OBJECTIVE To study the clinical characteristics and potential risk factors for infection in patients with multiple myeloma （MM） following treatment with bortezomib. METHODS Clinical data were retrospectively collected from MM patients who received bortezomib-based treatment regimens at the Department of Hematology， the Second Affiliated Hospital of Soochow University， from October 2021 to February 2025. The collected data primarily included demographic characteristics， disease characteristics of MM， treatment regimens， occurrence of infections and corresponding management measures， and prophylactic medication use. Univariate and multivariate Logistic regression analyses were conducted to identify potential risk factors for MM complicated with infection. RESULTS Among the 284 MM patients treated with bortezomib， 132 patients （46.5%） experienced at least one infection. The predominant types of infections were respiratory tract infections and gastrointestinal infections. Univariate analysis showed that age at initial diagnosis， pathological classification， and grade of myelosuppression were influencing factors for infection in MM patients （ P ＜0.05）. Further analysis of influencing factors for the two main types of infections revealed that sex， age at initial diagnosis， pathological classification， treatment regimen， and smoking history were influencing factor s for respiratory tract infections in MM patients （ P ＜0.05）； BMI， pathological classification， treatment regimen， and grade of myelosuppression were influencing factors for gastrointestinal infections in MM patients （ P ＜0.05）. Multivariate Logistic regression analysis indicated that age≥70 years and the presence of grade Ⅳ myelosuppression before treatment were risk factors for infection in MM patients， while the IgG-λ type was a protective factor against infection （ P ＜0.05）. CONCLUSIONS The incidence of infection is relatively high in MM patients receiving bortezomib-based treatment regimens， with respiratory and gastrointestinal infections being the most common. Age at initial diagnosis， grade of myelosuppression， and pathological classification are influencing factors for infection in MM patients.

Objective To investigate the effect of miR-486-5P on ferroptosis in H9c2 cardiomyocytes after hypoxia/reoxygenation(H/R),and to analyze its mechanism.Methods Using H9c2 cardiomyocytes as the research object,a H/R injury model was established using cobalt chloride(CoCl2)and fresh culture medium.The cells were divided into control group,H/R group,H/R+miR-486-5P mimic NC group,H/R+miR-486-5P mimic group,H/R+miR-486-5P inhibitor NC group and H/R+miR-486-5P inhibitor group.The relative expression level of miR-486-5P was detected by quantitative reverse transcription-polymerase chain reaction(qRT-PCR).The cell viability was detected by CCK-8 method.The activities or levels of lactate dehydrogen-ase(LDH),glutathione(GSH),Fe2+and malondialdehyde(MDA)were detected by colorimetric method.The levels of reactive oxygen species(ROS)and mitochondrial membrane potential(MMP)were detected by DCFH-DA fluorescent probe and JC-1 assay,respectively.Western blot was used to detect the levels of AkT/mTOR signaling pathway proteins and ferroptosis related protein solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4)and acyl-coa synthetase long chain family member 4(ACSL4).Results Compared with the control group,the level of miR-486-5P and cell viability in the H/R group de-creased significantly(P＜0.05),while LDH activity,MDA,Fe2+level,ROS level and ACSL4 protein level in-creased significantly(P＜0.05).The GSH,MMP,SLC7A11 and GPX4 levels and p-Akt/Akt and p-mTOR/mTOR ratios were significantly decreased(P＜0.05).After H/R treatment,compared with the H/R+miR-486-5P mimic NC group,the cell viability of the H/R+miR-486-5P mimic group was significantly increased(P＜0.05).The LDH activity,MDA,Fe2+level,ROS level and ACSL4 protein level were significantly de-creased(P＜0.05),while GSH,MMP,SLC7A11 and GPX4 levels and p-Akt/Akt and p-mTOR/mTOR ratios were significantly increased(P＜0.05).Compared with the H/R+miR-486-5P inhibitor NC group,the trend of the above indicators in the H/R+miR-486-5P inhibitor group was opposite.Conclusion miR-486-5P allevi-ates hypoxia/reoxygenation-induced ferroptosis in H9c2 cells by regulating Akt/mTOR signaling pathway,and thus alleviates hypoxia/reoxygenation induced cardiomyocyte injury.

Objective:To investigate the effect of ribonucleotide reductase regulatory subunit M2 (RRM2) on the malignant biological behavior and aerobic glycolysis of gastric cancer cells by regulating cyclin-dependent kinase (CDK) 1.Methods:Human gastric cancer MKN-45 cells were divided into si-NC group (transfected with blank fragment) , CoCl 2+si-NC group (hypoxia control transfected with blank fragment) , CoCl 2+si-RRM2 group (hypoxia with RRM2 silencing) , CoCl 2+si-RRM2+pcDNA3.1 NC group (hypoxia with RRM2 silencing and blank vector) and CoCl 2+si-RRM2+pcDNA3.1 CDK1 group (hypoxia with RRM2 silencing and CDK1 overexpression) . The mRNA relative expression levels of RRM2 and CDK1 were analyzed by real time fluorescent quantitative reverse transcription PCR. Co-immunoprecipitation (CoIP) was used to analyze the interaction between RRM2 and CDK1 protein. MTT assay was used to analyze the proliferation activity of cells. The cell migration distance was detected by cell scratch assay. Cell apoptosis was detected by flow cytometry. Adenosine triphosphate (ATP) and glucose kit were used to detect ATP production and glucose consumption. The protein expressions of ENO1, RRM2, HK2, PKM2, GLUT1 and p-CDK1/CDK1 were detected by Western blotting. Results:Real time fluorescent quantitative reverse transcription PCR results showed that the relative expression levels of CDK1 mRNA in si-NC group, CoCl 2+si-NC group and CoCl 2+si-RRM2 group were 1.01±0.15, 1.30±0.06 and 0.51±0.18, and the relative expression levels of RRM2 mRNA were 1.03±0.32, 1.59±0.28 and 0.44±0.17, respectively, and there were statistically significant differences ( F=25.52, P=0.001; F=14.47, P=0.005) . The mRNA expressions of RRM2 and CDK1 in CoCl 2+si-NC group were higher than those in si-NC group. Compared with the si-NC group and the CoCl 2+si-NC group, the mRNA expressions of RRM2 and CDK1 were lower in the CoCl 2+si-RRM2 group (all P<0.05) . CoIP results showed that there was interaction between RRM2 and CDK1. MTT assay, cell scratch assay and flow cytometry showed that the cell proliferation activity of si-NC group, CoCl 2+si-NC group, CoCl 2+si-RRM2 group, CoCl 2+si-RRM2+pcDNA3.1 NC group and CoCl 2+si-RRM2+pcDNA3.1 CDK1 group were 1.04±0.01, 1.18±0.04, 0.84±0.03, 0.81±0.03 and 0.93±0.05, respectively. The cell migration distances were (301.83±2.75) , (369.67±0.76) , (176.50±6.38) , (175.83±3.69) , (254.17±1.61) μm, respectively. The apoptosis rates were 8.05%±0.21%, 5.75%± 0.20%, 28.28%±0.04%, 30.18%±1.51% and 17.79%±0.22%, respectively, all with statistically significant differences ( F=73.82, P<0.001; F=1 600.01, P<0.001; F=787.15, P<0.001) . Compared with the si-NC group and CoCl 2+si-NC group, the proliferation and migration ability of cells in the CoCl 2+si-RRM2 group, CoCl 2+si-RRM2+pcDNA3.1 NC group and CoCl 2+si-RRM2+pcDNA3.1 CDK1 group were weaker, and the apoptosis rates were higher (all P<0.05) . Compared with the CoCl 2+si-RRM2+pcDNA3.1 NC group, the proliferation and migration ability of cells in the CoCl 2+si-RRM2+pcDNA3.1 CDK1 group were stronger, and the apoptosis rate was lower (all P<0.05) . The results of ATP and glucose detection showed that there were statistically significant differences in the amount of ATP production and glucose consumption among the above five groups ( F=12.53, P<0.001; F=19.21, P<0.001) . Compared with the si-NC group, the glucose consumption of cells was lower in the CoCl 2+si-RRM2+pcDNA3.1 CDK1 group ( P<0.05) . Compared with the CoCl 2+si-NC group, the ATP production and glucose consumption of cells in the CoCl 2+si-RRM2+pcDNA3.1 CDK1 group were lower (both P<0.05) . Compared with the CoCl 2+si-RRM2+pcDNA3.1 NC group, the ATP production and glucose consumption of the CoCl 2+si-RRM2+pcDNA3.1 CDK1 group were higher (both P<0.05) . Western blotting showed that there were statistically significant differences in the protein expressions of ENO1, RRM2, HK2, PKM2, GLUT1, and p-CDK1/CDK1 among the above five groups (all P<0.001) . Compared with the si-NC group and the CoCl 2+si-NC group, the protein expressions of ENO1, RRM2, HK2, PKM2, GLUT1 and p-CDK1/CDK1 in the CoCl 2+si-RRM2+pcDNA3.1 CDK1 group were lower (all P<0.05) . Compared with the CoCl 2+si-RRM2+pcDNA3.1 NC group, the protein expressions of ENO1, RRM2, PKM2, GLUT1 and p-CDK1/CDK1 in the CoCl 2+si-RRM2+pcDNA3.1 CDK1 group were higher (all P<0.05) . Conclusions:Silencing RRM2 can inhibit the malignant biological behavior of gastric cancer cells and the occurrence of aerobic glycolysis by regulating CDK1.

ObjectiveTo explore the mechanism of action of Wendantang on ApoE^-/- hyperlipidemic mice using non-targeted metabolomics technology. MethodsMale C57BL/6J mice served as the normal control group （n=6）， and they were fed with regular chow， while male ApoE^-/- mice constituted the high-fat group （n=30）， and they were fed with a 60% high-fat diet. After 11 weeks of model establishment， the mice in the high-fat group were randomly divided into the model group， simvastatin group （3.3 mg·kg^-1）， and high-dose， medium-dose， and low-dose groups of Wendantang （26， 13， 6.5 g·kg^-1， respectively， in terms of crude drug amount）， with six mice in each group. The normal control group and the model group were gavaged with an equivalent volume of normal saline， and all groups continued to be fed their respective diets， receiving daily medication for 10 weeks with weekly body weight measurements. Serum levels of total cholesterol （TC）， triglycerides （TG）， high-density lipoprotein cholesterol （HDL-C）， low-density lipoprotein cholesterol （LDL-C）， free fatty acids （NEFA）， blood glucose （GLU）， alanine aminotransferase （ALT）， and aspartate aminotransferase （AST） were detected in the mice. Pathological changes in liver tissue were observed using hematoxylin-eosin （HE） staining， and ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-Q-TOF-MS/MS） was employed for metabolomic analysis of mouse liver tissue. ResultsCompared to the normal control group， the model group exhibited significantly increased body weight， blood lipid levels， and liver function （P<0.05， P<0.01）， with disordered liver tissue structure， swollen hepatocytes， and accompanying vacuolar fatty degeneration and inflammatory cell infiltration. Compared to the model group， the simvastatin group and Wendantang groups showed significantly reduced body weight， TG， NEFA， GLU， ALT， and AST levels （P<0.05， P<0.01）， with a significant increase in HDL-C levels （P<0.05， P<0.01）， demonstrating a dose-dependent effect. The lesion of the liver tissue section was obviously improved after administration， tending towards a normal liver tissue morphology. Analysis of liver metabolites revealed 86 differential metabolites between the normal control group and the model group， with the high-dose group of Wendantang able to regulate 56 of these metabolites. Twenty-two differential metabolites associated with hyperlipidemia were identified， mainly including chenodeoxycholic acid， hyocholic acid， taurine， glycocholic acid， dihydroceramide， hydroxy sphingomyelin C14∶1， arachidonic acid， and linoleic acid， enriching 22 metabolic pathways， with 4 being the most significant （P<0.05）， namely primary bile acid biosynthesis， sphingolipid metabolism， unsaturated fatty acid biosynthesis， and linoleic acid metabolism pathways. ConclusionWendantang can improve blood lipid levels and liver function in ApoE^-/- hyperlipidemic mice， which may be related to the regulation of primary bile acid biosynthesis， sphingolipid metabolism， unsaturated fatty acid biosynthesis， and linoleic acid metabolism pathways.

OBJECTIVE: To explore the clinical manifestation and genotype of a child with Progressive familial intrahepatic cholestasis 8 (PFIC8) due to variant of KIF12 gene. METHODS: A child diangosed with PFIC8 at Changzhou Children's Hospital in October 2017 was selected as the study subject. Clinical data of the child was collected. Peripheral blood samples (3 mL each) were collected from the patient, her parents and younger sister. Following extraction of genomic DNA, whole exome sequencing (WES) was carried out. Candidate variants were validated using Sanger sequencing. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the pathogenicity of candidate variants was classified. This study has been approved by the Medical Ethics Committee of Changzhou Children's Hospital (Ethics No.: 2023-002). RESULTS: The main clinical manifestations of the child included high GGT cholestasis, portal hypertension, splenomegaly, and abnormal liver enzymes. WES revealed that she has harbored compound heterozygous variants of the KIF12 gene, namely c.245G >A (p.Arg82Gln) and c.1291del (p.Ser431Valfs*13). Bioinformatics analyses showed that both variants were pathogenic. A total of 25 cases were reported in 7 English literature, including 13 males and 12 females. All patients had presented with high GGT cholestasis. Some had progressed to cirrhosis, and 3 cases also had renal lesions. No death was reported. Six children were treated with LTx. Nineteen children were found to harbor homozygous variants of the KIF12 gene, and the remaining six harbored compound heterozygous variants of the same gene. The most common mutation was c.655C>T (p.Arg219*). The mutation sites are mainly located in the Kinesin motor catalytic domain, with high GGT cholestasis as the main clinical feature. No correlation was found between the genotype and phenotype. CONCLUSION PFIC8 caused by KIF12 deficiency is mainly characterized by high GGT cholestasis, for which there is no effective treatment. The c.245G>A and c.1291del compound heterozygous variants of the KIF12 gene probably underlay the pathogenesis in this child.
Humans ; Kinesins/genetics* ; Female ; Cholestasis, Intrahepatic/genetics* ; Phenotype ; Heterozygote ; Child ; Mutation ; Child, Preschool ; Male ; Exome Sequencing

Plant-derived bioactive peptides have become a research hotspot in the fields of food and medicine due to their high source safety,easy absorption and utilization by the human body,and potential edible and medicinal value.Bioactive peptides can be classified into antihypertensive,hypoglycemic,hypolipidemic,anticancer,antioxidant,antimicrobial,and anti-inflammatory peptides according to their functions.Among these,antihypertensive,hypoglycemic,and hypolipidemic peptides are collectively referred to as cardiovascular active peptides,which can be used for the treatment and prevention of cardiovascular diseases and have an important role in the development of modem biomedicine.This review focused on the preparation methods,separation,purification,and identification techniques of bioactive peptides,as well as their mechanisms of action and applications in regulating cardiovascular diseases,aiming to provide a reference for further development and application of plant-derived cardiovascular peptides.

Objective To establish a pediatric rare disease catalog,analyze the current status of therapeutic drugs and their coverage of the medical insurance in China,and propose strategies to enhance drug accessibility.Methods Pediatric rare diseases were identified from China's two national rare disease catalogs combined with the EU Orphanet database,US FDA orphan drug database,and the Diagnosis and Treatment Standards for Rare Diseases in Children.We created a specialized drug catalog for pediatric rare diseases,then analyzed drug types(ATC classification),pricing,and medical insurance coverage using descriptive statistics based on Yaozhi.com drug bidding prices and the 2024 Drug of List National Basic Medical Insurance(NBMIDL).Drug affordability was assessed through annual treatment cost calculations.Results The national catalogs included 151 pediatric rare diseases(72.95%of listed conditions),spanning 13 disease systems.We identified 94 dedicated orphan drugs(by generic name)for these conditions,among which 43 were approved internationally but unavailable in China.The average unit price per package was 6 113.53 yuan.Overall NBMIDL coverage was 68.83%,but drugs priced above 7 000 yuan per unit had only 7.69%coverage.Annual treatment costs reached 4.54 million for laronidase(mucopolysaccharidosis).Conclusions Critical gaps persist in China's pediatric rare disease treatment landscape,including catalog deficiencies,inadequate coverage for high-cost drugs and insufficient domestic innovation.It is recommended to establish a list of orphan drugs for pediatric rare diseases,accelerate the import of foreign drugs and the local innovative drugs through policy incentives,optimizing medical insurance reimbursement mechanisms for pediatric rare disease drugs to comprehensively improve therapeutic accessibility.

This paper summarizes the current status of research on the prevention and treatment of malignant tumors with traditional Chinese medicine(TCM),and points out that TCM has the advantages of being based on the holistic view and advocating the preven-tive treatment of diseases.The strategies of TCM in preventing and treating malignant tumors are proposed:first,it is necessary to clar-ify the leading or auxiliary treatment role in different stages of tumors and give full play to its strengths and advantages;second,find the characteristics of the superior and inferior populations and microscopic markers of tumor diagnosis and treatment to promote accurate di-agnosis and treatment;third,improve the overall diagnosis and treatment level of tumors by grasping the core pathogenesis and ensure clinical efficacy;fourth,incorporate modern medical therapy factors into the TCM tumor diagnosis and treatment system in order to in-tercept the disease;fifth,add TCM psychological intervention on the basis of the four-in-one holistic syndrome differentiation view to achieve harmony between body and spirit;sixth,improve the rehabilitation and health care system of tumors combined with traditional Chinese and Western medicine through the use of multiple methods to promote the recovery of diseases.In this way,the clinical effica-cy of TCM in preventing and treating tumors can be continuously improved,and the great goal of TCM in preventing and treating tumors and benefiting all mankind can be truly realized.

OBJECTIVE To investigate the inhibitory effect mechanism of Anzheng Kangliu Decoction against colorectal cancer by suppressing glycolysis through regulation of the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin(mTOR)signaling pathway.METHODS Human colorectal cancer SW620 cells were treated with Anzheng Kangliu De-coction,and cell proliferation and migration abilities were assessed.Forty-two BALB/c nude mice were randomly divided into a blank control group,model group,5-fluorouracil(5-FU)group(0.025 g·kg-1),Anzheng Kangliu Decoction low-dose group(7.67 g·kg-1),medium-dose group(15.34 g·kg-1),and high-dose group(30.68 g·kg-1).The inhibitory effect of Anzheng Kan-gliu Decoction on subcutaneous xenograft tumors was evaluated by observing body weight,tumor volume,tumor mass,HE staining,im-munohistochemical staining of Ki67 and other indicators.High-throughput transcriptome sequencing was performed to identify differen-tially expressed genes and pathways in tumor tissues between the model group and the Anzheng Kangliu Decoction medium-dose group,elucidating the potential mechanism of Anzheng Kangliu Decoction against colorectal cancer.Glucose and lactate assay kits were used to measure glucose consumption and lactate production in SW620 cells and tumor tissues after Anzheng Kangliu Decoction intervention.Western blot was employed to detect the expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,hexokinase 2(HK2),and lactate dehydrogenase A(LDHA)in SW620 cells and tumor tissues following Anzheng Kangliu Decoction treatment.RE-SULTS In vitro cell experiments demonstrated that,compared with the blank control group,Anzheng Kangliu Decoction intervention significantly inhibited the proliferation and migration of SW620 cells(P<0.01),reduced glucose consumption and lactate production(P<0.05,P<0.01),and downregulated the protein expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,HK2,and LDHA(P<0.05,P<0.01).In vivo animal experiments revealed that,compared with the model group,Anzheng Kangliu Decoction suppressed the growth of subcutaneous xenograft tumors in nude mice(P<0.01),increased tumor tissue necrosis,decreased glucose consumption and lactate production in tumor tissues(P<0.05,P<0.01),and reduced the protein expression levels of p-PI3K/PI3K,p-Akt/Akt,p-mTOR/mTOR,HK2,and LDHA(P<0.05,P<0.01).CONCLUSION Anzheng Kangliu Decoction exerts an in-hibitory effect on colorectal cancer,and its mechanism may be associated with the suppression of glycolysis through regulation of the PI3K/Akt/mTOR signaling pathway.

Small cell lung cancer (SCLC) is a highly malignant disease that has garnered significant attention in terms of treatment modalities and course management. Gaining an understanding of the clinical characteristics of SCLC, acquiring proficiency in screening, diagnosis, and treatment methods for this condition, as well as promptly addressing any adverse reactions to treatment are essential foundations for developing a scientific and rational pathological management plan for SCLC. By utilizing an intelligent whole course follow-up management platform, dynamic follow-up, timely warnings, and early interventions can enable high-quality whole life cycle management. This article aims to review the current treatment landscape of SCLC while exploring the challenges associated with implementing a comprehensive process-oriented management approach. The goal is to provide valuable insights for better managing SCLC patients and ultimately improving their quality of life and prognosis.
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Humans ; Small Cell Lung Carcinoma/diagnosis* ; Lung Neoplasms/diagnosis* ; Quality of Life ; Follow-Up Studies