ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point， this study employed gas chromatography-mass spectrometry （GC-MS） to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis （IC） and ulcerative colitis （UC） from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate （ANIT）-induced cholestasis and 2，4，6-trinitro-benzenesulfonic acid （TNBS）-induced UC were treated with low （0.6 g·kg^-1） and high （1.2 g·kg^-1） doses of Zhuyuwan by gavage. In the experiment regarding IC， 24 Sprague-Dawley （SD） rats were randomly assigned into four groups： normal， ANIT model， low-dose Zhuyuwan， and high-dose Zhuyuwan. In the experiment regarding UC， 24 SD rats were randomly allocated into four groups： normal， TNBS model， low-dose Zhuyuwan， and high-dose Zhuyuwan. Firstly， the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators ［alanine aminotransferase （ALT）， aspartate transaminase （AST）， γ-glutamyltranspeptidase （γ-GT）， and total bile acid （TBA）］， colon damage score， colon weight index， disease activity index， and histopathological changes in rats. Secondly， the rat serum samples were analyzed by gas chromatography-mass spectrometry （GC-MS） to screen the common core pathways of the two disease models， and the expression of core genes in the pathways was determined by Real-time PCR， on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT， AST， γ-GT， and TBA levels than the normal group （P<0.01）. Compared with the ANIT model group， the low-dose Zhuyuwan group showed declined ALT and TBA levels （P<0.01） and the high-dose Zhuyuwan group showed lowered ALT， TBA， AST， and γ-GT levels （P<0.01）. The results of the experiment regarding UC showed that compared with the normal group， the TNBS model group presented increases in the colonic damage score， colon weight index， and disease activity index （P<0.01）. Compared with the TNBS model group， the low-dose Zhuyuwan group showcased declines in colon weight index （P<0.01） and disease activity index （P<0.05）， and the high-dose Zhuyuwan group showed reductions in the colon damage score， colon weight index， and disease activity index （P<0.01）. GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC， and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.

ObjectiveThe theory of homotherapy for heteropathy is one of the classical rules in traditional Chinese medicine. Taking this theory as a breakthrough point， this study employed gas chromatography-mass spectrometry （GC-MS） to elucidate the mechanism underlying the therapeutic effects of Zhuyuwan on both intrahepatic cholestasis （IC） and ulcerative colitis （UC） from the viewpoint of serum metabolic homeostasis. MethodsThe rat models of α-naphthylisothiocyanate （ANIT）-induced cholestasis and 2，4，6-trinitro-benzenesulfonic acid （TNBS）-induced UC were treated with low （0.6 g·kg^-1） and high （1.2 g·kg^-1） doses of Zhuyuwan by gavage. In the experiment regarding IC， 24 Sprague-Dawley （SD） rats were randomly assigned into four groups： normal， ANIT model， low-dose Zhuyuwan， and high-dose Zhuyuwan. In the experiment regarding UC， 24 SD rats were randomly allocated into four groups： normal， TNBS model， low-dose Zhuyuwan， and high-dose Zhuyuwan. Firstly， the two disease models and the intervention effects of Zhuyuwan on the two diseases were evaluated based on serum levels of biochemical indicators ［alanine aminotransferase （ALT）， aspartate transaminase （AST）， γ-glutamyltranspeptidase （γ-GT）， and total bile acid （TBA）］， colon damage score， colon weight index， disease activity index， and histopathological changes in rats. Secondly， the rat serum samples were analyzed by gas chromatography-mass spectrometry （GC-MS） to screen the common core pathways of the two disease models， and the expression of core genes in the pathways was determined by Real-time PCR， on the basis of which the biological mechanism of the treatment of the two disease models by Zhuyuwan was ultimately elucidated. ResultsThe results of the experiment regarding IC showed that the ANIT model group had higher ALT， AST， γ-GT， and TBA levels than the normal group （P<0.01）. Compared with the ANIT model group， the low-dose Zhuyuwan group showed declined ALT and TBA levels （P<0.01） and the high-dose Zhuyuwan group showed lowered ALT， TBA， AST， and γ-GT levels （P<0.01）. The results of the experiment regarding UC showed that compared with the normal group， the TNBS model group presented increases in the colonic damage score， colon weight index， and disease activity index （P<0.01）. Compared with the TNBS model group， the low-dose Zhuyuwan group showcased declines in colon weight index （P<0.01） and disease activity index （P<0.05）， and the high-dose Zhuyuwan group showed reductions in the colon damage score， colon weight index， and disease activity index （P<0.01）. GC-MS metabolomics analysis combined with qRT-PCR demonstrated that Zhuyuwan had a similar inverse regulatory effect on arginine metabolism disruption in the above two disease models. ConclusionZhuyuwan exhibited definite therapeutic effects on both IC and UC， and the regulation of arginine biosynthesis pathway is the core mechanism for the treatment of both diseases by Zhuyuwan.

OBJECTIVE To analyze the current status and challenges in importing rare disease drugs in China， providing references for optimizing the import process and improving relevant policies. METHODS Questionnaires and interviews were conducted with stakeholders involved in rare disease drug importation， including government departments， multinational pharmaceutical enterprises， healthcare institutions， and patient organizations. This explored the current situation and challenges encountered by each party. Expert opinions were synthesized to propose improvement suggestions. RESULTS A questionnaire survey of representatives from 25 multinational pharmaceutical companies in the rare disease field revealed that these companies had a strong willingness to import rare disease drugs， with 58.33% of them practicing diverse import models. However， significant challenges hindered this process， including unclear regulations （54.17%）， complex approval procedures （45.83%）， and excessively long approval cycles （41.67%）， negatively impacting their motivation. Meanwhile， interviews with 13 experts from government departments， healthcare institutions， pharmaceutical enterprises， and patient organizations identified deficiencies in policy design， approval processes， sampling inspection costs， and communication efficiency with regulators. Additionally， the drug import model in special medical zones also required improvement. CONCLUSIONS The importation of rare disease drugs in China faces challenges such as incomplete policies， inflexible regulatory mechanisms， and insufficient communication channels. It is recommended to enhance the rare disease definition criteria， optimize import incentive policies， and refine regulatory models， so as to further optimize the import process of rare disease drugs and improve relevant policies.

OBJECTIVES: To investigate the mechanism by which transforming growth factor‑β (TGF‑β) regulates major histocompatibility complex class I (MHC-I) expression in hepatocellular carcinoma (HCC) cells and its role in immune evasion of HCC. METHODS: HCC cells treated with TGF‑β alone or in combination with SB-431542 (a TGF-β type I receptor inhibitor) were examined for changes in MHC-I expression using RT-qPCR and Western blotting. A RNA interference experiment was used to explore the role of miR-23a-3p/IRF1 signaling in TGF‑β‑mediated regulation of MHC-I. HCC cells with different treatments were co-cultured with human peripheral blood mononuclear cells (PBMCs), and the changes in HCC cell proliferation was assessed using CCK-8 and colony formation assays. T-cell cytotoxicity in the co-culture systems was assessed with lactate dehydrogenase (LDH) release and JC-1 mitochondrial membrane potential assays, and T-cell activation was evaluated by flow cytometric analysis of CD69 cells and ELISA for TNF-α secretion. RESULTS: TGF‑β treatment significantly suppressed MHC-I expression in HCC cells and reduced T-cell activation, leading to increased tumor cell proliferation and decreased HCC cell death in the co-culture systems. Mechanistically, TGF-β upregulated miR-23a-3p, which directly targeted IRF1 to inhibit MHC-I transcription. Overexpression of miR-23a-3p phenocopied TGF‑β‑induced suppression of IRF1 and MHC-I. CONCLUSIONS We reveal a novel immune escape mechanism of HCC, in which TGF‑β attenuates T cell-mediated antitumor immunity by suppressing MHC-I expression through the miR-23a-3p/IRF1 signaling axis.
Humans ; MicroRNAs/genetics* ; Carcinoma, Hepatocellular/metabolism* ; Liver Neoplasms/metabolism* ; Interferon Regulatory Factor-1/metabolism* ; Transforming Growth Factor beta/metabolism* ; Signal Transduction ; Histocompatibility Antigens Class I/metabolism* ; Cell Line, Tumor ; Tumor Escape ; Coculture Techniques

Objective To evaluate the clinical practical value of the golden angle radial sparse parallel(GRASP)technology in the MR imaging quality of lung cancer under free-breathing state.Methods The imaging data of 30 lung cancer patients diagnosed with CT screening were collected by using a large-aperture 3.0T MR scanner.All patients underwent routine Cartesian breath-hold volume interpolation(BH-VIBE)scanning,then free-breathing dynamic contrast-enhanced magnetic resonance imaging(DCE-MRI)scanning based on GRASP technology,and another repetitive BH-VIBE scanning.The MR imaging quality was independently evaluated by two experienced thoracic radiologists including overall image quality,lesion outline,artifact grade and diagnostic confidence,mean-while,the CT images of the patient at the same time were used as a reference.The sequence information on MR images was also pro-cessed blindly.Results The GRASP sequence could effectively eliminate the interference of motion artifacts such as respiration and cardiac large vessel beats,and the image quality,lesion outline,artifact grade,and diagnostic confidence of the GRASP sequence were significantly better than the BH-VIBE(P＜0.01).The image quality of the GRASP sequence was more satisfactory with clea-rer tumor boundary and more details.Conclusion Free-breathing high-temporal-spatial resolution GRASP technology has better image quality than traditional BH-VIBE scanning,and it is a reliable method for high-resolution imaging of lung cancer.

Epilepsy is one of common diseases of nervous system,which is mainly manifested as repeat-ed abnormal neuronal discharges in the brain.If it cannot be effectively controlled,it can cause irreversible neuronal damage in the brain.Non-coding RNAs plays an important role in the development and progression process of epilepsy and are involved in regulating autophagy,apoptosis,neuroinflammation,synaptic remode-ling and other physiological and pathological processes,especially in the regulation of autophagy in epileptic neuronal cells.This article reviews the regulatory relationship between microRNA and long non-coding RNAs,circRNAs in non-coding RNAs with autophagy in the occurrence and development of epilepsy to pro-vide a direction for the precise treatment and prevention of epilepsy.

Objective To explore the correlation between changes of gray matter volume and related cognitive impairment domains in patients with cognitive impairment of cerebral small vessel disease(CSVD)based on 7.0T magnetic resonance imaging(MRI)and voxel-based morphometry(VBM).Methods All subjects were recruited from the study on Correlation between Cerebral Deep Medullary Vein Morphology and Cognitive Impairment due to Cerebral Small Vessel Disease(registration No.:ChiCTR2100045136)from September 2021 to June 2023.We retrospectively enrolled CSVD patients with cognitive impairment as CSVD group and healthy controls with matched age,gender and education level as control group according to inclusion and exclusion criteria.Montreal cognitive assessment(MoCA)scale(Beijing version)score＜26 was divided into cognitive impairment.All subjects was assessed with MoCA,digit span test(DST),digit symbol substitution test(DSST),trail making test-A(TMT-A),verbal fluency test(VFT),Boston naming test(BNT)and auditory verbal learning test(AVLT).All subjects underwent 7.0T brain MRI scan to acquire T1-weighted three-dimensional magnetization prepared 2 rapid gradient echo(T1WI-MP2RAGE)for VBM analysis.General data and above cognitive function scores were compared between 2 groups.VBM analysis was used to compare the gray matter volume(GMV)between 2 groups and get mean GMV of significant brain regions of CSVD to explore the correlation between regions and cognitive function scores.Results(1)There were 18 individuals in control group,aged 55-70 years,and 19 individuals in CSVD group,aged 57-75 years.There was no significant difference in age,gender,education,body mass index,history of coronary heart disease,history of hyperlipidemia,smoking,drinking,total cholesterol,triglyceride,low density lipoprotein and high density lipoprotein between the two groups(all P＞0.05).But the proportion of hypertension and diabetes history in the CSVD group was higher than control group,and there were significant differences between the two groups(12/19 vs.5/18,7/19 vs.0;all P＜0.05).(2)The scores of MoCA scale(22.0[20.0,23.0]vs.27.0[26.0,28.0],Z=-5.242),DSST(18±9 vs.40±4,t=5.212),DST(10.6±2.5 vs.13.9±2.0,t=4.364),VFT(38±11 vs.47±8,t=3.224),AVLT-immediate memory(13±3 vs.21±4,t=6.877),AVLT-short delay recall(3.4±2.5 vs.6.9±2.2,t=4.555)and BNT(22.7±3.6 vs.27.0±2.1,t=4.357)in CSVD group were lower than those in the control group.The time taken to complete TMT-A in CSVD group was longer than the control group(93.00[76.04,125.69]s vs.29.77[25.75,40.97]s,Z=-4.832).The difference of the above between two group was statistically significant(all P＜0.01).(3)Brain parenchymal fraction in CSVD group was lower than control group,and there was significant difference between two group([78.2±4.3]％vs.[80.9±3.7]％,t=2.079,P＜0.05).VBM analysis showed that gray matter volume of right inferior temporal gyrus(rITG)and right Crus 2 of cerebellar hemisphere(rCERCRU2)in CSVD group was significantly lower than control group(both P＜0.05 and corrected by false discovery rate).(4)Partial correlation analysis showed a positive correlation between gray matter volume in rITG and AVLT-short delay recall score(r=0.543,P=0.036).Conclusions CSVD patients with cognitive impairment had gray matter atrophy in rITG and rCERCRU2 and the gray matter volume in rITG was correlated with delayed memory impairment.The results of this study need to be further verified.

Objective To explore the correlation between childhood trauma and plasma adiponectin levels in patients with depression.Methods A total of 121 patients with depression and 39 healthy controls(control group)were enrolled.Childhood trauma questionnaire(CTQ-SF)was used to assess the experience of childhood abuse and neglect,and the patients with depression were divided into trauma group(n=53)and non-trauma group(n=68)according to the CTQ-SF score.The 17-item Hamilton depression scale-17(HAMD17)and the Hamilton anxiety scale(HAMA)were used to evaluate the severity of depression and anxiety symptoms,respectively.Plasma adiponectin levels of subjects were measured by enzyme-linked immunosorbent assay.Results The plasma adiponectin level of trauma group[3.82(2.44,4.92)μg/mL]was significantly lower than that of non-trauma group[4.64(2.98,6.43)μg/mL,P=0.01]and the control group[6.29(4.54,7.51)μg/mL,P＜0.01].The plasma adiponectin level of non-trauma group was lower than that of the control group(P＜0.01).Correlation analysis showed that plasma adiponectin level in patients with depression was negatively correlated with childhood trauma(r=-0.34,P＜0.01).Multivariate linear regression analysis showed that plasma adiponectin level was negatively correlated with childhood trauma scores in patients with depression(β=-0.05,P＜0.01).Conclusions Patients with depression who have experienced childhood trauma have lower plasma levels of adiponectin,and childhood trauma may be associated with decreased plasma adiponectin levels in patients with depression.

Objective To explore whether indoor light-assisted therapy can rapidly improve depression and anxiety symptoms in patients with depression,as well as the safety of indoor-light-assisted therapy.Methods From September 2021 to December 2022,patients with depression were recruited from the Mental Health Center of the First Hospital of Hebei Medical University.According to the random number table method,patients were divided into test group and control group.The test group was treated with light therapy 30 minutes from 7:30 am to 8:00 am daily for 2 weeks in addition to antidepressant therapy.Antidepressant therapy was continued after completion of light therapy and patients were followed up for 2 weeks.The control group was treated with regular antidepressants throughout the four-week trial.Hamilton depression scale(HAMD17)and the Hamilton anxiety scale(HAMA)were used to assess the clinical symptoms at the baseline and the end of every week of treatment.Safety was evaluated using patient adverse events,anterior segment photography and visual testing.Results A total of 80 patients were enrolled,including 40 in the test group and 40 in the control group.The data of dropped were processed for missing values and then included in the statistical analysis.At the 1st(20.0％vs.0.0％)and 2nd(45.0％vs.17.5％)weekend of treatment,the response rate in the test group was significantly higher than that in the control group.There was an interaction between the time point and the group in HAMD17 total score(F=9.66,P<0.01).The scores of HAMD17 at the end of every week in the test group were significantly lower than that in the control group(P<0.05).There were significant differences in the reduction rate of total score in HAMD17[33.3％(25.0％,43.3％)vs.13.9％(9.9％,19.8％)]and HAMA[22.4％(16.5％,35.3％)vs.14.2％(4.4％,26.9％)]between the two groups(P<0.05).Incidences of adverse effect were not significantly different between the two groups(12.5％vs.10.0％,P=1.00).There were no severe adverse events or mania was reported in the test group and the eye examination showed no abnormality.Conclusion Compared with antidepressant therapy alone,indoor light therapy combined with antidepressant can quickly improve depression and anxiety symptoms in patients with depression,shorten the duration of depression treatment,and has good safety.

OBJECTIVE: To explore the clinical feature and genetic variant of a child with autosomal recessive Charlevoix-Saguenay type spastic ataxia (ARSACS). METHODS: Clinical data of a child who was admitted to the West China Second Hospital of Sichuan University on April 30, 2021 was collected. Whole exome sequencing (WES) was carried out for the child and his parents. Candidate variants were verified by Sanger sequencing and bioinformatic analysis based on the guidelines from the American College of Medical Genetics and Genomics (ACMG). RESULTS: The child, a 3-year-and-3-month-old female, had a complain of "walking instability for over a year". Physical and laboratory examination revealed progressive and aggravated gait instability, increased muscle tone of the right limbs, peripheral neuropathy of the lower limbs, and thickening of retinal nerve fiber layer. The results of WES revealed that she has harbored a maternally derived heterozygous deletion of exons 1 to 10 of the SACS gene, in addition with a de novo heterozygous c.3328dupA variant in exon 10 of the SACS gene. Based on the ACMG guidelines, the exons 1-10 deletion was rated as likely pathogenic (PVS1+PM2_Supporting), and the c.3328dupA was rated as a pathogenic variant (PVS1_Strong+PS2+PM2_Supporting). Neither variant was recorded in the human population databases. CONCLUSION The c.3328dupA variant and the deletion of exons 1-10 of the SACS gene probably underlay the ARSACS in this patient.
Female ; Humans ; Heat-Shock Proteins/genetics* ; Muscle Spasticity/genetics* ; Mutation ; Spinocerebellar Ataxias/pathology* ; Child, Preschool