ObjectiveTo establish an ultra-performance liquid fingerprint and multi-components determination method for Naomaili granules. To evaluate the quality of different batches by chemometrics， and the anti-neuroinflammatory effects of water extract and main components of Naomaili granules were tested in vitro. MethodsThe similarity and common peaks of 27 batches of Naomaili granules were evaluated by using Ultra performance liquid chromatography （UPLC） fingerprint detection. Ultra-performance liquid chromatography-tandem mass spectrometry （UPLC-MS/MS） technology was used to determine the content of the index components in Naomaili granules and to evaluate the quality of different batches of Naomaili granules by chemometrics. LPS-induced BV-2 cell inflammation model was used to investigate the anti-neuroinflammatory effects of the water extract and main components of Naomaili granules. ResultsThe similarity of fingerprints of 27 batches of samples was > 0.90. A total of 32 common peaks were calibrated， and 23 of them were identified and assigned. In 27 batches of Naomaili granules， the mass fractions of 14 components that were stachydrine hydrochloride， leonurine hydrochloride， calycosin-7-O-glucoside， calycosin，tanshinoneⅠ， cryptotanshinone， tanshinoneⅡ_A， ginsenoside Rb₁， notoginsenoside R₁， ginsenoside Rg₁， paeoniflorin， albiflorin， lactiflorin， and salvianolic acid B were found to be 2.902-3.498， 0.233-0.343， 0.111-0.301， 0.07-0.152， 0.136-0.228， 0.195-0.390， 0.324-0.482， 1.056-1.435， 0.271-0.397， 1.318-1.649， 3.038-4.059， 2.263-3.455， 0.152-0.232， 2.931-3.991 mg∙g^-1， respectively. Multivariate statistical analysis showed that paeoniflorin， ginsenoside Rg₁， ginsenoside Rb₁ and staphylline hydrochloride were quality difference markers to control the stability of the preparation. The results of bioactive experiment showed that the water extract of Naomaili granules and the eight main components with high content in the prescription had a dose-dependent inhibitory effect on the release of NO in the cell supernatant. Among them， salvianolic acid B and ginsenoside Rb₁ had strong anti-inflammatory activity， with IC₅₀ values of （36.11±0.15） mg∙L^-1 and （27.24±0.54） mg∙L^-1， respectively. ConclusionThe quality evaluation method of Naomaili granules established in this study was accurate and reproducible. Four quality difference markers were screened out， and eight key pharmacodynamic substances of Naomaili granules against neuroinflammation were screened out by in vitro cell experiments.

ObjectiveTo evaluate the clinical efficacy of Shenqi Yangxin decoction in the treatment of ischemic cardiomyopathy （ICM） with Qi and Yin deficiency and blood stasis syndrome and its effect on serum hydrogen sulfide （H₂S） and calcium ion （Ca²⁺）. MethodsA total of 64 ICM patients with Qi and Yin deficiency and blood stasis syndrome who met the inclusion criteria were randomly divided into a control group （n=32） and a treatment group （n=32）. All patients received conventional Western medicine treatment. The treatment group was additionally given Shenqi Yangxin decoction. The TCM syndrome score， Minnesota Living with Heart Failure Questionnaire （MLHFQ） score， left ventricular ejection fraction （LVEF）， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， 6-minute walk test （6MWT）， New York Heart Association （NYHA） cardiac function classification， and serum H₂S and Ca²⁺ levels were compared between the two groups pre- and post-treatment. ResultsTwo cases dropped out from each group during the study. Finally， 30 patients in each group were included in the analysis. There were no significant differences in age， gender， course of coronary heart disease， underlying diseases， and laboratory tests between the two groups. Compared with baseline， the TCM syndrome score， MLHFQ score， and NT-proBNP in both treatment group and control group decreased significantly （P<0.01）， LVEF， 6MWT， and H₂S increased significantly （P<0.01）， and serum Ca²⁺ increased （P<0.05）. Compared with the control group after treatment， the MLHFQ score and NT-proBNP in the treatment group decreased （P<0.05）， the TCM syndrome score decreased significantly （P<0.01）， LVEF， 6MWT， and serum Ca²⁺ increased （P<0.05）， and H₂S increased significantly （P<0.01）. The improvement degree of the NYHA cardiac function classification in the treatment group was higher than that in the control group， but there was no significant difference. ConclusionShenqi Yangxin decoction is effective in treating ICM patients with Qi and Yin deficiency and blood stasis， which could significantly improve cardiac function and quality of life， and its therapeutic effect may be related to the regulation of serum H₂S and Ca²⁺ levels.

Objective To investigate the prevalence of Clonorchis sinensis human infections in Congjiang County, Guizhou Province in 2023, so as to provide insights into formulation of the clonorchiasis control strategy. Methods Congjiang County was divided into eastern, western, southern, northern and central areas according to the geographical locations, and one township was randomly sampled from each area. Then, each administrative village was randomly sampled from each township, and 200 permanent residents over 3 years of age were randomly sampled from each village. Participants’ stool samples were collected for detection of C. sinensis eggs with the Kato-Katz technique (two slides for each stool sample), and the prevalence and intensity of C. sinensis infections were calculated. In addition, the risk factors of clonorchiasis were identified among participants using a questionnaire survey. Results A total of 1 001 residents were included, and the prevalence of C. sinensis infections was 16.28% (163/1 001), with mild infections as the predominant category of infection intensity [73.01% (119/163)]. The prevalence rates of C. sinensis human infections were 30.50% (61/200), 1.50% (3/200), 30.35% (61/201), 12.50% (25/200), and 6.50% (13/200) at five survey sites, respectively (χ² = 107.03, P < 0.05), and there was a significant difference in the prevalence of C. sinensis infections between men [22.44% (112/499)] and women [10.16% (51/502)] (χ² = 27.71, P < 0.05). The prevalence of C. sinensis infections was relatively high among participants at ages of 60 to 70 years [26.14% (23/88)], public servants [46.15% (6/13)], and Han ethnic participants [33.33% (5/15)]. The prevalence of C. sinensis infections was higher among participants with a habit of consuming raw or un-dercooked freshwater fish and shrimp [22.06% (90/408)] than among those without the habit [12.31% (73/593)] (χ² = 16.85, P < 0.05), and there was no significant difference in the prevalence of C. sinensis infections between participants with [13.99% (41/293)] and without separation of raw and cooked chopping boards [17.23% (122/708)] (χ² = 1.59, P > 0.05). In addition, the prevalence of C. sinensis infections was 8.70% (2/23) and 16.46% (161/978) among participants with and without fever complicated by discomfort in the right upper abdomen during the past half year (χ² = 0.99, P > 0.05). Conclusions The prevalence of C. sinensis human infections was high in Congjiang County, Guizhou Province in 2023, and infections predominantly occurred among young and middle-aged men. Intensified health education among high-risk residents and alteration of dietary habits of consuming raw or undercooked freshwater fish or shrimp are recommended to reduce the prevalence of C. sinensis human infections.

BACKGROUND:Neutrophil extracellular traps and activated platelets are involved in the invasion,metastasis,growth,and angiogenesis of lung cancer,and are closely related to the development and prognosis of lung cancer.OBJECTIVE:To review the mechanism of neutrophil extracellular traps and activated platelets in lung cancer and their application in diagnosis,prognosis,and treatment of lung cancer.METHODS:"Platelet activation,lung neoplasms,extracellular traps,treatment"for English search terms and"lung cancer,neutrophil-extracellular traps,platelet activation,P-selectin,treatment"for Chinese search terms were searched in PubMed and CNKI databases.After reading the title and abstract of the literature,according to the inclusion and exclusion criteria,63 articles with high relevance were finally included.RESULTS AND CONCLUSION:(1)Formation of neutrophil extracellular traps and platelet activation were induced by lung tumor.(2)Neutrophil extracellular traps and activated platelets jointly promote the proliferation,growth and metastasis of lung cancer.(3)Neutrophil extracellular traps can be used as a novel biomarker for the diagnosis,prognosis and progression of lung cancer.(4)Targeting neutrophil extracellular traps and activating platelets can be used as potential therapies for lung cancer.

BACKGROUND:Neutrophil extracellular traps and activated platelets are involved in the invasion,metastasis,growth,and angiogenesis of lung cancer,and are closely related to the development and prognosis of lung cancer.OBJECTIVE:To review the mechanism of neutrophil extracellular traps and activated platelets in lung cancer and their application in diagnosis,prognosis,and treatment of lung cancer.METHODS:"Platelet activation,lung neoplasms,extracellular traps,treatment"for English search terms and"lung cancer,neutrophil-extracellular traps,platelet activation,P-selectin,treatment"for Chinese search terms were searched in PubMed and CNKI databases.After reading the title and abstract of the literature,according to the inclusion and exclusion criteria,63 articles with high relevance were finally included.RESULTS AND CONCLUSION:(1)Formation of neutrophil extracellular traps and platelet activation were induced by lung tumor.(2)Neutrophil extracellular traps and activated platelets jointly promote the proliferation,growth and metastasis of lung cancer.(3)Neutrophil extracellular traps can be used as a novel biomarker for the diagnosis,prognosis and progression of lung cancer.(4)Targeting neutrophil extracellular traps and activating platelets can be used as potential therapies for lung cancer.

Objectives: . This study aimed to explore the role of the Pcdh15 gene in hearing maintenance and to examine the effects of its deficiency on cochlear structure, cochlear function, and hearing loss in mice. Methods: . CRISPR/Cas9 technology was used to generate Pcdh15 knockout (KO) mice. Auditory function was evaluated using hearing tests, while histological approaches were employed to assess morphological changes in cochlear hair cells and spiral ganglion neurons (SGNs). RNA sequencing (RNA-seq) was performed on cochlear tissue from postnatal day 18 (P18) wild-type (WT) and Pcdh15 KO mice to identify differentially expressed genes (DEGs). These DEGs were subjected to functional annotation and pathway analysis, with particular emphasis on oxidative phosphorylation (OXPHOS). Reactive oxygen species (ROS) levels were quantified using flow cytometry and DCFH-DA assays. Results: . Pcdh15 KO mice exhibited progressive sensorineural hearing loss, which worsened to profound deafness by P18. Notably, cochlear hair cells and SGNs showed substantial loss and pronounced morphological abnormalities, particularly within the basal high-frequency region. RNA-seq analysis identified 1,359 DEGs, including 1,024 downregulated and 335 upregulated genes. Pathway analysis indicated that Pcdh15 deficiency was associated with inhibition of the OXPHOS pathway, potentially disrupting mitochondrial respiratory chain complexes I, III, IV, and V and thereby impairing energy production and ATP metabolism. In addition, early-stage cochleae from KO mice demonstrated elevated ROS levels and increased oxidative stress, suggesting that redox imbalance may contribute to hearing damage. Conclusion . Pcdh15 plays a critical role in hearing maintenance. Its deficiency is associated with severe hearing loss and marked cochlear abnormalities, which are linked to inhibition of OXPHOS, disruption of energy metabolism, and exacerbation of oxidative stress. Together, these findings provide new insights into the mechanisms underlying hearing loss and suggest potential targets for therapeutic intervention.

ObjectiveCerebral ischemic injury triggers a complex pathological cascade characterized by excessive reactive oxygen species (ROS) accumulation, persistent oxidative stress, and sustained neuroinflammation in the injured brain microenvironment. These events collectively drive mitochondrial dysfunction, microglial overactivation, pro-inflammatory cytokine release, and progressive neuronal apoptosis, ultimately leading to severe and irreversible neurological deficits. However, conventional therapeutic strategies face critical limitations, including poor blood-brain barrier penetration, insufficient local drug concentration, uncontrolled drug release, and off-target systemic side effects. To address this pathological process, we rationally designed and fabricated an injectable ROS-responsive hydrogel loaded with polydopamine nanoparticles (PDA NPs) for spatiotemporally controlled antioxidation, anti-inflammation, and neuroprotection in the ischemic injury microenvironment. The present study aimed to systematically characterize the physicochemical properties, ROS-responsive drug release behavior, biocompatibility, and neuroprotective efficacy of this composite hydrogel system in vitro. MethodsPDA NPs were fabricated via oxidative self-polymerization. The ROS-responsive hydrogel was cross-linked using N1-(4-boronobenzyl)-N3-(4-boronophenyl)-N1,N1,N3,N3-tetramethylpropane-1, 3-diaminium (TSPBA) and polyvinyl alcohol (PVA). Morphology, particle size, Zeta potential, and structure of PDA NPs were characterized by dynamic light scattering (DLS), Zeta potential analysis, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Microstructure, rheological properties, shear-thinning behavior, and ROS-triggered release profiles of the hydrogel were examined by SEM and rheometry. Biocompatibility was evaluated using HT22 mouse hippocampal neurons with CCK-8 and live/dead staining. An oxygen-glucose deprivation/reoxygenation (OGD/R) model was established to simulate ischemic injury in vitro. ROS levels and neuronal apoptosis were detected by DHE staining and TUNEL assay. Microglial polarization and pro-inflammatory cytokine expression were analyzed using immunofluorescence and RT-qPCR in BV-2 microglia. Transwell co-culture was used to verify the indirect neuroprotection mediated by modulated microglia. ResultsCharacterization results confirmed that the as-prepared PDA NPs were monodispersed spherical nanoparticles with uniform diameter and negative surface potential, demonstrating favorable dispersibility and robust ROS-scavenging activity. The TSPBA-PVA hydrogel exhibited a highly porous interconnected network, suitable mechanical strength, and obvious shear-thinning behavior, supporting its application as an injectable implant. More importantly, the hydrogel displayed typical ROS-responsive degradation and on-demand PDA NP release in a ROS-concentration-dependent manner. In vitro cellular experiments demonstrated that the PDA NP-loaded hydrogel possessed excellent biocompatibility with HT22 cells. In the OGD/R model, the hydrogel significantly reduced intracellular ROS accumulation and markedly suppressed neuronal apoptosis. Furthermore, the composite hydrogel effectively redirected BV-2 microglia from the pro-inflammatory M1 toward the anti-inflammatory M2 phenotypes, downregulated the expression of pro-inflammatory cytokines including TNF-α, IL-1β, and IL-6, and reduced inflammatory damage. Transwell co-culture assays further validated that M2-polarized microglia mediated by the hydrogel significantly enhanced the survival of OGD/R-injured HT22 neurons and attenuated apoptosis. ConclusionIn this study, we successfully developed a novel injectable ROS-responsive hydrogel loaded with PDA NPs for synergistic antioxidative and anti-inflammatory neuroprotection. This intelligent hydrogel system enables ROS-triggered on-demand release of PDA NPs, efficiently scavenges excessive ROS, inhibits oxidative stress injury, modulates microglial polarization, and suppresses neuroinflammation, thereby exerting robust neuroprotective effects in vitro. This biomaterial platform provides a promising strategy for the targeted and controlled delivery of bioactive nanomaterials in the central nervous system diseases and establishes a solid experimental foundation for the development of in situ injectable therapies for ischemic brain injury.

By reviewing modern research and integrating clinical practice， this paper interprets the correlation between "deep heat， deep syncope" and the "macrocirculation-microcirculation" uncoupling in sepsis， alongside its clinical applications in sepsis prevention and treatment. It is considered that "deep heat" corresponds to peripheral vasodilation and the hypermetabolic state at the macrocirculation level， whereas "deep syncope" manifests as hypoperfusion and impaired oxygen utilization at the microcirculation level. These two states interact detrimentally， forming the core contradiction of macrocirculation-microcirculation uncoupling in sepsis. Based on the traditional Chinese medicine （TCM） connotations of "deep heat， deep syncope" and modern medical research， this paper elucidates the systemic pathological evolution of sepsis from the inflammatory cascade to impaired oxygen utilization. Accordingly， the following therapeutic principles are proposed. In the early stage， it is suggested to clear heat and drain fire to vent the constrained yang. In the progressive stage， the focus is put on unblocking the lower jiao （焦） and expelling stasis to dredge the vessels and collaterals. In the recovery stage， the method of regulating and harmonizing yin and yang can be used to smooth the flow of qi and blood.

[摘 要] 目的：探讨叉头框K1（FOXK1）在喉鳞状细胞癌（LSCC）中的表达、临床意义及对细胞增殖、迁移、侵袭的影响，并阐明其分子机制。方法：RT-qPCR、免疫组化检测LSCC组织及LSCC细胞TU177中FOXK1表达，分析其与临床病理参数及预后的相关性；通过瞬时转染构建FOXK1过表达与敲低细胞模型，通过MTS法、克隆形成实验、划痕愈合实验和Transwell实验检测细胞恶性生物学行为的变化；采用RT-qPCR检测上皮-间充质转化（EMT）相关因子mRNA的表达；采用WB法检测PI3K/AKT信号通路相关蛋白的表达；结合生物信息学预测与功能回复实验，验证FOXK1对AKT2的调控作用。结果：FOXK1在LSCC组织及细胞中高表达（P < 0.01），且主要定位于细胞核；FOXK1高表达与较晚TNM分期相关（P < 0.05），且FOXK1高表达患者5年生存率较低（P < 0.05）；过表达FOXK1显著增强TU177细胞增殖、迁移与侵袭能力并诱导EMT（P < 0.01或P < 0.05），敲低FOXK1则产生相反的效应；FOXK1可上调AKT2表达并激活PI3K/AKT信号通路；敲低AKT2可部分逆转FOXK1过表达对细胞增殖、迁移、侵袭及EMT进程的促进作用（P < 0.01或P < 0.05）。结论：FOXK1在LSCC中高表达，与肿瘤进展及不良预后密切相关。FOXK1可能通过上调AKT2激活PI3K/AKT信号通路，诱导EMT，从而促进LSCC细胞的恶性生物学行为。

Background Shift work is increasingly common in modern industries as economic globalization continues to advance, and has been associated with type 2 diabetes mellitus (T2DM). Objective To investigate the independent and interactive effects of shift work types and physical labor intensity on the risk of T2DM within an occupational cohort of petroleum workers, aiming to provide a scientific basis for reducing the risk of T2DM among workers engaged in shift work and physical labor. Methods This cohort study enrolled petroleum workers who underwent occupational health examinations at Karamay Central Hospital in Xinjiang from 2013 to 2015. Using stratified sampling, employees aged 20–60 years who had been actively employed and had been working in their current positions for at least one year were selected. A total of 3720 participants completed the baseline questionnaire survey and health examination, and follow-up was conducted in 2023. T2DM was diagnosed according to the 2020 Chinese Guidelines for the Prevention and Treatment of Type 2 Diabetes. Shift work type was categorized into fixed day shift, two-shift rotation, three-team two-shift rotation, four-team three-shift rotation, and other shift schedules. Physical labor intensity was classified as light, moderate, heavy, and extremely heavy according to the Classification of Physical Labor Intensity for Petroleum Field Operations (SY/T 6358—2008). Poisson regression models were used to estimate the associations of shift work type, physical labor intensity, and their joint exposure categories with T2DM risk after adjustment for potential confounders. Results A total of 3473 participants completed follow-up. Poisson regression analysis showed that shift work type was associated with T2DM risk. After adjustment for confounders, compared with fixed day shift workers, those engaged in two-shift rotation, three-team two-shift rotation, four-team three-shift rotation, and other shift schedules had higher risks of T2DM, with RRs of 2.17 (95%CI: 1.44, 3.27), 1.86 (95%CI: 1.16, 2.97), 1.85 (95%CI: 1.17, 2.93), and 2.15 (95%CI: 1.20, 3.88), respectively. T2DM risk also differed across physical labor intensity groups, with the extremely heavy group showing the highest risk (RR=2.26, 95%CI: 1.44, 3.56), followed by the heavy group (RR=1.91, 95%CI: 1.29, 2.82). Compared with workers exposed to fixed day shift + light intensity, increased T2DM risks were observed in those exposed to fixed day shift + heavy intensity (RR=2.38, 95%CI: 1.16, 4.72) or extremely heavy intensity (RR=2.64, 95%CI: 1.13, 5.82); two-shift rotation + light (RR=2.71, 95%CI: 1.11, 6.14), moderate (RR=3.38, 95%CI: 1.43, 7.34), heavy (RR=3.61, 95%CI: 1.52, 7.84), or extremely heavy intensity (RR=4.93, 95%CI: 1.87, 11.12); three-shift two-team rotation + light (RR=2.75, 95%CI: 1.14, 6.19), moderate (RR=3.08, 95%CI: 1.14, 7.51), or heavy/extremely heavy intensity (RR=4.06, 95%CI: 1.77, 8.50); four-shift three-team rotation + heavy/extremely heavy intensity (RR=3.89, 95%CI: 1.78, 7.84); and other shift types + heavy/extremely heavy intensity (RR=4.57, 95%CI: 1.55, 11.30). Conclusion This study demonstrates that various types of shift work significantly increase the risk of T2DM, and that concurrent exposure to high physical labor intensity exacerbates this risk. Regular blood glucose monitoring and targeted health interventions are recommended for workers exposed to rotating shift schedules and high physical work intensity.