Ischemic stroke （IS） represents a major global health challenge with complex pathological mechanisms. Although modern therapies such as intravenous thrombolysis and endovascular thrombectomy have advanced， their application remains constrained by narrow therapeutic time windows， hemorrhagic risks， and uneven distribution of medical resources. Traditional Chinese medicine （TCM） demonstrates unique value in the prevention and treatment of IS， owing to its multi-component， multi-target， and holistic regulatory characteristics. This review summarized the molecular mechanisms by which active ingredients and compound formulations of TCM exert therapeutic effects against IS through the regulation of inflammatory responses， oxidative stress， excitatory toxicity， apoptosis， and autophagy. Studies have indicated that components such as curcumin， baicalin， and astragaloside Ⅳ inhibit microglial activation and the nucleotide-binding oligomerization domain （NOD）-like receptor protein 3 （NLRP3） inflammasome to attenuate neuroinflammation， activate the nuclear factor erythroid 2-related factor 2（Nrf2）/heme oxygenase-1 （HO-1） pathway to alleviate oxidative stress， modulate glutamate receptor function to counteract excitatory toxicity， and regulate the B-cell lymphoma 2（Bcl-2）/Bcl-2-associated X protein （Bax）， cysteine aspartate-specific protease （Caspase）， and phosphatidylinositol 3 kinases （PI3K）/protein kinase B （Akt） signaling pathways to suppress neuronal apoptosis. Recent research has further revealed that TCM can modulate ferroptosis by targeting key proteins glutathione peroxidase 4 （GPX4） and acyl-coenzyme A synthetase long-chain family member 4 （ACSL4） to maintain iron homeostasis， intervene in the "microbiota-gut-brain axis" to ameliorate dysbiosis and reduce neuroinflammation， utilize exosomes for brain-targeted drug delivery， and influence neural repair processes through epigenetic regulation. Furthermore， the review discussed the integrated mechanisms of compound formulations， such as Buyang Huanwu Decoction， in improving cerebral microcirculation and promoting neurovascular remodeling via multi-component synergy. It also analyzed the strategy and advantages of integrating TCM with Western medicine for IS treatment， providing a novel theoretical foundation and research directions for future investigations and clinical translation of TCM in IS management.

OBJECTIVES: To investigate the clinicopathological characteristics and prognostic factors of pediatric Hodgkin lymphoma (HL). METHODS: A retrospective analysis was conducted on the clinical data of children with newly diagnosed HL from January 2011 to December 2023 at four hospitals: Fujian Medical University Union Hospital, Fujian Medical University Zhangzhou Hospital, First Affiliated Hospital of Xiamen University, and Fujian Children's Hospital. Patients were categorized into low-risk (R1), intermediate-risk (R2), and high-risk (R3) groups based on HL staging and pre-treatment risk factors. The patients received ABVD regimen or Chinese Pediatric HL-2013 regimen chemotherapy. Early treatment response and long-term efficacy were assessed, and prognostic factors were analyzed using the Cox proportional hazards regression model. RESULTS: The overall complete response (CR) rates after 2 and 4 cycles of chemotherapy were 42% and 68%, respectively. Compared with the ABVD regimen group, patients treated with the HL-2013 regimen in the R1 group showed significantly higher CR rates after both 2 and 4 cycles (P<0.05). However, no statistically significant differences in CR rates were observed between the two regimens in the R2 and R3 groups (P>0.05). The 5-year event-free survival (EFS) rate, overall survival rate, and freedom from treatment failure rate were 83%±4%, 97%±2%, and 88%±4%, respectively. Cox analysis indicated that the presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy were independent risk factors for lower EFS rates (P<0.05). CONCLUSIONS Pediatric HL generally has a favorable prognosis. The presence of a large tumor mass at diagnosis and failure to achieve CR after 4 cycles of chemotherapy indicate poor prognosis.
Humans ; Hodgkin Disease/pathology* ; Male ; Child ; Female ; Adolescent ; Retrospective Studies ; Child, Preschool ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Prognosis ; Proportional Hazards Models ; Survival Analysis ; Infant

Osteosarcoma, a highly malignant tumor originating from bone tissue, is characterized by a high mortality along with a poor prognosis. The heterogeneity of the tumor microenvironment plays a pivotal role in its development and prognosis. Single-cell sequencing technology emerges as a crucial tool in elucidating this heterogeneity by delineating the functional characteristics and gene expression patterns of tumor cells, immune cells, and stromal cells within osteosarcoma tissues. This technology enables the depiction of the intricate interaction network between these cells. Utilizing the high-resolution advantage of single-cell sequencing, novel cell subtypes such as SPP1 (+) macrophages, C1QC (+) macrophages, and CLEC11A (+) B cells have been identified in osteosarcoma tissues, contributing to tumor growth and invasion within the tumor microenvironment. Identification of osteosarcoma stem cell subpopulations suggests that SERPINA1_CSCL1, FUS_CSCL2, and SPP1_CSCL3 populations may serve as the origin of osteosarcoma cells. Moreover, single-cell sequencing has revealed that mregDCs promote immune escape and tumor progression by selectively expressing CCR7, CCL17, CCL19, and CCL22 factors, thereby recruiting Treg cells. Additionally, this technology aids in the development of personalized chemotherapy regimens by pinpointing potential drug resistance targets in osteosarcoma, leading to the establishment of a drug resistance risk score model. In terms of disease prognosis, single-cell sequencing has identified immune infiltration-associated genes in osteosarcoma (e.g., EPHX2, FDPS, GBP1, MMD, ZYX), facilitating the construction of a prognostic analysis model for osteosarcoma patients, thus aiding in prognostic prediction.

Osteosarcoma (OS) stood as the most prevalent primary malignant bone tumor among children and adolescents, characterized by its aggressive nature and high propensity for metastasis, thus earning its classification as a highly malignant disease. The primary routes of metastasis in osteosarcoma encompassed hematogenous dissemination (the most common metastasis was lung metastasis) and lymph node involvement, with lymph node metastasis carrying a notably poorer prognosis when contrasted with lung metastasis. However, it was noteworthy that, at that time, clinical practice often overlooked the crucial aspect of conducting regional lymph node screening for newly diagnosed osteosarcoma patients, and there remained a dearth of standardized treatment protocols for osteosarcoma lymph node metastasis. The intricate mechanisms at the heart of osteosarcoma lymph node metastasis primarily revolved around the infiltration of lymphatic vessels by osteosarcoma cells possessing metastatic capabilities and the induction of lymphatic vessel formation by these cells. Nevertheless, it was imperative to underscore that our understanding of the comprehensive mechanisms underpinning the initiation and progression of these processes still remained incomplete. Moreover, following the adaptive proliferation of osteosarcoma cells within regional lymph nodes, there existed a complex biological process that involved a myriad of cytokines and signaling pathways. This process facilitated the metastasis of osteosarcoma cells to distant target organs, most notably the lungs, by virtue of the intimate anatomical relationships between the lymphatic and circulatory systems. Consequently, that comprehensive review sought to provide an all-encompassing exposition on various facets of osteosarcoma lymph node metastasis. These facets included the direct invasion of surrounding lymphatic vessels by osteosarcoma cells, the osteosarcoma cell-induced development of lymphatic vessels through the VEGFC/VEGFR-3 signaling axis, the remodeling of the lymph node microenvironment by osteosarcoma cells via Hsp5B and the Wnt/β-Catenin signaling pathway to ensure their adaptation and survival, the epithelial-mesenchymal transition of osteosarcoma cells promoting metastasis from lymph nodes to the lung, and the utilization of small-molecule compounds in the battle against osteosarcoma lymph node metastasis. The aim was to provide a comprehensive and systematic elucidation of the intricate mechanisms governing osteosarcoma lymph node metastasis and to furnish invaluable insights for the development of therapeutic strategies.

OBJECTIVE: To observe the effects of acupuncture on neurologic function and serum inflammatory factors in patients after thrombolysis in acute ischemic stroke (AIS). METHODS: A total of 102 AIS patients with onset to treatment time (OTT) ≤3 h were randomly divided into an observation group and a control group, 51 cases each group. In the control group, thrombolysis and conventional medical treatment were applied. On the basis of the treatment as the control group, acupuncture at Shuigou (GV 26), Zhongwan (CV 12), Qihai (CV 6), Neiguan (PC 6), etc. was applied in the observation group, 30 min each time, once a day. Both groups were treated for 2 weeks. Before and after treatment, the scores of National Institutes of Health stroke scale (NIHSS), modified Rankin scale (mRS), modified Barthel index (MBI) and serum level of homocysteine (Hcy), hypersensitive C-reactive protein (hs-CRP) were compared, and the clinical efficacy was evaluated in the two groups. RESULTS: After treatment, the scores of NIHSS, mRS and serum level of Hcy, hs-CRP were decreased compared with those before treatment (P<0.05), while the MBI scores were increased (P<0.05) in the two groups. The scores of NIHSS, mRS and serum level of Hcy, hs-CRP in the observation group were lower than those in the control group (P<0.05, P<0.01), the MBI score in the observation group was higher than that in the control group (P<0.01). The total effective rate was 88.2% (45/51) in the observation group, which was superior to 70.6% (36/51) in the control group (P<0.05). CONCLUSION Acupuncture could promote the recovery of neurologic function in patients after thrombolysis in AIS, improve the ability of daily living, which may be related to reducing the level of inflammatory factors, thus inhibiting inflammatory response and improving cerebral ischemia reperfusion injury.
United States ; Humans ; Ischemic Stroke ; C-Reactive Protein ; Acupuncture Therapy ; Inflammation ; Homocysteine ; Hypersensitivity ; Thrombolytic Therapy

OBJECTIVE: This study aimed to estimate spatiotemporal variations of global heat-related cardiovascular disease (CVD) burden from 1990 to 2019. METHODS: Data on the burden of heat-related CVD were derived from the Global Burden of Disease Study 2019. Deaths and disability-adjusted life years (DALYs) were used to quantify heat-induced CVD burden. We calculated the age-standardized mortality rate (ASMR) and DALY rate (ASDR) per 100,000 population to compare this burden across regions. Generalized linear models were applied to evaluate estimated annual percentage changes (EAPC) for temporal trends from 1990 to 2019. The correlation between the socio-demographic index (SDI) and age-standardized rate was measured using the Spearman rank test. RESULTS: Heat-induced CVD caused approximately 90 thousand deaths worldwide in 2019. Global ASMR and ASDR of heat-related CVD in 2019 were 1.17 [95% confidence interval ( CI): 0.13-1.98] and 25.59 (95% CI: 2.07-44.17) per 100,000 population, respectively. The burden was significantly increased in middle and low-SDI regions and slightly decreased in high-SDI regions from 1990 to 2019. ASMR showed an upward trend, with the most considerable increase in low-latitude countries. We observed a negative correlation between SDI and EAPC in ASMR ( r _s = -0.57, P < 0.01) and ASDR ( r _s = -0.59, P < 0.01) among 204 countries. CONCLUSION Heat-attributable CVD burden substantially increased in most developing countries and tropical regions.
Humans ; Quality-Adjusted Life Years ; Cardiovascular Diseases/etiology* ; Hot Temperature ; Temperature ; Global Health ; Global Burden of Disease

Objective: To understand the current status of diagnosis and treatment of chronic lymphocytic leukemia (CLL) /small lymphocytic lymphoma (SLL) among hematologists, oncologists, and lymphoma physicians from hospitals of different levels in China. Methods: This multicenter questionnaire survey was conducted from March 2021 to July 2021 and included 1,000 eligible physicians. A combination of face-to-face interviews and online questionnaire surveys was used. A standardized questionnaire regarding the composition of patients treated for CLL/SLL, disease diagnosis and prognosis evaluation, concomitant diseases, organ function evaluation, treatment selection, and Bruton tyrosine kinase (BTK) inhibitor was used. Results: ①The interviewed physicians stated that the proportion of male patients treated for CLL/SLL is higher than that of females, and the age is mainly concentrated in 61-70 years old. ②Most of the interviewed physicians conducted tests, such as bone marrow biopsies and immunohistochemistry, for patient diagnosis, in addition to the blood test. ③Only 13.7% of the interviewed physicians fully grasped the initial treatment indications recommended by the existing guidelines. ④In terms of cognition of high-risk prognostic factors, physicians' knowledge of unmutated immunoglobulin heavy-chain variable and 11q- is far inferior to that of TP53 mutation and complex karyotype, which are two high-risk prognostic factors, and only 17.1% of the interviewed physicians fully mastered CLL International Prognostic Index scoring system. ⑤Among the first-line treatment strategy, BTK inhibitors are used for different types of patients, and physicians have formed a certain understanding that BTK inhibitors should be preferentially used in patients with high-risk factors and elderly patients, but the actual use of BTK inhibitors in different types of patients is not high (31.6%-46.0%). ⑥BTK inhibitors at a reduced dose in actual clinical treatment were used by 69.0% of the physicians, and 66.8% of the physicians had interrupted the BTK inhibitor for >12 days in actual clinical treatment. The use of BTK inhibitors is reduced or interrupted mainly because of adverse reactions, such as atrial fibrillation, severe bone marrow suppression, hemorrhage, and pulmonary infection, as well as patients' payment capacity and effective disease progression control. ⑦Some differences were found in the perceptions and behaviors of hematologists and oncologists regarding the prognostic assessment of CLL/SLL, the choice of treatment options, the clinical use of BTK inhibitors, etc. Conclusion: At present, a gap remains between the diagnosis and treatment of CLL/SLL among Chinese physicians compared with the recommendations in the guidelines regarding the diagnostic criteria, treatment indications, prognosis assessment, accompanying disease assessment, treatment strategy selection, and rational BTK inhibitor use, especially the proportion of dose reduction or BTK inhibitor discontinuation due to high adverse events.
Female ; Humans ; Male ; Aged ; Middle Aged ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy* ; Prognosis ; Lymphoma, B-Cell ; Immunohistochemistry ; Immunoglobulin Heavy Chains/therapeutic use*

Macrophages play an important role in maintaining homeostasis of the body, and they are also one of the most abundant immune cells in the tumor microenvironment (TME). These macrophages are often called tumor-associated macrophages (TAMs), which play an important role in the development of tumor and are an important target for tumor therapy. Studies have shown that tumor growth and metastasis can be inhibited by regulating the function of macrophages, but the therapeutic efficacy was often hampered by the poor performance of the drugs such as lack of targeting, poor solubility, low bioavailability, and severe side effects. After introduction of the background of macrophage and tumor therapy, this review focuses on the research progress of nano-drug delivery systems in the modulation of the function of macrophages to enhance tumor immunotherapy. Nano-drug delivery systems are diverse in structures and functions, and can regulate macrophage functions through a variety of mechanisms. Four important aspects of macrophage modulation, which included TAMs depletion, repolarization of TAMs, promoted phagocytosis of TAMs, and combinational modulation of TAMs were summarized. Each strategy together with typical examples was reviewed and future directions in this field were also prospected.

OBJECTIVE: To evaluate the effect of sonication, repeated freeze-thaw cycles, calcium salt solution and their combination on the content of related growth factors (GFs) released by platelet rich plasma (PRP). METHODS: Twenty PRPs from healthy blood donors were divided into 9 groups, including sonication group, freeze-thaw group, calcium gluconate group, calcium chloride group, sonication + calcium gluconate group, sonication + calcium chloride group, freeze-thaw + calcium gluconate group, freeze-thaw + calcium chloride group, and sonication + freeze-thaw group. After PRP activated by above 9 methods, the content of transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), and platelet-derived growth factor-BB (PDGF-BB) were detected by ELISA. RESULTS: The platelet concentration of the samples was (966.7±202.6)×10⁹/L. The content of TGF-β1 in sonication + freeze-thaw group was the highest, while the lowest was in freeze-thaw group. The content of VEGF in freeze-thaw + calcium chloride group was the highest, while the lowest was in calcium gluconate group. The content of PDGF-BB in sonication + freeze-thaw group was the highest, while the lowest was in calcium gluconate group. There was no significant differences in the three GFs between calcium gluconate group and calcium chloride group. CONCLUSION Among the 9 activated methods of PRP, there is no difference between two calcium salt solutions. And the combination of repeated freeze-thaw cycles and sonication may be the best treatment method to promote PRP to release GFs, while calcium gluconate is the weakest way.
Humans ; Transforming Growth Factor beta1 ; Vascular Endothelial Growth Factor A ; Calcium Gluconate ; Calcium ; Calcium Chloride ; Becaplermin ; Platelet-Rich Plasma

SARS-CoV-2 has infected more than 600 million people worldwide and caused more than 6 million deaths. The emerging novel variants have made the epidemic rebound in many places. Meteorological factors can affect the epidemic spread by changing virus activity, transmission dynamic parameters and host susceptibility. This paper systematically analyzed the currently available laboratory and epidemiological studies on the association between the meteorological factors and COVID-19 incidence, in order to provide scientific evidence for future epidemic control and prevention, as well as developing early warning system.
Humans ; SARS-CoV-2 ; COVID-19 ; Meteorological Concepts ; Laboratories ; Epidemiologic Studies