[摘 要] 目的：探讨胰岛素样生长因子2 mRNA结合蛋白3（IGF2BP3）、尿苷二磷酸-葡萄糖醛酸脱羧酶1（UXS1）在肝细胞癌（HCC）中的表达特征、预后价值及两者协同作用的分子机制。方法：整合UALCAN、cBioPortal、ENCORI、TISCH2、GDSC等公共数据库的转录组数据，对IGF2BP3和UXS1进行表达、预后评估、功能富集及药物敏感性等分析。收集GEO数据库的单细胞RNA测序（scRNA-seq）数据，分析细胞通信、单细胞代谢评分，系统解析IGF2BP3-UXS1轴在HCC中的具体作用。结果：IGF2BP3、UXS1在HCC组织中均显著高表达，且高表达患者总生存期显著缩短（均P < 0.05）。采用CRISPP技术敲除IGF2BP3或UXS1后，多种HCC细胞的增殖能力受到明显抑制。scRNA-seq分析揭示了IGF2BP3、UXS1在肝细胞等细胞类型中的广泛表达分布，前者在细胞分化晚期上调，后者则在细胞分化早、中期高表达。IGF2BP3、UXS1高表达组均显著激活了MIF通路，同时IGF2BP3的高表达削弱了成纤维细胞的相互作用，而UXS1的高表达则增强了T细胞的信号转导功能。IGF2BP3与UXS1在表达相关性中存在显著的正相关（r = 0.432，P < 0.05）。沉默IGF2BP3结合位点会导致UXS1表达水平变化（F = 0.333）。功能富集分析提示，IGF2BP3与UXS1协同调控能量代谢、蛋白质翻译等生物学过程。在IGF2BP3或UXS1高表达的细胞亚群中，发现两者与多个糖代谢相关通路存在显著关联。IGF2BP3、UXS1高表达的患者对优普色替等药物表现出显著的敏感性，还对药物那维托克等表现出显著的耐药性。结论： IGF2BP3、UXS1在HCC中高表达，两者通过调控糖代谢重编程的协同作用促进HCC恶性生物学行为。

The prescription of Qidong Yixin oral liquid is derived from the experience of national medical master Ren Jixue in treating viral myocarditis （VMC）. It has the functions of tonifying Qi， nourishing the heart，calming the mind， and relieving palpitations. It is used to treat VMC and angina pectoris of coronary heart disease caused by deficiency of both Qi and Yin. However，the understanding of its efficacy evidence， advantageous aspects， dosage and administration， and medication safety remains insufficient in clinical practice. Therefore，the development of the Expert Consensus on the Clinical Application of Qidong Yixin Oral Liquid （hereinafter referred to as consensus） was initiated. Consensus strictly followed the process and methods of the expert consensus on the clinical application of Chinese patent medicines of the China Association of Chinese Medicine，successively completing multiple tasks such as the consensus project initiation，determination of clinical problems，evidence search and evaluation，formation of recommendation opinions and consensus suggestions，solicitation of opinions，peer review， submission for review and release， and so on. Consensus formed a total of 10 recommendation opinions and 12 consensus suggestions，clarifying the clinical positioning，efficacy advantages，syndrome differentiation，dosage and administration，combination therapy，timing of medication，adverse reactions，contraindications， and precautions of Qidong Yixin oral liquid，indicating that it has good clinical advantages and safety in the treatment of VMC and angina pectoris of coronary heart disease，providing norms and references for physicians to safely and rationally apply Qidong Yixin oral liquid. Consensus was reviewed and approved for release by the Standardization Office of the China Association of Chinese Medicine on December 23， 2024. Standard number：GSCACM-376-2024.

BACKGROUND:In previous studies,glass materials were infiltrated into 5Y-PSZ ultra-translucent zirconia by a double sintering method to prepare 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia materials that can maintain high transparency and high flexural strength.OBJECTIVE:To evaluate the in vitro biocompatibility of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia materials.METHODS:(1)Glass materials were infiltrated into 5Y-PSZ ultra-translucent zirconia by double sintering to prepare 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia.5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia(or 5Y-PSZ ultra-translucent zirconia,3Y-TZP transparent zirconia)was placed in DMEM culture medium containing 10％fetal bovine serum for 12,24 and 72 hours,and the surface area ratio of culture medium to sample was 3 mL/cm2,and the 12-,24-and 72-hour material extracts were obtained.(2)After culturing mouse fibroblast L929 for 24 hours,the original culture medium was discarded and divided into 7 groups for culture:the control group was replaced with DMEM culture medium containing 10％fetal bovine serum by volume,and the other 6 groups were replaced with 24-hour extract of 3Y-TZP transparent zirconia,24-hour extract of 5Y-PSZ ultra-translucent zirconia,24-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,72-hour extract of 3Y-TZP transparent zirconia,72-hour extract of 5Y-PSZ ultra-translucent zirconia,and 72-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia.After 1,3,and 5 days of culture,cell growth was observed under a microscope,and the cell proliferation rate was obtained by CCK-8 assay to determine cytotoxicity.(3)Human anticoagulated blood was mixed with 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,5Y-PSZ ultra-translucent zirconia,and 3Y-TZP transparent zirconia,and the hemolysis rate was detected after 0.5 hours.Human anticoagulated blood was mixed with 12-hour extract of 3Y-TZP transparent zirconia,12-hour extract of 5Y-PSZ ultra-translucent zirconia,and 12-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,and the hemolysis rate was detected after 0.5 hours.RESULTS AND CONCLUSION:(1)Under the microscope,it could be seen that the number of cells in each group increased with the extension of culture time,and the cell morphology of each experimental group was basically the same as that of the control group.The cytotoxicity grade of the 24-hour extract of 3Y-TZP transparent zirconia group on the first day of culture was grade 0,and the cytotoxicity grade of the other experimental groups at each time period was grade 1.(2)Neither the material nor the material extract caused obvious hemolytic reaction,and the hemolytic rate was less than 5％.(3)The results showed that 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia had no significant effect on the growth and proliferation of mouse fibroblasts L929,and did not cause hemolytic reaction with human blood,and had good in vitro biocompatibility.

BACKGROUND:In previous studies,glass materials were infiltrated into 5Y-PSZ ultra-translucent zirconia by a double sintering method to prepare 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia materials that can maintain high transparency and high flexural strength.OBJECTIVE:To evaluate the in vitro biocompatibility of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia materials.METHODS:(1)Glass materials were infiltrated into 5Y-PSZ ultra-translucent zirconia by double sintering to prepare 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia.5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia(or 5Y-PSZ ultra-translucent zirconia,3Y-TZP transparent zirconia)was placed in DMEM culture medium containing 10％fetal bovine serum for 12,24 and 72 hours,and the surface area ratio of culture medium to sample was 3 mL/cm2,and the 12-,24-and 72-hour material extracts were obtained.(2)After culturing mouse fibroblast L929 for 24 hours,the original culture medium was discarded and divided into 7 groups for culture:the control group was replaced with DMEM culture medium containing 10％fetal bovine serum by volume,and the other 6 groups were replaced with 24-hour extract of 3Y-TZP transparent zirconia,24-hour extract of 5Y-PSZ ultra-translucent zirconia,24-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,72-hour extract of 3Y-TZP transparent zirconia,72-hour extract of 5Y-PSZ ultra-translucent zirconia,and 72-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia.After 1,3,and 5 days of culture,cell growth was observed under a microscope,and the cell proliferation rate was obtained by CCK-8 assay to determine cytotoxicity.(3)Human anticoagulated blood was mixed with 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,5Y-PSZ ultra-translucent zirconia,and 3Y-TZP transparent zirconia,and the hemolysis rate was detected after 0.5 hours.Human anticoagulated blood was mixed with 12-hour extract of 3Y-TZP transparent zirconia,12-hour extract of 5Y-PSZ ultra-translucent zirconia,and 12-hour extract of 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia,and the hemolysis rate was detected after 0.5 hours.RESULTS AND CONCLUSION:(1)Under the microscope,it could be seen that the number of cells in each group increased with the extension of culture time,and the cell morphology of each experimental group was basically the same as that of the control group.The cytotoxicity grade of the 24-hour extract of 3Y-TZP transparent zirconia group on the first day of culture was grade 0,and the cytotoxicity grade of the other experimental groups at each time period was grade 1.(2)Neither the material nor the material extract caused obvious hemolytic reaction,and the hemolytic rate was less than 5％.(3)The results showed that 5Y-PSZ-YGI graded glass infiltrated ultra-translucent zirconia had no significant effect on the growth and proliferation of mouse fibroblasts L929,and did not cause hemolytic reaction with human blood,and had good in vitro biocompatibility.

Flowering and bolting are important agronomic traits in cruciferous crops such as Brassica juncea. Timely flowering can ensure the crop organ yield and quality, as well as seed propagation. The WRKY family plays an important role in regulating plant bolting and flowering, while the function and mechanism of WRKY12 in B. juncea remain unknown. To explore its function and mechanism in bolting and flowering of B. juncea, we cloned and characterized the BjuWRKY12 gene in B. juncea and found that its expression levels were significantly higher in flowers and inflorescences than in leaves. BjuWRKY12 belonged to the Ⅱc subfamily of the WRKY family, and subcellular localization indicated that the protein was located in the nucleus. Ectopic overexpression of BjuWRKY12 in transgenic lines promoted bolting and flowering, leading to significant increases in the expression levels of flowering integrators SOC1 and FUL. Furthermore, yeast one-hybrid and dual luciferase reporter system assays confirmed that BjuWRKY12 directly bound to the promoters of BjuSOC1 and BjuFUL, undergoing protein-DNA interactions. This discovery gives new insights into the regulation network and molecular mechanisms of BjuWRKY12, laying a theoretical foundation for the breeding of high-yield and high-quality varieties of B. juncea.
Mustard Plant/metabolism* ; Flowers/growth & development* ; Plant Proteins/physiology* ; Promoter Regions, Genetic/genetics* ; Gene Expression Regulation, Plant ; Plants, Genetically Modified/genetics* ; Transcription Factors/metabolism* ; MADS Domain Proteins/metabolism*

Xiaoji Yinzi is one of the classic prescriptions for treating urinary diseases， originated from the Yan's Prescriptions to Aid the Living （Yan Shi Ji Sheng Fang） written by YAN Yonghe in the Song dynasty. Xiaoji Yinzi is composed of Rehmanniae Radix， Cirsii Herba， Talcum， Akebiae Caulis， Typhae Pollen， Nelumbinis Rhizomatis Nodus， Lophatheri Herba， Angelicae Sinensis Radix， Gardeniae Fructus， and Glycyrrhizae Radix et Rhizoma and has the effects of cooling blood and stopping bleeding， draining water and relieving stranguria. The medical experts of later generations have inherited the original prescription recorded in the Yan's Prescriptions to Aid the Living， while dispute has emerged during the inheritance of this prescription. In this study， the method of bibliometrics was employed to review and analyze the ancient documents and modern clinical studies involving Xiaoji Yinzi. The results showed that Xiaoji Yinzi has two dosage forms： powder and decoction. According to the measurement system in the Song Dynasty， the modern doses of hers in Xiaoji Yinzi were transformed. In the prepration of Xiaoji Yinzi powder， 149.2 g of Rehmanniae Radix and 20.65 g each of Cirsii Herba， Talcum， Akebiae Caulis， stir-fried Typhae Pollen， Nelumbinis Rhizomatis Nodus， Lophatheri Herba， wine-processed Angelicae Sinensis Radix， stir-fried Gardeniae Fructus， and stir-fried Glycyrrhizae Radix et Rhizoma are grounded into fine powder with the particle size of 4-10 meshes and a decocted with 450 mL water to reach a volume of 240 mL. After removal of the residue， the decoction was taken warm before meals， 3 times a day （i.e.， 7.77 g Rehmanniae Radix and 0.97 g each of the other herbs each time）. In the preparation of Xiaoji Yinzi decoction， 20.65 g each of the above 10 herbs are used， with stir-fried Typhae Pollen， wine-processed Angelica Sinensis Radix， stir-fired Gardeniae Fructus， stir-fired Glycyrrhizae Radix et Rhizoma， and raw materials of other herbs. Xiaoji Yinzi is specialized in treating hematuresis and blood stranguria due to heat accumulation in lower energizer， which causes injury of the blood collaterals of gallbladder and dysfunction of Qi transformation. In modern clinical practice， Xiaoji Yinzi is specifically used for treating urinary diseases and can be expanded to treat diseases of the cardiovascular system and other systems according to pathogenesis. The comprehensive research on the key information could provide a scientific reference for the future development of Xiaoji Yinzi.

Serine protease inhibitor Kazal-type (SPINK) is a skin keratinizing protease inhibitor, which was initially found in animal serum and is widely present in plants, animals, bacteria, and viruses, and they act as key regulators of skin keratinizing proteases and are involved in the regulation of keratinocyte proliferation and inflammation, primarily through the inhibition of deregulated tissue kinin-releasing enzymes (KLKs) in skin response. This process plays a crucial role in alleviating various skin problems caused by hyperkeratinization and inflammation, and can greatly improve the overall condition of the skin. Specifically, the different members of the SPINK family, such as SPINK5, SPINK6, SPINK7, and SPINK9, each have unique biological functions and mechanisms of action. The existence of these members demonstrates the diversity and complexity of skin health and disease. First, SPINK5 mutations are closely associated with the development of various skin diseases, such as Netherton’s syndrome and atopic dermatitis, and SPINK5 is able to inhibit the activation of the STAT3 signaling pathway, thereby effectively preventing the metastasis of melanoma cells, which is important in preventing the invasion and migration of malignant tumors. Secondly, SPINK6 is mainly distributed in the epidermis and contains lysine and glutamate residues, which can act as a substrate for epidermal transglutaminase to maintain the normal structure and function of the skin. In addition, SPINK6 can activate the intracellular ERK1/2 and AKT signaling pathways through the activation of epidermal growth factor receptor and protease receptor-2 (EphA2), which can promote the migration of melanoma cells, and SPINK6 further deepens its role in stimulating the migration of malignant tumor cells by inhibiting the activation of STAT3 signaling pathway. This process further deepens its potential impact in stimulating tumor invasive migration. Furthermore, SPINK7 plays a role in the pathology of some inflammatory skin diseases, and is likely to be an important factor contributing to the exacerbation of skin diseases by promoting aberrant proliferation of keratinocytes and local inflammatory responses. Finally, SPINK9 can induce cell migration and promote skin wound healing by activating purinergic receptor 2 (P2R) to induce phosphorylation of epidermal growth factor and further activating the downstream ERK1/2 signaling pathway. In addition, SPINK9 also plays an antimicrobial role, preventing the interference of some pathogenic microorganisms. Taken as a whole, some members of the SPINK family may be potential targets for the treatment of dermatological disorders by regulating multiple biological processes such as keratinization metabolism and immuno-inflammatory processes in the skin. The development of drugs such as small molecule inhibitors and monoclonal antibodies has great potential for the treatment of dermatologic diseases, and future research on SPINK will help to gain a deeper understanding of the physiopathologic processes of the skin. Through its functions and regulatory mechanisms, the formation and maintenance of the skin barrier and the occurrence and development of inflammatory responses can be better understood, which will provide novel ideas and methods for the prevention and treatment of skin diseases.

BackgroundPatients with depressive disorder often exhibit impaired decision-making functions. However， the relationship between decision-making abilities and depressive and anxiety symptoms in these patients remains unclear. ObjectiveTo explore the characteristics of decision-making behavior in patients with depressive disorder， and to analyze its relationship with clinical symptoms. MethodsA total of 48 patients diagnosed with depressive disorder according to the Diagnostic and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） were recruited from the Department of Psychosomatic Medicine of the Affiliated Hospital of Southwest Medical University from October 2020 to May 2023. Concurrently， 52 healthy individuals matched for age and gender were recruited from Luzhou as the control group. Beck Depression Inventory （BDI） and Beck Anxiety Inventory （BAI） were used for assessment， and decision-making behavior was evaluated using Probabilistic Reversal Learning （PRL） task. Indicators assessed included the number of trials to criterion， perseverative errors， win-stay rate and lose-shift rate. Spearman correlation analysis was used to assess the correlation between BDI and BAI scores and PRL task indicators. ResultsThe depression group showed a significantly higher lose-shift rate compared with the control group （t=3.684， P<0.01）. There were no statistically significant differences between two groups in trials to criterion， perseverative errors and win-stay rate （t=0.329， 0.132， 0.609， P>0.05）. In depression group， BDI and BAI scores were positively correlated with the win-stay rate（r=0.450， 0.398， P<0.01）. ConclusionPatients with depressive disorder are more likely to change their decision-making strategies following negative outcomes. Furthermore， the severity of depressive and anxiety symptoms is associated with a greater propensity to maintain existing decisions after receiving positive feedback. ［Funded by 2019 Joint Project of Luzhou Science and Technology Bureau-Southwest Medical University （number， 2019LZXNYDJ39］

ObjectiveTo study the effect of Wulingsan on cerebral edema after intracerebral hemorrhage （ICH） in mice and explore the treatment mechanism. MethodsThe mouse model of ICH was established by injection of collagenase into the caudate nucleus. Mice were randomly assigned into the following groups： sham， ICH， intervention before modeling with low-dose and high-dose （3.69， 11.07 g·kg^-1， respectively） Wulingsan， and intervention after modeling with high-dose Wulingsan. The modified neurological severity score （mNSS） was recorded， and the small animal MRI T2 sequential scanning was performed to measure the volume of cerebral hemorrhage after the modeling of ICH in each group. The Y-maze test， open field test， and Morris water maze test were conducted to evaluate the neurological behaviors of mice in each group. Hematoxylin-eosin staining was employed to observe the pathological changes in the brain tissue. Immunohistochemistry was employed to observe the expression of aquaporin 4 （AQP4）， neuronal nuclei （NeuN）， and glial fibrillary acidic protein （GFAP） in the brain tissue. Western blot was employed to determine the protein levels of AQP4， Claudin-5， and zonula occludens-1 （ZO-1） in the hematoma area. ResultsCompared with the sham group， the ICH group showed increases in the mNSS， the cerebral hemorrhage volume， and the escape latency in the Morris water maze test （P<0.01）， decreases in the times of touching the platform and times of entering the quadrant where the platform was located in the Morris water maze test， and reductions in the spontaneous alternation rate in the Y-maze test and the ratio of distance of center travel to total travel distance in the open field test （P<0.01）. Moreover， pathological changes such as cell disarrangement， cell space enlargement， and cell swelling were observed in the ICH group. Immunohistochemistry results showed that the ICH group had higher proportions of AQP4- and GFAP-positive cells and lower proportion of NeuN-positive cells than the sham group （P<0.01）. Compared with the sham group， the ICH group showed an up-regulated protein level of AQP4 and down-regulated protein levels of Claudin-5 and ZO-1 （P<0.01）. Compared with the ICH group， the intervention with Wulingsan decreased the mNSS， the volume of cerebral hemorrhage， and the escape latency in the Morris water maze test （P<0.05， P<0.01）， while increasing the times of touching the platform and times of entering the quadrant where the platform was located in the Morris water maze test， the spontaneous alternation rate in the Y-maze test， and the ratio of distance of center travel to total travel distance in the open field test （P<0.05， P<0.01）. Furthermore， the intervention with Wulingsan alleviated the pathological changes in the brain tissue after ICH， decreased the proportion of AQP4- and GFAP-positive cells （P<0.01）， increased the proportion of NeuN-positive cells （P<0.01）， down-regulated the protein level of AQP4 （P<0.01）， and up-regulated the protein levels of Claudin-5 and ZO-1 （P<0.01）. ConclusionThe intervention with Wulingsan could reduce the neural function score and the cerebral hemorrhage volume， up-regulate the expression of Claudin-5 and ZO-1， and down-regulate the expression of AQP4 to ameliorate the neurological function defect and cerebral edema after ICH， thereby protecting the brain.

Background: and Purpose Ruptured intracranial aneurysms (RIA) are associated with a mortality rate of up to 40% in the Chinese population, highlighting the critical need for targeted treatment interventions for at-risk individuals. Although the impact of aldehyde dehydrogenase 2 (ALDH2) gene mutations on susceptibility to intracranial aneurysms (IA) is well documented, the potential connection between ALDH2 rs671 single-nucleotide polymorphism (SNP) and RIA remains unexplored. Given the increased prevalence of ALDH2 gene mutations among Chinese Han individuals, it is clinically relevant to investigate the link between ALDH2 rs671 SNP and IA rupture. Methods: A prospective study was conducted on 546 patients diagnosed with IA to investigate the association between ALDH2 rs671 SNP and the risk of IA rupture. Results: The ALDH2 rs671 SNP (ALDH2*2) was significantly more prevalent in patients with unruptured IA (UIA) than in those with RIA (32.56% vs. 18.58%, P=0.004). Multivariate logistic regression analysis revealed that people with the ALDH2 mutation (ALDH2*1/*2 and ALDH2*2/*2 gene type) had a significantly reduced odds ratio (OR=0.49; 95% confidence level [CI] 0.27–0.88; P=0.018) for RIAs. Age-specific subgroup analysis indicated that the ALDH2 mutation provided a stronger protective effect in individuals aged 60 years and above with IA compared to those under 60 years old (OR=0.38 vs. OR=0.52, both P<0.05). Conclusion The incidence of RIA was significantly higher in individuals with a normal ALDH2 gene (ALDH2*1/*1) than in those with an ALDH2 rs671 SNP (ALDH2*1/*2 or ALDH2*2/*2). ALDH2 rs671 SNP may serve as a protective factor against RIA in the Chinese Han population.