Hepatocellular carcinoma (HCC) is a lethal cancer with high morbidity rates worldwide. It is a major threat to public health in China, due to the combination of known and new risk factors, such as endemic hepatitis B virus (HBV), dietary aflatoxin exposure, and the occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD). Although many methods for surveillance and multimodal therapies, such as surgery, local ablation, transarterial therapy, and new systemic agents, have been available, the survival rates of HCC remains poor. They have very limited durable responses, long post-treatment recurrence rates, and high resistance to treatment. This reflects an imperfect picture of the biological cause of the disease and a need for new mechanistic or targeted techniques. A significant characteristic of HCC, in common with other aggressive cancers, is the presence of reprogrammed, hyperactive cell metabolism. Tumor cells hijack metabolic pathways to promote their uncontrolled growth, stress survival, invasion and metastasis. While classical mechanisms such as the Warburg effect, lipid metabolism and glutamine utilization have been understood, the lysosome, which was once viewed as a static “waste disposal unit” to remove old organelles and proteins, is instead a dynamic signaling and metabolic core. The lysosomes incorporate nutrients, energy and stress signals by master regulators such as mTORC1 (activated on its surface) that balance anabolic growth and catabolic recycling to the cellular demands. In HCC, lysosomes are not passive, but are highly active and dysregulated. HCC cells upregulate lysosomes, which scavenge intracellular components via enhanced autophagy and engulf extracellular proteins via macropinocytosis, crucial for survival in the nutrient-poor, hypoxic tumor microenvironment. In addition to metabolism, lysosomes exhibit pro-invasive functions by secreting hydrolases to remodel the extracellular matrix, promote angiogenesis, and suppress stromal immune cells to foster a pro-tumor microenvironment. In a clinical context, lysosomes play an important role in therapeutic resistance: they sequester and inactivate chemotherapeutics via lysosomal sequestration, and enhanced autophagic flux protects the cell from therapy-induced damage, contributing to relapse, as lysosomal dysfunction is a key cause of treatment failure. This makes lysosomes promising yet challenging therapeutic targets in HCC. Recent preclinical and early clinical studies investigate multiple strategies to exploit the susceptibility of lysosomes: lysosome-specific agents, alkalinizing the lysosome lumen or inducing membrane permeabilization and lysosome-dependent cell death; pharmacological inhibition of key lysosomal enzymes or autophagy to impair nutrient recycling and stress adaptation; smart nanotherapeutic agents or antibody-drug conjugates, specifically activated in the acidic lysosomal environment or utilizing lysosomal pathways for efficient intracellular drug release; and combination strategies of lysosome-targeting agents with tyrosine kinase inhibitors or immunotherapy to overcome resistance and achieve synergistic antitumor effects. In summary, our review systematically presents the role of lysosomes in HCC, from metabolic reprogramming and microenvironmental adaptation to therapeutic resistance. By synthesizing the latest mechanistic insights and preclinical advances, this review highlights the indispensable role of lysosomes in the complex HCC biological network, emphasizing that an in-depth understanding of this dynamic organelle holds great promise for developing innovative, targeted therapies, offering new hope for improving the poor prognosis of global HCC patients.

ObjectiveTo investigate the feasibility， safety， and efficacy of surgery-assisted transjugular intrahepatic portosystemic shunt （SA-TIPS） in the treatment of portal hypertension comorbid with complex portal vein thrombosis， including cavernous transformation of the portal vein （CTPV）. MethodsAn analysis was performed for the data of 36 patients with portal hypertension and complex portal vein thrombosis who underwent SA-TIPS in Beijing Shijitan Hospital， Capital Medical University， from November 2023 to January 2025， including general status， technical data of the surgical process （surgical success rate， puncture times， time of operation， the number of stents used， and the length of shunt）， perioperative complications， and surgical recovery. The change in portal pressure gradient （PPG） after shunt was compared， and the rate of reaching the standard for PPG reduction was calculated， as well as stent patency rate within 1 week after surgery. The paired samples t-test was used for comparison of continuous data between two groups. ResultsAmong the 36 patients， 34 （94.4%） underwent SA-TIPS successfully. The incidence rate of perioperative complications was 16.7% （6/36）， including 3 cases of thoraco-abdominal hemorrhage， 2 cases of intraoperative arrhythmia， and 1 case of incision infection. There was a significant reduction in PPG after SA-TIPS （t=19.85， P<0.01）， and the patients achieving a ≥50% reduction in PPG accounted for 76.5% （26/34）. Imaging reexamination within 1 week showed a shunt patency rate of 100%. ConclusionSA-TIPS has a high technical success rate， a favorable safety profile， and good efficacy in the treatment of portal hypertension comorbid with complex portal vein thrombosis （including CTPV）， and therefore， it holds promise for clinical application.

OBJECTIVE To explore the potential mechanism by which drug-containing serum of Dianxianqing granules （DXQ） inhibits microglial ferroptosis. METHODS Male SD rats were given normal saline and Dianxianqing granules solution via intragastric administration to prepare normal serum and DXQ， respectively. Mice microglia BV2 cells were collected and successfully transfected with a negative control small interfering RNA （si-NC）， and then they were included in the si-NC group and cultured under normal conditions. Cells successfully transfected with small interfering RNA targeting glutathione peroxidase 4 （GPX4） （si-GPX4） were divided into the si-GPX4 group， the CsA group （treated with 1 μmol/L cyclosporine A）， and the DXQ- L， DXQ-M and DXQ-H groups （treated with 5%， 7% and 10% DXQ， respectively）. These groups were subsequently treated with their corresponding drug solutions and ferroptosis inducer Erastin （10 μmol/L）. The intracellular levels of total iron ions， glutathione （GSH）， reactive oxygen species （ROS）， and the expression of mitochondrial superoxide were determined in each group after 48 h of treatment. Additionally， mitochondrial membrane potential， the opening degree of mitochondrial permeability transition pore （MPTP）， and mRNA expressions of GPX4 and cyclophilin D （CypD） were detected. Furthermore， the expressions of ferroptosis-related proteins[GPX4， transferrin receptor 1 （TfR1） and ferritin heavy chain 1 （FTH1）]， as well as MPTP-related proteins [adenine nucleotide translocator （ANT）， cytochrome C （CytC）， mitochondrial calcium uniporter （MCU） and CypD] were assessed. RESULTS Compared with si-NC group， the levels of total iron ions and ROS， the expression level of mitochondrial superoxide， the opening degree of MPTP， protein and its mRNA expressions of CypD as well as protein expressions of TfR1 and MCU were increased or up-regulated significantly （P＜0.01）； however， GSH content， mitochondrial membrane potential， protein and mRNA expressions of GPX4， and protein expressions of FTH1， ANT and CytC were decreased or down-regulated significantly （P＜0.01）. Compared with the si-GPX4 group， the cells in the DXQ-M， DXQ-H groups showed a general improvement in the above quantitative indicators （P＜0.01 or P＜0.05）. CONCLUSIONS DXQ can enhance antioxidant capacity by activating the GSH/GPX4 pathway， regulate the expressions of TfR1 and FTH1 protein to correct iron ion homeostasis， inhibit excessive opening of MPTP to improve mitochondrial function， and ultimately suppress microglial ferroptosis.

Objective To investigate the influencing factors of stroke patients with hypertension and their compliance with antihypertensive drugs, and to provide targeted intervention measures for stroke prevention in hypertensive patients.  Methods Using the method of multi-stage cluster sampling, a total of 59,434 permanent residents aged 40 and above were selected from 48 monitoring sites in 9 cities of Hebei Province from December 2019 to December 2020. Unconditional logistic regression analysis was used to explore the influencing factors of stroke complicated with hypertension and the compliance of patients with antihypertensive drugs.  Results Among the 59 434 subjects, the prevalence rate of stroke was 4.33% and the prevalence rate of stroke complicated with hypertension was 82.47%. The results of univariate analysis showed that the proportion of women, rural areas, dyslipidemia, diabetes, obesity, and people with family history of stroke was higher in stroke patients with hypertension, and the difference was statistically significant (P<0.05). Multivariate logistic regression analysis showed that rural areas, dyslipidemia, diabetes, obesity, and family history of stroke significantly increased the risk of stroke, and the OR (95%CI) values were 1.29 (1.03-1.62), 1.39 (1.12-1.72), 1.58 (1.25-1.99), 1.61 (1.22-2.12) and 1.60 (1.26-2.04), respectively. Among stroke patients with hypertension, 92.71% of patients took antihypertensive drugs. It was found that women's compliance with antihypertensive drugs was good, with an OR (95%CI) value of 1.46 (1.01-2.09).  Conclusion The prevalence rate of stroke complicated with hypertension is high in people aged 40 and above in Hebei Province. Hypertensive people should lower blood lipids, control blood glucose, and lose weight as soon as possible to prevent the occurrence of stroke.

Objective: To enhance the solubility expression of carbonyl reductase ChKRED20 and investigate its enzymatic properties. Methods : The ChKRED20 gene was synthesized and transformed into Escherichia coli BL21(DE3) for heterologous expression. The solubility of the protein was evaluated by adding or removing His⁃tag ,changing its position , and adjusting the induction conditions. Further optimization was performed by varying the in⁃duction time , temperature and IPTG concentration. Subsequently , the enzymatic properties of the recombinant en⁃zyme were examined. Results: The ChKRED20 was cloned within the Escherichia coli system to achieve soluble protein expression . This was achieved by removing the His_tag and optimizing expression conditions . Compared to enzymes with the N_terminal and C _terminal His_tags , the enzyme activity of ChKRED20 without His_tag increased by 0. 77 and 1 . 28 times , respectively. The optimal temperature and pH for enzyme activity were 55 ℃ and 8. 0 , respectively. Furthermore , the enzyme demonstrated good adaptability in higher temperature and alkaline environ_ ments . Conclusion The removal of the His_tag and the optimization of expression conditions can significantly im_ prove the soluble expression of ChKRED20 in Escherichia coli .

Objective: To investigate the protective effect of dulaglutide on lipopolysaccharide (LPS)-induced inju- ry in MLE-12 cells. Methods: An in vitro model of acute lung injury was established by inducing MLE-12 cells with LPS ( 1 μg/mL) , followed by treatment with dulaglutide for 24 hours. The cells were divided into four groups : CON group , LPS group , LPS + 100 nmol/L dulaglutide group , and LPS + 200 nmol/L dulaglutide group. Protein and RNA were extracted from each group. The mRNA levels of inflammatory factors , including interleukin (IL)-6 , tumor necrosis factor-α (TNF-α ) , IL-1β , monocyte chemotactic protein 1 (CCL2) , C-X-C motif chemokine lig- and (CXCL) 1 and CXCL2 , were detected by qRT-PCR. Cell apoptosis was assessed by TUNEL assay , and the expression levels of phosphorylated protein kinase B (P-Akt) and phosphorylated extracellular signal-regulated ki- nase (P-Erk) were measured by Western blot. Results: Compared with the CON group , the LPS group showed in- creased mRNA levels of inflammatory mediators (TNF-α , IL-6 , IL-1β , CCL2 , CXCL1 , and CXCL2) , increased TUNEL-positive cells , and elevated expression of P-Akt and P-Erk proteins. Compared with the LPS group , the LPS + 100 nmol/L dulaglutide treatment group exhibited reduced mRNA levels of TNF-α , IL-6 , IL-1β , CCL2 , CXCL1 , and CXCL2 , decreased TUNEL-positive cells , and downregulated expression of P-Akt and P-Erk pro- teins. However, the LPS + 200 nmol/L dulaglutide treatment group showed less pronounced improvement in inflam- matory factors compared to the LPS + 100 nmol/L dulaglutide group. Conclusion Dulaglutide has a protective effect on LPS-induced injury in MLE-12 cells , potentially through inhibiting Akt and Erk phosphorylation , thereby reducing the expression of inflammatory mediators and alleviating inflammatory damage , ultimately protecting the lungs.

Objective To observe the ultrasound biomicroscopy(UBM)findings of lacrimal canaliculitis.Methods Totally 35 patients with single eye lacrimal canaliculitis who underwent surgical treatment were retrospectively enrolled,including 3 cases of simple superior lacrimal tubule abnormalities,19 cases of simple inferior lacrimal tubule abnormalities and 13 cases with both superior and inferior lacrimal tubules.UBM data and postoperative laboratory examination results were comparatively analyzed.Results The detection rate of UBM for lacrimal canaliculitis was 100％.Abnormal coenobium-like structures in lacrimal tubule were characterized by elliptical or irregular low echo,with unclear boundaries and uneven internal echo,some with punctate high echoes,while polyps presented as oval or strip-shaped high echo with clear boundaries and uniform internal echoes in UBM.UBM findings of tumor like hyperplasia were similar to abnormal coenobium-like structures but with relatively uniform internal echoes.Sulfur particles extracted from lacrimal tubule revealed no fungi in 35 cases by postoperation pathology,while actinomycete was observed in 24 cases,with UBM finding of abnormal coenobium-like structures and punctate high echoes.Conclusion UBM findings of lacrimal canaliculitis had certain characteristics.Coenobium-like structures and punctate high echoes in lacrimal tubule could be observed after infection of actinomycete.

[Objective]To investigate the etiology and pathological mechanisms of prediabetes based on the theory of"excessive earth stagnation,"thereby expanding novel therapeutic approaches for prediabetes management.[Methods]Integrating classical Chinese medical literature with contemporary clinical insights,this study elucidates the correlation between Dunfu(thickened stagnation)and excessive earth stagnation and its pivotal role in prediabetes pathogenesis,and proposes the therapeutic strategies.[Results]The Dunfu mechanism documented in The Inner Canon of the Yellow Emperor demonstrates significant correlation with the"spleen-earth stagnation"pathological state in prediabetes,which primarily disrupts the ascending-descending dynamic of Qi in middle-Jiao and contributes to glucose metabolism dysregulation.Dunfu(thickened stagnation)acts as a quintessential manifestation of excessive earth stagnation.When Dunfu develops,damp-heat pathogens accumulate,causing retention of food essence and further aggravating earth stagnation,the retained food and essence transforming into dampness,heat and phlegm.These turbid pathogens obstruct the middle-Jiao,impairing spleen function and Qi-blood flow,eventually generating heat that scorches the Zang-Fu organs.This progression from Pidan to Xiaodan underscores Dunfu as the root pathology.Treatment should prioritize resolving stagnation,clearing heat and eliminating turbidity,with tailored Zang-Fu syndrome differentiation to restore Beihua(preparation and transformation).[Conclusion]"Excessive earth stagnation"is the core pathological mechanisms of prediabetes,leading to retention of food essence and further aggravation earth stagnation,and the treatment should prioritize resolving stagnation.Treating prediabetes based on"excessive earth stagnation"has clinical guidance significance.

The global incidence of head and neck cancer (HNC) is rising, with over 60% of patients presenting at a locally advanced stage. Radiotherapy remains a cornerstone of HNC treatment, and advancements in modern techniques and concurrent chemotherapy have improved local control and survival rates of HNC patients. However, these benefits also bring challenges in the management of toxicities. Due to the proximity of salivary glands and tumors, especially the highly radiosensitive parotid and submandibular glands, this condition is among the most common adverse effects of radiotherapy. Radiation damages acinar cells and ducts, causing glandular atrophy, fibrosis, and reduced saliva secretion, thereby leading to xerostomia and related complications. The risk and severity of injury are associated with the radiation dose and volume affecting the glands. Prevention and management strategies emphasize precise radiotherapy planning, target optimization, and supportive care. Emerging multimodal imaging techniques offer potential for non-invasive prediction and early diagnosis and treatment of radiation-induced salivary gland injury. Future research in regenerative medicine, tissue engineering, and molecular biology aims to elucidate molecular mechanisms, such as signaling pathways and genomics, facilitating personalized strategies to mitigate radiotherapy-induced toxicities and enhance the quality of life of patients.

Objective:To investigate the clinical features and multi-slice spiral computed tomography(CT)imaging features of acute appendicitis in soldiers who have been living in plateau for a long time.Methods:The clinical features and imaging data of 56 cases of acute appendicitis in soldiers who have been living in plateau for a long time confirmed by surgery from February 2022 to August 2024 were retrospectively analyzed.Results:In 56 cases with acute appendicitis in soldiers who have been living in plateau for a long time,the appendectomy position results showed:anterior ileum 4 cases(7.14％),lower ileum 10 cases(17.86％),posterior cecum 16 cases(28.57％),lower cecum 9 cases(16.07％),lateral cecum 2 cases(3.58％),posterior ileum 6 cases(10.71％),high(subhepatic)9 cases(16.07％),and left lower abdominal 0 cases,retroperitoneal appendicitis 0 cases,which was suggested that the anatomical position variation of appendicitis in soldiers with acute appendicitis who have been living at high altitude for a long time was relatively large.The direct manifestations of multi-slice spiral CT showed:appendectomy enlarged diameter＞6 mm in 49 cases(87.50％),appendicular wall thickening＞2 mm in 42 cases(75.00％),ppendiceal dilation lumen and effusion in 29 cases(51.79％),appendix indistinctness in 3 cases(5.36％),lppendix fecalith:27 cases(48.21％),gas in the appendix in 16 cases(28.57％).Indirect findings of multi-slice spiral CT showed that,periappendiceal exudation with shadow in 32 cases(57.14％),appendiceal cellulitis with peripheral abscess in 9 cases(16.07％),peritonitis and ascites in 13 cases(23.21％),ileocecal intestinal wall thickening in 22 cases(39.29％),mesenteric lymph node enlargement in 16 cases(28.57％),reflexive intestinal stasis in ileocecal region was observed in 19 cases(33.93％).Conclusion:In the officers and soldiers with acute appendicitis who lived at high altitude for a long time,multi-slice spiral CT showed the direct manifestations of appendiceal thickening,tube wall thickening,lumen dilatation,fluid accumulation,etc.,and the indirect manifestations were periappendiceal exudation with shadow,appendiceal cellulitis with peripheral abscess,ileocecal intestinal wall thickening,reflexes of small intestine and mesenteric lymph node enlargement.Multi-slice spiral CT has the advantages of clear and intuitive,high safety,high resolution and simple operation in the diagnosis of acute appendicitis.