ObjectiveTo elucidate the chemical composition of the reference sample of Jinshui Liujunjian and its distribution characteristics in blood and tissues of rats. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect the reference sample solution， plasma， and tissue samples of Jinshui Liujunjian under positive and negative ion modes， respectively. Qualitative Analysis 10.0 software and a self-constructed database were employed for primary mass spectrum matching.Compound identification was further validated by comparing retention times， secondary mass spectral fragments， reference standards， and literature data to deduce fragmentation pathways. ResultsA total of 122 compounds were identified in the reference sample of Jinshui Liujunjian， including 47 flavonoids， 5 amino acids， 13 iridoids， 16 triterpenoid saponins， etc.， of which 42 compounds were confirmed by comparison with reference substances. A total of 21 prototype components were identified in blood components； 50 prototype components were identified in different tissues， among which 13， 10， 7， 21， 11， 6， 14， and 40 prototype components were identified in the heart， liver， spleen， lung， kidney， brain， large intestine， and stomach， respectively. Among them， 7 compounds such as ferulic acid， glycyrrhizic acid， and nobiletin were exposed in the target organs of lung and kidney. ConclusionThis study elucidates the material basis of the reference samples of Jinshui Liujunjian， primarily composed of flavonoids and triterpenoid saponins， along with their in vivo distribution characteristics. These findings provide a scientific basis for establishing quality evaluation indicators and offer references for subsequent pharmacodynamic and pharmacokinetic investigations.

ObjectiveTo elucidate the chemical composition of the reference sample of Jinshui Liujunjian and its distribution characteristics in blood and tissues of rats. MethodsUltra performance liquid chromatography-quadrupole-time-of-flight tandem mass spectrometry（UPLC-Q-TOF-MS/MS） was used to detect the reference sample solution， plasma， and tissue samples of Jinshui Liujunjian under positive and negative ion modes， respectively. Qualitative Analysis 10.0 software and a self-constructed database were employed for primary mass spectrum matching.Compound identification was further validated by comparing retention times， secondary mass spectral fragments， reference standards， and literature data to deduce fragmentation pathways. ResultsA total of 122 compounds were identified in the reference sample of Jinshui Liujunjian， including 47 flavonoids， 5 amino acids， 13 iridoids， 16 triterpenoid saponins， etc.， of which 42 compounds were confirmed by comparison with reference substances. A total of 21 prototype components were identified in blood components； 50 prototype components were identified in different tissues， among which 13， 10， 7， 21， 11， 6， 14， and 40 prototype components were identified in the heart， liver， spleen， lung， kidney， brain， large intestine， and stomach， respectively. Among them， 7 compounds such as ferulic acid， glycyrrhizic acid， and nobiletin were exposed in the target organs of lung and kidney. ConclusionThis study elucidates the material basis of the reference samples of Jinshui Liujunjian， primarily composed of flavonoids and triterpenoid saponins， along with their in vivo distribution characteristics. These findings provide a scientific basis for establishing quality evaluation indicators and offer references for subsequent pharmacodynamic and pharmacokinetic investigations.

Lymphoma is a highly heterogeneous malignancy characterized by complex molecular regulatory mechanisms that result in significant differences in aggressiveness and prognosis across its subtypes.Gene copy number alteration(CNA)analysis,an emerging technology,has become a pivotal tool in the precision re-search and management of lymphoma.By detecting DNA deletions,amplifications,and chromosomal copy number changes,CNA analysis addresses the limitations of traditional cytogenetic techniques,enhances the ac-curacy of subtype classification,and aids in evaluating tumor heterogeneity and disease progression.This re-view provides a comprehensive summary of CNA detection methods and their applications in lymphoma,with a focus on recent advancements in the field.It offers a comparative analysis of CNA detection techniques and discusses their role in precision diagnosis,subtype classification,monitoring disease progression,predicting therapeutic resistance,and assessing prognosis.Additionally,the review explores the potential applications of CNA analysis in uncovering molecular regulatory mechanisms,optimizing therapeutic strategies,and impro-ving patient survival outcomes.

Atherosclerosis(As)is a chronic inflammatory vascular disease and serves as the pathological basis for various cardiovascular diseases.Epigallocatechin-3-O-gallate(EGCG)is the most abundant and biologically active com-pound in green tea,possessing multiple pharmacological effects such as anti-inflammatory,antiviral,and antioxidative stress properties.In recent years,studies have found that EGCG can regulate lipid metabolism,improve vascular endo-thelial function,and enhance plaque stability,demonstrating its potential value in combating As.This article provides a systematic review of the mechanisms underlying EGCG's anti-As effects,aiming to offer multi-faceted theoretical support for its further research and clinical application in the prevention and treatment of As.

This article highlights the limitations of traditional treatment methods for non-muscle-invasive bladder cancer and the multi-dimensional exploration of emerging strategies.It firsty reviews the history and challenges of BCG immunotherapy,pointing out its bottlenecks in efficacy,tolerance,and supply,and focuses on its chemicobiological modifications,such as the optimization of nanoparticle drug delivery systems and immune-active components.Subsequently,it summarizes the development of various new treatment approaches,including gene therapy,photodynamic/sonodynamic therapy,chemodynamic therapy,and proteolysis-targeting chimeras for targeted protein degradation strategies.It particularly emphasizes the enhancement of drug delivery efficiency and targeting in the bladder through nanotechnology,aptamer-mediated systems,and biomimetic carriers.The treatment of bladder cancer is gradually transforming from local and single-mode to precise,synergistic,and low-toxicity directions,with chemicobiological means playing a core role in driving this transformation.Interdisciplinary integration provides a broad space and new hope for the treatment of bladder cancer.

BACKGROUND:Fasudil has a regulatory effect on mitochondrial dynamics in the brain of Alzheimer's disease mice and can inhibit neuroinflammation,but whether it can reduce the toxicity of β-amyloid protein by regulating mitophagy-NLRP3 inflammasome pathway remains unclear.OBJECTIVE:To investigate the regulatory effect of fasudil on β-amyloid 1-42-induced apoptosis and mitophagy and NLRP3 inflammasome in human derived neuroblastoma cell line SH-SY5Y cells.METHODS:SH-SY5Y cells were inoculated into the pore plate.After adhesion,cells were divided into three groups for intervention:No drug was added to the control group;20 μmol/L β-amyloid 1-42 was added to the model group,and 20 μmol/L β-amyloid 1-42 and 15 mg/L fasudil were added to the fasudil group at the same time.After 24 hours of intervention,the cell activity was detected by MTT assay and apoptosis was detected by TUNEL staining.The expression of apoptosis-related proteins was detected by qRT-PCR and western blot assay.The expression of mitochondrial autophagy related proteins was detected by immunofluorescence staining and western blot assay.The expression of NLRP3 inflammasome related proteins was detected by immunofluorescence staining and western blot assay.RESULTS AND CONCLUSION:(1)Compared with control group,the cell activity of the model group was decreased and the apoptosis rate was increased(P<0.05).Compared with model group,cell activity in the fasudil group was increased and apoptosis rate was decreased(P<0.05).(2)The results of qRT-PCR and western blot assay showed that compared with the control group,the expression of Bax mRNA and protein was increased in the model group(P<0.05),while the expression of Bcl-2 mRNA and protein was decreased(P<0.05).Compared with the model group,the expression of Bax mRNA and protein was decreased(P<0.05),and the expression of Bcl-2 mRNA and protein was increased(P<0.05)in the fasudil group.(3)The results of immunofluorescence staining and western blot assay showed that compared with the control group,the expressions of PINK1,Parkinson's disease protein and LC3 protein were decreased(P<0.05),while the expression of p62 protein was increased(P<0.05)in the model group.Compared with model group,the expression levels of PINK1,Parkinson's disease protein,and LC3 protein were increased(P<0.05),while the expression of p62 protein was decreased(P<0.05)in the fasudil group.(4)The results of immunofluorescence staining and western blot assay showed that compared with the control group,the expression levels of NLRP3,ASC,Caspase-1,and interleukin1β protein were increased in the model group(P<0.05).Compared with the model group,the expression levels of NLRP3,ASC,Caspase-1,and interleukin1β were decreased in the fasudil group(P<0.05).(5)The results show that fasudil can reduce the apoptosis of SH-SY5Y cells induced by β-amyloid 1-42,and its mechanism may be related to the activation of mitophagy and the inhibition of NLRP3 inflammasome activation.

This study explores the effect of total secondary ginsenosides(TSG) on apoptosis and energy metabolism in H9c2 cells under hypoxia and its potential mechanisms. H9c2 cell viability was observed and the apoptosis rate was calculated to determine suitable intervention concentrations of TSG, antimycin A complex(AMA), and coenzyme Q10(CoQ10), along with the duration of hypoxia. H9c2 cells at the logarithmic phase were divided into a normal group, a model group, a TSG group, an AMA group, a TSG+AMA group, and a CoQ10 group. All groups, except the normal group, were treated with their respective intervention drugs and cultured under hypoxic conditions. Adenosine triphosphate(ATP) content and creatine kinase(CK) activity were measured using an ATP chemiluminescence assay kit and a CK colorimetric assay kit. Flow cytometry was used to assess apoptosis rates, and Western blot evaluated the expression levels of apoptosis-related proteins, including B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), cysteinyl aspartate-specific protease(caspase)-3, caspase-8, and caspase-9, as well as mitochondrial biogenesis-related proteins peroxisome proliferator-activated receptor-γ coactivator 1α(PGC-1α), estrogen-related receptor-α(ERRα), nuclear respiratory factor(NRF)-1, NRF-2, peroxisome proliferator activated receptor-α(PPARα), and Na~+-K~+-ATPase. RT-PCR was employed to analyze the mRNA expression of mitochondrial biogenesis factors, including PGC-1α, ERRα, NRF-1, NRF-2, PPARα, mitochondrial transcription factor A(TFAM), mitochondrial cytochrome C oxidase 1(COX1), and mitochondrial NADH dehydrogenase subunit 1(ND1), ND2. The selected intervention concentrations were 7.5 μg·mL~(-1) for TSG, 10 μmol·L~(-1) for AMA, and 1×10~(-4) mol·L~(-1) for CoQ10, with a hypoxia duration of 6 h. Compared with the normal group, the model group showed decreased ATP content and CK activity, increased apoptosis rates, decreased Bcl-2 expression, and increased Bax, caspase-3, caspase-8, and caspase-9 expression in H9c2 cells. Additionally, the protein and mRNA expression levels of mitochondrial biogenesis-related factors(PGC-1α, ERRα, NRF-1, NRF-2, PPARα), mRNA expression of TFAM, COX1, and ND1, ND2, and protein expression of Na~+-K~+-ATPase in mitochondrial DNA, were also reduced. In the TSG and CoQ10 groups, ATP content and CK activity increased, and apoptosis rates decreased compared with those in the model group. The TSG group showed decreased protein expression of apoptosis-related proteins Bax, caspase-3, caspase-8, and caspase-9, increased protein and mRNA expression of mitochondrial biogenesis factors PGC-1α, ERRα, NRF-1, and PPARα, and increased NRF-2 protein expression and TFAM mRNA expression in mitochondrial DNA. Conversely, in the AMA group, ATP content and CK activity decreased, the apoptosis rate increased, Bcl-2 expression decreased, and Bax, caspase-3, caspase-8, and caspase-9 expression increased, alongside reductions in PGC-1α, ERRα, NRF-1, NRF-2, PPARα protein and mRNA expression, as well as TFAM, COX1, ND1, ND2 mRNA expression and Na~+-K~+-ATPase protein expression. Compared with the TSG group, the TSG+AMA group exhibited decreased ATP content and CK activity, increased apoptosis rates, decreased Bcl-2 expression, and increased Bax, caspase-3, caspase-8, and caspase-9 expression, along with decreased PGC-1α, ERRα, NRF-1, NRF-2, and PPARα protein and mRNA expression and TFAM, COX1, and ND1, ND2 mRNA expression. Compared with the AMA group, the TSG+AMA group showed increased CK activity, decreased apoptosis rate, increased Bcl-2 expression, and decreased Bax, caspase-8, and caspase-9 expression. Additionally, the protein and mRNA expression of PGC-1α, ERRα, NRF-1, PPARα, mRNA expression of TFAM, COX1, ND1, ND2, and Na~+-K~+-ATPase protein expression increased. In conclusion, TSG enhance ATP content and CK activity and inhibit apoptosis in H9c2 cells under hypoxia, and the mechanisms may be related to the regulation of PGC-1α, ERRα, NRF-1, NRF-2, PPARα, and TFAM expression, thus promoting mitochondrial biogenesis.
Apoptosis/drug effects* ; Ginsenosides/pharmacology* ; Energy Metabolism/drug effects* ; Mitochondria/metabolism* ; Animals ; Rats ; Cell Line ; Cell Hypoxia/drug effects* ; Organelle Biogenesis ; Adenosine Triphosphate/metabolism* ; Humans ; Cell Survival/drug effects*

Drug administration via hollow microneedles (HMN) have the advantages of painlessness, avoidance of first-pass effect, capability of sustained infusion, and no need for professional personnel operation. In addition, HMN can also be applied in the fields of body fluid extraction and biosensors, showing broad application prospects. However, traditional manufacturing technologies cannot meet the demand for low-cost mass production of HMN, limiting its widespread application. This paper reviews the main manufacturing technologies used for HMN in recent years, which include photolithography and etching, laser etching, sputtering and electroplating, micro-molding, three-dimensional (3D) printing and drawing lithography. It further analyzes the characteristics and limitations of existing manufacturing technologies and points out that the combination of various manufacturing technologies can improve production efficiency to a certain extent. In addition, this paper looks forward to the future trends of HMN manufacturing technology and proposes possible directions for its development. In conclusion, it is expected that this review can provide new ideas and references for follow-up research.
Printing, Three-Dimensional ; Needles ; Humans ; Drug Delivery Systems/methods* ; Equipment Design ; Microinjections/methods*

Objective To investigate the predictive value of preoperative ultrasound in combination with neutrophil-to-lymphocyte ratio(NLR),calcitonin(Ctn),and carcinoembryonic antigen(CEA)for cervical lymph node metastasis in patients with papillary thyroid carcinoma.Methods A total of 103 patients diagnosed with papillary thyroid carcinoma(PTC)who were admitted to the hospital between October 2021 and October 2024 were selected as the case group.Among them,34 patients with cervical lymph node metastasis confirmed by surgical and pathological examination were assigned to the metastatic group,and 69 patients without cervical lymph node metas-tasis were assigned to the non-metastatic group.Additionally,103 patients with benign thyroid nodules admitted during the same period were enrolled as the control group.Clinical data,ultrasonographic features,and serum levels of NLR,Ctn,and CEA were compared between the metastatic and non-metastatic groups.The predictive value of ultrasonographic features and the combined detection of NLR,Ctn,and CEA levels for cervical lymph node metastasis in PTC was evaluated using receiver operating characteristic(ROC)curve analysis.Results Compared to the control group,the case group exhibited a higher proportion of patients with microcalcification and grade 3 blood flow,as well as elevated levels of NLR,Ctn,and CEA(P<0.05).Similarly,compared to the non-metastatic group,the metastatic group showed a higher proportion of patients with microcalcification and grade 3 blood flow,along with increased levels of NLR,Ctn,and CEA(P<0.05).The metastatic group tested positive,whereas the non-metastatic group tested negative.The area under the curve(AUC)for ultrasound features(micro-calcification,blood flow classification)combined with NLR,Ctn,and CEA levels in diagnosing cervical lymph node metastasis in papillary thyroid carcinoma was higher than that of individual indicators(P<0.05).Conclusions Preoperative ultrasound combined with the assessment of NLR,Ctn,and CEA levels demonstrates significant predictive value for cervical lymph node metastasis in papillary thyroid carcinoma.

Atherosclerosis(As)is a chronic inflammatory vascular disease and serves as the pathological basis for various cardiovascular diseases.Epigallocatechin-3-O-gallate(EGCG)is the most abundant and biologically active com-pound in green tea,possessing multiple pharmacological effects such as anti-inflammatory,antiviral,and antioxidative stress properties.In recent years,studies have found that EGCG can regulate lipid metabolism,improve vascular endo-thelial function,and enhance plaque stability,demonstrating its potential value in combating As.This article provides a systematic review of the mechanisms underlying EGCG's anti-As effects,aiming to offer multi-faceted theoretical support for its further research and clinical application in the prevention and treatment of As.