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.

This paper provides a systematic review of the policies, regulations, and management requirements in the development and use of in vitro diagnostic reagents by healthcare institutions, along with their current implementation status both domestically and internationally, and includes a case analysis of the pilot program at Peking Union Medical College Hospital (PUMCH). The Medical Affairs Department of PUMCH, serving as the leading and operational management unit, established a multi-department collaborative governance structure and developed a full-lifecycle management model encompassing project selection, manufacturing approach determination, regulatory submission and approval, batch production, and clinical implementation. Under this management model, the hospital successfully completed five projects within just one year, achieving the highest number of project filings nationwide. Economic benefit evaluation of the first approved reagent, which is urgently required by clinical practice and named allergen-specific immunoglobulin E detection assay for Fraxinus pennsylvanica pollen, demonstrates that the project realized controllable risk and predictable commercial value, and proves that proactive implementation of systematic management model and project systematic construction is the key to successfully advancing laboratory-developed test programs. The experiences provide both theoretical insights and practical guidance for peer medical institutions seeking to develop and implement self-developed in vitro diagnostic reagents.

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

Objective:To predict pre-treatment clinical parameters that are associated with poor response and prognosis to ursodeoxycholic acid (UDCA) in patients with primary biliary cholangitis (PBC) and to use second-line treatment drugs in the early stages to delay the progression of the disease so that patients can benefit from early-stage treatment.Methods:Patients diagnosed with PBC at the Second Affiliated Hospital of Kunming Medical University from 2013 to 2022 were collected. Two hundred fifty-seven cases were screened in accordance with the inclusion and exclusion criteria. The response and prognosis conditions one year after treatment were followed up in outpatient and inpatient departments, as well as through telephone calls. Statistical analyses were performed using t-tests, Mann-Whitney U test, χ2 test, Fisher's exact test, and logistic regression analysis according to different data. Results:A total of 257 PBC cases were included, with 223 females (86.80%) and 34 males (13.20%). Univariate and multivariate binary logistic regression analyses showed that baseline high albumin levels [odds ratio ( OR): 0.882, 95% confidence interval ( CI): 0.805～0.967, P=0.008] were a protective factor for PBC patients' response to UDCA treatment after adjusting for different confounding factors, while baseline high alkaline phosphatase ( OR: 1.012, 95% CI: 1.008～1.016, P<0.001) and baseline high neutrophil/lymphocyte ratio (NLR) level ( OR: 1.462, 95% CI:1.079～1.981, P=0.014) were risk factors for a poor response to UDCA. Trend analysis showed that the baseline NLR quantile was positively correlated with the risk of poor response to UDCA ( OR: 5.512, 95% CI: 1.040～29.216, P=0.045) in patients with PBC. Cox proportional hazards regression analysis identified that age [hazard ratio ( HR): 1.050, 95% CI: 1.019～1.082] and NLR value ( HR:1.089, 95% CI:1.021～1.161) were independent influencing risk factors for all-cause mortality in PBC patients ( P<0.05). Conclusion:Baseline high albumin levels are protective factors against a poor biochemical response to UDCA, while baseline high alkaline phosphatase levels and high NLR are risk factors for a poor biochemical response to UDCA in patients with PBC. Additionally, baseline high NLR values are positively correlated with poor biochemical response to UDCA treatment.

The development of malignant tumors is influenced by multiple factors,including genetics,environment,lifestyle,and pathogen infection.Viral infection plays a significant role in tumor development and progression.This article integrates the common pathways of seven oncogenic viruses(HPV,EBV,HBV,HCV,KSHV,HTLV-1,and HIV)based on the theory of cancer toxin pathomechanism.The findings reveal that cancer toxin formation is influenced by both internal factors(healthy qi deficiency,viscus dysfunction,and qi,blood,and body fluid stagnation)and external factors(viral infection,environmental factors,and the six exogenous pathogens),driving tumor development,metastasis,and recurrence.Viral infection not only provides the material foundation for cancer toxin but also accelerates its maturation and spread through chronic inflammation and immune imbalance,forming a complex pathogen-esis of"viral toxicity-endogenous cancer toxin",which translates into a three-stage strategy of"prevention,treatment,and post-recovery prevention".This article systematically discusses the pathogenesis of major cancer toxins and their associated tumors.Inte-grating the cancer toxin theory,the article explores preventive and therapeutic strategies for virus-associated malignancies,providing a theoretical basis and practical reference for the integrated prevention and treatment of tumors using traditional Chinese and Western medicine.

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.

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.