ObjectiveAngelicae Sinensis Radix， a commonly used medicinal herb with both medicinal and edible properties， is frequently adulterated in the market， severely affecting the clinical efficacy of preparations. While qualitative identification techniques for adulterants and counterfeits are now relatively mature， quantitative detection methods for adulterated processed products remain unexplored. Quantitative detection research of Angelicae Sinensis Radix and its primary closely related adulterant， "Tu Danggui" （Angelica gigas）， was conducted to establish a herbal quantitative molecular detection （Herb-Q） method for Angelicae Sinensis Radix and its processed products， providing a model for the establishment of quantitative detection technologies for Angelicae Sinensis Radix and related health products. MethodsThe specific single-nucleotide polymorphism （SNP） loci of Angelicae Sinensis Radix and Angelica gigas Nakai were screened based on the complete chloroplast genome sequence. The specific SNP loci of Angelicae Sinensis Radix were selected for quantitative methodological investigations （linearity， limit of quantification， limit of detection， and reproducibility） by mixing the powder of the herbs with different adulteration ratios. Huoxue Zhitong powder with three distinct adulteration ratios （15%， 25%， and 35%） was utilized to ascertain the precision of the Herb-Q method for the quantitative detection of Chinese patent medicines containing Angelicae Sinensis Radix. ResultsBy comparing the 123 chloroplast genome sequences of Angelicae Sinensis Radix， based on the principles of intraspecies conservation， interspecies specificity， and meeting the requirements of pyrophosphate high-throughput sequencing， it was determined that 9 674^th locus （A/G） in the chloroplast genome sequence NC_042826.1 and 38 592^nd locus （T/C） in the chloroplast genome sequence NC_029393.1 could be the exclusive molecular identification loci of Angelicae Sinensis Radix and Angelica gigas Nakai， respectively. The linear relationship R² of the Herb-Q method established by selecting the specific 9 674^th locus （A/G） of Angelicae Sinensis Radix was 0.997 4 （R²>0.99）， indicating an excellent linear relationship. The limits of quantification and detection were established at 2.0%， exhibiting excellent reproducibility ［relative standard deviation（RSD）<2.0%］. The established quantitative system based on the Herb-Q method detected the adulteration amount of counterfeit A. gigas in the Huoxue Zhitong powder， with an average deviation of 1.3% for three molecular quantitative replicates. ConclusionThis research demonstrates that the Herb-Q quantitative detection method established based on the 9 674^th locus （A/G） in the chloroplast genome sequence NC_042826.1 of Angelicae Sinensis Radix has good applicability， objectivity， and accuracy for Angelicae Sinensis Radix and A. gigas， and its processed products. This method has the capacity to provide technical support for the quantitative detection of commercially available Angelicae Sinensis Radix derivatives， including traditional Chinese medicinal preparations， dietary supplements， and nutraceuticals.

ObjectiveAngelicae Sinensis Radix， a commonly used medicinal herb with both medicinal and edible properties， is frequently adulterated in the market， severely affecting the clinical efficacy of preparations. While qualitative identification techniques for adulterants and counterfeits are now relatively mature， quantitative detection methods for adulterated processed products remain unexplored. Quantitative detection research of Angelicae Sinensis Radix and its primary closely related adulterant， "Tu Danggui" （Angelica gigas）， was conducted to establish a herbal quantitative molecular detection （Herb-Q） method for Angelicae Sinensis Radix and its processed products， providing a model for the establishment of quantitative detection technologies for Angelicae Sinensis Radix and related health products. MethodsThe specific single-nucleotide polymorphism （SNP） loci of Angelicae Sinensis Radix and Angelica gigas Nakai were screened based on the complete chloroplast genome sequence. The specific SNP loci of Angelicae Sinensis Radix were selected for quantitative methodological investigations （linearity， limit of quantification， limit of detection， and reproducibility） by mixing the powder of the herbs with different adulteration ratios. Huoxue Zhitong powder with three distinct adulteration ratios （15%， 25%， and 35%） was utilized to ascertain the precision of the Herb-Q method for the quantitative detection of Chinese patent medicines containing Angelicae Sinensis Radix. ResultsBy comparing the 123 chloroplast genome sequences of Angelicae Sinensis Radix， based on the principles of intraspecies conservation， interspecies specificity， and meeting the requirements of pyrophosphate high-throughput sequencing， it was determined that 9 674^th locus （A/G） in the chloroplast genome sequence NC_042826.1 and 38 592^nd locus （T/C） in the chloroplast genome sequence NC_029393.1 could be the exclusive molecular identification loci of Angelicae Sinensis Radix and Angelica gigas Nakai， respectively. The linear relationship R² of the Herb-Q method established by selecting the specific 9 674^th locus （A/G） of Angelicae Sinensis Radix was 0.997 4 （R²>0.99）， indicating an excellent linear relationship. The limits of quantification and detection were established at 2.0%， exhibiting excellent reproducibility ［relative standard deviation（RSD）<2.0%］. The established quantitative system based on the Herb-Q method detected the adulteration amount of counterfeit A. gigas in the Huoxue Zhitong powder， with an average deviation of 1.3% for three molecular quantitative replicates. ConclusionThis research demonstrates that the Herb-Q quantitative detection method established based on the 9 674^th locus （A/G） in the chloroplast genome sequence NC_042826.1 of Angelicae Sinensis Radix has good applicability， objectivity， and accuracy for Angelicae Sinensis Radix and A. gigas， and its processed products. This method has the capacity to provide technical support for the quantitative detection of commercially available Angelicae Sinensis Radix derivatives， including traditional Chinese medicinal preparations， dietary supplements， and nutraceuticals.

Gorham-Stout disease(GSD) is a rare osteolytic disorder characterized by spontaneous and progressive osteolysis, along with abnormal angiogenesis and lymphangiogenesis, with no new bone formation. We present a case of a 15-year-old female admitted due to " recurrent right leg pain for 5 years, 11 months after undergoing right femoral fracture surgery". Through comprehensive integration of the patient's clinical phenotype, laboratory tests, imaging findings, pathological examinations, and molecular biological test results, GSD was considered highly likely. A multidisciplinary treatment approach was conducted, including a combination of zoledronic acid and sirolimus to inhibit osteolysis, along with rehabilitation training and orthopedic intervention, providing a personalized and comprehensive treatment strategy.

Based on the theory of diseased collaterals and the progression pattern of diabetic kidney disease （DKD）， this paper proposes a staged treatment system based on the "three states of kidney collaterals" including collateral distention， collateral bi （痹） and collateral accumulation. In the collateral distention stage， the primary pathogenesis is heat damaging the kidney collaterals and collateral vessel dilation， corresponding to the early state of DKD characterized by hyperfiltration and microalbuminuria； the clearing method is suggested， and Shenling Jiangtang Formula （参苓降糖方） can be used to promote the remission of proteinuria by ameliorating insulin resistance and regulating intestinal microecology. In the collateral bi stage， the core pathogenesis lies in the binding of phlegm and stasis， and the formation of concretions and conglomerations in the kidney collaterals， corresponding to massive proteinuria and the decline of renal function， for which the unblocking method should be taken， using Jinchan Yishen Tongluo Formula （金蝉益肾通络方） and Qingre Xiaozheng Formula （清热消癥方） to alleviate renal pathological damage by regulating the autophagy-lysosome pathway and repairing mitochondrial energy metabolism. The collateral accumulation stage is characterized by the internal retention of turbid toxins and accumulations of concretions in the kidney collaterals， corresponding to renal fibrosis and end-stage renal disease （ESRD）； the dispersion method is suggested， and Yiqi Tongluo Xiezhuo Formula （益气通络泄浊方） and Shenyan Fangshuai Fluid （肾炎防衰液） can be used to inhibit extracellular matrix accumulation and delay the progressive loss of renal function. Collateral deficiency runs through the entire course of the disease and is closely related to cellular senescence and the imbalance of the ubiquitin-proteasome/autophagy system. The concept of the "three states of kidney collaterals" integrates the evolution of traditional Chinese medicine pathogenesis with modern pathological staging， forming a whole-course intervention system of "staging-syndrome differentiation-target-formula"， thereby providing novel insights for prevention and treatment of DKD using integrated traditional Chinese and western medicine.

Hyperlipidemia is a common metabolic disorder driven by dysregulated lipid metabolism， whose pathological progression involves multifaceted interactions across various signaling pathways， including disrupted cholesterol homeostasis， insulin resistance， chronic inflammation， and oxidative stress. Although existing clinical medications such as statins can effectively reduce low-density lipoprotein cholesterol through single-target inhibition， significant limitations remain in comprehensively improving reverse cholesterol transport， metabolic inflammation， and coordinated regulation of glucose and lipid metabolism. Curcumin， the primary polyphenolic active compound derived from the traditional medicinal herb turmeric， exhibits multi-dimensional pharmacological effects including modulation of lipid metabolism， improvement of insulin sensitivity， suppression of inflammatory responses， and enhancement of antioxidant defense. This review systematically integrates the multi-target regulatory network of curcumin， elucidating its key mechanisms： Balancing the low density lipoprotein receptor/proprotein convertase subtilisin/kexin type 9 （LDLR/PCSK9） signaling pathway to promote reverse cholesterol transport， activating peroxisome proliferator-activated receptor α/γ （PPARα/γ） signaling pathways to coordinate glucolipid metabolic homeostasis， remodeling the gut microbiota-bile acid axis， inhibiting nuclear factor kappa-B （NF-κB）-mediated inflammatory responses， and activating the nuclear factor erythroid 2-related factor 2/antioxidant response element （Nrf2/ARE） antioxidant signaling pathway. Furthermore， supported by clinical research data， the review validates curcumin's therapeutic potential in reducing total cholesterol （TC） and triglyceride （TG） levels， increasing high-density lipoprotein cholesterol （HDL-C）， as well as improving vascular endothelial function and insulin sensitivity. The study highlights the multi-target regulatory properties of curcumin and discusses future clinical applications based on nano-delivery systems and personalized treatment strategies， providing a theoretical basis and novel insights for the prevention and treatment of hyperlipidemia and related metabolic disorders.

Objective To investigate the application value of peripheral blood soluble human leukocyte antigen-G(sHLA-G)combined with immune cytokines in the differential diagnosis of renal transplant rejection.Methods This case-control study retrospectively analyzed 81 renal transplant patients hospitalized in the Department of Organ Transplantation,the Second Affiliated Hospital of Naval Medical University from April 2020 to December 2023,due to elevated serum creatinine.Among them,32 patients were diagnosed with acute rejection(acute rejection group),29 with chronic rejection(chronic rejection group),and 20 with elevated creatinine due to non-rejection causes(non-rejection group).Fifty renal transplant inpatients and outpatients with normal and stable serum creatinine were selected as control group during the same period.Clinical data such as gender,age,serum creatinine,estimated glomerular filtration rate(eGFR),and urine protein positive rate,etc.were collected.Peripheral blood of patients was sampled to measure the levels of plasma sHLA-G and immune cytokines[interferon-γ(IFN-γ),tumor necrosis factor-β(TNF-β),interleukin(IL)-2,IL-4,IL-10,IL-5,IL-6,IL-17]using enzyme-linked immunosorbent assay(ELISA).Stratify and compare the differences in sHLA-G levels among different groups and all renal transplant inpatients by gender.Results Compared with control group,serum creatinine levels and urine protein positive rate were significantly higher in acute rejection group,chronic rejection group,and non-rejection group,while eGFR was significantly lower,serum creatinine levels in chronic rejection group and non-rejection group were higher than those in acute rejection group,while eGFR was lower than that in acute rejection group,with statistically significant differences(P<0.05).No statistically significant differences were observed in gender,age,blood type,body mass index,transplantation duration,and immunosuppressive agent use among acute rejection,chronic rejection,non-rejection,and control groups(P>0.05).Plasma sHLA-G levels in acute rejection and chronic rejection groups were significantly lower than those in control group[(19.665±11.233)U/ml vs.(24.785±21.668)U/ml vs.(44.918±39.898)U/ml,P<0.05].The sHLA-G/IL-2 ratio in chronic rejection group was significantly higher than that in acute rejection group(5.844±6.248 vs.1.825±1.574,P<0.05),and the sHLA-G/IFN-γ ratio in non-rejection group was significantly higher than that in chronic rejection group(3.452±3.283 vs.1.543±2.030,P<0.05).Among 131 renal transplant inpatients,female sHLA-G levels were significantly higher than male(P<0.05).Within each group,female sHLA-G levels in chronic rejection group were significantly higher than male(P<0.05).Although female sHLA-G levels in acute rejection,non-rejection,and control groups were higher than those of male,the gender difference was not statistically significant(P>0.05).Conclusions Peripheral blood sHLA-G levels are correlated with renal transplantation rejection.The application of sHLA-G/IL-2 and sHLA-G/IFN-γ ratios has potential value in the diagnosis and differentiation of elevated creatinine caused by acute/chronic rejection,chronic rejection and non-rejection causes,respectively.

Tianxiangdan (TXD), a traditional Chinese herbal remedy, demonstrates efficacy in mitigating myocardial ischemia-reperfusion (I/R)-induced damage. This study employed network pharmacology to evaluate the therapeutic targets and mechanisms of TXD in treating I/R. High-performance liquid chromatography-mass spectrometry (HPLC-MS) identified 86 compounds in TXD. Network pharmacological analysis predicted potential target genes and their modes of action. Cardiac function, ischaemic ST changes, lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD) activity, myocardial fiber, and infarct size were assessed using in vivo and in vitro I/R injury models. Estrogen receptor alpha (ERα) protein expression and estradiol (E2) levels were measured to confirm TXD's impact on estrogen levels and ERα expression. To examine if TXD reduces I/R injury through ERα, an AZD group (300 nmol·L^-1 AZD9496 and 15% TXD serum) was compared to a TXD group (15% TXD serum). The study hypothesized that TXD upregulates the ERα-mediated iron metamorphosis pathway. I/R injury-induced ferroptosis was identified using a Fer-1 group (1.0 μmol·L^-1 Fer-1 and 15% TXD serum) to elucidate the potential association between ferroptosis and ERα proteins. A DCFH-DA probe detected reactive oxygen species (ROS) and Fe²⁺, while Western blotting assessed target protein expression. Both in vitro and in vivo experiments demonstrated that TXD attenuated I/R injury by reducing elevated ST-segment levels, improving cardiac injury biomarkers (LDH, MDA, and SOD), alleviating pathological features, and preventing I/R-induced loss of cell viability in vitro. The effects and mechanisms of TXD on I/R injury-associated ferroptosis were investigated using I/R-induced H9c2 cells. The TXD group showed significantly decreased ROS and Fe²⁺ levels, while the AZ group (treated with AZD9496) exhibited increased levels. The TXD group demonstrated enhanced expression of ERα and glutathione peroxidase 4 (GPX4), with reduced levels of P53 protein and ferritin-heavy polypeptide 1 (FTH1). The AZ group exhibited contrasting effects on these expression levels. The literature indicated a novel connection between ERα and ferroptosis. TXD activates the ERα signaling pathway, promoting protection against I/R-induced myocardial cell ferroptosis. This study provides evidence supporting TXD use for myocardial ischemia treatment, particularly in older female patients who may benefit from its therapeutic outcomes.
Animals ; Ferroptosis/drug effects* ; Estrogen Receptor alpha/genetics* ; Myocardial Reperfusion Injury/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Male ; Mice ; Humans ; Mice, Inbred C57BL ; Estradiol/metabolism*

OBJECTIVE: To explore the relationship between serum chloride levels and prognosis in patients with hepatic coma in the intensive care unit (ICU). METHODS: We analyzed 545 patients with hepatic coma in the ICU from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Associations between serum chloride levels and 28-day and 1-year mortality rates were assessed using restricted cubic splines (RCSs), Kaplan-Meier (KM) curves, and Cox regression. Subgroup analyses, external validation, and mechanistic studies were also performed. RESULTS: A total of 545 patients were included in the study. RCS analysis revealed a U-shaped association between serum chloride levels and mortality in patients with hepatic coma. The KM curves indicated lower survival rates among patients with low chloride levels (< 103 mmol/L). Low chloride levels were independently linked to increased 28-day and 1-year all-cause mortality rates. In the multivariate models, the hazard ratio ( HR) for 28-day mortality in the low-chloride group was 1.424 (95% confidence interval [ CI]: 1.041-1.949), while the adjusted hazard ratio for 1-year mortality was 1.313 (95% CI: 1.026-1.679). Subgroup analyses and external validation supported these findings. Cytological experiments suggested that low chloride levels may activate the phosphorylation of the NF-κB signaling pathway, promote the expression of pro-inflammatory cytokines, and reduce neuronal cell viability. CONCLUSION Low serum chloride levels are independently associated with increased mortality in patients with hepatic coma.
Humans ; Male ; Female ; Middle Aged ; Intensive Care Units ; Prognosis ; Chlorides/blood* ; Aged ; Coma/blood* ; Adult

Cucumber (Cucumis sativus L.) is one of the most widely cultivated vegetables in the world. High temperature and other stress conditions can affect the growth and development of this plant, even leading to the decreases in yield and quality. The mitogen-activated protein kinase (MAPK) family plays a crucial role in plant stress responses. However, the role of MPK4 in the stress response of cucumber remains to be reported. In this study, we cloned CsMPK4, which encoded 383 amino acid residues. The qRT-PCR results showed that the expression level of CsMPK4 was the highest in leaves and flowers, moderate in roots, and the lowest in stems and tendrils. CsMPK4 was located in the nucleus and cytoplasm, and it had a close relationship with CmMPK4 in muskmelon. The cucumber plants overexpressing CsMPK4 became stronger and shorter, with reduced length and quantity of tendrils. Moreover, the transgenic seedlings were more resistant to high temperatures, with decreased malondialdehyde (MDA) content and increased activities of peroxidase (POD) and superoxide dismutase (SOD) in young leaves. Furthermore, the protein-protein interaction between CsMPK4 and CsVQ10, a member of the valine-glutamine family, was confirmed by yeast two-hybrid and bimolecular fluorescence complementation (BiFC) assays. The results suggested that CsVQ10 cooperated with CsMPK4 in response to the high temperature stress in cucumber. This study laid a foundation for the further study on the stress response mechanism of CsMPK4 and the breeding of stress-resistant cucumber varieties.
Cucumis sativus/metabolism* ; Mitogen-Activated Protein Kinases/physiology* ; Plant Proteins/metabolism* ; Plants, Genetically Modified/metabolism* ; Gene Expression Regulation, Plant ; Stress, Physiological/genetics* ; Cloning, Molecular