ObjectiveTo reveal the influence of Jianchangbang characteristic processing method on the change process of volatile components and the processing mechanism of reducing toxicity and increasing efficiency of Magnoliae Officinalis Cortex（MOC） by studying the changes in the composition and content of volatile components during the processing of ginger processed Xingpo pieces. MethodSamples of raw products， ginger juice moisturized products and stir-fried and heap moisturized products of MOC were taken according to the set time points， and headspace gas chromatography-mass spectrometry（HS-GC-MS） was used to determine the contents of volatile components in the samples， and the relative content of each component was obtained by peak area normalization. Principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA） were performed on the sample data using SIMCA 14.1 software， and the differential components during the processing were screened with variable importance in the projection（VIP） value>1 as the indicator. ResultA total of 68 volatile components were identified in the samples， among which some of the chemical components with similar structures showed similar trends of changes， and there was also the phenomenon of interconversion between compounds. Compared with the raw products， the contents of 42 components in ginger juice moisturized products increased， while the contents of 25 components decreased， 19 components were unique， and 4 components were unique to the raw products. Compared with ginger juice moisturized products， MOC in the early stage of piling had three unique components， and the contents of 11 components such as cyclosativene and （+）-α-pinene increased， and the contents of 5 components such as tricyclic terpene and α-curcumene decreased， and ginger juice moisturized products had four unique components. Compared with the early stage of piling， in the later stage， the contents of 8 components such as （+）-α-pinene and camphene significantly increased， while the contents of 6 components such as linalool and α-selinene significantly decreased. During the processing of MOC， there were significant changes in the chemical composition of the samples before and after 20 days. The differences between ginger juice moistening and the early stage of piling， the early stage and the later stage of piling could be clearly distinguished. ConclusionDuring the preparation process of ginger processed Xingpo pieces， the addition of ginger juice can reduce the contents of stimulating components， and the contents of active components continue to increase in several stages， such as the addition of ginger juice， frying and heap moisturizing， the quality of the decoction pieces may change significantly at about 20 d of processing. This study can provide a research basis for exploring the processing mechanism of ginger processed Xingpo pieces.

OBJECTIVE To establish an ultra-performance liquid chromatography-tandem mass spectrometry method for the simultaneous determination of 30 compounds(including antianginal drugs, anticoagulant, anti-platelet aggregators and anti-inflammatory analgesics) illegally added in Chinese patent medicine for promoting blood circulation and removing blood stasis. METHODS The sample was extracted by ultrasonication with 60% methanol. The analysis was performed on Phenomenex Kinetex C18 column (2.1 mm×100 mm, 2.6 μm) with gradient elution using 0.1% formic acid solution and acetonitrile as the mobile phase at the flow rate of 0.3 mL·min–1, and the column temperature was 40 ℃. Mass spectrometry was collected using electrospray ionization (ESI), simultaneous scanning of positive and negative ions, and multiple reaction monitoring mode. RESULTS The linearity of the 30 compounds was good in the mass range examined, with the correlation coefficients all >0.999. The limits of detection of each compound ranged from 1.3 to 238.4 ng·g–1 and the average recoveries ranged from 63.7% to 108.2% with the RSDs of 1.0% to 6.7%. The method was used to test 90 batches of Shujin Huoxue tablets. Paracetamol was detected in 3 batches, while the rest of the compounds were not detected. The amount of paracetamol detected ranged from 0.16 to 0.93 μg per tablet, which was much lower than the minimum daily dose of the corresponding drug, excluding intentional addition. The probable explanation was the residues caused by incomplete cleaning validation of the enterprise’s collinear production. CONCLUSION This method is rapid, accurate, highly sensitive, and highly selective, and can be used for qualitative screening and quantitative determination of 30 chemical compounds illegally added in Chinese patent medicine for promoting blood circulation and removing blood stasis.

Most patients with differentiated thyroid cancer have a good prognosis after radioiodine-131 therapy,but a small number of patients are insensitive to radioiodine-131 therapy and even continue to develop disease.At present,some targeted drugs can improve progression-free survival in patients with radioactive iodine-refractory differentiated thyroid cancer(RAIR-DTC),such as sorafenib and levatinib,have been approved for the treatment of RAIR-DTC.However,due to the presence of primary and acquired drug resistance,drug efficacy in these patients is unsatisfactory.This review introduces the acquired drug resistance mechanism of sorafenib in the regulation of mitogen-activated protein kinase(MAPK)and phosphatidylinositol-3-kinase(PI3K)pathways and proposes related treatment strategies,in order to provide a reference for similar drug resistance mechanism of sorafenib and effective treatment of RAIR-DTC.

Objective To investigate the differential diagnostic value of 18F-fluorodeoxyglucose(18F-FDG)/PET/CT combined with serum lactate dehydrogenase(LDH),β2-microglobulin(β2-MG),and C-reactive protein(CRP)in sarcoidosis and lymphoma.Methods The 18F-FDG PET/CT images of 19 patients with sarcoidosis and 33 patients with lymphoma were analyzed retrospectively.The lymph node maximum diameter,density,distribution morphology,maximum standardized uptake value(SUVmax),extra-nodal involvement,and serum LDH,β2-MG,and CRP results were analyzed and compared.Results There was no statistically significant difference between sarcoidosis and lymphoma in lymph node density,necrosis rate,and SUVmax(P＞0.05).There was statistically significant difference in the maximum diameter between lymph nodes in sarcoidosis(2.4±0.7)cm and lymphoma(3.3±1.3)cm(P＜0.05).The incidence of symmetric enlargement of mediastinal and hilar lymph nodes was 84.2％in sarcoidosis,the lymph node fusion rate was 21.1％,the lung involvement rate was 57.8％,the spleen involvement rate was 10.5％,and the rates of lymphoma were 15.2％,63.6％,0.0％,and 36.4％,with statistically significant differences(P＜0.05).There were statistically significant differences in LDH and β2-MG between the two groups(P＜0.05),but the differences in CRP were not statistically significant(P＞0.05).Conclusion PET/CT can show the anatomy of mediastinal and hilar lymph nodes and extra-nodal affected organs as well as glucose metabolism,showing a certain differential diagnostic value of sarcoidosis and lymphoma when combined with serum LDH and β2-MG levels.

This study utilized ultra-performance liquid chromatography coupled with quadrupole-time-of-flight mass spectrometry(UPLC-Q-TOF-MS) to rapidly analyze and identify the chemical constituents in five processed products of Strychni Semen(raw, sand-roasted, fried, urine-soaked, and vinegar-processed products). Using PeakView software to extract compound information, 50 chemical components were identified based on retention time, accurate molecular ion peaks, secondary mass spectrometry data, and comparison with reference standards and relevant literature. Specifically, 41 components were identified in raw Strychni Semen, 48 in sand-roasted, 43 in fried, 41 in urine-soaked, and 40 in vinegar-processed products. Principal component analysis(PCA) and orthogonal partial least squares discriminant analysis(OPLS-DA) were employed to identify differential components among the processed products, with variable importance in projection(VIP) values>1 and a t-test with P<0.05 as criteria. PCA revealed significant differences among the five processed products, demonstrating good clustering and separation. OPLS-DA identified 13 differential components, including brucine, strychnine, loganic acid, and chlorogenic acid. The results indicated that S. nux-vomica primarily contained alkaloids, organic acids, and glycosides, with significant compositional differences among the various processed products. Notably, the content of key components such as brucine and strychnine decreased after processing, with the most significant reduction observed in vinegar-processed Strychni Semen. In conclusion, this study provides a comprehensive comparison of the effects of different processing methods on the chemical composition of Strychni Semen, exploring the differences in the material basis of the processed products and offering data to support the scientific rationale behind the processing of Strychni Semen.
Chromatography, High Pressure Liquid/methods* ; Drugs, Chinese Herbal/analysis* ; Mass Spectrometry/methods* ; Strychnos/chemistry* ; Principal Component Analysis

Objective: To analyze and compare therapy responses, outcomes, and incidence of severe hematologic adverse events of flumatinib and imatinib in patients newly diagnosed with chronic phase chronic myeloid leukemia (CML) . Methods: Data of patients with chronic phase CML diagnosed between January 2006 and November 2022 from 76 centers, aged ≥18 years, and received initial flumatinib or imatinib therapy within 6 months after diagnosis in China were retrospectively interrogated. Propensity score matching (PSM) analysis was performed to reduce the bias of the initial TKI selection, and the therapy responses and outcomes of patients receiving initial flumatinib or imatinib therapy were compared. Results: A total of 4 833 adult patients with CML receiving initial imatinib (n=4 380) or flumatinib (n=453) therapy were included in the study. In the imatinib cohort, the median follow-up time was 54 [interquartile range (IQR), 31-85] months, and the 7-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.2%, 88.4%, 78.3%, and 63.0%, respectively. The 7-year FFS, PFS, and OS rates were 71.8%, 93.0%, and 96.9%, respectively. With the median follow-up of 18 (IQR, 13-25) months in the flumatinib cohort, the 2-year cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) were 95.4%, 86.5%, 58.4%, and 46.6%, respectively. The 2-year FFS, PFS, and OS rates were 80.1%, 95.0%, and 99.5%, respectively. The PSM analysis indicated that patients receiving initial flumatinib therapy had significantly higher cumulative incidences of CCyR, MMR, MR(4), and MR(4.5) and higher probabilities of FFS than those receiving the initial imatinib therapy (all P<0.001), whereas the PFS (P=0.230) and OS (P=0.268) were comparable between the two cohorts. The incidence of severe hematologic adverse events (grade≥Ⅲ) was comparable in the two cohorts. Conclusion: Patients receiving initial flumatinib therapy had higher cumulative incidences of therapy responses and higher probability of FFS than those receiving initial imatinib therapy, whereas the incidence of severe hematologic adverse events was comparable between the two cohorts.
Adult ; Humans ; Adolescent ; Imatinib Mesylate/adverse effects* ; Incidence ; Antineoplastic Agents/adverse effects* ; Retrospective Studies ; Pyrimidines/adverse effects* ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy* ; Treatment Outcome ; Benzamides/adverse effects* ; Leukemia, Myeloid, Chronic-Phase/drug therapy* ; Aminopyridines/therapeutic use* ; Protein Kinase Inhibitors/therapeutic use*

Adenosine triphosphate (ATP) regeneration systems are essential for efficient biocatalytic phosphoryl transfer reactions. Polyphosphate kinase (PPK) is a versatile enzyme that can transfer phosphate groups among adenosine monophosphate (AMP), adenosine diphosphate (ADP), ATP, and polyphosphate (Poly P). Utilization of PPK is an attractive solution to address the problem of ATP regeneration due to its ability to use a variety of inexpensive and stable Poly P salts as phosphate group donors. This review comprehensively summarizes the structural characteristics and catalytic mechanisms of different types of PPKs, as well as the variations in enzyme activity, catalytic efficiency, stability, and coenzyme preference observed in PPKs from different sources. Moreover, recent advances in PPK-mediated ATP regeneration systems and protein engineering of wild-type PPK are summarized.
Adenosine Triphosphate/metabolism* ; Adenosine Monophosphate ; Polyphosphates/metabolism* ; Catalysis ; Regeneration

In acute lung injury, two subsets of lung macrophages exist in the alveoli: tissue-resident alveolar macrophages (AMs) and monocyte-derived alveolar macrophages (MDMs).However, it is unclear whether these 2 subsets of macrophages have different functions and characteristics during the recovery phase. RNA-sequencing of AMs and MDMs from the recovery period of LPS-induced lung injury mice revealed their differences in proliferation, cell death, phagocytosis, inflammation and tissue repair. Using flow cytometry, we found that AMs showed a higher ability to proliferate, whereas MDMs expressed a larger amount of cell death. We also compared the ability of phagocytosing apoptotic cells and activating adaptive immunity and found that AMs have a stronger ability to phagocytose, while MDMs are the cells that activate lymphocytes during the resolving phase. By testing surface markers, we found that MDMs were more prone to the M1 phenotype, but expressed a higher level of pro-repairing genes. Finally, analysis of a publicly available set of single-cell RNA-sequencing data on bronchoalveolar lavage cells from patients with SARS-CoV-2 infection validated the double-sided role of MDMs. Blockade of inflammatory MDM recruitment using CCR2 −/− mice effectively attenuates lung injury. Therefore, AMs and MDMs exhibited large differences during recovery. AMs are long-lived M2-like tissue-resident macrophages that have a strong ability to proliferate and phagocytose. MDMs are a paradoxical group of macrophages that promote the repair of tissue damage despite being strongly pro-inflammatory early in infection, and they may undergo cell death as inflammation fades. Preventing the massive recruitment of inflammatory MDMs or promoting their transition to pro-repairing phenotype may be a new direction for the treatment of acute lung injury.

Background: Brucella infection induces brucellosis, a zoonotic disease. The intracellular circulation process and virulence of Brucella mainly depend on its type IV secretion system (T4SS) expressing secretory effectors. Secreted protein BspJ is a nucleomodulin of Brucella that invades the host cell nucleus. BspJ mediates host energy synthesis and apoptosis through interaction with proteins. However, the mechanism of BspJ as it affects the intracellular survival of Brucella remains to be clarified. Objectives: To verify the functions of nucleomodulin BspJ in Brucella's intracellular infection cycles. Methods: Constructed Brucella abortus BspJ gene deletion strain (B. abortus ΔBspJ) and complement strain (B. abortus pBspJ) and studied their roles in the proliferation of Brucella both in vivo and in vitro. Results: BspJ gene deletion reduced the survival and intracellular proliferation of Brucellaat the replicating Brucella-containing vacuoles (rBCV) stage. Compared with the parent strain, the colonization ability of the bacteria in mice was significantly reduced, causing less inflammatory infiltration and pathological damage. We also found that the knockout of BspJ altered the secretion of cytokines (interleukin [IL]-6, IL-1β, IL-10, tumor necrosis factor-α, interferon-γ) in host cells and in mice to affect the intracellular survival of Brucella. Conclusions BspJ is extremely important for the circulatory proliferation of Brucella in the host, and it may be involved in a previously unknown mechanism of Brucella's intracellular survival.

OBJECTIVES: To evaluate the ability of the ForenSeq^TM DNA Signature Prep kit (ForenSeq kit) in analyzing the sequence information of STRs in Zhejiang She ethnic group and its forensic application efficacy. METHODS: A total of 50 Zhejiang She ethnic group samples were sequenced with the ForenSeq kit on the MiSeq FGx platform. The data was analyzed using ForenSeq^TM universal analysis software to obtain the motif structure and flank regions of the 58 STRs, then compared with PCR-CE typing results to test the consistency. At last, the allele frequency and population genetic parameters were calculated. RESULTS: A total of 448 sequence polymorphic alleles were detected in 50 samples of Zhejiang She ethnic group. Compared with fragment length polymorphism detected by PCR-CE, 82 alleles were increased by MPS detection based on ForenSeq kit, and 7 SNPs variation were detected in the flanking regions of 6 loci. The 22 male individuals were genotyped, and total 19 haplotypes were detected in 24 Y chromosome STRs of these 22 males. The cumulative discrimination power of the 27 autosomal STRs was 1-8.87×10^-30, the cumulative probability of exclusion of duo-testing was 0.999 999 962 640 657, the cumulative probability of exclusion of trios-testing was 0.999 999 999 999 633. CONCLUSIONS Based on MPS typing technology, using the ForenSeq kit greatly improves the detection efficiency. In addition, the 58 STRs have good genetic polymorphisms in Zhejiang She ethnic group, which are suitable for individual identification and paternity identification in forensic application.
DNA ; DNA Fingerprinting/methods* ; Ethnicity/genetics* ; Gene Frequency ; High-Throughput Nucleotide Sequencing/methods* ; Humans ; Male ; Microsatellite Repeats ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA/methods*