ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang （WDD） on mice with ischemic heart disease （IHD） presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group， WDD low-dose group （WDD-L）， WDD medium-dose group （WDD-M）， WDD high-dose group （WDD-H）， and atorvastatin calcium tablet group， with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91， 17.81， 35.62 g·kg^-1， and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg^-1， twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration， the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin （HE） staining. Serum N-terminal pro-B-type natriuretic peptide （pro-BNP） content was measured by enzyme-linked immunosorbent assay （ELISA）. Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL） were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group， model serum group， WDD-L drug-containing serum group， WDD-M drug-containing serum group， and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group， the model group showed a significantly increased cardiac index （P0.01）， significantly decreased fractional shortening （FS） （P0.01）， and significantly increased left ventricular end-diastolic internal diameter （LVDD） and left ventricular end-systolic internal diameter （LVDS） （P0.01）. Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated （P0.01）， and whole-blood viscosity （BV） at high， medium， and low shear rates was significantly increased （P0.01）. Compared with the model group， the WDD groups showed significantly reduced cardiac index （P0.05， P0.01）， significantly increased FS （P0.05， P0.01）， significantly decreased LVDD and LVDS （P0.01）， markedly improved cardiomyocyte morphology， significantly reduced inflammatory infiltration， significantly decreased serum pro-BNP levels （P0.01）， and significantly decreased BV at high， medium， and low shear rates （P0.01）， with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group， TC， TG， and LDL levels were significantly increased in the model group （P0.05， P0.01）， while HDL levels were significantly decreased （P0.05）. After WDD-H treatment， TC， TG， and LDL levels were significantly reduced and HDL levels were significantly increased in mice （P0.05， P0.01）. Compared with the sham-operation group， classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group （P0.01）， whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased （P0.01）. After WDD administration， all circulating monocyte subsets in blood and bone marrow were significantly alleviated （P0.05， P0.01）， with the WDD-M group showing the optimal effect. In vitro， compared with the blank group， CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group （P0.01）， and CD36 expression was significantly upregulated on RAW264.7 cells （P0.01）. Compared with the model serum group， all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation （P0.01）. WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines （P0.05， P0.01）， with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.

ObjectiveTo investigate the ameliorative effect of Wendantang combined with Danshenyin and Dushentang （WDD） on mice with ischemic heart disease （IHD） presenting phlegm-stasis syndrome based on the inflammatory phenotype and differentiation of circulating monocytes. MethodsA model of IHD with phlegm-stasis syndrome was established using left anterior descending coronary artery ligation supplemented with a high-fat diet. Eighty model mice were randomly assigned to the model group， WDD low-dose group （WDD-L）， WDD medium-dose group （WDD-M）， WDD high-dose group （WDD-H）， and atorvastatin calcium tablet group， with 16 mice in each group. An additional 16 C57BL/6J mice were designated as the sham-operation group. The WDD groups received intragastric administration at doses of 8.91， 17.81， 35.62 g·kg^-1， and the atorvastatin calcium tablet group received the corresponding drug at 1.3 mg·kg^-1， twice daily. The sham-operation and model groups were given the same volume of pure water by gavage each day. After 5 consecutive weeks of administration， the cardiac index was calculated. Cardiac function was assessed by echocardiography. Myocardial histopathology was examined by hematoxylin-eosin （HE） staining. Serum N-terminal pro-B-type natriuretic peptide （pro-BNP） content was measured by enzyme-linked immunosorbent assay （ELISA）. Hemorheological parameters were analyzed using an automated hemorheology analyzer. Serum levels of total cholesterol （TC）， triglycerides （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL） were determined using an automated biochemical analyzer. Changes in circulating monocytes were detected by flow cytometry. Mouse bone marrow mononuclear cells were isolated in vitro and divided into blank group， model serum group， WDD-L drug-containing serum group， WDD-M drug-containing serum group， and WDD-H drug-containing serum group. CD36 expression and macrophage differentiation in each group were assessed by flow cytometry. The mechanism by which WDD mediates circulating monocyte differentiation was further explored using CD36 knockdown/overexpression RAW264.7 cell lines. ResultsCompared with the sham-operation group， the model group showed a significantly increased cardiac index （P<0.01）， significantly decreased fractional shortening （FS） （P<0.01）， and significantly increased left ventricular end-diastolic internal diameter （LVDD） and left ventricular end-systolic internal diameter （LVDS） （P<0.01）. Cardiomyocytes exhibited marked deformation and necrosis with inflammatory cell infiltration. Serum pro-BNP levels were significantly elevated （P<0.01）， and whole-blood viscosity （BV） at high， medium， and low shear rates was significantly increased （P<0.01）. Compared with the model group， the WDD groups showed significantly reduced cardiac index （P<0.05， P<0.01）， significantly increased FS （P<0.05， P<0.01）， significantly decreased LVDD and LVDS （P<0.01）， markedly improved cardiomyocyte morphology， significantly reduced inflammatory infiltration， significantly decreased serum pro-BNP levels （P<0.01）， and significantly decreased BV at high， medium， and low shear rates （P<0.01）， with the most pronounced improvement observed in the WDD-M group. Compared with the sham-operation group， TC， TG， and LDL levels were significantly increased in the model group （P<0.05， P<0.01）， while HDL levels were significantly decreased （P<0.05）. After WDD-H treatment， TC， TG， and LDL levels were significantly reduced and HDL levels were significantly increased in mice （P<0.05， P<0.01）. Compared with the sham-operation group， classical monocytes in blood and bone marrow and intermediate monocytes in blood were significantly increased in the model group （P<0.01）， whereas intermediate monocytes in bone marrow and non-classical monocytes in blood were significantly decreased （P<0.01）. After WDD administration， all circulating monocyte subsets in blood and bone marrow were significantly alleviated （P<0.05， P<0.01）， with the WDD-M group showing the optimal effect. In vitro， compared with the blank group， CD36 expression on bone marrow monocytes and the proportion of differentiated macrophages were significantly increased in the model serum group （P<0.01）， and CD36 expression was significantly upregulated on RAW264.7 cells （P<0.01）. Compared with the model serum group， all drug-containing serum groups exhibited significantly reduced CD36 expression on bone marrow monocytes and significantly reduced macrophage differentiation （P<0.01）. WDD downregulated CD36 expression in both CD36 knockdown and overexpression RAW264.7 cell lines （P<0.05， P<0.01）， with the strongest regulatory effect observed in the WDD-M drug-containing serum group. ConclusionWDD can significantly improve the manifestations of phlegm-stasis syndrome in IHD mice and reduce the proportion of classical circulating monocytes. Its mechanism may be related to the inhibition of CD36 expression on classical circulating monocytes.

ObjectiveTo conduct a theoretical study on the medical-rehabilitation integration. MethodsStarting from the background, objectives and content of the medical-rehabilitation integration, this study analyzed its innovative points from the dimensions of conceptual innovation, organizational innovation, model innovation and technological innovation. Results and ConclusionThe medical-rehabilitation integration is an innovation in medical services that takes conceptual innovation as the forerunner, organizational innovation as the foundation, model innovation as the carrier and technological innovation as the core.

To investigate the clinical efficacy of neoadjuvant imatinib in the treatment of rectal gastrointestinal stromal tumor (GIST).

Background Lead is a typical persistent environmental pollutant that can accumulate in bones for decades. During pregnancy, alterations in calcium metabolism promote the mobilization of bone lead, resulting in secondary exposure; however, the mechanisms by which pregnancy-associated bone lead mobilization affects maternal renal function remain unclear. Objective To investigate the role of mitochondrial dysfunction in pregnancy-related bone lead mobilization-induced renal injury. Methods Newly weaned female Wistar rats were randomly assigned to a control or a lead-exposed group administered either 0.05% sodium acetate or 0.05% lead acetate in drinking water. Following a 4-week lead exposure and a 4-week washout period, the females were co-housed with healthy age-matched males for mating. Rats were sacrificed at early (gestational day 3) and late (gestational day 17) pregnancystages, respectively. Renal histopathology was assessed using hematoxylin and eosin staining staining. Mitochondria-related indicators, including oxidative stress, inflammatory responses, and energy metabolism, were measured. Differential metabolites were identified using serum metabolomics. Results Renal injury in the lead-exposed pregnant rats progressed in a time-dependent manner, characterized by degeneration of proximal tubular epithelial cells, glomerular hyaline changes, and interstitial inflammatory cell infiltration. Repeated measures ANOVA indicated a significant interaction between the treatment factor (lead exposure) and the temporal factor (gestational stage) on renal injury (P<0.001). Further analysis of mitochondrial function-related indicators in late-pregnancy renal tissue revealed that the lead exposure group exhibited significantly increased levels of malondialdehyde (MDA) and reactive oxygen species (ROS) (P<0.05), accompanied by a reduction in superoxide dismutase (SOD) and reduced glutathione (GSH) activities (P<0.05); regarding inflammatory markers, levels of interleukin-18 (IL-18) and interleukin-1β (IL-1β) were elevated (P<0.01), whereas interleukin-33 (IL-33) was decreased in the lead-exposed group (P<0.05); energy metabolism-related indicators, including adenosine triphosphate (ATP) level, Na⁺-K⁺-ATPase and Ca²⁺-Mg²⁺-ATPase activities, and mitochondrial respiratory chain complexes I, III, and V activities, were significantly reduced (P<0.05) in the lead-exposed gorup. The typical differential metabolite N-methylisoleucine, identified through serum metabolomics analysis, was negatively correlated with blood lead levels, kidney injury scores, and IL-1β, while positively correlated with catalase (CAT) activity and Ca²⁺-Mg²⁺-ATPase. Conclusions Mitochondrial dysfunction may play a critical role in renal injury induced by bone lead mobilization during late gestation.

Fungal infections have emerged as a critical public health issue endangering human health. However, the existing arsenal of antifungal agents is limited in diversity and is commonly plagued by drawbacks including narrow antimicrobial spectrums and the frequent emergence of drug resistance, which severely compromises the efficacy of clinical treatments. Pathogenic fungi can develop extensive adaptability to currently available drugs through multiple mechanisms, which are mainly manifested in three aspects: drug resistance, tolerance and persistence. The molecular mechanisms and regulatory pathways underlying drug resistance, tolerance and persistence in pathogenic fungi were systematically summarized in this review, and the counteractive strategies such as combination therapy and the development of novel antifungal agents were further discussed, which aimed to provide theoretical basis and practical reference for the precision treatment of fungal infections.

OBJECTIVE To investigate the effects of total flavonoids of Drynariae Rhizoma （TFRD） on autophagy and apoptosis in LPS-induced chondrocytes via the regulation of the Notch1/hairy and enhancer of split 1 （Notch1/Hes1） signaling axis. METHODS Human chondrocyte cell line C28/I2 cells were cultured with 5 μg/mL LPS to esta blish in vitro inflammatory injury model. The cells were separated into normal control group， model group， TFRD group （200 μg/mL）， TFRD+peroxiredoxin 1 （Prdx1） small interfering RNA （si-Prdx1） group and TFRD+si-Prdx1 negative control （si-NC） group， with 6 replicate wells in each group. Cells were transfected with si-Prdx1 or si-NC for 24 hours， pretreated with TFRD for 2 hours， and then exposed to LPS， with a total culture duration of 48 hours. Apoptotic rate， the proportion of apoptotic cells， monodansylcadaverine （MDC） fluorescence intensity， as well as the contents of matrix metalloproteinase-13 （MMP-13）， a disintegrin and metalloproteinase with thrombospondin motifs 5 （ADAMTS5）， and cartilage oligomeric matrix protein （COMP） were measured. Additionally， the protein expression levels of X-linked inhibitor of apoptosis protein （XIAP）， poly（ADP-ribose） polymerase 1 （PARP1）， Beclin-1， microtubule-associated protein 1 light chain 3 Ⅱ/Ⅰ （LC3-Ⅱ/Ⅰ）， PTEN-induced putative kinase 1 （PINK1）， Notch1， Hes1， and Prdx1 were assessed. RESULTS Compared with model group， the apoptotic rate， the proportion of apoptotic cells， the contents of MMP-13 and ADAMTS5 as well as protein expressions of PARP1 were significantly decreased， while MDC fluorescence intensity， COMP content， protein expressions of XIAP， Beclin-1， LC3-Ⅱ/Ⅰ， PINK1， Notch1， Hes1 and Prdx1 were significantly increased （ P ＜0.05）. Compared with TFRD+si-NC group， the changes in the aforementioned indicators （except for Notch1 and Hes1） in the cells of the TFRD+si-Prdx1 group were significantly reversed （ P ＜0.05）. CONCLUSIONS TFRD may activate the Notch1/Hes1 signaling axis， and up-regulate the expression of the downstream target molecule Prdx1， thereby inhibiting LPS-induced chondrocyte apoptosis， promoting protective autophagy， and consequently improving cartilage metabolic homeostasis.

OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

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.

Organophosphate flame retardants (OPFRs) have been widely used as the main alternatives to bromine-based flame retardants, resulting in their widespread detection in environmental media and even in human blood. The potential health risks arising therefrom, particularly the direct impacts on the blood system, have become a focus in the field of environmental health. This article systematically reviewed the latest research progress on the hematotoxicity of OPFRs, covering three core aspects: the toxic effects aspect, which systematically elaborated on the bidirectional interference of OPFRs with coagulation function, their toxic effects on the hematopoietic system, and their disruptive effects on blood biochemical metabolism; the mechanistic analysis aspect, which dissected the multi-pathway, multi-target toxic mechanism network of OPFRs, including common pathways based on oxidative stress and inflammatory responses, the direct and indirect regulation of coagulation function mediated by nuclear receptors and endocrine disruption, and the disturbance of blood cell production at the source through disruption of the hematopoietic microenvironment; and the risk assessment aspect, which, in response to the limitations of traditional methods, focused on the application prospects and core advantages of novel approaches based on structure-activity relationships in filling data gaps and achieving precise risk prediction. This review aims to systematically summarize the research progress on the mechanisms of OPFR-induced hematotoxicity, providing systematic theoretical support for subsequent in-depth mechanistic studies, targeted epidemiological investigations, and the optimization of risk assessment models.