Myelodysplastic syndrome (MDS) is a chronic hematologic disorder characterized by ineffective hematopoiesis, dysplasia of one or more cell lines with or without definite genetic changes. Its diagnosis requires a comprehensive analysis combining morphology, immunology, cytogenetics, and molecular biology findings. In recent years, the development of second-generation sequencing (NGS) has provided great assistance in exploring the molecular pathogenesis of hematological malignancies and guidance for clinical practice. Mutations of a series of gene involved in RNA splicing, DNA methylation, transcriptional regulation, signal transduction, chromatin modification and cohesin complex have been identified as important mechanisms for the development of MDS, among which some mutations have been found to play important roles in the diagnosis, treatment, and prognosis of MDS. This article has provided a comprehensive review the the common molecular genetic abnormalities involved in MDS.
Humans ; Myelodysplastic Syndromes/diagnosis* ; Mutation ; DNA Methylation ; RNA Splicing ; High-Throughput Nucleotide Sequencing

ObjectiveTo investigate the effects of Jianpi Qinghua granules on blood glucose fluctuations in patients with newly diagnosed overweight/obese type 2 diabetes mellitus （T2DM） and Qi-Yin deficiency syndrome from the perspective of skeletal muscle mass and function， while providing new insights for the treatment of diabetes. MethodsThis study employed a randomized， double-blind， placebo-controlled design. A total of 110 newly diagnosed overweight/obese T2DM patients meeting the inclusion criteria were randomly assigned to either the traditional Chinese medicine （TCM） group （54 cases） or the control group （56 cases）. Patients in the TCM group received Jianpi Qinghua Granules， while those in the control group received a placebo. Both groups underwent dietary and exercise guidance. After 12 weeks of intervention， blood glucose fluctuations were assessed using the following parameters： time in the target blood glucose range （TIR）， mean daily blood glucose （MBG）， standard deviation of mean daily blood glucose （SDBG）， mean amplitude of glycemic excursions （MAGE）， coefficient of variation of blood glucose （CV）， glycated hemoglobin （HbA1c） achievement rate， fasting plasma glucose （FPG）， and 2 hour postprandial glucose （2 hPG）. Skeletal muscle mass was measured by dual-energy X-ray absorptiometry （DXA）， while skeletal muscle function was evaluated using a handheld dynamometer for distal muscle strength and a 5-time sit-to-stand test for lower limb function. Additionally， pancreatic islet function and TCM syndrome scores were analyzed. ResultsNo significant differences were observed in baseline data between the two groups before intervention， ensuring comparability. After treatment， compared to the control group， the TCM group showed a significant increase in TIR （P<0.01）. While the SDBG and CV decreased， and MBG and MAGE increased in the TCM group， these differences were not statistically significant. Notably， the TCM group exhibited significant reductions in 2 hPG （P<0.01） and HbA1c （P<0.05）， though the decrease in FPG was not statistically significant. The HbA1c achievement rate in the TCM group was significantly higher than that in the control group （χ²=45.498， P<0.01）. In terms of skeletal muscle mass and function， the TCM group demonstrated a significant increase in handgrip strength （P<0.01） and a significant reduction in the 5-time sit-to-stand duration （P<0.05）. However， although body fat percentage increased， leading to a decrease in skeletal muscle mass and the ratio of skeletal muscle to fat， these changes were not statistically significant. For pancreatic islet function， the TCM group showed significant reductions in fasting insulin （FINS） and homeostasis model assessment of insulin resistance （HOMA-IR） （P<0.01）. Additionally， the TCM syndrome score in the TCM group was significantly reduced （P<0.01）. ConclusionJianpi Qinghua granules may reduce blood glucose fluctuations in newly diagnosed overweight/obese T2DM patients with Qi-Yin deficiency syndrome by enhancing skeletal muscle function， improving pancreatic islet function， and ameliorating related TCM syndromes.

The research and development of innovative drug have progressed remarkably, but the long development circle and high failure rate have become the bottleneck. Drug repurposing, discovering new indications of approved drugs, is a strategy to overcome these obstacles. By exploring new indications for approved drugs, rapid progress has been made in basic research and clinical translation in recent years. Rich resources of drugs, proven security, efficient development workflow and reduced cost are core advantages of this strategy, making the strategy a crucial direction of optimizing the pipeline of drug research and development. This review systematically summarizes drug repurposing cases that have received clinical approval over the past five years, and proposes core strategies for drug repurposing, including approaches based on targets, pathways, drug similarity, post-treatment phenotypes, and clinical side effects, aiming to provide some strategic guidance for drug repurposing efforts.

Objective To investigate the cluster spectrum and functional-associated mutation characteristics of the neuraminidase (NA) gene of A (H3N2) viruses in Tangshan, Hebei Province from 2010 to 2024. Methods A total of 30 influenza A (H3N2) virus strains in Tangshan from 2010 to 2024 were selected, which was based on the seasonal distribution of influenza sample collection. Phylogenetic tree of NA gene was constructed, and BioEdit was used for alignments of amino acid sequences to identify variations on functional-associated sites. Homologous models for B.4.3 subgroup and A/Darwin/9/2021 were constructed to analyze the conformational variation at mutation sites. Results From 2010-2024, influenza A (H3N2) virus strains in Tangshan, Hebei were divided into eight branches: A, A.2, A.2.1, A.2.2, B, B.1.1, B.4, and B.4.3. The strains in subgroups B, B.4 and B.4.3 appeared from 2023 to 2024. The NA protein antigen epitopes, resistance sites, and potential glycosylation sites all had amino acid mutations. The homologous model analysis of NA functional-associated regions of B.4.3 subgroup and A/Darwin/9/2021 revealed spatial conformation changes in amino acid 83, 150 and 331, which could influence the functional performance of associated sites. Conclusion The NA gene of influenza A (H3N2) viruses in Tangshan continues to mutate at functional sites. Mutational analysis and structural modeling indicate potential antigenic drift and drug-resistant mutations. In the future, attention should be paid to the variation trend of epidemic strains under branch B.4.3.

Flap transplantation is a critical surgical strategy for the reconstruction of tissue defects caused by trauma, tumor resection, and congenital malformations, and its survival rate directly determines surgical efficacy and patient prognosis. Following transplantation, flaps inevitably undergo ischemia-reperfusion (I/R) injury, during which oxidative stress, inflammatory responses, and metabolic disturbances are intricately intertwined, ultimately leading to cellular injury and tissue necrosis. Recent studies have demonstrated that multiple forms of programmed cell death—including apoptosis, pyroptosis, ferroptosis, necroptosis, and PANoptosis—play central roles in flap I/R injury. The extensive crosstalk and molecular interactions among these pathways form a highly complex cell death network. Specifically, apoptosis is mediated by the imbalance of Bcl-2 family proteins and the activation of cysteine-dependent aspartate-specific protease (caspase) cascades; pyroptosis is driven by the NLRP3-caspase-1-GSDMD axis, resulting in membrane pore formation and the release of pro-inflammatory cytokines; ferroptosis is characterized by iron-dependent lipid peroxidation and dysfunction of glutathione peroxidase 4 (GPX4); necroptosis is triggered by the receptor-interacting serine/threonine-protein kinase 1 (RIPK1)-RIPK3-MLKL signaling complex, leading to membrane rupture; and PANoptosis represents an integrated form of inflammatory cell death that coordinates multiple death pathways. Importantly, these forms of programmed cell death are not independent but are interconnected through extensive signaling crosstalk. Key regulatory molecules, including caspase-8, reactive oxygen species (ROS), nuclear factor-κB (NF-κB), and nuclear factor erythroid 2-related factor 2 (Nrf2), collectively modulate the dynamic balance among these pathways. Therefore, the multidimensional interplay and spatiotemporal dynamics of programmed cell death constitute a fundamental pathological basis of flap I/R injury. This review systematically summarizes the latest advances in the mechanisms and interactions of various programmed cell death pathways in flap I/R injury, aiming to elucidate the underlying regulatory network. These insights may provide novel theoretical foundations for optimizing flap protection strategies, improving flap survival, and promoting tissue repair.

AIM: To investigate the association between dyslipidemia and macular hard exudates(HEs)in non-proliferative diabetic retinopathy(NPDR)secondary to type 2 diabetes mellitus(T2DM).METHODS: NPDR patients attending the outpatient ophthalmology clinic from January 2021 to December 2023 were selected and divided into three groups according to the severity of macular HEs. Group A: None or minimal HEs; Group B: Definite HEs; Group C: Prominent HEs. Total cholesterol(TC), triglycerides(TG), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C), lipoprotein(a)[Lp(a)] levels and other lipid-related indicators were routinely measured. The correlation between these indicators and HEs was analyzed.RESULTS:Group A(24 eyes)consisted of 9 males and 15 females with the mean age of 54.71±6.15 y, group B(52 eyes)consisted of 20 males and 32 females with the mean age of 55.08±6.27 y, group C(14 eyes)consisted of 9 males and 5 females with the mean age of 53.93±6.08 y. The concentration of TC, TG, LDL-C and Lp(a)was highest in group C, followed by group B and lowest in group A with statistically significant differences(P<0.001). There were no statistically significant differences between the three groups for fasting plasma glucose(FPG), glycated hemoglobin A1c(HbA1c), creatinine(Cr), and HDL-C(P>0.05). The results of multivariate Logistic regression analysis showed that elevated levels of TC, TG, LDL-C, and Lp(a)were associated with the presence of macular HEs. Receiver operating characteristiccurve analysis showed that the area under the curve(AUC)for TC, TG, LDL-C, Lp(a), and their combination in predicting macular HEs in NPDR were 0.785, 0.718, 0.784, 0.742, and 0.911, respectively, with the combined model demonstrating the highest predictive performance.CONCLUSION: Dyslipidemia is closely associated with the development and progression of macular HEs in patients with NPDR and T2DM. The levels of TC, TG, LDL-C, and Lp(a)were correlated with the severity of macular HEs, suggesting that dyslipidemia may be involved in the pathological process of macular HEs formation.

Patients with inflammatory bowel disease (IBD) require long-term pharmacotherapy. Due to the wide variety of clinically available drugs, medication safety has become increasingly concerning. As an indispensable component of pharmaceutical formulations, drug excipients may induce various adverse reactions, including rash, allergic responses, and gastrointestinal discomfort, and may even lead to severe organic injury. However, they are often overlooked in clinical practice. Therefore, identifying and managing excipient-related adverse reactions is crucial for ensuring medication safety. To address this issue, this article systematically reviews common excipients in IBD therapeutics, the underlying mechanisms of excipient-induced adverse reactions, and corresponding management strategies, aiming to enhance clinicians' awareness of excipient-related issues, improve their ability to recognize and manage such reactions, and ultimately ensure patient safety.

ObjectiveTo investigate the ameliorating effect of Xiao Chaihutang combined with Erchen Tang （XAE） on metabolic-associated fatty liver disease （MAFLD） in mice and the influence of this therapy on the silent information regulator 1 （SIRT1）/peroxisome proliferator-activated receptor γ coactivator-1α （PGC-1α）/peroxisome proliferator-activated receptor α （PPARα） signaling pathway. MethodsForty-eight C57BL/6 mice were randomized into six groups： normal （CHOW）， atorvastatin （ATO， 0.05 g·kg^-1）， high-fat diet （HFD）， low-dose XAE （XAE-L， 10 g·kg^-1）， medium-dose XAE （XAE-M， 20 g·kg^-1）， and high-dose XAE （XAE-H， 40 g·kg^-1）. Each group contained 8 mice. Except the CHOW group， the other groups of mice were fed a HFD for the modeling of MAFLD. The experiment lasted for 20 weeks. Starting from the 13th week， mice were administered corresponding agents daily by gavage， and the mice in both the CHOW and HFD groups received equal volumes of purified water. At the end of the experiment， cardiac blood， liver， and adipose tissue samples were collected. Pathological staining was performed on the liver and adipose tissue separately. The levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， triglycerides （TG）， and total cholesterol （TC） in the serum， as well as TG and TC in the liver， were determined. Additionally， the mRNA levels of fatty acid synthetase （FASN）， stearoyl-CoA desaturase 1 （SCD1）， sterol regulatory element-binding protein 1c （SREBP-1c）， SIRT1， PPARα， PGC-1α， interleukin 6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-α （TNF-α） in the liver were measured by real-time PCR. The protein levels of SIRT1， PGC-1α， PPARα， and CPT1α in the mouse liver tissue were determined by Western blot. ResultsCompared with the CHOW group， the HFD group exhibited increased body weight， liver weight， and white adipose tissue weight （P<0.01）. After XAE intervention， these parameters were reduced compared with those in the HFD group （P<0.01）. Pathological section results showed that the morphology of hepatocytes and epididymal white adipocytes in the model mice was significantly improved after XAE intervention， with decreases in both the number and volume of lipid droplets. Furthermore， the XAE groups had lower levels of AST， ALT， HDL-C， LDL-C， TG， and TC in the serum and TG and TC in the liver than the HFD group （P<0.05，P<0.01）. Moreover， XAE administration downregulated the mRNA levels of lipid synthesis-related genes （FASN and SCD1） （P<0.05） and upregulated the mRNA levels of lipid oxidation-related genes （SIRT1， PPARα， and PGC-1α） （P<0.05，P<0.01）. Additionally， the protein levels of SIRT1， PGC-1α， PPARα， and CPT1α in the liver were upregulated after XAE treatment compared with those in the HFD group （P<0.05，P<0.01）. ConclusionXAE exerts a therapeutic effect on MAFLD by activating the SIRT1/PGC-1α/PPARα signaling pathway.

BACKGROUND:It has been shown that Gushukang affects bone metabolism by regulating nucleotide and amino acid metabolism and immune mechanisms.Current research on the mechanism of Gushukang in the treatment of osteoporosis primarily focuses on osteoblast regulation and requires further improvement from the perspective of osteoclasts. OBJECTIVE:To investigate the mechanism by which Gushukang interferes with osteoclasts in the treatment of osteoporosis using RAW264.7 cells as the research model. METHODS:Twenty-four 8-week-old female Sprague-Dawley rats were randomly divided into four groups(n=6 per group):the three experimental groups were given 1,2 and 4 g/kg osteoporosis solution by gavage(2 times per day),and the control group was given an equal amount of distilled water by gavage(2 times per day).After 7 days of intragastric administration,aortic blood samples were extracted to collect serum samples using centrifugation,and serum samples from the same groups were combined to obtain the low-,medium-,and high-concentration Gushukang-containing and normal sera for the subsequent experiments.(1)RAW264.7 cells were cultured in six groups:normal serum was added to the control group;low,medium,and high concentration groups were added with low,medium,and high concentrations of Gushukang-containing serum,respectively;ML385,a nuclear factor erythroid 2-related factor 2(Nrf2)inhibitor was given in the Nrf2 inhibitor group;and t-BHQ,a Nrf2 activator,was added in the Nrf2 activator group.Cell viability was detected using the cell counting kit-8 assay.(2)The 3rd generation RAW 264.7 cells were cultured and divided into five groups:the blank control group was added with normal serum,the osteoclast group was added with receptor activator of nuclear factor κB ligand(RANKL),and the low-,medium-,and high-concentration groups were added with low-,medium-,and high-concentration Gushukang-containing serum based on the addition of RANKL.Tartrate-resistant acid phosphate staining was performed after 5 days of culture.(3)RAW264.7 cells were cultured and divided into five groups:blank control group was cultured with normal serum,osteoclast group cultured with normal serum and RANKL,high concentration+osteoclast group cultured with RANKL+high concentration Gushukang-containing serum,osteoclast+Nrf2 agonist group cultured with RANKL+t-BHQ,and high concentration+osteoclast+Nrf2 inhibitor group cultured with RANKL+high concentration Gushukang-containing serum+ML385.Western blot assay and determination of reactive oxygen content were performed after 5 days of culture. RESULTS AND CONCLUSION:The cell counting kit-8 results indicated that Gushukang-containing serum,NRF2 inhibitor or agonist had no significant effect on RAW264.7 cell viability.Tartrate-resistant acid phosphate staining results demonstrated that Gushukang-containing serum exhibited a concentration-dependent inhibitory effect on osteoclast differentiation.Western blot analysis and determination of reactive oxygen species revealed that compared with the blank control group,Nrf2 protein expression was decreased in the osteoclast group(P<0.05),while c-Fos and NFATc1 protein expression and reactive oxygen species content were elevated(P<0.05);compared with the osteoclast group,Nrf2 protein expression was elevated and reactive oxygen species content was decreased in the high-concentration+osteoclast group,osteoclast+Nrf2 agonist group,and high-concentration+osteoclast+Nrf2 inhibitor group(P<0.05),while c-Fos and NFATc1 protein expression was decreased in the high concentration+osteoclast group and osteoclast+Nrf2 agonist group(P<0.05);compared with the high concentration+osteoclast group,Nrf2 protein expression was decreased(P<0.05)and reactive oxygen species content was elevated(P<0.05)in the high concentration+osteoclast+Nrf2 inhibitor group.To conclude,Gushukang reduces reactive oxygen species production by activating Nrf2,thereby inhibiting downstream of the c-Fos/NFATc1 pathway and suppressing osteoclast differentiation.

BACKGROUND:Pyroptosis participate in the degradation of the extracellular matrix of chondrocytes,synovial inflammation and pain,and plays an important role in the prevention and treatment of osteoarthritis.In addition,exercise can inhibit the occurrence of pyroptosis to regulate the progression of osteoarthritis,which has become a research hot spot in the prevention and treatment of osteoarthritis. OBJECTIVE:To summarize the regulatory role of pyroptosis in osteoarthritis and the mechanism of exercise-mediated pyroptosis in osteoarthritis. METHODS:PubMed and CNKI databases were searched during 1992 to 2024 with the keywords"pyroptosis,osteoarthritis,chondrocyte pyroptosis,synovial cell pyroptosis,exercise"in English and Chinese,respectively.Finally,71 relevant articles were selected according to the inclusion and exclusion criteria. RESULTS AND CONCLUSION:(1)Osteoarthritis is a chronic degenerative joint disease characterized by the breakdown of cartilage extracellular matrix,synovial inflammation,and subchondral bone remodeling.This condition often leads to organic lesions,bone pain,and functional impairment.(2)Pyroptosis,a distinct programmed cell death mechanism,involves cell lysis and the release of inflammatory cytokines,triggering a robust inflammatory response,and is closely related to the development of osteoarthritis.Pyroptosis can result in the release of numerous inflammatory factors,thereby activate the nuclear factor kappa-B transcription and increase pyroptosis protein production,and in turn exacerbate the occurrence and development of osteoarthritis.Therefore,pyroptosis can be a new direction for the prevention and treatment of osteoarthritis.(3)Exercise has been shown to down-regulate the pyroptosis protein signaling pathway and inhibit the expression of related inflammatory factors,thereby playing a pivotal role in osteoarthritis prevention and treatment.Aerobic and anaerobic exercises can delay the pathological process of osteoarthritis by inhibiting the occurrence of pyroptosis.Moderate-intensity aerobic exercise is most effective in improving osteoarthritis by inhibiting pyroptosis signaling pathways,while anaerobic exercise can have beneficial effects on osteoarthritis by improving muscle mass.