Cancer stem cells (CSCs) represent a distinct subpopulation of cells characterized by self-renewal capacity, differentiation potential, and critical roles in driving tumor progression, therapeutic resistance, recurrence, and maintenance of the tumor microenvironment. Targeting CSCs has emerged as a pivotal direction in cancer research, offering novel strategies to overcome drug resistance and prevent metastasis and relapse. Lysosomes, traditionally recognized as central organelles for intracellular degradation and recycling, are indispensable for cellular homeostasis. Dysregulation of lysosomal function is intimately linked to various diseases, including cancer. In tumors, aberrant lysosomal activity can promote malignant progression through mechanisms such as altering metabolic pathways, enhancing lysosomal exocytosis, modulating drug resistance, and interfering with autophagy-lysosomal pathways. Recent studies have underscored the involvement of lysosomes in regulating CSC properties. This review synthesizes findings on lysosomal regulation of CSCs through the following aspects. (1) Lysosomes exert complex and critical bidirectional control over CSC stemness maintenance through three degradation pathways that are dependent on their degradative function. (i) The lysophagy pathway. This pathway exhibits dual roles. Activation can sustain CSC functions; for instance, in glioblastoma, hypoxia upregulates Gal-8 via the STAT3/HIF1α signaling axis to induce autophagy, supporting stem cell survival. In head and neck squamous cell carcinoma, degradation of GSK3β activates the Wnt pathway, enhancing stemness. Conversely, this pathway can suppress stemness by degrading stemness-related proteins such as BMI-1 and OCT4A, thereby impairing CSC self-renewal capacity. (ii) Mitophagy pathway. In non-small cell lung cancer stem cells, mitophagy-related mechanisms, such as the accumulation of mitochondrial DNA (mtDNA) activating the TLR9-Notch1-AMPK signaling axis, have been shown to promote CSC proliferation. (iii) Autophagosome-dependent lysosomal degradation pathway. This pathway directly regulates stemness-related proteins in a bidirectional manner. Enhanced degradative function can promote CSC properties, exemplified by the degradation of NUMB to activate Notch signaling. Conversely, attenuated degradative function can also enhance stemness by stabilizing oncoproteins (e.g., protecting Frizzled-1 from degradation to sustain Wnt signaling) or preventing the degradation of tumor suppressors (e.g., inhibiting Notch degradation). (2) Constituent proteins of lysosomes, including membrane proteins and luminal acid hydrolases, participate in regulating CSC stemness. Regarding membrane proteins, LAMP2A facilitates chaperone-mediated autophagy to maintain stemness in glioblastoma and ovarian cancer. V-ATPase, by maintaining an acidic luminal environment, promotes proliferation and drug resistance in glioma stem cells. Among hydrolases, cathepsins B and L are highly expressed in pancreatic and ovarian cancers and correlate with poor prognosis. Furthermore, targeting lysosomes to induce lysosomal membrane permeabilization (LMP) triggers lysosome-mediated cell death, presenting a potential therapeutic strategy for eradicating CSCs.(3) The acidic luminal environment, single-membrane structure, and the presence of transmembrane transporters (e.g., ABCA3) enable lysosomes to passively trap or actively uptake and sequester chemotherapeutic drugs. Subsequent drug extrusion via exocytosis confers drug resistance. In CSCs, this lysosome-mediated drug sequestration, often cooperating with autophagy, establishes multimodal drug resistance. Therefore, targeting lysosomal function represents a potential strategy to overcome therapy resistance. The central role of lysosomes in regulating CSC stemness and resistance positions them as highly promising therapeutic targets. Strategies aimed at disrupting lysosomal function to selectively eliminate CSCs include: inhibiting the lysosome-autophagy system using agents like IITZ or lovastatin; inducing lysosomal membrane permeabilization (LMP) with compounds such as hexamethylene amiloride to compromise membrane stability; and disrupting the acidic luminal environment using drugs like siramesine or the K/H transport compound 2. In conclusion, lysosomes critically regulate CSC stemness maintenance and drug resistance through degradative pathways, membrane protein functions, luminal hydrolase activities, and drug sequestration mechanisms. This redefines the lysosome from a traditional “waste disposal unit” to a “signal integration center” in CSCs. The duality and context-dependency of lysosomal function in CSCs offer novel insights into the heterogeneity observed across different tumors. Targeting lysosomal vulnerabilities—such as inducing LMP, disrupting acidity, or blocking autophagic flux—provides a strategy to bypass canonical CSC resistance mechanisms and directly trigger cell death. This establishes the lysosome as a key target to overcome CSC-mediated therapy resistance, paving the way for developing diverse candidate drugs and innovative combination therapies in oncology.

The Rotated Bipedicled Tram Flap: Maximising Breast Projection but Minimising Donor Morbidity - A Case Report Autologous breast reconstruction using the transverse rectus abdominis myocutaneous (TRAM) flap remains a cornerstone of breast reconstructive surgery. However, with the classical TRAM flap, it is challenging to close a large post mastectomy defect in nulliparous and/or slim women. The resultant reconstructed breast also lacks projection. This case reported a novel modified TRAM flap technique performed in a nullipara. She had previously undergone a hysterectomy and oophorectomy for endometrial carcinoma via a pfannenstiel incision. She presented with a large left breast invasive micropapillary carcinoma (ER/PR negative HER2 3+) with only marginal response to neoadjuvant chemotherapy. She underwent a left mastectomy with axillary dissection and immediate breast reconstruction. The rotated bipedicled TRAM Flap was used to close the large defect, maximising breast projection while minimising donor site morbidity.

AIM:To compare the clinical efficacy of pterygium excision combined with autologous conjunctival limbal transplantation versus the same procedure plus dehydrated amniotic membrane coverage for pterygium treatment in Qiandongnan region.

METHODS: This single-center retrospective cohort study enrolled patients diagnosed with primary nasal pterygium who received treatment at Qiandongnan Aier Eye Hospital from April 2023 to June 2025. All participants had resided locally for at least 5 y. Subjects were divided into two groups by surgical modality. Group A underwent pterygium excision combined with autologous conjunctival-limbal stem cell transplantation; Group B received identical core surgery supplemented with 10 mm×15 mm dehydrated biological amniotic membrane to cover the surgical wound. Preoperative baseline data, postoperative day 1 pain and ocular irritation symptoms, the incidence of postoperative complications, 6-month pterygium recurrence rate, and surgical outcome grading were compared between the two groups.

RESULTS: A total of 60 patients(60 eyes)were included, with 30 patients(30 eyes)assigned to each group. Group A consisted of 18 males and 12 females, with a mean age of 56.57±9.34 y; Group B contained 12 males and 18 females, with a mean age of 55.60±9.23 y. No statistically significant intergroup differences were observed in preoperative gender composition, age, or the length of pterygial corneal invasion(all P>0.05), indicating comparable baseline profiles. On postoperative day 1, painful sensation was recorded in 18 eyes(60%)in Group A and 10 eyes(33%)in Group B(P=0.038). Ocular irritation including foreign body sensation, photophobia, and lacrimation occurred in 17 eyes(57%)in Group A versus 5 eyes(17%)in Group B(P=0.001), indicating statistically significance. Regarding short-term postoperative complications: conjunctival hyperemia was noted in 11 eyes of Group A and 7 eyes of Group B on postoperative day 10(P=0.260); conjunctival granulomas developed in 3 eyes of Group A within 1 mo postoperatively, whereas no such lesions appeared in Group B(P=0.237). At the 6-month follow-up, pterygium recurrence was identified in 4 eyes(13%)of Group A, while no recurrence was detected in Group B(P=0.112), with no significant intergroup difference. At 6 mo postoperatively, the surgical outcome grading distribution was as follows: in Group A, Grade 1 was observed in 9 eyes(30%), Grade 2 in 11 eyes(37%), Grade 3 in 6 eyes(20%), and Grade 4 in 4 eyes(13%); in Group B, Grade 1 was observed in 15 eyes(50%), Grade 2 in 14 eyes(47%), Grade 3 in 1 eye(3%), and Grade 4 in 0 eyes(0%). Group B achieved superior overall grading results compared with Group A(P=0.013).

CONCLUSION:For patients in Qiandongnan region, intraoperative application of dehydrated biological amniotic membrane can markedly alleviate early postoperative ocular irritation and improve surgical outcome grading. Nevertheless, this adjunct material only yields a favorable trend in reducing recurrence risk; further studies with expanded sample sizes are required for verification.

BACKGROUND : The Indonesian chronic disease management program (PROLANIS) was introduced to provide structured chronic disease management for hypertension and type 2 diabetes (T2D) at the primary healthcare level. This study aimed to evaluate the health-related outcomes of PROLANIS among T2D patients in the eastern border region. METHODS : This retrospective cohort study used secondary data from PROLANIS reports of all primary healthcare facilities in Atambua Regency, East Nusa Tenggara Province, Indonesia. Inclusion criteria were all T2D patients who participated in routine 6-month evaluations conducted between June 2023 and December 2023. The assessed parameters and their defined targets were body mass index (BMI) (18.5–23 kg/m²), systolic blood pressure (SBP) (<140 mmHg), diastolic blood pressure (DBP) (<90 mmHg), hemoglobin A1c (HbA1c) (<7%), total cholesterol (TC) (<200 mg/dl), high-density lipoprotein (HDL) (>40 mg/dl for males and >50 mg/dl for females), low-density lipoprotein (LDL) (<100 mg/dl), and triglycerides (TGs) (<150 mg/dl). Wilcoxon signed-rank and paired t-tests were used for statistical analyses. RESULTS : There were 51 T2D patients included in the analyses. Of these, 84% achieved SBP and 96% achieved DBP targets. However, only 45% achieved HbA1c, and 33% achieved BMI targets. For lipid profiles, 55%, 51%, 47%, and 41% achieved TC, LDL, HDL, and TG targets, respectively. No significant differences were found between baseline and follow-up across these parameters (all p>0.05). CONCLUSIONS In the border region, while PROLANIS maintains blood pressure levels, it does not significantly improve other health-related outcomes in T2D patients. This underscores the need to strengthen program intensity, support adherence, and address contextual barriers to achieve meaningful metabolic improvements.
chronic disease ; government programs health services ; Indonesia ; primary healthcare ; type 2 diabetes mellitus

Renal fibrosis is the common pathological endpoint of many forms of chronic kidney disease (CKD), yet the mechanisms determining effective repair versus persistent fibrotic remodeling remain incompletely understood. Peritubular capillaries (PTCs) are not merely passive targets of fibrotic injury, but form a dynamic vascular microenvironment linking regional perfusion, oxygen delivery, tubular metabolism, endothelial barrier integrity, pericyte support, immune-cell trafficking, and extracellular matrix (ECM) remodeling. We propose that PTC abnormalities should not be interpreted simply as reduced capillary density, but as a multidimensional disturbance of microvascular structure and function. Structural vascular preservation does not necessarily indicate effective microcirculation: anatomically detectable capillaries may still exhibit impaired perfusion, barrier dysfunction, abnormal endothelial-pericyte interactions, disturbed oxygen metabolism, or reduced network connectivity. Conversely, increased angiogenesis does not necessarily signify successful vascular repair if vessels remain immature, poorly perfused, or inadequately integrated into the existing network. To organize these abnormalities, we conceptualize PTC remodeling into four predominant but nonexclusive states: endothelial barrier disruption with inflammatory adhesion; endothelial-pericyte uncoupling with no-reflow; dysregulated angiogenesis with network simplification; and capillary rarefaction with fibrotic matrix locking. These states are not sequential stages of CKD. They may coexist within the same kidney, overlap within the same anatomical region, and vary with disease etiology, injury phase, vascular compartment, and treatment exposure. We further propose six dimensions for evaluating PTC status—structural presence, functional perfusion, barrier integrity, pericyte coupling, oxygen metabolism, and network connectivity—so that vascular quantity, function, and reparative capacity are assessed separately rather than inferred from a single endothelial marker or capillary-density measurement. Mechanistically, these states converge on a bidirectional microvascular-fibrotic feedback loop. Barrier disruption facilitates leukocyte recruitment and alters vascular paracrine signaling. Endothelial-pericyte uncoupling compromises capillary stability, whereas abnormal pericyte contraction may increase local vascular resistance and contribute to no-reflow before overt capillary loss. Dysregulated angiogenesis may generate vessels that fail to mature or connect to an effective perfusion network. Progressive capillary rarefaction compromises oxygen delivery, while sustained tubular transport demand and mitochondrial dysfunction may aggravate regional oxygen supply-demand mismatch. Injured tubules, immune cells, endothelial cells, pericytes, and fibroblasts communicate through soluble mediators, extracellular vesicles, direct cell contact, and cell-matrix signaling. Importantly, fibrosis is not merely a downstream consequence of microvascular injury. Altered ECM may increase diffusion distance, modify mechanotransduction, impair endothelial survival and migration, and restrict capillary reopening and regeneration. We use the term matrix locking to describe this sustained constraint on vascular repair, while emphasizing that current evidence does not establish irreversible disease in humans. This framework also has therapeutic implications. PTC-directed treatment should not be reduced to increasing vessel number or uniformly promoting angiogenesis. Instead, intervention should be matched to the dominant and potentially reversible abnormality: preserving endothelial barrier function; restoring endothelial-pericyte stability and reducing pathological microvascular resistance; normalizing angiogenesis so that vascular growth is accompanied by maturation, barrier competence, network integration, and effective perfusion; and, in advanced rarefaction, relieving matrix-related constraints while supporting vascular regeneration. The context- and time-dependent effects of signaling through VEGF, Tie2, PDGF-B/PDGFRβ, eNOS/NO, and related pathways indicate that the same molecular signal may exert different effects depending on disease context and timing. Therapeutic efficacy should therefore be evaluated by restoration of effective microcirculation and tissue function rather than by isolated molecular changes or capillary counts alone. Despite increasing mechanistic evidence, the translational basis for this framework remains limited. Most causal and interventional data derive from animal or cell models, whereas human evidence is largely limited to pathological observations, patient-sample associations, and prognostic studies. Currently available circulating and urinary candidate biomarkers generally lack sufficient specificity for PTC injury or state assignment, and no standardized quantitative thresholds have been externally validated. The four-state model should therefore be regarded as a hypothesis-generating analytical framework rather than a clinicopathological classification system. Future studies should integrate spatially resolved tissue phenotyping, blood and urine biomarkers, and dynamic microcirculatory assessment in longitudinal cohorts. They should test reproducibility, assess prognostic value beyond conventional pathology, estimated glomerular filtration rate, and proteinuria, and determine whether changes in PTC status precede or mediate therapeutic benefit. Linking reproducible microvascular phenotypes to defined mechanisms, treatment response, and long-term renal outcomes will be essential to determine whether state-directed assessment and restoration of the PTC microenvironment can ultimately inform patient stratification and therapeutic decision-making.

Objective: To assess the effect of transarterial embolization (TAE) for adhesive capsulitis (AC) by evaluating clinical outcomes and changes in inflammation using magnetic resonance imaging (MRI). Materials and Methods: Patients who had undergone TAE between August 2020 and August 2023 for AC refractory to conservative treatments without any invasive procedures for more than 3 months, and had undergone baseline and 3-month post-AC follow-up contrast-enhanced MRI evaluations, were included. A suspension mixture of 500 mg imipenem/cilastatin in 10 mL of iodinated contrast agent was used for TAE. MRI results were analyzed to assess periarticular capsule/ligament inflammation. Clinical assessments included pain scores using the numeric rating scale (NRS) and functional scores using the quick disabilities of the arm, shoulder, and hand (Quick DASH) questionnaire. Results: Twenty-five patients (female:male, 14:11; age, 54.9 ± 7.1 years) were included. Significant reductions in average NRS pain scores as well as improvements in Quick DASH scores and range of motion, including anterior flexion and abduction, were observed at 1, 3, and 6 months after TAE (all P < 0.001). MRI analyses revealed that TAE significantly decreased the grades of axillary recess capsule enhancement, rotator interval (RI) capsule T2 signal intensity, and RI capsule enhancement (all P ≤ 0.004). Conclusion TAE may be an effective and safe therapeutic approach for AC refractory to conservative treatments, alleviating pain and supporting functional recovery. The observed MRI findings suggest that the effectiveness of TAE for AC may be attributed to the reduction of inflammation and the elimination of angiogenesis.

Objective: To assess the effect of transarterial embolization (TAE) for adhesive capsulitis (AC) by evaluating clinical outcomes and changes in inflammation using magnetic resonance imaging (MRI). Materials and Methods: Patients who had undergone TAE between August 2020 and August 2023 for AC refractory to conservative treatments without any invasive procedures for more than 3 months, and had undergone baseline and 3-month post-AC follow-up contrast-enhanced MRI evaluations, were included. A suspension mixture of 500 mg imipenem/cilastatin in 10 mL of iodinated contrast agent was used for TAE. MRI results were analyzed to assess periarticular capsule/ligament inflammation. Clinical assessments included pain scores using the numeric rating scale (NRS) and functional scores using the quick disabilities of the arm, shoulder, and hand (Quick DASH) questionnaire. Results: Twenty-five patients (female:male, 14:11; age, 54.9 ± 7.1 years) were included. Significant reductions in average NRS pain scores as well as improvements in Quick DASH scores and range of motion, including anterior flexion and abduction, were observed at 1, 3, and 6 months after TAE (all P < 0.001). MRI analyses revealed that TAE significantly decreased the grades of axillary recess capsule enhancement, rotator interval (RI) capsule T2 signal intensity, and RI capsule enhancement (all P ≤ 0.004). Conclusion TAE may be an effective and safe therapeutic approach for AC refractory to conservative treatments, alleviating pain and supporting functional recovery. The observed MRI findings suggest that the effectiveness of TAE for AC may be attributed to the reduction of inflammation and the elimination of angiogenesis.

Objective: To assess the effect of transarterial embolization (TAE) for adhesive capsulitis (AC) by evaluating clinical outcomes and changes in inflammation using magnetic resonance imaging (MRI). Materials and Methods: Patients who had undergone TAE between August 2020 and August 2023 for AC refractory to conservative treatments without any invasive procedures for more than 3 months, and had undergone baseline and 3-month post-AC follow-up contrast-enhanced MRI evaluations, were included. A suspension mixture of 500 mg imipenem/cilastatin in 10 mL of iodinated contrast agent was used for TAE. MRI results were analyzed to assess periarticular capsule/ligament inflammation. Clinical assessments included pain scores using the numeric rating scale (NRS) and functional scores using the quick disabilities of the arm, shoulder, and hand (Quick DASH) questionnaire. Results: Twenty-five patients (female:male, 14:11; age, 54.9 ± 7.1 years) were included. Significant reductions in average NRS pain scores as well as improvements in Quick DASH scores and range of motion, including anterior flexion and abduction, were observed at 1, 3, and 6 months after TAE (all P < 0.001). MRI analyses revealed that TAE significantly decreased the grades of axillary recess capsule enhancement, rotator interval (RI) capsule T2 signal intensity, and RI capsule enhancement (all P ≤ 0.004). Conclusion TAE may be an effective and safe therapeutic approach for AC refractory to conservative treatments, alleviating pain and supporting functional recovery. The observed MRI findings suggest that the effectiveness of TAE for AC may be attributed to the reduction of inflammation and the elimination of angiogenesis.

AIM To study the chemical constituents from ethyl acetate fraction of Balanophora harlandii Hook.f.and their tyrosinase inhibitory activity.METHODS Separation and purification were performed using silica gel,MCI,ODS,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The monophenolase inhibitory activity was determined by the tyrosinase-catalyzed oxidation of L-tyrosine.RESULTS Twenty-four compounds were isolated and identified as sesamin(1),methyl caffeate(2),quercetin(3),5,7-dihydroxychromanone(4),methyl 3,4-dihydroxybenzoate(5),esculetin(6),kaempferol(7),naringenin(8),pyrogallic acid(9),pinosylvin(10),methyl propionate(11),caffeic acid(12),saccharinol(13),ferulic acid(14),trans-p-hydroxycinnamic acid(15),cinnamic acid(16),vanillic acid(17),vanillin(18),4-hydroxyacetophenone(19),4-hydroxybenzaldehyde(20),apigenin(21),(-)-isolariciresinol(22),(-)-secoisolariciresinol(23)and meso-2,3-di(3′,4′-methylenedioxybenzyl)butane-1,4-diol(24).The IC50 values of compounds 3,5,7,8,19,and 20 ranged from(0.246 5±0.028 3)to(1.278 2±0.021 3)mmol/L.CONCLUSION Compounds 1-9、11、15、17-21、24 are isolated from this plant for the first time,and 1,6,9,17-19,24 are first isolated from genus Balanophora.Compounds 3、5、7、8、19 and 20 have tyrosinase inhibitory activity.

Objective:To identify the risk factors for postoperative sleep disturbance (PSD) in patients undergoing spine surgery.Methods:In this case-control study, patients who underwent spine surgery from December 2023 to June 2024 at Beijing Tiantan Hospital of Capital Medical University, were selected as the subjects of the study. The quality of postoperative sleep was assessed using the Athens Insomnia Scale (AIS). The baseline characteristics and various perioperative indicators of the patients were collected. The patients were divided into PSD group and non-PSD group according to whether they had PSD. The variables with statistically significant differences from the univariate analysis were included in a multivariate logistic regression to identify the risk factors for PSD.Results:The results of the multivariate logistic regression analysis showed that preoperative sleep disturbance (odds ratio [ OR]=2.23, 95% confidence interval [ CI] 1.06-4.72, P=0.036), course of disease > 12 months ( OR=2.20, 95% CI 1.14-4.24, P=0.019) and AIS score > 2 on the night before surgery ( OR=2.06, 95% CI 1.02-4.16, P=0.045) were the independent risk factors for PSD in patients undergoing spine surgery. Conclusions:Preoperative sleep disturbance, course of disease > 12 months and AIS score > 2 on the night before surgery are independent risk factors for PSD in patients undergoing spine surgery.