Arsenic (organoarsenic) compound is one of the oldest drugs used by humans to treat various diseases. From its initial application in treating various skin diseases to the 1970s when arsenic trioxide (ATO) was proven to be able to significantly relieve acute promyelocytic leukemia (APL), arsenic (organoarsenic) compounds gradually occupied an important position in the history of medical development. This article reviews the pharmaceutical research progress of inorganic arsenic compounds and organic arsine compounds, covering anticancer, antiparasitic, antiviral and antibiotic aspects. It further explores the potential for developing new arsenic (organoarsenic) drugs with higher efficacy and lower toxicity, aiming to provide new research directions and ideas for the application of arsenic (organoarsenic) compounds in disease treatment.

Objective To identify determinants of subtherapeutic voriconazole(VRCZ)concentrations in allogeneic hematopoietic stem cell transplantation(allo-HSCT)recipients and to develop/validate a nomogram-based risk prediction model.Methods This study retrospectively analyzed 310 VRCZ therapeutic drug monitoring(TDM)measurements from allo-HSCT recipients at 310 patients who under went allo-HSCT surgery at Hebei Yanda Ludaopei Hospital from October 2022 to October 2024 and received VRCZ for the prevention and treatment of invasive fungal infections before transplantion were selected as the study subjects.Cases were stratified into target-concentration group(0.5～5.0μg/ml)and subtherapeutic group(<0.5μg/ml).Through single factor and multiple factor Logistic regression analysis,indeipendent predictive factors forvecz plasma concentration non-compliance were screened,and a column chart prediction model(NPM)was constructed.The performance of the model was evaluateding area under the receiver operating characteristic curve(AUC),Hosmer-Lemeshow(H-L)goodness-of-fit test,and decision curve analysis(DCA).Results Among 310 VRCZ-TDM measurements,71.61%(222/310)achieved target concentrations.Multivariate analysis showed that CYP2C19 intermediate metabolite,daily dose of cyclosporine A(CSA),daily dose of VRCZ,creatinine(Cr)>97 μmol/L,albumin(Alb)and C-reactive protein(CRP)were independent influencing factors for VRCZ blood drug concentration non-compliance(Wald χ2=4.046～13.221,all P＜0.05).The nomogram demonstrated excellent discrimination,calibration(H-L goodness of fit test χ2=2.663,P=0.954),and clinical utility with net benefit across 0.05～0.96 risk thresholds.Conclusion The nomogram incorporating CYP2C19 gene phenotype,daily CSA dosing,daily VRCZ dosing,Cr levels,Alb and CRP provides a validated tool for optimizing VRCZ therapy in allo-HSCT recipients,enabling precision dosing strategies.

Objective To identify determinants of subtherapeutic voriconazole(VRCZ)concentrations in allogeneic hematopoietic stem cell transplantation(allo-HSCT)recipients and to develop/validate a nomogram-based risk prediction model.Methods This study retrospectively analyzed 310 VRCZ therapeutic drug monitoring(TDM)measurements from allo-HSCT recipients at 310 patients who under went allo-HSCT surgery at Hebei Yanda Ludaopei Hospital from October 2022 to October 2024 and received VRCZ for the prevention and treatment of invasive fungal infections before transplantion were selected as the study subjects.Cases were stratified into target-concentration group(0.5～5.0μg/ml)and subtherapeutic group(<0.5μg/ml).Through single factor and multiple factor Logistic regression analysis,indeipendent predictive factors forvecz plasma concentration non-compliance were screened,and a column chart prediction model(NPM)was constructed.The performance of the model was evaluateding area under the receiver operating characteristic curve(AUC),Hosmer-Lemeshow(H-L)goodness-of-fit test,and decision curve analysis(DCA).Results Among 310 VRCZ-TDM measurements,71.61%(222/310)achieved target concentrations.Multivariate analysis showed that CYP2C19 intermediate metabolite,daily dose of cyclosporine A(CSA),daily dose of VRCZ,creatinine(Cr)>97 μmol/L,albumin(Alb)and C-reactive protein(CRP)were independent influencing factors for VRCZ blood drug concentration non-compliance(Wald χ2=4.046～13.221,all P＜0.05).The nomogram demonstrated excellent discrimination,calibration(H-L goodness of fit test χ2=2.663,P=0.954),and clinical utility with net benefit across 0.05～0.96 risk thresholds.Conclusion The nomogram incorporating CYP2C19 gene phenotype,daily CSA dosing,daily VRCZ dosing,Cr levels,Alb and CRP provides a validated tool for optimizing VRCZ therapy in allo-HSCT recipients,enabling precision dosing strategies.

Arsenic (organoarsenic) compound is one of the oldest drugs used by humans to treat various diseases. From its initial application in treating various skin diseases to the 1970s when arsenic trioxide (ATO) was proven to be able to significantly relieve acute promyelocytic leukemia (APL), arsenic (organoarsenic) compounds gradually occupied an important position in the history of medical development. This article reviews the pharmaceutical research progress of inorganic arsenic compounds and organic arsine compounds, covering anticancer, antiparasitic, antiviral and antibiotic aspects. It further explores the potential for developing new arsenic (organoarsenic) drugs with higher efficacy and lower toxicity, aiming to provide new research directions and ideas for the application of arsenic (organoarsenic) compounds in disease treatment.

Objective To establish a high-performance liquid chromatography tandem mass spectrometry(HPLC-MS/MS)method for determining the plasma concentration of olverembatinib in leukemia patients,apply it to clinical drug monitoring,and provide reliable basis for rational drug use in clinical practice.Methods Ponatinib-d8 was used as an internal standard,and methanol was used to precipitate plasma proteins and extract olverembatinib.The chromatographic column was Welch Ultimate XB-C18 cloumn(50 mmx4.6 mm,5 μm),with a column temperature of 60 ℃.The mobile phase consisted of an aqueous solution(containing 0.1％formic acid+2 mmol/L ammonium acetate)-methanol solution(containing 0.1％formic acid),with a flow rate of 0.8 mL/min and gradient elution.Electrospray positive ion mode was used,with multiple reaction monitoring scanning.The quantitative ion pair of olverembatinib was m/z 533.3→260.1,the qualitative ion pair was m/z 533.3→433.3,and the internal standard ion pair was m/z 541.1 →260.2.The plasma samples of 40 leukemia patients taking olverembatinib were monitored and analyzed for concentration,and IBM SPSS Statistics 27.0 and OriginPro 2021 softwares were used for statistical analysis of the results.Results The linear range of olverembatinib was 1-250 ng/mL(r=0.998 0),the lower limit of quantification was 1 ng/mL,the extraction recovery rate was 100.28％～101.27％,the intra-day precision RSD was 1.15％～3.87％,and the inter-day precision RSD was 2.32％～3.68％.Conclusion This method is easy to operate,highly specific and sensitive,and can be used to determine the blood concentration of olverembatinib in leukemia patients.

The dihydrofolate reductase (dhfr) and dihydropteroate synthetase (dhps) genes of Plasmodium vivax, as antifolate resistance-associated genes were used for drug resistance surveillance. A total of 375 P. vivax isolates collected from different geographical locations in China in 2009-2019 were used to sequence Pvdhfr and Pvdhps. The majority of the isolates harbored a mutant type allele for Pvdhfr (94.5%) and Pvdhps (68.2%). The most predominant point mutations were S117T/N (77.7%) in Pvdhfr and A383G (66.8%) in Pvdhps. Amino acid changes were identified at nine residues in Pvdhfr. A quadruple-mutant haplotype at 57, 58, 61, and 117 was the most frequent (57.4%) among 16 distinct Pvdhfr haplotypes. Mutations in Pvdhps were detected at six codons, and the double-mutant A383G/A553G was the most prevalent (39.3%). Pvdhfr exhibited a higher mutation prevalence and greater diversity than Pvdhps in China. Most isolates from Yunnan carried multiple mutant haplotypes, while the majority of samples from temperate regions and Hainan Island harbored the wild type or single mutant type. This study indicated that the antifolate resistance levels of P. vivax parasites were different across China and molecular markers could be used to rapidly monitor drug resistance. Results provided evidence for updating national drug policy and treatment guidelines.
Antimalarials/pharmacology* ; China/epidemiology* ; Drug Combinations ; Drug Resistance/genetics* ; Folic Acid Antagonists/pharmacology* ; Humans ; Mutation ; Plasmodium vivax/genetics* ; Prevalence

BACKGROUND:According to the core functional zone of amino acid sequence of the osteoinduction in bone morphogenetic proteins, our research group synthesized bone morphogenetic protein (BMP) active polypeptides Ⅰ and Ⅱ by artificial solid-state synthesis method. OBJECTIVE: To evaluate the osteoinductive ability of BMP active polypeptides Ⅰ and Ⅱ in animals. METHODS:Forty-two Sprague-Dawley rats were randomly divided into seven groups, and respectively implanted with hydroxyapatite/polylactic acid carrying 0.2, 0.4, 0.8 g/L BMP active polypeptides I, hydroxyapatite/polylactic acid carrying 0.2, 0.4, 0.8 g/L BMP active polypeptides Ⅱ, and hydroxyapatite/polylactic acid alone. At 3 and 5 weeks postoperatively, X-ray, CT and histological detection were conducted to evaluate osteoinductive conditions in the seven groups. RESULTS AND CONCLUSION:At 3 and 5 weeks postoperatively, there were better local osteoinductive effects in the groups hydroxyapatite/polylactic acid carrying BMP active polypeptides Ⅰ and Ⅱ than the group of hydroxyapatite/polylactic acid, indicating both two kinds of BMP active polypeptides possessed a certain osteoinductive ability. Moreover, this osteoinductive ability became stronger with time. At 5 weeks postoperatively, the osteoinductive effect in the 0.4 and 0.8 g/L BMP active polypeptides I groups was better than that in the 0.2 g/L BMP active polypeptides I group and the 0.2, 0.4 and 0.8 BMP active polypeptides Ⅱ groups (P < 0.05). In addition, there was no difference in the osteoinductive effect of 0.4 and 0.8 g/L BMP active polypeptides I groups. These results indicate that BMP active polypeptides I has a stronger osteoinductive ability than BMP active polypeptides Ⅱ.

In contrast to the gradual reduction in the number of locally transmitted malaria cases in China, the number of imported malaria cases has been increasing since 2008. Here, we report a case of a 39-year-old Chinese man who acquired Plasmodium ovale wallikeri infection while staying in Ghana, West Africa for 6 months in 2012. Microscopic examinations of Giemsa-stained thin and thick blood smears indicated Plasmodium vivax infection. However, the results of rapid diagnostic tests, which were conducted 3 times, were not in agreement with P. vivax. To further check the diagnosis, standard PCR analysis of the small-subunit rRNA gene was conducted, based on which a phylogeny tree was constructed. The results of gene sequencing indicated that this malaria is a variant of P. ovale (P. ovale wallikeri). The infection in this patient was not a new infection, but a relapse of the infection from the one that he had contracted in West Africa.
Adult ; Azure Stains ; Base Sequence ; China ; DNA, Protozoan/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Ghana ; Humans ; Malaria/*diagnosis/parasitology ; Male ; Molecular Sequence Data ; Phylogeny ; Plasmodium ovale/*classification/genetics/isolation & purification ; Polymerase Chain Reaction ; Recurrence ; Sequence Analysis, DNA ; Travel