[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。

OBJECTIVE To evaluate the impact of the specialized centralized procurement policy for insulin on daily cost and affordability of insulin， and provide data support for the enhancement of relevant policies. METHODS In this research， the insulin purchasing data were obtained from provincial centralized procurement platforms in provinces before and after the specialized centralized procurement of insulin （October-December 2021 and October-December 2022）， and the cost variations of insulin before and after the centralized procurement were analyzed by the defined daily dose cost （DDDc） of various types of insulins. The changes in the affordability of various types of insulins before and after the specialized centralized procurement were evaluated， using the percentage of annual expenditure on various types of insulins relative to annual per capita disposable income （i.e. the proportion of annual expenditure） as an indicator. RESULTS After the specialized centralized procurement， DDDc of various types of insulins decreased by 20.7%-71.8%， with an average reduction of 45.7%. Moreover， the reduction in DDDc for third-generation insulin exceeded that for second-generation insulin. The reduction in the proportion of annual expenditure on insulin ranged from 24.3% to 73.4%， with an average decrease of 48.5%. Premixed insulin analogs experienced the greatest reduction （73.4%）. Following the specialized centralized procurement， DDDc of insulin decreased in all provinces. Except for Guangxi （10.2%）， the average proportion of annual expenditure on insulin in the remaining provinces dropped to below 10%. CONCLUSIONS The specialized centralized procurement policy for insulin has significantly reduced insulin costs and improved affordability， thereby alleviating the economic pressure on patients with diabetes. There are notable cost disparities among provinces and among insulin categories， which require attention.

Objective To analyze the epidemiological characteristics of influenza-like illness outbreaks in Yunnan Province from 2017 to 2023,and to provide the evidence for the prevention and control of influenza in Yunnan Province.Methods The data of influenza-like illness outbreaks and outbreak specimens were collected in Yunnan Province from 2017 to 2023.Descriptive epidemiological methods were used to describe and analyze the epidemic time,population,region and pathogen distribution.Results A total of 340 influenza-like illness outbreaks were reported in Yunnan Province from 2017 to 2023,with 12586 reported cases and a cumulative incidence of 2.34%.The outbreaks were mainly concentrated in November to January and March of the following year,with a high incidence in winter and spring.Schools were the most important place of outbreak,with primary and secondary school students being the main affected group.The cumulative number of reported cases in Dali Prefecture,Dehong Prefecture,Yuxi City and Kunming City ranked among the top in the province,accounting for 79.71%of the total number of outbreaks in the province.The pathogen types alternated and were mainly prevalent in H1N1(119 cases),H3N2(81 cases),and Victoria(83 cases).Conclusion The outbreak of influenza-like illness in Yunnan Province shows the obvious seasonality,and primary and secondary schools are the main outbreak sites.The outbreak surveillance in schools should be strengthened continuously to control the occurrence and development of the epidemic.

OBJECTIVE To provide reference for basic analysis of the pharmacodynamic substance in Stahlianthus involucratus. METHODS Overall 24 SD male rats were randomly divided into blank group （purified water）， and administration group （ethanol extract of S. involucratus， 15.75 g/kg， calculated by crude drug）， with 12 rats in each group. They were given drug liquid/purified water intragastrically， twice a day， every 6-8 h， for consecutive 3 days. After medication， the blood， urine and fecal samples were collected from two groups of rats. UPLC-Q-Exactive-MS technology was used to identify the chemical constituents in the ethanol extract of S. involucratus， and metabolites in the blood， urine and fecal of rats after intragastrical administration of the ethanol extract of S. involucratus. Multivariate statistical analysis was employed to screen various serum metabolites. Metabolic pathways were analyzed by MetaboAnalyst 5.0 platform. RESULTS A total of 38 chemical constituents were identified from the ethanol extract of S. involucratus， including fourteen prototype components and three metabolites identified from 5 urine samples， nine prototype components identified from fecal samples， and ten prototype components and one metabolite identified from serum samples. A total of 71 differential metabolites were screened from two groups of rat serum samples， of which 44 differential metabolites， such as ferulic acid， glycyrrhizin， were up-regulated and 27 differential metabolites， such as arachidonic acid， phenylacetylglutamine， were down-regulated. The 71 differential metabolites were mainly enriched in 11 metabolic pathways， including phenylalanine metabolism， linoleic acid metabolism， arachidonic acid metabolism， and tryptophan metabolism. CONCLUSIONS Ferulic acid， liquiritigenin， isofraxidin and formononetin may be the material basis that directly exert pharmacological effects of S. involucratus. S. involucratus may exert anti-inflammatory effects by affecting metabolic pathways， including arachidonic acid metabolism and tryptophan metabolism.

OBJECTIVE To establish the quality standard of the leaves of Litchi chinensis Sonn.. METHODS The identification of medicinal properties, microscopic characteristics, TLC and content determination method of the leaves of Litchi chinensis Sonn. was conducted. The moisture, total ash, acid insoluble ash and extract of the leaves of Litchi chinensis Sonn. were determined according to Chinese Pharmacopoeia(Volume IV), 2020. RESULTS The leaves of Litchi chinensis Sonn. under forest exhibited specific properties in characteristics, microscopic features and TLC results. The moisture content of the medicinal materials was 2.66%-6.42%, the total ash content was 2.96%-4.52%, the acid insoluble ash content was 0.17%-0.94%, the water soluble extract was 15.38%-19.87%, and the alcohol soluble extract was 24.94%-30.33%. The eight components of gallic acid, protocatechin, catechin, epicatechin, rutin, astragalin, quercetin and kaempferol had a good linear relationship in 0.003 3-0.052 0 mg·mL-1, 0.006 9-0.109 6 mg·mL-1, 0.013 0-0.208 0 mg·mL-1, 0.057 5-0.920 0 mg·mL-1, 0.013 4-0.213 6 mg·mL-1, 0.013 2-0.211 2 mg·mL-1, 0.002 9-0.045 6 mg·mL-1, 0.003 6-0.056 8 mg·mL-1(r>0.999). The average sample recovery rate was 97.43%-102.97% and the RSD was 1.70%-2.90%. CONCLUSION The established quality standard of the leaves of Litchi chinensis Sonn. medicinal material has good specificity, accuracy and reproducibility, which can be used for quality control research of the leaves of Litchi chinensis Sonn..

To retrospectively analyze the safety and efficacy of low dose rituximab regimen in patients with Epstein-Barr virus (EBV) infection after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Among 12 cases, 11 achieved complete remission (CR), 1 with partial remission (PR). Patients received 15 infusions with a median of 2.5(1-4) in each. The EBV DNA negative transformation period was 5-25 days with median 12 days. Low dose rituximab could be an alternative choice in patients with EBV infection after allo-HSCT.

Objective To investigate the inhibitory effect of a disintegrin and metalloprotease 12 silenced by shR?NA on self-renewal capacity of CD133 positive giloma cells. Methods The shRNA recombinant lentivirus aimed at si?lencing ADAM12 was prepared. Human glioma cells U87 were employed in this study and assigned into three groups:shRNA-ADAM12, shRNA-NCandshRNA-C. ADAM12 expression was detected at mRNA and protein level using Re?al-time quantitative-PCR and western bloting, respectively. U87 cells were cultured with stem cell culture medium, to obtain cell sphere formation in which CD133 positive glioma cells were enriched. Immunofluorescence was employed to detect the expression of ADAM12 and CD133 in cell spheres and U87 cells; Self-renewal was tested by using tumor sphere formation assay. Molecular markers for differentiated or undifferentiated cells (CD133,GFAP and Tuj1) were de?tected at protein using western blotting. Western blotting was employed to test protein expression of HES1. Results AD?AM12 shRNA significantly down-regulated the mRNA and protein expression levels of ADAM12. Compared with shRNA–C group, the relative expression levels of mRNA in shRNA-ADAM12 group and shRNA-NC group were 0.22 ± 0.03 and 0.98 ± 0.06 (F=425.37,P<0.01). The relative expression levels of protein in shRNA-ADAM12 group, shRNA-NC group and shRNA-C group were 28.72%±2.36%, 69.21%±3.92%and 69.04%±3.57%, respectively (F=145.42,P<0.01). Immunofluorescence staining showed that expression levels of ADAM12 and CD133 in cell spheres were significantly higher than those in normal cells. The number of spheres in three groups were 45.5±2.3、104.2±5.8 and 109.6±6.2, tumor sphere formation ability of shRNA-ADAM12 group was lower than that of shRNA-NC group and shRNA-C group (F=147.03,P<0.01). Compared with the shRNA-NC group and shRNA-C group, the protain expression of GFAP and Tuj1 were increased up to 166% and 146% (P<0.01) whereas the protein expression levels of CD133 and HES1 were down-regulated by 54% and 50% (P<0.01). Conclusion Knockdown of ADAM12 may suppress self-renewal ability of CD133 positive glioma cells by inhibiting the Notch pathway activity.

AIM:To investigate the mammalian target of rapamycin ( mTOR) signaling pathway as the center playing a role in the crizotinib-induced apoptosis of non-small cell lung cancer (NSCLC) cell line H2228, which represents positive echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) fusion gene. METHODS:H2228 cells were processed according to different purposes .Fluorescence quantitative PCR is used to ob-serve the gene states .MTT assay is used to detect the cell inhibition rates .The cell apoptosis and cell cycle were analyzed by flow cytometry .The expression and activation levels of the key proteins in the mTOR signaling pathway were determined by Western blotting .RESULTS:Crizotinib promoted the apoptosis of H 2228 cells in a time-and dose-dependent manner . Crizotinib blocked the H2228 cells staying at the G1 phase.In apoptotic H2228 cells processed with crizotinib, the activa-tion level of mTOR was decreased , and the activation levels of the key proteins in upstream and downstream of mTOR path -way were both declined .The expression level of the fusion protein EML 4-ALK variant 3 was not affected , but its active form of p-ALK was significantly suppressed .CONCLUSION:mTOR signaling pathway has a certain relationship with the crizotinib-induced apoptosis of lung cancer cell H 2228, which represents positive EML4-ALK fusion gene.

[ ABSTRACT] AIM: To investigate the influence of advanced glycosylation end products-modified bovine serum albumin (AGE-BSA) on mammalian target of rapamycin complex 1 (mTORC1), urokinase-type plasminogen activator re-ceptor ( uPAR) , and cell mobility in the podocytes, and to further explore the probable relationship.METHODS: The conditionally immortalized mouse podocyte cell line was cultured in vitro.MTT assay and immunofluorescence were used to analyze the cell viability and cytoskeleton of the podocytes treated with the stimuli and intervention agents.The activity of mTORC1 and the expression level of uPAR in normal podocytes and podocytes treated with control BSA or AGE-BSA were detected by Western blotting.The migration ability of the podocytes was determined by would-healing assay.Rapamycin was added to inhibit the activity of mTORC1 along with the addition of AGE-BSA to observe the changes of uPAR and the motility of podocytes.RESULTS:No significant difference of the cell viability or cytoskeleton in the podocytes treated with the stimuli and intervention agents was observed.AGE-BSA up-regulated the activity of mTORC1 and the expression of uPAR, and induced the high mobility of the podocytes.Rapamycin obviously reduced the high expression level of uPAR and the increase in the migration ability of podocytes caused by AGE-BSA treatment.CONCLUSION: AGE-BSA might cause the high migration of podocytes through the mTORC1/uPAR signaling pathway.

Objective To evaluate the influence of simple subtalar arthrodesis to the motion and degeneration of midfoot.Methods Data of 37 patients (27 males,10 females) with an average age of 42.6 years who had undergone subtalar joint fusion from January 1996 to August 2011 were retrospectively analyzed.The MOS item short form health survey (SF-36),American Orthopaedic Foot and Ankle Society (AOFAS) midfoot score were used.Midfoot sagittal and coronal motion were measured on ankle radiographs of maximum plantar flexion and dorsiflexion.On sagittal plane,the Meary angle was measured and the bilateral tarsometatarsal joints mobility was compared.On coronal plane,tibio-plantar angles (TPA) on 30 degrees varus slope and 30 degrees valgus slope were respectively measured on the anterio-posterior ankle X-ray films to observe the changes of midfoot activities.Besides,single photon emission computed tomography/computed tomography (SPECT/CT) of bilateral foot and ankle was taken to estimate the degeneration of midfoot joint.Results All the 37 patients were followed-up,with mean follow-up period of 9.2 years.The average SF-36 scores was increased from 34.26± 11.02 points preoperatively to 77.59± 12.57 points postoperatively.The average AOFAS midfoot scores were 86.14± 16.79 points preoperatively and 86.43± 16.70 points postoperatively without any statistical significant difference.On sagittal plane,medial tarsometatarsal joints mobility was limited by 20％.According to coronal plane of varus slope,the average TPA of healthy side and operated side were 61.32° and 64.91°,respectively,so the varus mobility of operated side was limited by 12.5％.While standing on the valgus slope,the average TPA of both sides were 76.54° and 82.28°,which indicated that valgus mobility of operated side was reduced by 42.6％.35.1％ patients of talonavicular joint,56.8％ patients of calcaneocuboid joint,and 27.0％ patients of metatarsal cuboid joint were found mild joint degeneration on SPECT/CT images without any clinical symptoms.Conclusion Subtalar arthrodesis can affect midfoot with less limit of sagittal mobility and more limit of coronal movement.And the lateral joints degeneration is more likely to happen for their compensatory activity.