OBJECTIVE: To explore the application of targeted mRNA sequencing in fusion gene diagnosis of hematologic diseases. METHODS: Bone marrow or peripheral blood samples of 105 patients with abnormally elevated eosinophil proportions and 291 acute leukemia patients from January 2015 to June 2023 in the First Affiliated Hospital of Soochow University were analyzed and gene structural variants were detected by targeted mRNA sequencing. RESULTS: Among 105 patients with abnormally elevated eosinophil proportions, 6 cases were detected with gene structural variants, among which fusion gene testing results in 5 cases could serve as diagnostic indicators for myeloid neoplasms with eosinophilia. In addition, a IL3∷ETV6 fusion gene was detected in one patient with chronic eosinophilic leukemia, not otherwise specified. Among 119 patients with acute myeloid leukemia (AML), 38 cases were detected structural variants by targeted mRNA sequencing, accounting for 31.9%, which was significantly higher than 20.2% (24/119) detected by multiple quantitative PCR (P < 0.05). We also found one patient with AML had both NUP98∷PRRX2 and KCTD5∷JAK2 fusion genes. A total of 104 patients were detected structural variants by targeted mRNA sequencing in 172 cases with acute B-lymphoblastic leukemia who were tested negative by multiple quantitative PCR, with a detection rate of 60.5% (102/172). CONCLUSION Targeted mRNA sequencing can effectively detect fusion gene and has potential clinical application value in diagnosis and classificatation in hematologic diseases.
Humans ; Hematologic Diseases/diagnosis* ; RNA, Messenger/genetics* ; Oncogene Proteins, Fusion/genetics* ; Sequence Analysis, RNA ; Leukemia, Myeloid, Acute/diagnosis*

Due to its synergistic effects and reduced side effects, combination therapy has become an important strategy for treating complex diseases. In traditional Chinese medicine (TCM), the "monarch, minister, assistant, envoy" compatibilities theory provides a systematic framework for drug compatibility and has guided the formation of a large number of classic formulas. However, due to the complex compositions and diverse mechanisms of action of TCM, it is difficult to comprehensively reveal its potential synergistic patterns using traditional methods. Synergistic prediction based on molecular compatibility theory provides new ideas for identifying combinations of active compounds in TCM. Compared to resource-intensive traditional experimental methods, artificial intelligence possesses the ability to mine synergistic patterns from multi-omics and structural data, providing an efficient means for modeling and optimizing TCM combinations. This paper systematically reviews the application progress of AI in the synergistic prediction of TCM active compounds and explores the challenges and prospects of its application in modeling combination relationships, thereby contributing to the modernization of TCM theory and methodological innovation.
Artificial Intelligence ; Medicine, Chinese Traditional/methods* ; Drugs, Chinese Herbal/pharmacology* ; Humans ; Drug Synergism

The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Arthritis, encompassing osteoarthritis (OA), rheumatoid arthritis (RA), and gouty arthritis (GA), is a prevalent inflammatory disease that significantly impacts quality of life. Natural products (NPs), derived from animals, plants, marine organisms, and microorganisms, have demonstrated beneficial effects in arthritis treatment both domestically and internationally. These natural compounds offer advantages in drug discovery due to their skeletal diversity, structural complexity, and multi-effect, multi-target, and low-toxicity properties compared to conventional small-molecule medicines. However, unclear mechanisms have hindered the development and clinical application of NPs. This review summarizes recent experimental studies from the past decade on natural medicine for arthritis treatment, emphasizing key NPs with therapeutic effects on OA, RA, and GA. It examines the effects and molecular mechanisms of NPs acting on different cells to treat arthritis. Furthermore, this review provides insights into the future prospects of NP research in this field, which is crucial for advancing NP-based arthritis treatments.
Humans ; Biological Products/therapeutic use* ; Animals ; Arthritis, Rheumatoid/drug therapy* ; Arthritis, Gouty/drug therapy* ; Arthritis/drug therapy* ; Osteoarthritis/drug therapy*

Kidney stones are a urinary system disease with a high incidence,among which calcium oxalate stones are the most common.Metabolic disorders such as hypertension,diabetes,obesity,hyperlipidemia,and hyperuricemia can cause changes in oxalate,uric acid,and pH and calcium ion concentrations in the urine through multiple pathways including inducing oxidative stress and inflammatory responses by generating reactive oxygen species,ultimately affecting the formation of calcium oxalate stones.This article reviews the possible pathways and mechanisms by which metabolic diseases influence the formation of calcium oxalate stones,providing new ideas for the clinical prevention and treatment of calcium oxalate stones.
Humans ; Calcium Oxalate/metabolism* ; Kidney Calculi/etiology* ; Metabolic Diseases/complications*

Hydronephrosis is a common urological disease,and pregnancy with hydronephrosis is also common.However,it is extremely rare that patients suffering from hydronephrosis after delivery cannot recover on their own.Moreover,due to the no specificity of clinical manifestations,it is easy to be ignored by clinicians.This paper reports a solitary kidney patient with severe dilatation and hydronephrosis of the kidney and ureter that were caused by late pregnancy,and the hydrops could not recover spontaneously after delivery.In addition,the methods of open surgery,ureteroscopy,and ureteral stent placement for many times in other hospital were ineffective for her.The purpose of this study is to improve the attention of clinicians to hydronephrosis during pregnancy and after delivery and provide the reference for clinical treatment.
Humans ; Female ; Hydronephrosis/etiology* ; Adult ; Pregnancy ; Solitary Kidney/complications* ; Pregnancy Complications ; Ureter

A method for determination and targeted screening of diflorasone components in health products using ultra performance liquid chromatography-quadrupole time of flight mass spectrometry(UPLC-Q-TOF/MS)was established.Four representative diflorasone and esters(diflorasone,diflorasone diacetate,diflorasone-17-propionate,and diflorasone-21-propionate)were selected to optimize the pretreatment conditions,and 10 mL of extraction solvent dosage,15 min of extraction time and 5 g of salting-out agent as the optimal conditions were selected by response surface methodology.The results showed that the four analytes exhibited good linearity within the concentration range of 2.0?100 μg/L with the chromatographic peak area,and the correlation coefficients(R2)were all greater than 0.9990,while the results of recovery and relative standard deviation could satisfy the requirements of determination.The common characteristic ions of diflorasone and esters werem/z121 andm/z335,and their specific structures were obtained by analyzing the cleavage pathway based on the optimized determination conditions.A targeted screening method for other esters of diflorasone based on characteristic ions guidance strategy was established.This method had many advantages such as high efficiency,high sensitivity and good reproducibility,and could be used for targeted screening of diflorasone and esters in health products.The developed characteristic ion guided strategy could be employed to construct mass spectral databases for various glucocorticoids,enabling comprehensive targeted screening across a broad range of compounds.

Objective To establish a quality standard for the medicinal bath formula for treating exogenous fever(composed of Forsythiae Fructus,Peucedani Radix,Schizonepetae Spica,Isatidis Radix,Gypsum Fibrosum,Chrysanthemi Flos,Lophatheri Herba,etc.)based on its efficacy and indications.Methods Thin-layer chromatography(TLC)was used to establish identification method for the monarch drugs Forsythiae Fructus and Peucedani Radix.Enzyme-linked immunosorbent assay(ELISA)was employed to measure the interleukin 1β(IL-1β)regulatory activity of the main components in the formula.High-performance liquid chromatography(HPLC)was used to determine the content of active components in 10 batches of samples.Results Spots of Forsythiae Fructus and Peucedani Radix were successfully detected in the test samples.ELISA identified active components in the formula,including praeruptorin A,pulegone,rutin,praeruptorin B,forsythoside,and(R,S)-goitrin.The content determination results of 10 batches of samples showed that the content of praeruptorin A ranged from 0.493 to 0.694 mg·mL-1.Conclusion Based on its efficacy and indications,TLC identification and HPLC content determination methods were established for the medicinal bath formula for treating exogenous fever.The obtained standard can more accurately control the efficacy of the formula.

Objective:To analyze the disease burden of Noise-Induced Hearing Loss (NIHL) in China from 1990 to 2019, forecast the disease burden of NIHL from 2020 to 2030, and provide data support for the prevention and control of NIHL.Methods:In July 2022, the disease burden data of NIHL in different age groups and genders in China during 1990-2019 were selected from the GBD database. The Jointpoint regression model was established to analyze the trend of the disease burden of NIHL in China. An age-period-cohort model was constructed to analyze the changing trend of NIHL in terms of age, period, and cohort, and a Bayesian age-period-cohort model was developed to predict the disease burden of NIHL in China from 2020 to 2030.Results:From 1990 to 2019, the disability adjusted life year (DALY) of China's NIHL increased from 1361600 to 2327700 years. The coarse rate of DALY increased from 115.03/100000 to 163.65/100000 (AAPC=1.23, P<0.001), and the normalization rate of DALY decreased from 127.67/100000 to 119.83/100000 (AAPC=-0.21, P<0.001). It is predicted that from 2020 to 2030, the DALYs of China's NIHL will increase from 2412900 in 2020 to 2655000 in 2030, and the DALY normalization rate will decrease from 241.29/100000 in 2020 to 125.71/100000 in 2030. Conclusion:The burden of noise-induced hearing loss (NIHL) in China is significant and should not be overlooked. To reduce this burden, we need to focus on strengthening source management, process control, personal protection, and comprehensive prevention and treatment through various methods.

A retrospective analysis of the clinical data of seven acute B-lymphoblastic leukemia (B-ALL) patients with TCF3-HLF fusion gene-positive admitted to the First Affiliated Hospital of Soochow University from June 2017 to August 2022 was conducted to summarize their clinical features and prognoses. The seven B-ALL patients comprised four males and three females, with a median age of 18 (11-33) years. Five patients tested positive for CD33 expression, and four patients had a normal karyotype. Two patients had hypercalcemia at the initial diagnosis, and one patient developed hypercalcemia at relapse. Six patients presented with coagulation dysfunction at diagnosis. After induction chemotherapy, five out of seven patients achieved complete remission, of which four subsequently relapsed. Two patients did not achieve remission even after two rounds of induction chemotherapy, with one achieving complete remission after treatment with blinatumomab immunotherapy. Three patients underwent chimeric antigen receptor T cell therapy, whereas three patients subsequently underwent hematopoietic stem cell transplantation. Five patients died, while two patients survived with sustained complete remission. TCF3-HLF-positive B-ALL is rare and has a high relapse rate and poor prognosis.