Non-small cell lung cancer is one of the primary types of cancer that leads to brain metastases. Approximately 10% of patients with non-small cell lung cancer have brain metastases at the time of diagnosis, and 26%-53% of patients develop brain metastases during the progression of their disease. However, the underlying mechanisms of lung cancer brain metastasis have not been fully elucidated. With the continuous development of single-cell and spatial transcriptomics, the genomic and transcriptomic characteristics of lung cancer brain metastasis are gradually being revealed. In February 2025, the journal Nature Medicine published an article titled "Single-cell and spatial genomic landscape of non-small cell lung cancer brain metastases". This article aims to provide a brief interpretation of the paper for colleagues in research and clinical practice.

Objective: To analyze the phylogenetic characteristics of VP1 gene of Coxsackievirus A10 (CVA10) isolates from 2004 to 2023, and to understand the genetic evolution and epidemic trends of CVA10, so as to provide references for the prevention and control of hand, foot, and mouth disease. Methods: The full-length sequences of the VP1 region of CVA10 isolates were retrieved from the BV-BRC database before December 15, 2024. Gene typing, sequence analysis, evolutionary analysis, and amino acid mutation site analysis were conducted using bioinformatics software. Results: A total of 1 253 CVA10 isolates VP1 region nucleotide full-length sequences from 2004 to 2023 were included, with 9 strains from 2004 to 2008, 338 strains from 2009 to 2012, and 906 strains from 2013 to 2023. China had the highest number of CVA10 isolates, with 1 143 strains accounting for 91.22%, and the predominant genotype was C3. Compared to the prototype strain, the nucleotide sequence homology of the VP1 region of CVA10 isolates ranged from 74.94% to 77.63%, while the amino acid sequence homology ranged from 88.59% to 93.62%. The third codon position preferred cytosine and thymine. The top three most abundant amino acids were threonine, alanine, and valine. The average relative synonymous codon usage of 30 amino acid codon groups was greater than 1. The average amino acid substitution entropy value was 0.04, with four amino acid mutation-prone sites identified, and the mutation-prone rate was 1.35%. Conclusions From 2004 to 2023, the majority of CVA10 isolates were primarily sourced from China, with genotype C3 being the predominant circulating strain in China. The nucleotide homology between the CVA10 isolates and the prototype strain was relatively low, and mutation-prone sites were identified, indicating that enhanced monitoring of viral variation is necessary.

BACKGROUND:Increasing studies have shown that autophagy plays an important role in the treatment of osteoarthritis,and moderate autophagy can preserve the normal physiological function of osteoarticular chondrocytes.Traditional Chinese medicine(TCM)monomers can target and modulate autophagy to treat osteoarthritis,and their characteristics such as single components,clear efficacy,low price,and easy availability have obvious benefits in the treatment of osteoarthritis.OBJECTIVE:To review the effects of TCM monomers on the targeted regulation of autophagy in the treatment of osteoarthritis and the research progress,with a view to laying a foundation for the treatment of osteoarthritis and even other bone metabolic diseases.METHODS:Relevant literature published from January 2012 to October 2022 was retrieved in PubMed,Web of Science,CNKI,and WanFang using the keywords of"traditional Chinese medicine,Chinese herbal monomer,autophagy,osteoarthritis"in English and Chinese.Inclusion and exclusion criteria were developed,and 63 relevant articles were finally included by screening through reading the title,abstract,and full-text content.RESULTS AND CONCLUSION:TCM monomers can treat osteoarthritis by targeting autophagy to inhibit chondrocyte apoptosis,protect cartilage extracellular matrix,reduce inflammation and antagonize oxidative stress injury.Different TCM monomers can regulate autophagy in the same way,and the same TCM monomers can affect autophagy in different ways.The combination of multiple monomers and the multi-target and multi-pathway regulation of autophagy by TCM monomers remain to be explored.The regulation of autophagy by TCM monomers can provide new ideas and strategies for the prevention and treatment of osteoarthritis.Moderate regulation of autophagy by TCM monomers to keep the autophagic flux unimpeded may be the key to treating osteoarthritis.

Lung cancer is the leading cause of cancer-related deaths worldwide, especially non-small cell lung cancer (NSCLC). With the popularization of low-dose CT and the improvement of people’s awareness of physical examinations, the number of detected pulmonary nodules is gradually increasing, and there is a greater demand for standardized diagnostic and treatment guidelines. On April 23, 2024, the National Comprehensive Cancer Network updated its clinical practice guidelines for NSCLC to the version 5. Compared with the version 5 in 2023, the version 5 in 2024 updates focus on diagnostic evaluation, perioperative systemic therapy, treatment of advanced NSCLC, and molecular marker testing, which will be interpreted in this article with the aim of providing the latest guidance and reference for the diagnosis and treatment of lung cancer in China.

[摘 要] 目的：探讨四个半LIM结构域2（FHL2）蛋白对胶质瘤细胞增殖的影响及其分子机制。方法：利用TCGA和CGGA数据库分析胶质瘤组织中FHL2 mRNA表达水平与患者预后的关系。通过WB法检测人胶质瘤组织标本及人胶质瘤细胞U87、T98G、U251、SNB19、GSC23、A172、LN229、G267和星形胶质细胞NHA中的FHL2蛋白表达水平。利用慢病毒载体构建稳定敲低FHL2的U87细胞和过表达FHL2的SNB19细胞，即U87-shGFP、U87-shFHL2-1#、U87-shFHL2-4#和SNB19-3flag、SNB19-3flag-FHL2组。通过CCK-8法、克隆形成实验检测敲低和过表达FHL2对细胞增殖的影响，免疫共沉淀（Co-IP）和液相色谱-串联质谱（LC/MS）法筛选FHL2在胶质瘤细胞中的相互作用蛋白，并用Co-IP和免疫荧光法验证它们的结合作用和共定位情况。使用酶标仪检测敲低和过表达FHL2细胞内乳酸产量和乳酸脱氢酶（LDH）活性的变化，WB法分析FHL2、LDHA及p-LDHA在正常脑组织和胶质瘤组织中的蛋白表达差异及其相互关系。在过表达 FHL2的SNB19细胞中使用LDHA的小分子抑制剂AT-101，通过CCK-8实验和酶标仪比色法验证FHL2在胶质瘤乳酸代谢中的作用，验证AT-101在胶质瘤中潜在的治疗效果。结果：Co-IP和LC/MS检测发现，FHL2与LDHA在胶质瘤细胞中存在相互作用。FHL2过表达可提高LDHA活性和乳酸生成（均P < 0.001），进而促进胶质瘤细胞增殖（P < 0.001）。相反，敲低FHL2会降低LDHA活性和乳酸产量（P < 0.001或P < 0.05）并抑制细胞增殖（P < 0.001）。AT101能抑制LDHA活性，并显著抑制FHL2促进胶质瘤细胞的增殖，同时恢复磷酸化LDHA（Y10）水平（P<0.01或P < 0.001）。结论：FHL2与LDHA蛋白相互作用，FHL2通过激活p-LDHA（Y10）的表达促进LDHA活性和乳酸产生，进而促进胶质瘤细胞的增殖，靶向这种相互作用可能成为治疗胶质瘤的潜在策略。

OBJECTIVE To analysis the structures of the impurities in aciclovir tablets and the compulsory degradation samples by high performance liquid chromatography coupled with hybrid quadrupole orbitrap mass spectrometry technology (HPLC-Q-Exactive Orbitrap-MS). METHODS The HPLC separation was carried out on a Waters Xbridge BEH Shield RP18 (4.6 mm×250 mm, 5 μm) by the gradient elution with a mobile phase consisting of 10 mmol·L–1 ammonium formate solution (0.15% formic acid)(A) and 10 mmol·L–1 ammonium formate solution(0.15% formic acid)-acetonitrile(50∶50)(B), and the detection wavelength was 254 nm. The Q-Exactive Orbitrap-MS was used to determine the precise first-order molecular weight and second-order fragment ions of these impurities, and the structures were identified. RESULTS Aciclovir and its impurities were well separated, and 8 major impurities with content>0.1% were detected and identified in aciclovir tablets and the compulsory degradation samples. Among them, 4 were the impurities listed in the European Pharmacopeia 10.0, and the others were unknown impurities identified for the first time. CONCLUSION The LC-MS/MS method can effectively identify the impurities in aciclovir tablets, which is significant for the production process optimization and quality control.

Objective To explore the computed tomography angiography(CTA)and clinical features of Takayasu's arteritis(TA)with peripheral artery involvement.Methods In this retrospective study,CTA scan was performed in a total of 184 TA patients.TA patients were divided into two groups:60 patients within peripheral artery involvement(peripheral artery involvement group)and 124 patients without peripheral artery involvement(peripheral artery non-involvement group).The difference in comparison of clini-cal data and CTA findings were analyzed.Results A total of 194 peripheral arteries were involved in 60 patients.The most suscep-tible peripheral artery were axillary artery(52,26.8％),middle cerebral artery(26,13.4％)and femoral artery(22,11.3％).In the peripheral artery involvement group,the most common CTA manifestation was luminal stenosis(141,72.7％).The lumen dilata-tion,lumen stenosis with dilatation and wall calcification were not easy to be observed.The age and duration of disease in peripheral artery involvement group were significantly greater than those in peripheral artery non-involvement group(P＜0.05).The proportion of the peripheral artery involvement group in the active phase was significantly lower than that of the peripheral artery non-involvement group(P＜0.05).The incidence of pain in the limbs in peripheral artery involvement group was significantly higher than that in peripheral artery non-involvement group(P＜0.05).The utilization rate of tocilizumab in the peripheral artery involvement group was significantly higher than that in the peripheral artery non-involvement group(P＜0.05).Conclusion TA involving peripheral arteries is more common in patients with a long course of disease and in the inactive phase.Patients are prone to pain in their limbs.The CT A manifestations of these patients are also special,that is,the involved peripheral arteries are not prone to lumen dilatation and wall calcification.

Objective To investigate the development and dynamic changes of cysts in the brain of mice following infection with different forms of Toxoplasma gondii, so as to provide insights into for toxoplasmosis prevention and control. Methods ICR mice at ages of 6 to 8 weeks, each weighing 20 to 25 g, were intraperitoneally injected with tachyzoites of the T. gondii PRU strain at a dose of 1 × 10⁵ tachyzoites per mouse, orally administered with cysts at a dose of 20 oocysts per mouse or oocysts at a dose of 200 oocysts per mouse for modeling chronic T. gondii infection in mice, and the clinical symptoms and survival of mice were observed post-infection. Mice were orally infected with T. gondii cysts at doses of 10 (low-dose group), 20 (medium-dose group), 40 cysts per mouse (high-dose group), and the effect of different doses of T. gondii infections on the number of cysts was examined in the mouse brain. Mice were orally administered with T. gondii cysts at a dose of 20 cysts per mouse, and grouped according to gender (female and male) and time points of infections (20, 30, 60, 90, 120, 150, 180 days post-infection), and the effects of gender and time points of infections on the number of cysts was examined in the mouse brain. In addition, mice were divided into the tachyzoite group (Group T), the first-generation cyst group (Group C1), the second-generation cyst group (Group C2), the third-generation cyst (Group C3) and the fourth-generation cyst group (Group C4). Mice in the Group T were intraperitoneally injected with T. gondii tachyzoites at a dose of 1 × 10⁵ tachyzoites per mouse, and the cysts were collected from the mouse brain tissues 30 days post-infection, while mice in the Group C1 were orally infected with the collected cysts at a dose of 30 cysts per mouse. Continuous passage was performed by oral administration with cysts produced by the previous generation in mice, and the effect of continuous passage on the number of cysts was examined in the mouse brain. Results Following infection with T. gondii tachyzoites, cysts and oocysts in mice, obvious clinical symptoms were observed on days 6 to 13 and mice frequently died on days 7 to 12. The survival rates of mice were 67.0%, 87.0% and 53.0%, and the mean numbers of cysts were (516.0 ± 257.2), (1 203.0 ± 502.0) and (581.0 ± 183.1) in the mouse brain (F = 11.94, P < 0.01) on day 30 post-infection with T. gondii tachyzoites, cysts and oocysts, respectively, and the numbers of cysts in the brain tissues were significantly lower in mice infected with T. gondii tachyzoites and oocysts than in those infected with cysts (all P values < 0.01). The survival rates of mice were 87.0%, 87.0% and 60.0%, and the mean numbers of cysts were (953.0 ± 355.5), (1 084.0 ± 474.3) and (1 113.0 ± 546.0) in the mouse brain in the low-, medium- and high-dose groups on day 30 post-infection, respectively (F = 0.42, P > 0.05). The survival rates of male and female mice were 73.0% and 80.0%, and the mean numbers of cysts were (946.4 ± 411.4) and (932.1 ± 322.4) in the brain tissues of male and female mice, respectively (F = 1.63, P > 0.05). Following continuous passage, the mean numbers of cysts were (516.0 ± 257.2), (1 203.0 ± 502.0), (896.8 ± 332.3), (782.5 ± 423.9) and (829.2 ± 306.0) in the brain tissues of mice in the T, C1, C2, C3 and C4 groups, respectively (F = 4.82, P < 0.01), and the number of cysts was higher in the mouse brain in Group 1 than in Group T (P < 0.01). Following oral administration of 20 T. gondii cysts in mice, cysts were found in the moues brain for the first time on day 20 post-infection, and the number of cysts gradually increased over time, peaked on days 30 and 90 post-infection and then gradually decreased; however, the cysts were still found in the mouse brain on day 180 post-infection. Conclusions There is a higher possibility of developing chronic T. gondii infection in mice following infection with cysts than with oocysts or tachyzoites and the most severe chronic infection is seen following infection with cysts. The number of cysts does not correlate with the severity of chronic T. gondii infection, and the number of cysts peaks in the mouse brain on days 30 and 90 post-infection.

BACKGROUND:More and more studies have shown that oxidative stress should play an important role in the treatment of osteoporosis.Oxidative stress should cause the accumulation of oxidation activity,which will damage bone-related cells.Finally,it causes the imbalance of bone resorption and bone formation,resulting in a decrease in bone volume and the destruction of the slight structure.Research in recent years has found that some natural products can regulate oxidative stress to treat osteoporosis.The characteristics of extensive sources and small side effects have obvious advantages in the treatment of osteoporosis,and the efficacy is objective. OBJECTIVE:To discuss the mechanism of natural product regulation of oxidation stress in treatment of osteoporosis,conduct a review based on the latest related research progress,provide reference and ideas for more natural products to treat osteoporosis in the future,and provide data support for the clinical application of natural compounds in the treatment of osteoporosis. METHODS:"oxidative stress,free radical,antioxidant,phytotherapy,plant extracts,medicinal plants,herbal medicine,osteoporosis,bone density,bone loss"were used as the keywords in PubMed,Web of Science,Embase,Cochrane,VIP,CBM,WanFang,and CNKI databases to search relevant articles published from January 2010 to February 2023.Inclusion and exclusion criteria were developed,and 64 relevant articles were selected by reading titles,abstracts,and full texts. RESULTS AND CONCLUSION:(1)Some natural products have antioxidant effects and can regulate osteogenic differentiation,osteoblast bone matrix mineralization,osteoclast-mediated bone resorption,proliferation,differentiation,activity,and apoptosis of bone-related cells by improving oxidative stress,thus affecting bone metabolism.(2)These natural products with antioxidant effects play a role in treating osteoporosis by improving bone remodeling balance.(3)The research on the combination of a variety of natural products to improve osteoporosis remains to be explored.(4)The use of natural products to regulate oxidative stress may become a powerful weapon for the clinical treatment of osteoporosis in the future.

BACKGROUND:"Tendon off-position"is a disease name included in the International Classification of Diseases 11th Revision,and also a clinical indication of manipulation,acupuncture and other treatments.However,its specific mechanism is still unclear.It is urgent to establish an animal model that can reflect the clinical and pathological characteristics of"tendon off-position,"so as to further study the mechanism of effective clinical treatments. OBJECTIVE:To establish an animal model of"tendon off-position"in rats based on isometric contraction of skeletal muscles,and to explore the changes of skeletal muscle function and morphological phenotype after"tendon off-position." METHODS:Sixty rats were randomly divided into control group,static-loading group and extra loading group,with twenty rats in each group.Rats in the control group were kept normally without treatment.In the latter two groups,the rats were fixed by the self-made static-loading modeling device and a static-loading(the body mass of each rats was applied as the static-loading)was applied to cause sustained isometric contraction of the upper limb muscles.Then,animal models of"tendon off-position"were successfully established.In the extra loading group,50%of the body mass was added to the ankle joint after modeling.The skeletal muscle samples were harvested at 2 and 4 weeks after modeling.The changes of limb grip strength,wet mass of skeletal muscle,and serum levels of creatine kinase-muscle and lactate dehydrogenase A were measured,and the changes of skeletal muscle histomorphology and ultrastructure were observed. RESULTS AND CONCLUSION:At 2 weeks after modeling,the rats in the static-loading group and extra loading group showed significantly decreased grip strength and wet muscle mass,significantly increased serum levels of creatine kinase-muscle and lactate dehydrogenase A,and abnormal muscle fiber morphology and structure accompanied by a large number of deposited collagen fibers.Electron microscopy results showed that the structure of myofibrils was disordered,the Z-line was distorted,and the light and dark boundaries were blurred.At 4 weeks after modeling,the grip strength of the model rats was increased compared with that at 2 weeks,the serum creatine kinase-muscle and lactate dehydrogenase A levels were decreased,and the changes of muscle fiber morphology and ultrastructure were recovered to varying degrees.It is suggested that the rat skeletal muscle injury model based on continuous isometric contraction of skeletal muscle can well reflect the pathological characteristics of"tendon off-position"at 2 weeks,and can be used to study the mechanism of acupuncture and manipulation in the treatment of"tendon off-position."