Background/Aims: Dysregulated cholesterol metabolism is a hallmark of hepatocellular carcinoma (HCC) that drives tumor initiation and progression. However, clinical targeting of cholesterol metabolism has yielded limited benefits due to stringent feedback in tumor cells. Identifying a central mediator capable of restoring cholesterol homeostasis within the cell’s intrinsically fine-tuned regulatory framework is urgently needed. Methods: We integrated a proteomic dataset from patients with cholesterol-dysregulated HCC into a global cholesterol metabolic regulatory network to identify potential therapeutic targets for disrupted cholesterol homeostasis. The prognostic significance of the candidate targets was further validated in an independent cohort through immunohistochemistry. Functional and mechanistic studies were conducted in vitro using HCC cell lines and in vivo using mouse models. The pharmacological efficacy of the candidate agent was evaluated in both subcutaneous and orthotopic HCC mouse models. Results: ER lipid raft-associated 1 (ERLIN1), a pivotal regulator of cholesterol metabolism reprogramming, was identified as an independent favorable prognostic indicator in HCC. ERLIN1 constrains HCC progression both in vitro and in vivo by stabilizing the INSIG1–SCAP–SREBP2 axis and maintaining the metabolic balance of intracellular cholesterol. Under hypoxia, impaired factor-inhibiting hypoxia-1-dependent hydroxylation of ASB11 at asparagine residues 90 and 92 enhances ASB11-mediated ERLIN1 degradation. Pharmacological targeting of this axis using zoledronic acid (ZoA) attenuated HCC progression by weakening the ASB11–ERLIN1 interaction and restoring cholesterol homeostasis. Conclusions ERLIN1 represents a druggable metabolic vulnerability in cholesterol-dysregulated HCC. Targeting the ASB11–ERLIN1 axis with the clinically approved ZoA reestablishes cholesterol homeostasis and offers a promising therapeutic strategy to overcome the current limitations of cholesterol-targeted HCC therapies.

Objective To explore the function of electroacupuncture(EA)on body mass,fasting blood glucose,heat pain threshold,and transient receptor potential vanilloid 4(TRPV4)in the dorsal root ganglia(DRG)of rats with diabetic neuropathic pain(DNP).Methods A DNP rat model was formed by intraperitoneally injecting the animals with STZ.From days 15 to 21,bilateral Zusanli and Kunlun points of the DNP rat model were treated with electroacupuncture once daily for 30 min.We then measured their body mass,fasting blood glucose,and heat pain threshold.The co-expression of TRPV4 and NeuN in the rat L4～L6 DRG was detected by immunofluorescence.The effects of the TRPV4 agonist GSK1016790A on body mass,fasting blood glucose,and the heat pain threshold of DNP rats treated with electroacupuncture were detected.Results After the 7th day,body mass was significantly decreased(P<0.01)and fasting glucose was significantly increased(P<0.01)in the model group compared with the normal group.After the 21st day,compared with the model group,heat pain threshold of the model+electroacupuncture group was significantly higher(P<0.01);the results of co-expression of TRPV4 and NeuN immunofluorescence on rat L4～L6 DRG showed that:the expression of positive cells in the model group was significantly higher(P<0.01)than that in the normal group,the co-expression of TRPV4 and NeuN positive cells in L4～L6 DRG of rats in the model+electroacupuncture group was significantly lower(P<0.01)than that in the model group.The TRPV4 agonist GSK1016790A can reverse the downregulation of thermal pain threshold induced by electroacupuncture in DNP rats(P<0.01).Conclusion Electroacupuncture alleviated the DNP induced by STZ,and its mechanism may involve the inhibition of TRPV4 protein expression in the DRG.

Objective To explore the function of electroacupuncture(EA)on body mass,fasting blood glucose,heat pain threshold,and transient receptor potential vanilloid 4(TRPV4)in the dorsal root ganglia(DRG)of rats with diabetic neuropathic pain(DNP).Methods A DNP rat model was formed by intraperitoneally injecting the animals with STZ.From days 15 to 21,bilateral Zusanli and Kunlun points of the DNP rat model were treated with electroacupuncture once daily for 30 min.We then measured their body mass,fasting blood glucose,and heat pain threshold.The co-expression of TRPV4 and NeuN in the rat L4～L6 DRG was detected by immunofluorescence.The effects of the TRPV4 agonist GSK1016790A on body mass,fasting blood glucose,and the heat pain threshold of DNP rats treated with electroacupuncture were detected.Results After the 7th day,body mass was significantly decreased(P<0.01)and fasting glucose was significantly increased(P<0.01)in the model group compared with the normal group.After the 21st day,compared with the model group,heat pain threshold of the model+electroacupuncture group was significantly higher(P<0.01);the results of co-expression of TRPV4 and NeuN immunofluorescence on rat L4～L6 DRG showed that:the expression of positive cells in the model group was significantly higher(P<0.01)than that in the normal group,the co-expression of TRPV4 and NeuN positive cells in L4～L6 DRG of rats in the model+electroacupuncture group was significantly lower(P<0.01)than that in the model group.The TRPV4 agonist GSK1016790A can reverse the downregulation of thermal pain threshold induced by electroacupuncture in DNP rats(P<0.01).Conclusion Electroacupuncture alleviated the DNP induced by STZ,and its mechanism may involve the inhibition of TRPV4 protein expression in the DRG.

Objective:To observe the clinical efficacy of acupuncture combined with cognitive training in treating mild-to-moderate poststroke cognitive impairment and the impact on cognitive function and cerebral blood flow.Methods:Eighty-eight participants with mild-to-moderate cognitive impairment after a stroke were allocated to an observation group and a control group using the random number table method,each consisting of 44 cases.The two groups received the same conventional symptomatic treatment.In addition,the control group was intervened by cognitive training,and the observation group by cognitive training and Tong Du Xing Shen(unblocking the Governor Vessel and awakening the mind)acupuncture.The intervention lasted 4 weeks in both groups.By the end of the intervention,the two groups were observed for clinical efficacy and the improvements in the symptom score of traditional Chinese medicine(TCM),cognitive function[mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA)],cerebral blood flow velocities[cerebral vascular resistance index(RI),arterial blood flow mean velocity(Vm),and arterial systolic velocity(Vs)],and serum biomarkers of neurological deficit[neuron-specific enolase(NSE)and S100 β protein(S100β)].Results:During the observation,each group had 2 eliminated cases.After the intervention,the observation group achieved a total effective rate of 90.5%,higher than that in the control group,which was 73.8%(P<0.05);increases were found in the MMSE and MoCA scores in both groups(P<0.05),and the observation group was higher than the control group(P<0.05);in contrast,decreases were found in the levels of RI and serum NSE and S100β(P<0.05),and the observation group was lower than the control group(P<0.05);the Vs and Vm levels increased in both groups(P<0.05)and were higher in the observation group than in the control group(P<0.05).Conclusion:Tong Du Xing Shen acupuncture plus cognitive training is effective in treating mild-to-moderate poststroke cognitive impairment and can enhance the patient's cognitive function;improving cerebral blood circulation and reducing cerebral nerve damage may be involved in the mechanism.

Objective:To observe the clinical efficacy of acupuncture combined with cognitive training in treating mild-to-moderate poststroke cognitive impairment and the impact on cognitive function and cerebral blood flow.Methods:Eighty-eight participants with mild-to-moderate cognitive impairment after a stroke were allocated to an observation group and a control group using the random number table method,each consisting of 44 cases.The two groups received the same conventional symptomatic treatment.In addition,the control group was intervened by cognitive training,and the observation group by cognitive training and Tong Du Xing Shen(unblocking the Governor Vessel and awakening the mind)acupuncture.The intervention lasted 4 weeks in both groups.By the end of the intervention,the two groups were observed for clinical efficacy and the improvements in the symptom score of traditional Chinese medicine(TCM),cognitive function[mini-mental state examination(MMSE)and Montreal cognitive assessment(MoCA)],cerebral blood flow velocities[cerebral vascular resistance index(RI),arterial blood flow mean velocity(Vm),and arterial systolic velocity(Vs)],and serum biomarkers of neurological deficit[neuron-specific enolase(NSE)and S100 β protein(S100β)].Results:During the observation,each group had 2 eliminated cases.After the intervention,the observation group achieved a total effective rate of 90.5%,higher than that in the control group,which was 73.8%(P<0.05);increases were found in the MMSE and MoCA scores in both groups(P<0.05),and the observation group was higher than the control group(P<0.05);in contrast,decreases were found in the levels of RI and serum NSE and S100β(P<0.05),and the observation group was lower than the control group(P<0.05);the Vs and Vm levels increased in both groups(P<0.05)and were higher in the observation group than in the control group(P<0.05).Conclusion:Tong Du Xing Shen acupuncture plus cognitive training is effective in treating mild-to-moderate poststroke cognitive impairment and can enhance the patient's cognitive function;improving cerebral blood circulation and reducing cerebral nerve damage may be involved in the mechanism.

It is believed that qi and blood disharmony is the key pathogenesis of essential hypertension， for which mildly regulating qi and blood is recommended. According to the different pathological states and related causes of qi and blood disorders， essential hypertension can be divided into five syndrome types for differentiation and treatment. In terms of blood deficiency and liver constraint， it is recommended to nourish the blood and soften the liver， rectify qi to resolve constraint， using Xiao Yao Powder （逍遥散） or self-made Qihua Jieyu Decoction （七花解郁汤）. For qi stagnation and blood stasis， the method of regulating qi and harmonizing blood， dissolving stasis and unblocking collaterals should be used， with self-made Guitao Tongluo Decoction （桂桃通络汤）. For phlegm-dampness internal obstruction， it is recommended to move qi and promote urination， dissolve phlegm and eliminate dampness， using self-made Zhuanqi Sanzhuo Formula （转气散浊方）. For binding of phlegm and stasis， dissolving phlegm and dispelling stasis， dredging the bowels and directing the turbid downward is advised， and self-made Sanren Tiaozhi Formula （三仁调脂方） can be used. In terms of deficiency of both qi and blood， it is recommended to boost qi and nourish blood， supplement deficiency and consolidate the root， using Gui Pi Decoction （归脾汤） or self-made Shenqi Zaizao Decoction （参芪再造汤）.

[Objective]Childhood trauma(CT)is considered one of the major risk factors for developing major depres-sive disorder(MDD)in adulthood.However,the neural basis of MDD patients with CT(CT-MDD)remains poorly under-stood.Therefore,the objective of our study is to explore the resting-state global brain functional connectivity(FC)in CT-MDD.[Methods]A total of 34 CT-MDD and 34 healthy controls performed resting-state fMRI.Whole-brain voxel-level degree centrality(DC)analysis was performed,and the brain regions with significant differences between the two groups were selected as region of interest(ROI)for further estimating the global brain FC.Subsequently,correlation analysis was performed between DC values,FC values in abnormal brain areas and clinical characteristics.[Results]The CT-MDD group showed increased DC value of the right middle frontal gyrus(MFG)compared with the healthy controls.Seed-based FC revealed that the CT-MDD group showed increased connections between the left precuneus and the right MFG or the right medial prefrontal cortex,relative to healthy controls(threshold at P<0.05).Additionally,the DC value of the right MFG was correlated with the severity of CT.[Conclusion]Our results show the increased FC between the left precuneus and the ROI(right MFG)as well as the right medial prefrontal cortex,which are two important brain regions within the de-fault mode network(DMN),and might suggest increased synchronism between the cognitive executive networks and DMN in CT-MDD.These findings may provide insights into the pathophysiological mechanisms underlying CT-MDD.

ObjectiveTo obtain high-quality chloroplast genome information on Stemona tuberosa and clarify its structure， sequence features， and phylogenetic status. MethodThe Illumina NovaSeq 6000 and PacBio RS Ⅱ platforms were used for library construction and sequencing of S. tuberosa， respectively. The data from both sequencing platforms were combined and subjected to bioinformatics analysis for genome assembly and base correction， resulting in a high-quality chloroplast genome. Subsequently， sequence features， repetitive sequences， gene diversity， and phylogeny were analyzed. ResultThe chloroplast genome size of S. tuberosa was determined to be 154 379 bp. The structure of the chloroplast genome followed the typical quadripartite circular form， consisting of a pair of inverted repeat regions （IRs） with a length of 27 074 bp， a small single-copy region （SSC） of 17 924 bp， and a large single-copy region （LSC） of 82 307 bp. The average GC content was 37.86%. A total of 121 genes were annotated， including 30 tRNA genes， four rRNA genes， and 87 protein-coding genes. Among them， six tRNA genes and 12 protein-coding genes contained introns. In the chloroplast genome of S. tuberosa， 49 long repetitive sequences and 59 single-nucleotide simple sequence repeats （SSRs） were identified. Comparative analysis of chloroplast genomes among four Stemona species revealed high diversity in the ycf1 and ndhF genes. The phylogenetic tree constructed based on the chloroplast genome showed consistent classification with the current taxonomic status of S. tuberosa. ConclusionThe high-quality chloroplast genome of S. tuberosa was successfully assembled， providing valuable information on the structure and sequence features of chloroplast genomes in four Stemona species， including S. tuberosa. These findings lay a foundation for the identification， evolution， and phylogenetic studies of medicinal plants in the genus Stemona.

Objective:To observe any effect of electroacupuncture (EA) on the expression of phosphorylated extracellular signal-regulated protein kinase (p-ERK1/2) and phosphorylated cyclic adenosine monophosphate response element binding protein (p-CREB) in the spinal dorsal horns of diabetics experiencing neuropathic pain.Methods:Eight rats were randomly selected from 30 healthy male Sprague-Dawley rats as the normal group (N), and the remaining twenty-two rats were treated with a single high-dose intraperitoneal injection of streptozotocin (STZ) to establish a neuropathic pain model. The rats modeled successfully were randomly divided into a model group (M, n=8) and an EA group ( n=8). In the EA group, electroacupuncture was applied at the bilateral Hou san li and Kunlun acupoints starting on the 15th day after the STZ injection. The daily sessions lasted 30 minutes for 1 week. Body weight (BW), fasting blood glucose (FBG) and paw withdrawal latency (PWL) were observed before the STZ injection and on the 7th, 14th, and 21st days afterward. The expression of p-ERK1/2 and p-CREB in the dorsal horns of the rats′ spinal cords was detected using western blotting. The count of p-CREB-positive cells in the dorsal horns and their co-localization with neurons was detected using immunofluorescence. Results:In comparison with the N group, the average BW of the M group on the 7th, 14th and 21st days after the STZ injection was significantly lower, while the average FBG was significantly higher. There was no significant difference between the M and N groups in the average PWL on the 7th day after the STZ injection, but it had decreased significantly in the M group on the 14th and 21st days. Compared with the M group, the average PWL of the EA group was significantly longer on the 21st day after the injection. The expression of p-ERK1/2 and p-CREB protein in the spines of the M group was significantly higher than in the N group. p-CREB positive cells were more numerous in the M group compared with the N group, while in the EA group they were fewer. P-CREB was co-located with neurons in the spinal dorsal horn.Conclusion:EA can alleviate neuropathic pain effectively, perhaps by inhibiting the expression of p-ERK1/2 and p-CREB in the dorsal horns of the spinal cord.

Objective:To analyze the changes in self-efficacy and its influencing factors in type 2 diabetic patients after community-based self-management group intervention.Methods:From August to November 2014, a 3-month community-based self-management intervention study of type 2 diabetes patients was implemented in Fangshan District, Beijing. 510 patients were recruited through posters, household inquiries and telephone notification and then were randomly divided into intervention group (260 patients) and control group (250 patients). Finally, 500 patients completed the study, including 259 in the intervention group and 241 in the control group. Self-efficacy score was measured through face-to-face interview at different time points, including pre-intervention, post-intervention, 2 years after the intervention and 5 years after the intervention, respectively. A two-level random coefficient model was fitted to analyze the long-term trend of self-efficacy and its relationship with group intervention.Results:Individual-level educational attainment, disease duration as well as their treatment plans had a positive correlation with self-efficacy of type 2 diabetic patients while gender and age did not affect their self-efficacy. Patients with junior middle school education, senior high school education and university and above education had 4.66 ( P<0.05), 6.40 ( P<0.05) and 11.02 ( P<0.05) points higher than those with primary education, respectively. The self-efficacy of diabetic patients increased by 0.23 ( P<0.05) for each additional course year. The effect of treatment plan on self-efficacy was mainly reflected in the self-efficacy of taking medication or insulin injection as prescribed and blood glucose monitoring. After controlling for the confounding factors, i.e., gender, age, disease duration, educational attainment, and treatment plan, self-efficacy scores at the post-intervention increased in both groups compared to those at the pre-intervention. The intervention group had 7.95 points higher than the control group ( P<0.05). After the intervention, the self-efficacy scores of both groups decreased year by year while the intervention group declined faster, with 5.41 points ( P<0.05) at 2 years after the intervention and 8.94 points ( P<0.05) at 5 years after the intervention. Conclusion:Community-based self-management group intervention could improve the self-efficacy of type 2 diabetic patients while the self-efficacy decreases year by year in the absence of follow-up intervention.