ObjectiveTo evaluate the clinical efficacy and safety of Jingmaiyan granules （composed of Lonicerae Japonicae Flos， Sedi Herba， Paeoniae Radix Rubra， Moutan Cortex， Rhei Radix et Rhizoma Praeparata， and Glycyrrhizae Radix et Rhizoma） combined with external application of Jinhuang Ointment in treating acute-stage blood heat stasis type superficial thrombophlebitis （ST） of lower extremities， and to explore their effects on hemorheology and serum inflammatory factors. MethodsA randomized， double-blind， placebo-controlled clinical trial was conducted. A total of 124 patients with lower extremity ST were randomized into two groups（62 cases in each group）. The control group received external application of Jinhuang ointment and oral placebo treatment， while the observation group received external application of Jinhuang ointment and oral Jingmaiyan granules. Both groups were treated for 2 weeks. The clinical symptom scores， therapeutic efficacy of traditional Chinese medicine （TCM） syndrome， pain visual analog scale （VAS） scores， hemorheological indices ［including whole blood high-shear， medium-shear， and low-shear viscosity， as well as plasma viscosity （PV）］， and inflammatory factors ［C-reactive protein （CRP）， interleukin-6 （IL-6）， tumor necrosis factor-α （TNF-α）］ were compared before and after treatment. ResultsAfter 2 weeks of treatment， the total effective rate in the observation group （98.3%， 60/62） was significantly higher than that in the control group （83.8%， 52/62）， with a statistically significant difference （Z=3.512 1， P<0.05）. Compared with pre-treatment scores， the scores for skin color， skin temperature， swelling， pain， and cord or nodules were significantly reduced in both groups （P<0.05）， with more pronounced improvement in the observation group （P<0.05）. Additionally， compared with pre-treatment levels， the whole blood viscosity （low-， medium-， and high-shear） significantly improved in both groups after treatment （P<0.05）， with more marked improvement in the observation group （P<0.05）. Furthermore， the plasma viscosity， CRP， IL-6， and TNF-α levels were significantly reduced in both groups after treatment （P<0.05）， with more pronounced improvement observed in the observation group （P<0.05）. ConclusionThe combination of external application of Jinhuang ointment and oral Jingmaiyan granules effectively improves clinical symptoms， hemorheological abnormalities， and inflammatory responses in patients with acute stage blood heat stasis type ST of lower extremities. The treatment is safe and holds clinical promotion value.

BackgroundPost-traumatic stress symptoms （PTSS） is highly prevalent in adolescents who have experienced earthquake， which seriously threatens their physical and mental health， yet there is currently a lack of research on the effects of loneliness， social support and social media use on PTSS among post-earthquake adolescents. ObjectiveTo assess the PTSS among adolescents experiencing MS6.0 Luxian， Sichuan， earthquake on 16 September 2021， and to investigate the effects of loneliness， social support and social media use on PTSS， so as to provide references for the intervention of PTSS among post-earthquake adolescents. MethodsOn November 12， 2021， simple random sampling technique was used to select 2 522 post-earthquake adolescents in Luxian county of Luzhou city in Sichuan province. All subjects were assessed using Post-Traumatic Stress Disorder Checklist for DSM-5 （PCL-5）， Multidimensional Scale of Perceived Social Support （MSPSS）， Short-form UCLA Loneliness Scale （ULS-3） and Social Media Use Scale （SM-10）. Binary Logistic regression was used to determine the factors influencing PTSS among post-earthquake adolescents. ResultsPTSS was detected in 91 （3.61%） adolescents. Binary Logistic regression revealed that perceived social support from family members （OR=0.926， 95% CI： 0.879~0.976） was a protective factor for PTSS among post-earthquake adolescents. Lack of companionship （OR=1.764， 95% CI： 1.141~2.727）， feeling isolated （OR=2.037， 95% CI： 1.282~3.236）， and viewing negative emotional response of disaster victims through social media （OR=1.615， 95% CI： 1.291~2.020） were risk factors for PTSS among post-earthquake adolescents. ConclusionLack of companionship， feeling isolated， and viewing negative emotional response of disaster victims through social media pose a negative impact on PTSS among post-earthquake adolescents， while perceived social support from family members exert a positive impact on PTSS among post-earthquake adolescents. ［Funded by Humanity and Social Science Youth foundation of Ministry of Education of China （number， 22YJC190019）； Natural Science Foundation of Sichuan Province （number， 2023NSFSC1486）］

BACKGROUND: Most studies have evaluated disability-adjusted life years (DALYs) of colorectal cancer (CRC) patients based on a set of generic disability weights (DWs). This study aimed to apply local CRC-stage-specific DWs to estimate the burden of DALYs for CRC (CRC-DALYs) in populations in China and consider the influence of local screening coverage of CRC. METHODS: A prevalence-based model was constructed using data from various sources. Years lived with disability (YLDs) were estimated mainly via cumulative prevalence data (based on CRC incidence rates, population numbers, and survival rates), stage-specific proportions of CRC, and DWs of the local population. Years of life lost (YLLs) were calculated based on the CRC mortality rates and standard life expectancies. CRC incidence and mortality rates for the years 2020, 2025, and 2030 were estimated by joinpoint regression, and the corresponding DALYs were predicted. The main assumption was made for CRC screening coverage. Sensitivity analyses were used to assess the impact of population, DWs, and coverage. RESULTS: In 2017, among the Chinese population, the estimated number of CRC-DALYs was 4,303,314 (11.9% for YLDs). If CRC screening coverage rate in China (2.3%) remains unchanged, the overall DALYs in 2030 are predicted to increase by 37.2% (45.1% of those aged ≥65 years). More optimistically, the DALYs would then decrease by 0.7% in 2030 (from 5,902,454 to 5,860,200) if the coverage could be increased to 25.0%. A sensitivity analysis revealed that using local DWs would change the base-case values by 5.7%. CONCLUSIONS The estimated CRC-DALYs in China using population-specific DWs were considerably lower (with a higher percentage of YLDs) than the global burden of disease (GBD) estimates (5,865,004, of 4.6% for YLDs), suggesting the impact extent of applying local parameters. Sustainable scale-up CRC screening needs to be in place to moderate the growth trend of CRC-DALYs in China.
Humans ; Colorectal Neoplasms/diagnosis* ; China/epidemiology* ; Disability-Adjusted Life Years ; Male ; Prevalence ; Female ; Middle Aged ; Aged ; Early Detection of Cancer ; Quality-Adjusted Life Years ; Adult ; Incidence

This study explored the potential therapeutic targets and mechanisms of Danggui Shaoyao San(DSS) in the prevention and treatment of Alzheimer's disease(AD) through transcriptomics and metabolomics, combined with animal experiments. Fifty male C57BL/6J mice, aged seven weeks, were randomly divided into the following five groups: control, model, positive drug, low-dose DSS, and high-dose DSS groups. After the intervention, the Morris water maze was used to assess learning and memory abilities of mice, and Nissl staining and hematoxylin-eosin(HE) staining were performed to observe pathological changes in the hippocampal tissue. Transcriptomics and metabolomics were employed to sequence brain tissue and identify differential metabolites, analyzing key genes and metabolites related to disease progression. Reverse transcription-quantitative polymerase chain reaction(RT-qPCR) was employed to validate the expression of key genes. The Morris water maze results indicated that DSS significantly improved learning and cognitive function in scopolamine(SCOP)-induced model mice, with the high-dose DSS group showing the best results. Pathological staining showed that DSS effectively reduced hippocampal neuronal damage, increased Nissl body numbers, and reduced nuclear pyknosis and neuronal loss. Transcriptomics identified seven key genes, including neurexin 1(Nrxn1) and sodium voltage-gated channel α subunit 1(Scn1a), and metabolomics revealed 113 differential metabolites, all of which were closely associated with synaptic function, oxidative stress, and metabolic regulation. RT-qPCR experiments confirmed that the expression of these seven key genes was consistent with the transcriptomics results. This study suggests that DSS significantly improves learning and memory in SCOP model mice and alleviates hippocampal neuronal pathological damage. The mechanisms likely involve the modulation of synaptic function, reduction of oxidative stress, and metabolic balance, with these seven key genes serving as important targets for DSS in the treatment of AD.
Animals ; Alzheimer Disease/genetics* ; Male ; Drugs, Chinese Herbal/administration & dosage* ; Mice ; Mice, Inbred C57BL ; Metabolomics ; Transcriptome/drug effects* ; Maze Learning/drug effects* ; Hippocampus/metabolism* ; Humans ; Disease Models, Animal ; Memory/drug effects*

Traditional Chinese medicine(TCM) capable of clearing heat and removing toxin is most commonly used in clinical practice and has the effect of removing fire-heat and toxin. Studies have shown that most of the Ilex plants have the effect of clearing heat and removing toxin, among which the varieties of I. cornuta, I. pubescens, I. rotunda, I. latifolia, and I. chinensis are most widely used. These plants generally contain triterpenoids and their glycosides, alkaloids, flavonoids, phenylpropanoids, and other chemical components, especially pentacyclic triterpenoids. According to their skeletons, pentacyclic triterpenoids can be divided into the oleanane type, the ursane type, the lupinane type, etc. Among them, ursane-type components are the most abundant, and 136 species have been found so far. These components have been proved to have pharmacological effects such as anti-inflammatory, anti-tumor, hypolipidemic, anti-thrombosis, cardiomyocyte-protective, antibacterial, and hepatoprotective effects. Therefore, this paper systematically reviews the domestic and foreign literature on Ilex plants with a focus on the research progress on pentacyclic triterpenoids and their pharmacological activities, aiming to provide reference for the development of TCM resources with the effect of clearing heat and removing toxin.
Ilex/chemistry* ; Plants, Medicinal/chemistry* ; Pentacyclic Triterpenes/pharmacology* ; Medicine, Chinese Traditional ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Animals

OBJECTIVES: To investigate the clinical characteristics and prognosis of infants and young children with basal ganglia infarction after minor head trauma (BGIMHT). METHODS: A retrospective analysis was conducted on the clinical data and follow-up results of children aged 28 days to 3 years with BGIMHT who were hospitalized at Children's Hospital of Soochow University from January 2011 to January 2022. RESULTS: A total of 45 cases of BGIMHT were included, with the most common symptom being limb movement disorders (96%, 43/45), followed by facioplegia (56%, 25/45). Cerebral imaging showed that 72% (31/43) had infarction accompanied by basal ganglia calcification. After conservative treatment, 42 children (93%) showed significant symptom improvement, while 3 children (7%) experienced recurrent strokes. The median follow-up time was 82 months (range: 17-141 months). At the last follow-up, 97% (29/30) had residual basal ganglia softening lesions. Among 29 cases participating in questionnaire follow-up, 66% (19/29) recovered normally, 17% (5/29) showed significant improvement in symptoms, and 17% (5/29) had poor improvement. According to the grading of the Global Burden of Disease Control Projects, only 1 child (3%) had severe sequelae. There were no significant differences in age at onset, gender, or presence of concomitant basal ganglia calcification between children with and without neurological sequelae (P>0.05). CONCLUSIONS The most common initial symptom of BGIMHT is limb movement disorder, and imaging results indicate that most children have concurrent intracranial calcifications. Most infarct lesions later transform into softening lesions, resulting in a generally good prognosis.
Humans ; Male ; Female ; Infant ; Child, Preschool ; Craniocerebral Trauma/complications* ; Follow-Up Studies ; Retrospective Studies ; Basal Ganglia/pathology* ; Infant, Newborn

OBJECTIVES: To investigate the clinical features of children with STAT gene mutations, and to explore corresponding immunotherapy strategies. METHODS: A retrospective analysis was performed for the clinical data of 10 children with STAT gene mutations who were admitted to the Department of Pediatrics of the First Affiliated Hospital of Guangzhou Medical University, from October 2015 to October 2024. Exploratory immunotherapy was implemented in some refractory cases, and the changes in symptoms, imaging manifestations, and cytokine levels were assessed after treatment. RESULTS: For the 10 children, the main clinical manifestations were recurrent rash since birth (7/10), cough (8/10), wheezing (5/10), expectoration (4/10), and purulent nasal discharge (4/10). Genotyping results showed that there was one child with heterozygous loss-of-function (LOF) mutation in the STAT1 gene, four children with heterozygous LOF mutation in the STAT3 gene, and five children with heterozygous gain-of-function (GOF) mutation in the STAT3 gene. Two children with LOF mutation in the STAT3 gene showed decreased interleukin-6 levels and improved clinical symptoms and imaging findings after omalizumab treatment. Three children with GOF mutation in the STAT3 gene achieved effective disease control after treatment with methylprednisolone (0.5 mg/kg per day). Two children with GOF mutation in the STAT3 gene received treatment with JAK inhibitor and then showed some improvement in symptoms. CONCLUSIONS STAT gene mutation screening should be considered for children with recurrent rash and purulent respiratory tract infections. Targeted immunotherapy may improve prognosis in patients with no response to conventional treatment.
Humans ; Male ; Immunotherapy ; Female ; Child, Preschool ; Child ; Gain of Function Mutation ; Retrospective Studies ; Infant ; Loss of Function Mutation ; STAT Transcription Factors/genetics*

OBJECTIVE: To investigate the efficacy and safety of chidamide combined with DICE regimen (cisplatin+ ifosfamide + etoposide + dexamethasone) for relapsed/refractory diffuse large B-cell lymphome(R/R DLBCL). METHODS: The clinical data of 31 R/R DLBCL patients treated by chidamide combined with DICE regimen in the Hematology Department of the Fourth Hospital of Hebei Medical University from October 2016 to October 2020 were retrospectively analyzed. The clinical efficacy and adverse events were observed. RESULTS: Among the 31 patients, 20 were male and 11 were female. The median age of the patients was 55 (range: 27-71) years old, 21 cases were < 60 years old, 10 cases were ≥60 years old. 26 cases were refractory and 5 cases were relapsed. There were 13 cases of germinal center B-cell like (GCB), 17 cases of non-GCB, and 1 case had missing Hans type. There were 17 cases of double-expression lymphoma (DEL) and 14 cases of non-DEL. The complete response rate of patients was 38.7%(12/31), the overall response rate was 67.7%(21/31). The median progression-free survival time and the median overall survival time were 9.8(95%CI : 4.048-15.552) months, 13.9(95%CI : 9.294-18.506) months, respectively. Multipvariate analysis showed that GCB and DEL reduced the risk of disease recurrence in R/R DLBCL patients. The main grade 3/4 hematological adverse events in this study were thrombocytopenia, agranulocytosis, anemia and leukopenia. CONCLUSION The chidamide combined with DICE regimen is effective in the treatment of R/R DLBCL, and hematological adverse events should be closely monitored.
Humans ; Lymphoma, Large B-Cell, Diffuse/drug therapy* ; Middle Aged ; Female ; Male ; Adult ; Aged ; Retrospective Studies ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Benzamides/administration & dosage* ; Aminopyridines/administration & dosage* ; Etoposide/therapeutic use* ; Cisplatin/administration & dosage* ; Ifosfamide/administration & dosage* ; Dexamethasone/therapeutic use*

OBJECTIVE: To explore the effect and mechanism of DNA methyltransferase 1 (DNMT1) knockout on the inhibition of acute myeloid leukemia (AML) by natural killer (NK) cells. METHODS: The peripheral blood NK cells of AML patients and controls were collected, and the mRNA and protein level of DNMT1 were measured by PCR and Western blot, respectively. The DNMT1 knockout mice were constructed to obtain NK^DNMT1-/- cells. The NK cells were stimulated with interleukin (IL)-12, IL-15, and IL-18 to construct memory NK cells, and then the interferon-γ (IFN-γ) levels were measured by ELISA. After co-culturing with memory NK cells and HL60 cells, the killing effect of NK^DNMT1-/- cells on HL60 cells was detected by LDH assay. Then, the HL60 cell apoptosis and NK cell NKG2D level were measured by flow cytometry. The perforin and granzyme B protein levels of NK cells were measured by Western blot. The AML model mice were constructed by injecting HL60 cells into the tail vein, meanwhile, memory NK cells were also injected, and then the mouse weights, CD33 positive rates, and survival time were detected. RESULTS: The mRNA and protein levels of DNMT1 in NK cells of AML patients were significantly higher than those in the control group (both P < 0.01), while the IFN-γ level induced by interleukin was significantly lower than that in the control group (P < 0.05). Compared with NK^DNMT1+/+ cells, the ability of NK^DNMT1-/- cells to secrete IFN-γ after interleukin stimulation was significantly increased (P < 0.05). The killing and apoptosis-inducing effects of NK^DNMT1-/- cells on HL60 cells were significantly stronger than those of NK^DNMT1+/+ cells (both P < 0.05). The NKG2D level and expression of perforin and granzyme B of NK^DNMT1-/- cells were significantly increased compared with NK^DNMT1+/+ cells (all P < 0.05). Compared with AML mice injected with NK^DNMT1+/+ cells, AML mice injected with NK^DNMT1-/- cells showed significantly increased body weight, decreased CD33 positive rate, and prolonged survival time (all P < 0.05). CONCLUSION Knocking out DNMT1 can enhance the inhibitory effect of NK cells on AML, which may be related to enhancing NK cell memory function.
Killer Cells, Natural/metabolism* ; Animals ; Leukemia, Myeloid, Acute ; Humans ; DNA (Cytosine-5-)-Methyltransferase 1 ; Mice ; Mice, Knockout ; HL-60 Cells ; Apoptosis ; Interferon-gamma/metabolism* ; Granzymes/metabolism* ; Perforin/metabolism* ; NK Cell Lectin-Like Receptor Subfamily K/metabolism*