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.

ObjectiveTranscranial magneto-acoustic stimulation (TMAS) is an emerging non-invasive neuromodulation technique that may provide a novel non-pharmacological intervention strategy for Parkinson's disease (PD). PD is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to motor impairments such as bradykinesia, tremor, and rigidity. Increasing evidence indicates that mitochondrial dysfunction and impaired mitochondrial quality control are central mechanisms underlying dopaminergic neuronal loss. In particular, abnormalities in mitophagy and mitochondrial fission-fusion balance contribute substantially to oxidative stress, energy metabolic failure, and neuronal injury. At present, most clinical treatments for PD mainly alleviate symptoms but do not effectively halt disease progression. Therefore, exploring new interventions targeting the core pathological mechanisms is of considerable significance. This study aims to investigate whether TMAS can improve neural damage and motor dysfunction in PD mice by regulating mitophagy and the fission/fusion dynamic balance, thereby providing theoretical and experimental support for its application in PD treatment. MethodsMale C57BL/6 mice were used in this study. A PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days. After model induction, mice in the intervention group received TMAS once daily for 14 consecutive days, whereas the corresponding control group received sham stimulation. The stimulation target was positioned over the primary motor cortex (M1). Motor performance was evaluated using the pole test and the open-field test. To verify the activation effect of TMAS on the target cortical region, c-Fos immunohistochemistry was performed in the M1. To assess nigral dopaminergic neuronal injury, tyrosine hydroxylase (TH) immunohistochemistry was used to quantify TH-positive neurons in the SNc. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels and adenosine triphosphate (ATP) content in the SNc. Western blot was further performed to determine the expression of mitophagy-related proteins, including PINK1, Parkin, LC3-II, and p62, as well as mitochondrial dynamics-related proteins, including Drp1 and Opa1. ResultsTMAS significantly increased the number of c-Fos-positive cells in M1 (P<0.000 1), indicating effective activation of neurons in the targeted cortical region. Compared with the control group, MPTP-treated mice exhibited marked motor dysfunction, including a significant reduction in total distance traveled in the open-field test (P<0.000 1) and mean speed (P=0.000 1), as well as significant prolongation of turn time and total climbing time in the pole test (P<0.000 1). These behavioral impairments were accompanied by a substantial loss of TH-positive dopaminergic neurons in the SNc, whereas TMAS significantly increased TH-positive neuron survival (P<0.000 1). In parallel, MPTP induced a pronounced increase in ROS levels and a significant reduction in ATP content, indicating severe mitochondrial dysfunction and energy metabolism impairment (P<0.01). TMAS treatment significantly improved motor performance, as reflected by the reversal of MPTP-induced impairment in the open-field and pole tests, and significantly reduced ROS accumulation (P<0.01) while restoring ATP production (P<0.001). At the molecular level, MPTP markedly downregulated PINK1 and Parkin, decreased p62 expression, increased LC3-II accumulation, elevated Drp1 expression, and reduced Opa1 expression, whereas TMAS significantly reversed these abnormalities, suggesting restoration of mitophagy-related mitochondrial quality control and re-establishment of mitochondrial fission-fusion balance. Collectively, these findings indicate that TMAS ameliorates MPTP-induced neurotoxicity and restores mitochondrial homeostasis and energy metabolism. ConclusionTMAS effectively attenuates neural damage and improves motor dysfunction in MPTP-induced PD mice. Its neuroprotective effects are closely associated with multidimensional regulation of the mitochondrial quality control system, including restoration of PINK1/Parkin-mediated mitophagy and rebalancing of Drp1/Opa1-related mitochondrial dynamics. Rather than acting only as a symptomatic neuromodulatory intervention, TMAS may influence a key pathological axis of PD by improving mitochondrial homeostasis in SNc and protecting nigral dopaminergic neurons. These findings provide experimental evidence supporting TMAS as a promising non-invasive physical intervention for PD.

ObjectiveTranscranial magneto-acoustic stimulation (TMAS) is an emerging non-invasive neuromodulation technique that may provide a novel non-pharmacological intervention strategy for Parkinson's disease (PD). PD is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to motor impairments such as bradykinesia, tremor, and rigidity. Increasing evidence indicates that mitochondrial dysfunction and impaired mitochondrial quality control are central mechanisms underlying dopaminergic neuronal loss. In particular, abnormalities in mitophagy and mitochondrial fission-fusion balance contribute substantially to oxidative stress, energy metabolic failure, and neuronal injury. At present, most clinical treatments for PD mainly alleviate symptoms but do not effectively halt disease progression. Therefore, exploring new interventions targeting the core pathological mechanisms is of considerable significance. This study aims to investigate whether TMAS can improve neural damage and motor dysfunction in PD mice by regulating mitophagy and the fission/fusion dynamic balance, thereby providing theoretical and experimental support for its application in PD treatment. MethodsMale C57BL/6 mice were used in this study. A PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days. After model induction, mice in the intervention group received TMAS once daily for 14 consecutive days, whereas the corresponding control group received sham stimulation. The stimulation target was positioned over the primary motor cortex (M1). Motor performance was evaluated using the pole test and the open-field test. To verify the activation effect of TMAS on the target cortical region, c-Fos immunohistochemistry was performed in the M1. To assess nigral dopaminergic neuronal injury, tyrosine hydroxylase (TH) immunohistochemistry was used to quantify TH-positive neurons in the SNc. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels and adenosine triphosphate (ATP) content in the SNc. Western blot was further performed to determine the expression of mitophagy-related proteins, including PINK1, Parkin, LC3-II, and p62, as well as mitochondrial dynamics-related proteins, including Drp1 and Opa1. ResultsTMAS significantly increased the number of c-Fos-positive cells in M1 (P<0.000 1), indicating effective activation of neurons in the targeted cortical region. Compared with the control group, MPTP-treated mice exhibited marked motor dysfunction, including a significant reduction in total distance traveled in the open-field test (P<0.000 1) and mean speed (P=0.000 1), as well as significant prolongation of turn time and total climbing time in the pole test (P<0.000 1). These behavioral impairments were accompanied by a substantial loss of TH-positive dopaminergic neurons in the SNc, whereas TMAS significantly increased TH-positive neuron survival (P<0.000 1). In parallel, MPTP induced a pronounced increase in ROS levels and a significant reduction in ATP content, indicating severe mitochondrial dysfunction and energy metabolism impairment (P<0.01). TMAS treatment significantly improved motor performance, as reflected by the reversal of MPTP-induced impairment in the open-field and pole tests, and significantly reduced ROS accumulation (P<0.01) while restoring ATP production (P<0.001). At the molecular level, MPTP markedly downregulated PINK1 and Parkin, decreased p62 expression, increased LC3-II accumulation, elevated Drp1 expression, and reduced Opa1 expression, whereas TMAS significantly reversed these abnormalities, suggesting restoration of mitophagy-related mitochondrial quality control and re-establishment of mitochondrial fission-fusion balance. Collectively, these findings indicate that TMAS ameliorates MPTP-induced neurotoxicity and restores mitochondrial homeostasis and energy metabolism. ConclusionTMAS effectively attenuates neural damage and improves motor dysfunction in MPTP-induced PD mice. Its neuroprotective effects are closely associated with multidimensional regulation of the mitochondrial quality control system, including restoration of PINK1/Parkin-mediated mitophagy and rebalancing of Drp1/Opa1-related mitochondrial dynamics. Rather than acting only as a symptomatic neuromodulatory intervention, TMAS may influence a key pathological axis of PD by improving mitochondrial homeostasis in SNc and protecting nigral dopaminergic neurons. These findings provide experimental evidence supporting TMAS as a promising non-invasive physical intervention for PD.

Objective: o develop an onset risk prediction nomogram for patients with homocysteine-type (H-type) hypertension (HTH) based on pulse diagram parameters to assist early clinical prediction and diagnosis of HTH. Methods: Patients diagnosed with essential hypertension and admitted to Shanghai Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai Hospital of Traditional Chinese Medicine, and Shanghai Hospital of Integrated Traditional Chinese and Western Medicine from July 6th 2020 to June 16th 2021, and from August 11th 2023 to January 22nd 2024, were enrolled in this retrospective research. The baselines and clinical biochemical indicators of patients were collected. The SMART-I TCM pulse instrument was applied to gather pulse diagram parameters. Multivariate logistic regression was adopted to analyze the risk factors for HTH. RStudio was employed to construct the nomogram model, receiver operating characteristic (ROC) curve, and calibration curve (bootstrap self-sampling 200 times), and clinical decision curve were drawn to evaluate the model’s discrimination and clinical effectiveness. Results: A total of 168 hospitalized patients with essential hypertension were selected and divided into non-HTH group (n = 29) and HTH group (n = 139). Compared with non-HTH group, HTH group had a lower body mass index (BMI), and higher proportions of male patients and drinkers (P < 0.05). The ventricular wall thickening (VWT) could not be determined. The proportions of left common carotid intima-media wall thickness (LCCIMWT) and serum creatinine (SCR) were higher in HTH group (P < 0.05). The pulse diagram parameter As was significantly higher, and H4/H1 and T1/T were lower in HTH group (P < 0.05). Gender, alcohol consumption, serum creatinine, and the pulse diagram parameter H4/H1 were identified as independent risk factors for HTH (P < 0.05). The nomogram’s area under the ROC curve (AUC) was 0.795 [95% confidence interval (CI): (0.706 6, 0.882 8)], with a specificity of 0.724 and sensitivity of 0.799. After 200 times repeated bootstrap self-samplings, the calibration curve showed that the simulated curve fits well with the actual curve (x2 = 9.5002, P = 0.301 9). The clinical decision curve indicated that the nomogram’s applicability was optimal when the threshold for predicting HTH was between 0.38 and 1.00. Conclusion The nomogram model could be valuable for predicting the onset risk of HTH and pulse diagram parameters can facilitate early screening and prevention of HTH.

ObjectiveTo explore quality difference factors of Perillae Caulis based on the contents of multiple chemical components and comprehensively evaluate the quality. MethodsA total of 32 batches of Perillae Caulis samples were collected from 12 producing areas such as Hebei， Anhui and Guangdong， and their diameter range， epidermis color and producing areas were recorded. Total flavonoids， total phenols， volatile oils， 5 active components and 84 volatile components in 32 batches of samples were quantitatively or semi-quantitatively determined by colorimetry， ultra performance liquid chromatography-photodiode array detector（UPLC-PDA） and gas chromatography-mass spectrometry（GC-MS）. Then the differences between the contents of these components were analyzed by principal component analysis（PCA） and non-parametric test. According to the weights of the index components determined by PCA model， entropy weight-technique for order preference by similarity to ideal solution（TOPSIS） model was constructed to evaluate the quality of Perillae Caulis with different characters and origins. ResultsThere were significant differences in the composition of Perillae Caulis with different diameters， epidermis colors and producing areas， and 9 differential components were screened out， including 6 index constituents（total flavonoids， total phenols， caffeic acid， scutellarin， rosmarinic acid and luteolin） and 3 volatile components（caryophyllene oxide， （-）-humulene epoxide Ⅱ， 14-hydroxycaryophyllene）， of which 6 index constituents were higher in samples with small diameter， purple-brown epidermis and southern origin， while the contents of 3 volatile components were higher in samples with large diameter， dark-brown epidermis and northern origin. A significant difference was shown in the model scores of different diameters， epidermis colors and origins（P<0.05）， and the scores of Perillae Caulis with small diameter and purple-brown epidermis from southern area， especially Guangdong， had a high score. ConclusionThere are significant differences in the composition and content of chemical constituents between different diameters， epidermal colors and production areas of Perillae Caulis， samples showing small diameter， owing purple-brown epidermis， and originating from Guangdong were of higher-quality due to their higher content of 8 key indices.

ObjectiveTo explore quality difference factors of Perillae Caulis based on the contents of multiple chemical components and comprehensively evaluate the quality. MethodsA total of 32 batches of Perillae Caulis samples were collected from 12 producing areas such as Hebei， Anhui and Guangdong， and their diameter range， epidermis color and producing areas were recorded. Total flavonoids， total phenols， volatile oils， 5 active components and 84 volatile components in 32 batches of samples were quantitatively or semi-quantitatively determined by colorimetry， ultra performance liquid chromatography-photodiode array detector（UPLC-PDA） and gas chromatography-mass spectrometry（GC-MS）. Then the differences between the contents of these components were analyzed by principal component analysis（PCA） and non-parametric test. According to the weights of the index components determined by PCA model， entropy weight-technique for order preference by similarity to ideal solution（TOPSIS） model was constructed to evaluate the quality of Perillae Caulis with different characters and origins. ResultsThere were significant differences in the composition of Perillae Caulis with different diameters， epidermis colors and producing areas， and 9 differential components were screened out， including 6 index constituents（total flavonoids， total phenols， caffeic acid， scutellarin， rosmarinic acid and luteolin） and 3 volatile components（caryophyllene oxide， （-）-humulene epoxide Ⅱ， 14-hydroxycaryophyllene）， of which 6 index constituents were higher in samples with small diameter， purple-brown epidermis and southern origin， while the contents of 3 volatile components were higher in samples with large diameter， dark-brown epidermis and northern origin. A significant difference was shown in the model scores of different diameters， epidermis colors and origins（P<0.05）， and the scores of Perillae Caulis with small diameter and purple-brown epidermis from southern area， especially Guangdong， had a high score. ConclusionThere are significant differences in the composition and content of chemical constituents between different diameters， epidermal colors and production areas of Perillae Caulis， samples showing small diameter， owing purple-brown epidermis， and originating from Guangdong were of higher-quality due to their higher content of 8 key indices.

This case report presents a 16-year-old male patient with deficiency of adenosine deaminase 2(DADA2). The patient had a history of Raynaud′s phenomenon with digital ulcers since childhood. As the disease progressed, the patient developed retinal vasculitis, intracranial hemorrhage, skin necrosis, severe malnutrition, refractory hypertension, and gastrointestinal bleeding. Genetic testing revealed compound heterozygous mutations in the ADA2 gene (paternal c.1072G > A pathogenic mutation + maternal c.1065C > A variant of unknown clinical significance). ADA2 enzyme activity was significantly reduced (0.1 U/L). A multidisciplinary treatment team developed an individualized plan to address key issues, including nutritional support, blood pressure control, rehabilitation, pain management, and balancing anticoagulation/bleeding risks. After systematic intervention, the patient′s condition showed partial improvement. This case reveals clinical challenges such as anticoagulation decisions and nutritional support of DADA2. It also emphasizes the importance of early molecular diagnosis, tumor necrosis factor-α inhibitor targeted therapy, and multidisciplinary collaboration in management, underlining the core value of precision medicine in rare disease management.

The body remains irreducible in medical development， and human reflections on life are mediated through the body. Living organ transplantation modifies the natural body， creating new identities for both donors and recipients. As the party that experiences only harm without benefit， the living donor’s body emerges in the illness of others， generating physical experiences ranging from the wholeness to the mutilation， the individual to the family， and the distinction to the intervention. The healthy body reemerges， disappears due to other’s disease， and becomes dependent on the recipient’s body. The complex physical experiences and feelings plunge the donor’s identity into confusion. Providing dual attention to the living donor’s body from both legal and ethical perspectives， dialectically thinking about bodily integrity， and deepening ethical considerations of personal self-determination and subjectivity may assist living donors in reshaping their bodily knowledge and rethinking their self-worth and the meaning of life from a different perspective.

Medical therapy and surgical intervention are the two primary approaches for treating myocardial bridge.However,there remains controversy regarding the use of coronary artery bypass grafting(CABG)and myocardial bridge unroofing.Here,we report a case of myocardial infarction following CABG in a patient with a myocardial bridge.The patient was admitted to Lanzhou First Peopie's Hospital with persistent chest pain,chest tightness,and shortness of breath lasting 2 hours.Physical examination revealed no significant abnormalities.Electrocardiography(ECG)indicated extensive anterior wall myocardial infarction.Laboratory findings showed myoglobin levels of 140.1 ng/ml and troponin Ⅰ levels of 2.59 ng/ml,with no other significant abnormalities.The initial diagnosis was acute extensive anterior wall myocardial infarction.Emergency coronary angiography revealed a myocardial bridge in the mid-segment of the left anterior descending artery(LAD).Emergency CABG using the left internal mammary artery to the LAD was performed,leading to symptomatic improvement,and the patient was discharged in stable condition.However,the patient experienced a recurrent myocardial infarction seven years post-surgery and received secondary preventive medical therapy.The patient is currently under ongoing follow-up care.CABG is an effective treatment for myocardial bridge.However,based on the case reported in this study,we recommend careful evaluation of whether a patient may benefit from CABG.

AIM To compare the chemical constituents in traditional decoction and formula granule decoction of classical famous prescription Wendan Decoction.METHODS The HPLC fingerprints were established,after which the contents of adenosine,synephrine,liquiritin,naringin,hesperidin,6-gingerol and adenosine cyclophosphate were determined,cluster analysis,principal component analysis and multidimensional scaling analysis were adopted in the investigation of component differences,and the equivalent of formula granules was adjusted.RESULTS The similarities of HPLC fingerprints for 10 batches of traditional decoctions were higher than those of HPLC fingerprints for 9 batches of formula granule decoctions(P＜0.01).Adenosine,synephrine,liquiritin,hesperidin and cyclic adenosine monophosphate demonstrated higher contents in traditional decoctions than those in formula granule decoctions(P＜0.05),6-gingerol displayed lower content than that in the latter produced by manufacturers A,C(P＜0.05),which was higher than that in the latter produced by manufacturer B(P＜0.01).Various batches of traditional decoctions and formula granule decoctions could be obviously distinguished,adenosine,synephrine and hesperidin exhibited great influences on the classification of principal component analysis,and the quality of formula granule decoctions produced by manufacturer C was closer to that of traditional decoctions.After equivalent correction,the contents of various constituents in formula granule decoctions produced by manufacturers A,C showed no significant differences as compared with those in traditional decoction(P＞0.05).CONCLUSION The formula granules of Wendan Decoction from different manufacturers exist quality differences,so the preparation process and extraction process of this preparation should be optimized to improve quality,and equivalent ratio should be adjusted according to actual requirements to ensure its scientific and rational clinical application.