Guided by the concept of quality by design(QbD), this study optimizes the calcination and quenching process of calcined Magnetitum and establishes the XRD characteristic spectra of calcined Magnetitum, providing a scientific basis for the formulation of quality standards. Based on the processing methods and quality requirements of Magnetitum in the Chinese Pharmacopoeia, the critical process parameters(CPPs) identified were calcination temperature, calcination time, particle size, laying thickness, and the number of vinegar quenching cycles. The critical quality attributes(CQAs) included Fe mass fraction, Fe~(2+) dissolution, and surface color. The weight coefficients were determined by combining Analytic Hierarchy Process(AHP) and the criteria importance though intercrieria correlation(CRITIC) method, and the calcination process was optimized using orthogonal experimentation. Surface color was selected as a CQA, and based on the principle of color value, the surface color of calcined Magnetitum was objectively quantified. The vinegar quenching process was then optimized to determine the best processing conditions. X-ray diffraction(XRD) was used to establish the characteristic spectra of calcined Magnetitum, and methods such as similarity evaluation, cluster analysis, and orthogonal partial least squares-discriminant analysis(OPLS-DA) were used to evaluate the quality of the spectra. The optimized calcined Magnetitum preparation process was found to be calcination at 750 ℃ for 1 h, with a laying thickness of 4 cm, a particle size of 0.4-0.8 cm, and one vinegar quenching cycle(Magnetitum-vinegar ratio 10∶3), which was stable and feasible. The XRD characteristic spectra analysis method, featuring 9 common peaks as fingerprint information, was established. The average correlation coefficient ranged from 0.839 5-0.988 1, and the average angle cosine ranged from 0.914 4 to 0.995 6, indicating good similarity. Cluster analysis results showed that Magnetitum and calcined Magnetitum could be grouped together, with similar compositions. OPLS-DA discriminant analysis identified three key characteristic peaks, with Fe_2O_3 being the distinguishing component between the two. The final optimized processing method is stable and feasible, and the XRD characteristic spectra of calcined Magnetitum was initially established, providing a reference for subsequent quality control and the formulation of quality standards for calcined Magnetitum.
X-Ray Diffraction/methods* ; Drugs, Chinese Herbal/chemistry* ; Quality Control ; Particle Size

OBJECTIVES: To investigate the genomic characteristics and prognostic factors of juvenile myelomonocytic leukemia (JMML) with RAS mutations. METHODS: A retrospective analysis was conducted on the clinical data of JMML children with RAS mutations treated at the Hematology Hospital of Chinese Academy of Medical Sciences, from January 2008 to November 2022. RESULTS: A total of 34 children were included, with 17 cases (50%) having isolated NRAS mutations, 9 cases (27%) having isolated KRAS mutations, and 8 cases (24%) having compound mutations. Compared to children with isolated NRAS mutations, those with NRAS compound mutations showed statistically significant differences in age at onset, platelet count, and fetal hemoglobin proportion (P<0.05). Cox proportional hazards regression model analysis revealed that hematopoietic stem cell transplantation (HSCT) and hepatomegaly (≥2 cm below the costal margin) were factors affecting the survival rate of JMML children with RAS mutations (P<0.05); hepatomegaly was a factor affecting survival in the non-HSCT group (P<0.05). CONCLUSIONS Children with NRAS compound mutations have a later onset age compared to those with isolated NRAS mutations. At initial diagnosis, children with NRAS compound mutations have poorer peripheral platelet and fetal hemoglobin levels than those with isolated NRAS mutations. Liver size at initial diagnosis is related to the prognosis of JMML children with RAS mutations. HSCT can improve the prognosis of JMML children with RAS mutations.
Humans ; Leukemia, Myelomonocytic, Juvenile/therapy* ; Mutation ; Male ; Female ; Child, Preschool ; Retrospective Studies ; Child ; Infant ; GTP Phosphohydrolases/genetics* ; Membrane Proteins/genetics* ; Adolescent ; Hematopoietic Stem Cell Transplantation ; Proportional Hazards Models ; Proto-Oncogene Proteins p21(ras)/genetics* ; Prognosis

Objective:To explore the effects of RNF113A on the proliferation,migration,in-vasion,apoptosis,and autophagy of hepatocellular carcinoma cells.Methods:Hep3B cells were divided into control group and RNF113A overexpression group(RNF113A-OE),HepG2 was divided into control group and RNF113A knockdown group(si-RNF113A),CCK-8 assay was used to detect changes in cell viability,clone formation assay was used to detect changes in cell proliferation abili-ty,Transwell assay was used to detect changes in cell invasion ability,wound healing assay was used to detect changes in cell migration ability,and flow cytometry was used to detect changes in cell apoptosis ability,Western blot experiments were used to detect changes in protein expression of autophagy related genes and AMPK signaling pathway related genes.Results:Compared with the control group,the proliferation,cloning,invasion,and migration abilities of Hep3B cells in the RNF113A-OE group were improved,while apoptosis and autophagy abilities were decreased,and the AMPK signaling pathway was inhibited;In the si-RNF113A group,the proliferation,cloning,in-vasion,and migration abilities of HepG2 cells were significantly reduced,while apoptosis and au-tophagy abilities were increased,and the activation of the AMPK signaling pathway was promoted.Conclusion:RNF113A promotes the proliferation,cloning,invasion,and migration of hepatocel-lular carcinoma cells,and inhibited apoptosis and autophagy by inhibiting the AMPK signaling path-way.

Aim To elucidate the mechanism by which Rg3 regulates the function of CD8

Humans ; Melphalan/therapeutic use* ; Multiple Myeloma/therapy* ; Hematopoietic Stem Cell Transplantation ; Transplantation, Autologous ; Transplantation Conditioning

By reviewing the relevant literature of ancient herbal works and modern codices， this paper sorted out the historical evolution and developmental venation of processing of Notoginseng Radix et Rhizoma. On this basis， the modern research of processed products of Notoginseng Radix et Rhizoma was used as the breakthrough point to analyze the literature in terms of processing technology， chemical composition changes and changes in pharmacological effects before and after processing. According to the research status of processing of Notoginseng Radix et Rhizoma， some existing problems were analyzed in this paper， such as not many ancient processing methods used in modern time， lack of standardized research on processing technology. And saponins， polysaccharides， amino acids， flavonoids and other chemical components in Notoginseng Radix et Rhizoma may change to different degrees before and after processing， which was the main reason for the difference of efficacy before and after processing. However， the current research on the pharmacological effects of Notoginseng Radix et Rhizoma mainly focuses on raw products， resulting in a lack of in-depth research on the transformation mechanism of Notoginseng Radix et Rhizoma in processing difference， and the scientific connotation of "Shengxiao Shubu" has not been clearly elaborated， which is not conducive to the standardized clinical use of drugs. Therefore， it is necessary to further analyze the material basis of Notoginseng Radix et Rhizoma and its processed products， and to explore the change rule of chemical components before and after processing and its correlation with pharmacodynamic activity， so as to clarify the processing mechanism for providing scientific basis for its standardized processing， quality control and clinical rational use.

Immune checkpoints (ICs) are immunosuppressive molecules expressed on immune cells, which can regulate immune cells' activation. Immune checkpoint inhibitors (ICIs) which can block the interaction of immune checkpoints and their ligands, improve the cytotoxic effect of the immune system on tumor cells. Immunotherapy such as employing ICIs has gradually become a conventional therapeutic strategy for cancer treatment. However, the low response rate and the emergence of drug resistance have seriously affected the clinical efficacy of ICIs. Reactive oxygen species (ROS) are electronic reduction products of active oxygen, as well as natural by-products of cell metabolism, which can be used as regulators of intercellular signals. Tumor microenvironment (TME) is often in the state of oxidative stress (OS), which is the imbalance between oxidative system and antioxidant system. ROS can affect the interaction with its ligands by regulating the expression and activity of immune checkpoints in TME, thus affecting the anti-tumor effect of immune cells. Accumulating studies have shown that ROS could regulate tumor immune checkpoints through several pathways. Due to different types and stages of tumor, it would be clinical beneficial to understand the mechanistic link of ROS on tumor immune checkpoint, and choose appropriate ROS regulators combined with immune checkpoint inhibitors to maximize anti-tumor effects. This article reviews the common metabolic sources and characteristics of ROS, the regulatory effect and mechanism of ROS on tumor immune checkpoints and its therapeutic application.

Objective: To explore the heterogeneity and correlation of clinical phenotypes and genotypes in children with disorders of sex development (DSD). Methods: A retrospective study of 1 235 patients with clinically proposed DSD in 36 pediatric medical institutions across the country from January 2017 to May 2021. After capturing 277 DSD-related candidate genes, second-generation sequencing was performed to analyzed the heterogeneity and correlation combined with clinical phenotypes. Results: Among 1 235 children with clinically proposed DSD, 980 were males and 255 were females of social gender at the time of initial diagnosis with the age ranged from 1 day of age to 17.92 years. A total of 443 children with pathogenic variants were detected through molecular genetic studies, with a positive detection rate of 35.9%. The most common clinical phenotypes were micropenis (455 cases), hypospadias (321 cases), and cryptorchidism (172 cases) and common mutations detected were in SRD5A2 gene (80 cases), AR gene (53 cases) and CYP21A2 gene (44 cases). Among them, the SRD5A2 mutation is the most common in children with simple micropenis and simple hypospadias, while the AMH mutation is the most common in children with simple cryptorchidism. Conclusions: The SRD5A2 mutation is the most common genetic variant in Chinese children with DSD, and micropenis, cryptorchidism, and hypospadias are the most common clinical phenotypes. Molecular diagnosis can provide clues about the biological basis of DSD, and can also guide clinicians to perform specific clinical examinations. Target sequence capture probes and next-generation sequencing technology can provide effective and economical genetic diagnosis for children with DSD.
3-Oxo-5-alpha-Steroid 4-Dehydrogenase/genetics* ; Child ; China/epidemiology* ; Cryptorchidism/genetics* ; Disorders of Sex Development/genetics* ; Female ; Genital Diseases, Male ; Genotype ; Humans ; Hypospadias/genetics* ; Male ; Membrane Proteins/genetics* ; Penis/abnormalities* ; Phenotype ; Retrospective Studies ; Steroid 21-Hydroxylase/genetics*

This study aims to explore the consistency between macroscopic identification and DNA barcoding identification of Amomi Fructus. With the DNA barcoding identification results, we evaluated the reliability of identifying Amomi Fructus quality by combining macroscopic traits with main volatile chemical components. Thirteen batches of Amomi Fructus samples were collected for identification. Firstly, the morphological and sensory characteristics of each sample were observed and recorded according to the standard in Chinese Pharmacopoeia(2020 edition). The 100-fruit weight, longitudinal diameter, transverse diameter, and longitudinal diameter-to-transverse diameter ratio were measured, which correspond to large, solid, and full kernel representing good quality in the sensory evaluation. The odor value detected by electronic nose and major volatile components(borneol, camphor, limonene, and borneol acetate) correspond to the sensory evaluation of strong odor representing good quality. Secondly, DNA barcoding was employed to identify the 13 batches of samples. Finally, clustering analysis was performed for the main volatile components and macroscopic traits, and the identification results were compared with those of DNA barcoding. Except two batches of samples(No.6 and No.10), the macroscopic identification showed the results consistent with those of DNA barcoding, with an identification rate of 84.62%. The clustering results of the content of four volatile chemical components and macroscopic traits were also consistent with the DNA barcoding identification results. DNA barcoding can verify the results of macroscopic identification and provide a scientific basis for the inheritance and development of macroscopic identification. Moreover, the combination of macroscopic traits and chemical components demonstrates higher accuracy in the quality evaluation of Chinese medicinal materials.
Camphanes ; Camphor/analysis* ; DNA Barcoding, Taxonomic ; Drugs, Chinese Herbal/chemistry* ; Fruit/genetics* ; Limonene/analysis* ; Reproducibility of Results

AIM: To prepare a folic acid-magnetic dual target, adriamycin(ADM)-loaded phase change liposome nanoparticles(FA-PFH-Fe3O4@ADM), and observe its ability to target retinoblastoma Y79 cells and its three-mode imaging ability of in vitro ultrasound/photoacoustic/magnetic resonance.METHODS: FA-PFH-Fe3O4@ADM was prepared by the double emulsification method, and its basic characteristics were tested. Test the cellular safety of nanoparticles. Observe the heating phenomenon and phase transition of nanoparticles under 808nm laser. Y79 cells in logarithmic growth phase were divided into four groups. The non-targeted group and the single magnetic target group were added with PFH-Fe3O4@ADM nanoparticles(0.625mg/mL). The single folic acid target group and folic acid-magnetic dual target group were added with FA-PFH-Fe3O4@ADM nanoparticles(0.625mg/mL). A 4T magnet was placed at the side of the orifice plate of the single magnetic target group and the folic acid-magnetic double target group to evaluate the targeting ability of nanoparticles on Y79 cells. In addition, the ability of FA-PFH-Fe3O4@ADM nanoparticles ultrasound/photoacoustic/magnetic resonance three-mode imaging in vitro was observed.RESULT: FA-PFH-Fe3O4@ADM nanoparticles were successfully prepared with uniform distribution and uniform spherical structure. The average particle size of nanoparticles was 338.6±2.20 nm. ADM and Fe3O4 were successfully loaded, with an encapsulation efficiency of(41.76±4.12)% and(59.06±13.63)%, respectively. Nanoparticles had good paramagnetic properties and showed no obvious toxicity to Y79 cells. The phagocytic rate of the folic acid-magnetic dual target group(86.19±0.55)% was significantly higher than that of the single folate target group(43.36±5.91)% and single magnetic target group [(28.58±3.23)%, P<0.05]. The FA-PFH-Fe3O4@ADM nanoparticles rapidly heat up and undergo phase transitions under the action of laser. Moreover, they can enhance ultrasound and photoacoustic imaging, and they can negatively enhance magnetic resonance imaging in T2 mode.CONCLUSION: FA-PFH-Fe3O4@ADM nanoparticles have been successfully prepared in this study, which not only has a good targeting effect on retinoblastoma Y79 cells, but also can achieve ultrasound/photoacoustic/magnetic resonance three-mode imaging in vitro.