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.

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.

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.
.
Humans ; Small Cell Lung Carcinoma/diagnosis* ; Lung Neoplasms/diagnosis* ; Quality of Life ; Follow-Up Studies

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.

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

As a practical carrier for promoting the tiered diagnosis and treatment model, the medical consor-tium is of great significance for balancing medical resources and boosting medical service efficiency. The construction of medical consortiums not only improves the accessibility of high-quality medical resources for patients, but also enhances the diagnostic and treatment level of member units. Meanwhile, it provides space for the leading hospital to adjust the structure of diseases and improve the level of discipline construction. As the core of medical insurance payment reform, DRG, through indicators such as the case mix index(CMI) and the number of diagnosis related group (DRG), provides objective and quantified data support for case management and disease structure optimization, thus effectively guiding the rational allocation of medical resources and the adjustmentof diseases and surgical types within the medical consortium. Comprehensive use of DRG evaluation indicators can construct a multidimensional medical consortium construction evaluation system, provides a clear direction for medical consortium cooperation, thereby promoting the overall healthy and sustainable development of medical consortiums and achieving a win-win situation for all parties involved. This paper, based on the "1+5+1" medical consortium cooperation model centered around Peking Union Medical College Hospital, utilizes DRG indicators to analyze the benefits for patients, member hospitals, and the leading hospital during the medical consortium construction process, with the hope of providing reference for the construction of a medical consortium evaluation system.

Objective:To construct the impact factor model of primary traditional Chinese medicine (TCM) health management service quality, and put forward corresponding policy suggestions.Methods:In this cross-sectional study, the typical sampling and random sampling method were used to select 39 insiders of primary TCM health management service from 15 communities in Zhejiang Province from August to October in 2022. Interviews on service projects, implementation effects and impact factors were conducted, the three-level coding of interview record was carried out using the grounded theory research method, a model of impact factor for health management service quality of basic TCM was constructed, and the corresponding policy recommendations were put forward.Results:Based on the open coding of 39 original interview data, a total of 516 reference points were obtained, and 53 initial concepts related to the topic were formed and summarized into 17 first-level categories. Through the summary of main axis coding, 6 main categories of “policy environment”，“health literacy”，“community orientation”，“capacity building”，“health preference” and “conflict of interest” were extracted. The logical correlation between the six main categories were analyzed with selective coding, an impact factor model was constructed in accordance with the story line of factors affecting service quality. The story line of this model was as follows: first, the policy environment was the external guarantee of community TCM service quality; second, as the demand-side of the services, the health literacy and requirement of residents was the regulatory factor for service quality; in addition, the community played the role of the supply-side of the services, the service ability construction was the key factor, and the community functions and target orientation was the internal driving factor, meanwhile, the internal/external conflicts of interest had a negative constraint on the service quality.Conclusions:The guarantee intensity of external policy environment is limited, the service demand side pays insufficient attention, and the service supply side functions are absent at the present stage. It is necessary to improve the external policy environment, deepen the connection between supply and demand sides in the field of TCM health service, promote the capacity building of TCM service at the grass-roots level, balance the interests of relevant departments of TCM service, in order to improve the quality of TCM health management service at the grass-roots level.

Objective:To study the immunotherapeutic effect of chimeric hepatitis B core protein virus-like particles in subcutaneous lung adenocarcinoma mouse model, lays the foundation for the progression of tumor nano-therapeutic technology development.Methods:The plasmid was constructed by inserting a B-cell epitope of the human epidermal growth factor receptor-2 (HER-2) at hepatitis B core protein′s major immunodominant region (MIR). The recombinant virus nanoparticle, denoted as HBc-HER2, was obtained by E. coli expression system, followed by a series of purification steps. The immune response to this recombinant protein nanoparticle was assessed by measuring levels of anti-HER-2 antibody levels and characterizing antibody isotypes in a subcutaneous tumor mice model of lung adenocarcinoma. While tumor therapeutic efficacy was evaluated by measuring tumor size changes with an electronic caliper and MRI photography of subcutaneous tumor in mice.Results:A high-purity HBc-HER2 recombinant protein was obtained and could assemble into nanoparticle. Animal studies had demonstrated the robust immunogenicity of this vaccine in inducing high levels of HER-2 specific antibodies, yielding positive therapeutic outcomes against tumors.Conclusions:The engineered HBc-HER2 demonstrated notable tumor therapy efficacy in a subcutaneous lung adenocarcinoma mouse model, offering a foundation for tumor therapeutic nanotechnology vaccine research.

Objective This project aimed to study the Miao medicine helleborus thibetanus franchon,including investigating its anti-inflammatory activity in collagen-induced arthritis CIA rats and its mechanism of VEGF/VEGFR2/P38 MAPK pathway regulation.Methods Sixty female Wistar rats were randomly divided into six groups:normal;model;positive drug;and low,medium,high dose groups,with 10 rats in each group.Bovine type Ⅱ collagen solution was injected into the tail of rats to construct the rheumatoid arthritis model,and the positive drug group was given MTX2.0 mg/(kg·d)by gavage once every other day.The three groups of helleborus thibetanus franchon low,medium,and high dose were gavaged with helleborus thibetanus franchon ethanol extract at 0.25,0.5 and 1 g/(kg·d)once a day.The normal and model groups were given an equivalent volume of NaCl solution,with continuous administration lasting for 28 days.During treatment,the general condition of the rats was observed,body weight changes recorded,and foot thickness measured.After treatment and euthanasia,the rats'hind limbs were removed for Micro-CT to detect bone destruction;hematoxylin and eosin staining for pathological investigattion of the synovial membrane;immunohistochemistry to observe neovascularization in the synovium;quantitative reverse-transcription PCR to detect mRNA levels of VEGF-A,VEGFR2,TNF-α in the synovial tissue;and Western Blot to detect the expression of VEGF,VEGFR2,p-P38,p-AKT.The analyses were used to explore the potential mechanisms of action of the Miao medicine helleborus thibetanus franchon in treating rheumatoid arthritis.Results Compared with the normal group,the model group showed significant weight loss(P＜0.01),increased foot swelling(P＜0.01),visible proliferative synovial tissue with inflammatory cell infiltration,erosive lesions on bone surfaces,increased neovascularization in the synovium,and significant bone destruction in Micro-CT,with reduced bone percentage,trabecular thickness,and bone density.The levels of VEGF-A,VEGFR2,TNF-α mRNA and VEGF-A,VEGFR2,p-P38,p-AKT proteins were significantly elevated(P＜0.01).Compared with the model group,the helleborus thibetanus franchon ethanol extract-treated groups showed improvements in these conditions in a dose-dependent manner,with the high-dose group receiving the best effect.There was a significant increase in the rats'body weight(P＜0.05);reduction in foot swelling(P＜0.05);amelioration of synovial and erosive bone lesions;reduction in neovascularization in the synovium;and significantly lower levels of VEGF-A,VEGFR2,and TNF-α mRNA,and VEGF-A,VEGFR2,p-P38,and p-AKT protein(P＜0.01).Conclusions The Miao medicine plant helleborus thibetanus franchon may alleviate joint inflammatory damage in CIA rats by modulating the VEGF/VEGFR2 signaling pathway,thereby exerting therapeutic effects on rheumatoid arthritis.