Radiation-induced thrombocytopenia(RIT)faces a perplexing challenge in the clinical treatment of cancer patients,and current therapeutic approaches are inadequate in the clinical settings.In this research,oxy-matrine,a new molecule capable of healing RIT was screened out,and the underlying regulatory mecha-nism associated with magakaryocyte(MK)differentiation and thrombopoiesis was demonstrated.The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro.The ability to induce thrombopoiesis was subsequently demonstrated in Tg(cd41:enhanced green fluorescent protein(eGFP))zebrafish and RIT model mice.In addition,we carried out network pharmacological pre-diction,drug affinity responsive target stability assay(DARTS)and cellular thermal shift assay(CETSA)analyses to explore the potential targets of oxymatrine.Moreover,the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses,Western blot(WB),and immunofluorescence.Oxymatrine markedly promoted MK differentiation and maturation in vitro.Moreover,oxymatrine induced thrombopoiesis in Tg(cd41:eGFP)zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice.Mechanistically,oxymatrine directly binds to toll-like receptor 2(TLR2)and further regulates the downstream pathway stimulator of interferon genes(STING)/nuclear factor-kappaB(NF-κB),which can be blocked by C29 and C-176,which are specific inhibitors of TLR2 and STING,respectively.Taken together,we demonstrated that oxymatrine,a novel TLR2 agonist,plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis,suggesting that oxymatrine is a promising candidate for RIT therapy.

Radiation-induced thrombocytopenia (RIT) faces a perplexing challenge in the clinical treatment of cancer patients, and current therapeutic approaches are inadequate in the clinical settings. In this research, oxymatrine, a new molecule capable of healing RIT was screened out, and the underlying regulatory mechanism associated with magakaryocyte (MK) differentiation and thrombopoiesis was demonstrated. The capacity of oxymatrine to induce MK differentiation was verified in K-562 and Meg-01 cells in vitro. The ability to induce thrombopoiesis was subsequently demonstrated in Tg (cd41:enhanced green fluorescent protein (eGFP)) zebrafish and RIT model mice. In addition, we carried out network pharmacological prediction, drug affinity responsive target stability assay (DARTS) and cellular thermal shift assay (CETSA) analyses to explore the potential targets of oxymatrine. Moreover, the pathway underlying the effects of oxymatrine was determined by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, Western blot (WB), and immunofluorescence. Oxymatrine markedly promoted MK differentiation and maturation in vitro. Moreover, oxymatrine induced thrombopoiesis in Tg (cd41:eGFP) zebrafish and accelerated thrombopoiesis and platelet function recovery in RIT model mice. Mechanistically, oxymatrine directly binds to toll-like receptor 2 (TLR2) and further regulates the downstream pathway stimulator of interferon genes (STING)/nuclear factor-kappaB (NF-κB), which can be blocked by C29 and C-176, which are specific inhibitors of TLR2 and STING, respectively. Taken together, we demonstrated that oxymatrine, a novel TLR2 agonist, plays a critical role in accelerating MK differentiation and thrombopoiesis via the STING/NF-κB axis, suggesting that oxymatrine is a promising candidate for RIT therapy.

Objective:To screen inflammatory markers that can be used for the diagnosis and intervention evaluation of patients with chronic kidney disease(CKD)with depression,and to systematically study the therapeutic effect and safety of modified Chaihu Longgu Muli decoction in patients with CKD with depression.Methods:This study was a prospective study,a total of 120 patients with CKD who were diagnosed and treated in the Department of Nephrology,Chongqing Traditional Chinese Medicine Hospital from April 2023 to October 2024 were included.They were divided into CKD with depression(CKD-D)group and CKD without depression(CKD-N)group according to the diagnostic criteria by random number table method.The results of routine laboratory tests were collected,and the severity of depressive disorder was evaluated by Hamilton Depression Rating Scale-17(HAMD-17).The levels of interleukin-18(IL-18),interferon-γ(IFN-γ),β-thromboglobulin(β-TG),platlet factor-4(PF-4),eosinophil chemotactic factor(Eotaxin),soluble tumor necrosis factor receptor-2(sTNFR-2)and CD40 ligand(CD40L)in serum were quantitatively evaluated by liquid chip technology.Pearson correlation analysis was used to analyze the correlation between HAMD-17 scores and inflammatory markers with statistical differences in CKD patients with depression at different stages.The patients in CKD-D group were randomly divided into control group and treatment group.The control group was given basic treatment of CKD,while the treatment group was treated with modified Chaihu Longgu Muli decoction on the basis of the control group.After 8 weeks of continuous intervention,the clinical effective rate,the changes of effective inflammatory markers and the occurrence of adverse reactions were compared between the two groups.Results:In the CKD-D group and the CKD-N group,the difference of HAMD-17 score,serum phosphorus(P),serum creatinine(Scr),estimated glomerular filtration rate(eGFR),albumin(ALB),serum iron(Fe3+),C-reactive protein(CRP),IL-18,IFN-γ,sTNFR-2 indicators were statistically significant(P＜0.05).Multivariate Logistic regression analysis showed that in addition to HAMD-17 score(OR=1.259,P=0.006),SCr(OR=1.748,P=0.003),eGFR(OR=1.354,P=0.005),serum IL-18(OR=0.924,P=0.011)and IFN-γ(OR=0.859,P=0.031)levels were also independent influencing factors for CKD patients with depression.Pearson correlation analysis showed that there was a significant positive correlation between HAMD-17 score and IL-18,IFN-γ,sTNFR-2 and CD40L.The total clinical effective rate of the treatment group was higher than that of the control group,and the serum levels of IL-18 and IFN-γ in the treatment group were lower than those in the control group,the differences were statistically significant(P＜0.05),and no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:IL-18 and IFN-γ can be used as effective serum markers for the diagnosis and treatment of depressive disorders in CKD patients.At the same time,the changes of serum levels of IL-18 and IFN-γ can be used to evaluate the severity of symptoms in CKD patients with depression at different stages to a certain extent.Modified Chaihu Longgu Muli decoction may improve CKD combined with depressive symptoms and improve the quality of life of patients by down-regulating the level of inflammatory factors.

Objective:To screen inflammatory markers that can be used for the diagnosis and intervention evaluation of patients with chronic kidney disease(CKD)with depression,and to systematically study the therapeutic effect and safety of modified Chaihu Longgu Muli decoction in patients with CKD with depression.Methods:This study was a prospective study,a total of 120 patients with CKD who were diagnosed and treated in the Department of Nephrology,Chongqing Traditional Chinese Medicine Hospital from April 2023 to October 2024 were included.They were divided into CKD with depression(CKD-D)group and CKD without depression(CKD-N)group according to the diagnostic criteria by random number table method.The results of routine laboratory tests were collected,and the severity of depressive disorder was evaluated by Hamilton Depression Rating Scale-17(HAMD-17).The levels of interleukin-18(IL-18),interferon-γ(IFN-γ),β-thromboglobulin(β-TG),platlet factor-4(PF-4),eosinophil chemotactic factor(Eotaxin),soluble tumor necrosis factor receptor-2(sTNFR-2)and CD40 ligand(CD40L)in serum were quantitatively evaluated by liquid chip technology.Pearson correlation analysis was used to analyze the correlation between HAMD-17 scores and inflammatory markers with statistical differences in CKD patients with depression at different stages.The patients in CKD-D group were randomly divided into control group and treatment group.The control group was given basic treatment of CKD,while the treatment group was treated with modified Chaihu Longgu Muli decoction on the basis of the control group.After 8 weeks of continuous intervention,the clinical effective rate,the changes of effective inflammatory markers and the occurrence of adverse reactions were compared between the two groups.Results:In the CKD-D group and the CKD-N group,the difference of HAMD-17 score,serum phosphorus(P),serum creatinine(Scr),estimated glomerular filtration rate(eGFR),albumin(ALB),serum iron(Fe3+),C-reactive protein(CRP),IL-18,IFN-γ,sTNFR-2 indicators were statistically significant(P＜0.05).Multivariate Logistic regression analysis showed that in addition to HAMD-17 score(OR=1.259,P=0.006),SCr(OR=1.748,P=0.003),eGFR(OR=1.354,P=0.005),serum IL-18(OR=0.924,P=0.011)and IFN-γ(OR=0.859,P=0.031)levels were also independent influencing factors for CKD patients with depression.Pearson correlation analysis showed that there was a significant positive correlation between HAMD-17 score and IL-18,IFN-γ,sTNFR-2 and CD40L.The total clinical effective rate of the treatment group was higher than that of the control group,and the serum levels of IL-18 and IFN-γ in the treatment group were lower than those in the control group,the differences were statistically significant(P＜0.05),and no significant difference in the incidence of adverse reactions between the two groups(P＞0.05).Conclusion:IL-18 and IFN-γ can be used as effective serum markers for the diagnosis and treatment of depressive disorders in CKD patients.At the same time,the changes of serum levels of IL-18 and IFN-γ can be used to evaluate the severity of symptoms in CKD patients with depression at different stages to a certain extent.Modified Chaihu Longgu Muli decoction may improve CKD combined with depressive symptoms and improve the quality of life of patients by down-regulating the level of inflammatory factors.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Objective:The incidence of infections in patients with malignant hematologic diseases is extremely high and significantly affects their prognosis.Identifying early and precise biomarkers for infection is crucial for guiding the treatment of infections in these patients.Previous studies have shown that procalcitonin(PCT)can serve as an early diagnostic marker for bloodstream infections in patients with malignant hematologic diseases.This study aims to compare serum PCT levels in these patients with different pathogens,disease types,infection sites,and severity levels. Methods:Clinical data and laboratory results of infected patients with malignant hematologic diseases treated at the Department of Hematology,the Third Xiangya Hospital of Central South University from January 2018 to August 2023 were collected.General patient information was retrospectively analyzed.Serum PCT levels were compared among patients with different pathogens,types of malignant hematologic diseases,infection sites,and infection severity;Receiver operator characteristic(ROC)curves were used to determine the cut-off values and diagnostic value of serum PCT levels in diagnosing bloodstream infections versus local infections and severe infections versus non-severe infections.Mortality rates after 4-7 days of anti-infective treatment were compared among groups with rising,falling,and unchanged PCT levels. Results:A total of 526 patients with malignant hematologic diseases were included.The main pathogens were Gram-negative bacteria(272 cases,51.7%),followed by Gram-positive bacteria(120 cases,22.8%),fungi(65 cases,12.4%),viruses(23 cases,4.4%),and mixed pathogens(46 cases,8.7%).The main types of malignant hematologic diseases were acute myeloid leukemia(216 cases,41.1%),acute lymphoblastic leukemia(107 cases,20.3%),and lymphoma(93 cases,17.7%).Granulocyte deficiency was present in 68.3%(359 cases)of the patients during infection,with severe infection in 24.1%(127 cases).Significant differences in serum PCT levels were found among patients with different types of pathogens(P<0.001),with the highest levels in Gram-negative bacterial infections.Significant differences in serum PCT levels were also found among patients with different types of malignant hematologic diseases(P<0.05),with the highest levels in lymphoma patients.Serum PCT levels were significantly higher in systemic infections and severe infections compared to local infections and non-severe infections(both P<0.001).ROC curve analysis showed that the cut-off values for diagnosing bloodstream infections and severe infections were 0.22 and 0.28 ng/mL,with areas under the curve of 0.670 and 0.673,respectively.After 4-7 days of anti-infective treatment,the mortality rates of the PCT declining,PCT unchanged,and PCT rising groups were 11.9%,21.2%,and 35.7%,respectively,and pairwise comparisons were statistically significant(all P<0.05). Conclusion:PCT can be used as an auxiliary indicator for early identification of different pathogens,infection sites,and severity levels in patients with malignant hematologic diseases combined with infections.Dynamic monitoring of PCT levels after empirical antibiotic treatment provides important guidance for assessing patient's prognosis.

As artificial intelligence technology rapidly advances, its deployment within the medical sector presents substantial ethical challenges. Consequently, it becomes crucial to create a standardized, transparent, and secure framework for processing medical data. This includes setting the ethical boundaries for medical artificial intelligence and safeguarding both patient rights and data integrity. This consensus governs every facet of medical data handling through artificial intelligence, encompassing data gathering, processing, storage, transmission, utilization, and sharing. Its purpose is to ensure the management of medical data adheres to ethical standards and legal requirements, while safeguarding patient privacy and data security. Concurrently, the principles of compliance with the law, patient privacy respect, patient interest protection, and safety and reliability are underscored. Key issues such as informed consent, data usage, intellectual property protection, conflict of interest, and benefit sharing are examined in depth. The enactment of this expert consensus is intended to foster the profound integration and sustainable advancement of artificial intelligence within the medical domain, while simultaneously ensuring that artificial intelligence adheres strictly to the relevant ethical norms and legal frameworks during the processing of medical data.
Artificial Intelligence/legislation & jurisprudence* ; Humans ; Consensus ; Computer Security/standards* ; Confidentiality/ethics* ; Informed Consent/ethics*

OBJECTIVES: To explore the cytotoxicity of four wild mushrooms involved in a case of Yunnan sudden unexplained death (YNSUD), to provide the experimental basis for prevention and treatment of YNSUD. METHODS: Four kinds of wild mushrooms that were eaten by family members in this YNSUD incident were collected and identified by expert identification and gene sequencing. Raw extracts from four wild mushrooms were extracted by ultrasonic extraction to intervene HEK293 cells, and the mushrooms with obvious cytotoxicity were screened by Cell Counting Kit-8 (CCK-8). The selected wild mushrooms were prepared into three kinds of extracts, which were raw, boiled, and boiled followed by enzymolysis. HEK293 cells were intervened with these three extracts at different concentrations. The cytotoxicity was detected by CCK-8 combined with lactate dehydrogenase (LDH) Assay Kit, and the morphological changes of HEK293 cells were observed under an inverted phase contrast microscope. RESULTS: Species identification indicated that the four wild mushrooms were Butyriboletus roseoflavus, Boletus edulis, Russula virescens and Amanita manginiana. Cytotoxicity was found only in Amanita manginiana. The raw extracts showed cytotoxicity at the mass concentration of 0.1 mg/mL, while the boiled extracts and the boiled followed by enzymolysis extracts showed obvious cytotoxicity at the mass concentration of 0.4 mg/mL and 0.7 mg/mL, respectively. In addition to the obvious decrease in the number of HEK293 cells, the number of synapses increased and the refraction of HEK293 cells was poor after the intervention of Amanita manginiana extracts. CONCLUSIONS The extracts of Amanita manginiana involved in this YNSUD case has obvious cytotoxicity, and some of its toxicity can be reduced by boiled and enzymolysis, but cannot be completely detoxicated. Therefore, the consumption of Amanita manginiana is potentially dangerous, and it may be one of the causes of the YNSUD.
Humans ; HEK293 Cells ; Sincalide ; China ; Amanita ; Death, Sudden

Objective    To investigate the short-term quality of life in patients after single-direction video-assisted thoracic surgery (VATS) for lung cancer, and explore the related influencing factors. Methods    Patients who underwent single-direction VATS for lung cancer in the Department of Thoracic Surgery, West China Hospital, Sichuan University from July 2020 to August 2021 were continuously selected. The QLQ-C30 and QLQ-LC13 were used to evaluate the quality of life of the patients after the surgery, and the influencing factors were analyzed. Results    A total of 193 patients were collected. There were 73 males aged 59.44±11.40 years, and 120 females aged 53.73±11.15 years. The QLQ-C30 score of the patients after single-direction VATS for lung cancer was 69.09±20.21 points. Univariate analysis and Pearson correlation analysis showed that age, occupation, anesthesia time, postoperative complications, postoperative antibiotic use time, postoperative hospital stay, insomnia, economic stress, hemoptysis, chest pain, dysphagia, arm or shoulder pain were associated with the quality of life (P≤0.05). The results of multiple regression analysis showed that anesthesia time, economic pressure, insomnia and chest pain had a significant impact on the overall quality of life 30 days after the surgery (P≤0.05). Conclusion    The anesthesia time, economic pressure, insomnia and chest pain are independent influencing factors for the quality of life after the VATS lung cancer surgery.