN Index, rMSSD, and PNN50% in the poor prognosis group were lower than those in the good prognosis group ( t=4.536, 4.181, 5.091, 4.384, 2.851, all P<0.01). The results of logistic regression analysis showed that heart rate variability parameter was an independent influencing factor for the severity and poor prognosis of ACI patients (all P<0.01). The area under the curve for the combined diagnosis of the severity of ACI patients using SDNN, SDANN, SDNN Index, rMSSD, and PNN50% was 0.950, and the area under the curve for the combined prediction of ACI patients′ prognosis was 0.970. Conclusions:The heart rate variability parameter is an independent influencing factor on the severity and prognosis of ACI patients, and its predictive power for the severity and prognosis of ACI patients is high. It can be used as an effective indicator for evaluating the severity and prognosis of ACI patients.

Objective:To investigate the status quo and influencing factors of the somatization of depressive emotions among college students, in order to provide a theoretical basis for the reform of mental health education and the formulation of operable mental health counseling for college students.Methods:Totally 297 college students from two institutions of higher education in Heilongjiang Province were selected by convenience sampling and investigated with the College Student Depressive Emotion Somatization Questionnaire, Attitudes Toward Seeking Professional Psychological Help Scale-Short Form (ATSPPH-SF), and the Type D Personality Scale (DS14) .Results:The total score for the College Student Depressive Emotion Somatization Questionnaire among the 297 students was (28.49±8.07), and the total score for the ATSPPH-SF was (21.98±2.73). Multiple linear regression analysis showed that the influencing factors for the somatization of depressive emotions in college students were professional psychological help-seeking attitudes and whether they had a Type D personality ( P < 0.05) . Conclusions:During university education, there should be a focus on students' personality traits and the positivity of their attitudes toward seeking professional psychological help in order to mitigate the occurrence of adverse psychological issues such as symptoms of depressive somatization.