Objective To explore the role and mechanism of cardiac resident macrophages in heart repair after myocardial infarction in mice.Methods Macrophage-specific Cre tool mice(CX3CR1CreER-YFP mice)with doubly transgenic mice(R26tdTomato/DTR mice)were hybridized to obtain cardiac resident macrophage-specific red fluorescent labels in mice.Sixty Cx3crlCreER-YFP:R26Td/DTR hybrid mice were randomly divided into 4 groups:Sham group,DT+Sham group,MI group,and DT+MI group,with 15 mice in each group.MI group and DT+MI group underwent myocardial infarction modeling by ligating the left anterior descending coronary artery.The DT+MI group mice were induced to deplete resident macrophages in the heart tissue using diphtheria toxin(DT)to establish a cardiac resident macrophage knockout model.On the 5th day after myocardial infarction modeling,heart tissue slices of mice were stained with H-E to observe inflammation infiltration and myocardial infarct size were calculated;on the 14th day of modeling,echocardiography was used to measure cardiac function-related parameters in mice,and mRNA expression levels of inflammatory cytokines were detected.Results Compared with the MI group,the DT+MI group mice showed a significant reduction in cardiac resident macrophages([53.75±4.62]vs[6.37±1.25],P＜0.05).On the 14th day after myocardial infarction modeling,compared with the Ml group,the DT+MI group mice had significantly increased left ventricular end-diastolic diameter([5.11±0.22]mm vs[5.92±0.26]mm,P＜0.05)and left ventricular end-systolic diameter([4.77±0.17]mm vs[5.38±0.16]mm,P＜0.05),while the ejection fraction significantly decreased([27.76±1.20]％vs[17.61±0.94]％,P＜0.05);in addition,the DT+MI group mice showed increased expression levels of inflammatory cytokines,increased inflammatory cell infiltration,and significantly larger myocardial infarct size.The protein expression levels of NF-KB/p-P65 in DT+MI group mice were significantly higher than those in the MI group([0.28±0.14]vs[1.09±0.12],P＜0.05).Conclusions Cardiac resident macrophages play an important role in heart tissue repair after myocardial infarction by reducing inflammation cell infiltration and myocardial infarct size.

Objective:To explore the efficacy and safety of the modified VIALE-A regimen in the treatment of elderly (>75 years old) patients with intermediate or high risk myelodysplastic syndromes (MDS).Methods:A retrospective case series analysis was conducted. Clinical data were collected from 7 MDS patients aged >75 years who were continuously treated with the modified VIALE-A regimen (azacytidine 75 mg/m 2 per day from day 1 to day 7 + venetoclax 200 mg per day from day 8 to day 28) from May 2021 to August 2023, and the patients were diagnosed according to the World Health Organization 2016 staging criteria and were determined to be at intermediate or high risk according to the revised International Prognostic Scoring System. The patients' efficacy and common adverse reactions were analyzed, and the Kaplan-Meier method was used for survival analysis. Results:Of the 7 patients, 5 were female and 2 were male; the median age [ M ( Q1, Q3)] was 84 years old (80 years old, 90 years old). One patient failed the initial treatment, and the remaining 6 achieved complete remission or complete remission in bone marrow after induction therapy with the modified VIALE-A regimen in 1-2 courses. By the follow-up cut-off date of December 31st, 2023, the median follow-up was 10 months (5 months, 18 months) and the median overall survival time was 18 months (95% CI: 0-39 months). Grade 3-4 myelosuppression occurred in all 7 patients during the induction phase, with granulocytopenia lasting 7-10 d; Of the 64 courses of maintenance treatment, 54 (84%) had grade 1-3 myelosuppression; non-hematologic adverse reactions were mild; no treatment interruptions occurred in the cumulative 73 courses. Conclusions:The modified VIALE-A regimen is moderately efficacious in elderly patients with intermediate or high risk MDS, with controllable adverse reactions.

Osteoporotic vertebral compression fracture (OVCF) can lead to lower back pain and may be even accompanied by scoliosis, neurological dysfunction and other complications, which will affect the daily activities and life quality of patients. Vertebral augmentation is an effective treatment method for OVCF, but it cannot correct unbalance of bone metabolism or improve the osteoporotic status, causing complications like lower back pain, limited spinal activities and vertebral refracture. The post-operative systematic and standardized rehabilitation treatments can improve curative effect and therapeutic efficacy of anti-osteoporosis, reduce risk of vertebral refracture, increase patient compliance and improve quality of life. Since there still lack relevant clinical treatment guidelines for postoperative rehabilitation treatments following vertebral augmentation for OVCF, the current treatments are varied with uneven therapeutic effect. In order to standardize the postoperative rehabilitation treatment, the Spine Trauma Group of the Orthopedic Branch of Chinese Medical Doctor Association organized relevant experts to refer to relevant literature and develop the "Guideline for postoperative rehabilitation treatment following vertebral augmentation for osteoporotic vertebral compression fracture (2022 version)" based on the clinical guidelines published by the American Academy of Orthopedic Surgeons (AAOS) as well as on the principles of scientificity, practicality and advancement. The guideline provided evidence-based recommendations on 10 important issues related to postoperative rehabilitation treatments of OVCF.

According to the pathological characteristics of symptomatic chronic thoracic and lumbar osteoporotic vertebral fracture (SCOVF), the different clinical treatment methods are selected, including vertebral augmentation, anterior-posterior fixation and fusion, posterior decompression fixation and fusion, and posterior correction osteotomy. However, there is still a lack of a unified understanding on how to choose appropriate treatment method for SCOVF. In order to reflect the new treatment concept and the evidence-based medicine progress of SCOVF in a timely manner and standardize its treatment, the clinical guideline for surgical treatment of SCOVF is formulated in compliance with the principle of scientificity, practicability and advancement and based on the level of evidence-based medicine.

Objective To investigate the relationship between circulating tumor cells(CTCs) in peripher-al blood and the prognosis of pancreatic cancer patients. Method From Mar 2010 to Mar 2015, patients with pancreatic cancer in guangzhou first people′s hospital were enrolled in this study. Immunomagetic negative en-richhment together with immunofluorescence were used to identify CTCs. The clinical data of all patients were analyzed. Result No CTCs were found in peripheral blood of healthy control cases. The detection date of CTCs was 60.0%. The positive rate of CTCs was closely correlated with cell differentiation and the clinical stage. Con clusion CTCs count in old patients with pancreatic cancer can reflect the status of the patients and is help-ful for the diagnosis of micrometastasis , re-determination of the clinical stage and the guidance of patients′s treatment. CTCs count can predict the survival time of elderly patients with pancreatic cancer.

Objective To explore the applied value of urine light chainκ、λand κ/λ ratio test in older people with B cell malignant proliferative disease.Methods Young volunteers, general older patients, kidney failure older patients and older patients with B cell malignant proliferative disease were selected and immunoephe-lometry method was applied to detect the level of urine light chainκ、λ and κ/λ ratio.Result The average levels (mg/L)of urine light chain κand λin older patients with kidney failure group(172.00 ±188.10,111.50 ± 109.32)were higher than that in general older patients group(32.72 ±33.60,15.02 ±15.58).In each of the ol-der patients groups,the levels of urine light chainκandλwere higher than that in young volunteers groups(9.30 ±5.80,4.97 ±2.61).The κ/λ ratios of urine light chain in older patients with kidney failure group(1.59 ± 0.4),general older patients group(2.19 ±0.54)and young volunteers group(1.92 ±0.48)were consistent,how-ever,it was significantly abnormal in older patients with B cell malignant proliferative disease group,the ratio was high inκtype(44.8 ±83.17)and low inλtype(0.06 ±0.08).After effective treatment, κ/λ ratio of urine light chain in older patients with B cell malignant proliferative disease tended to normal.Conclusion The level of u-rine light chainκandλis effected by renal function,but not involved the κ/λ ratio.B cell malignant proliferative disease significantly affects theκ/λratio of urine light chain.Constantly monitoring the change ofκ/λratio of u-rine light chain in older peoples with B cell malignant proliferative disease can reflect the proliferative degree of malignant B cell in vivo.

Objective This study was designed to investigate the prognostic implications of the intertumoral heterogeneity of molecular phenotype in multifocal and multicentric breast cancer ( MMBC ) . Methods The clinical and follow-up data of 146 patients with MMBC from Jan.2009 to Dec.2009 treated in Tumor Hospital Affiliated to Zhengzhou University were retrospectively analyzed .We used Kaplan-Meier curves to compare the survivals of patients who had tumors with molecular phenotypic heterogeneity and patients who had multifocal homogeneous tumors in molecular phenotype , and the survivals of patients who had heterogeneous tumor type and grade and who had homogeneous tumor type and grade .The corresponding hazard ratio was calculated by Cox proportional-hazards regression .Results Intertumoral heterogeneity in histological type and grade of multiple breast cancer was detected in 16 of 146 patients (11.0%) and in 10 of 146 patients( 6.8%), respectively.Interfocal heterogeneous molecular phenotype of multiple breast cancer was detected in 24 of 146 patients ( 16.4%) .There was no significant difference in 5-year disease-free survival in multifocal cancer patients who had heterogeneous histological type and grade and who had homogeneous type and grade tumors (75.0%vs.77.3%, P=0.808).Multifocal cancers patients who had heterogeneous tumorsin molecular phenotype compared with those with homogeneous tumors in molecular phenotype had worse 5-year disease-specific survival (78 .7%vs.58.3%,P =0.037) , and had a greater risk of recurrence( HR=2.130, 95%CI=1.027-4.420; P=0.042).Phenotyping the additional cancer foci influenced the therapeutic decision in up to 16 patients (11 .0%) .Conclusoi ns Multifocal breast cancer patients who had heterogeneous tumors in molecular phenotype have a statistically significantly shorter disease-free survival.Phenotyping the additional cancer foci and managing with proper therapeutic decision may reduce the risk of recurrence or metastasis , and improve the outcomes of the patients .

Objective This study was designed to investigate the prognostic implications of the intertumoral heterogeneity of molecular phenotype in multifocal and multicentric breast cancer ( MMBC ) . Methods The clinical and follow-up data of 146 patients with MMBC from Jan.2009 to Dec.2009 treated in Tumor Hospital Affiliated to Zhengzhou University were retrospectively analyzed .We used Kaplan-Meier curves to compare the survivals of patients who had tumors with molecular phenotypic heterogeneity and patients who had multifocal homogeneous tumors in molecular phenotype , and the survivals of patients who had heterogeneous tumor type and grade and who had homogeneous tumor type and grade .The corresponding hazard ratio was calculated by Cox proportional-hazards regression .Results Intertumoral heterogeneity in histological type and grade of multiple breast cancer was detected in 16 of 146 patients (11.0%) and in 10 of 146 patients( 6.8%), respectively.Interfocal heterogeneous molecular phenotype of multiple breast cancer was detected in 24 of 146 patients ( 16.4%) .There was no significant difference in 5-year disease-free survival in multifocal cancer patients who had heterogeneous histological type and grade and who had homogeneous type and grade tumors (75.0%vs.77.3%, P=0.808).Multifocal cancers patients who had heterogeneous tumorsin molecular phenotype compared with those with homogeneous tumors in molecular phenotype had worse 5-year disease-specific survival (78 .7%vs.58.3%,P =0.037) , and had a greater risk of recurrence( HR=2.130, 95%CI=1.027-4.420; P=0.042).Phenotyping the additional cancer foci influenced the therapeutic decision in up to 16 patients (11 .0%) .Conclusoi ns Multifocal breast cancer patients who had heterogeneous tumors in molecular phenotype have a statistically significantly shorter disease-free survival.Phenotyping the additional cancer foci and managing with proper therapeutic decision may reduce the risk of recurrence or metastasis , and improve the outcomes of the patients .

Genetic modification technology is a new molecular tool for targeted genome modification. It includes zinc finger nucleases (ZFN) technology, transcription activator-like effector nucleases (TALEN) technology and clustered regularly interspaced short palindromic repeat (CRISPR)-associated (Cas) (CRISPR-Cas) nucleases technology. All of these nucleases create DNA double-strand breaks (DSB) at chromosomal targeted sites and induce cell endogenous mechanisms that are primarily repaired by the non-homologous end joining (NHEJ) or homologous recombination (HR) pathway, resulting in targeted endogenous gene knock-out or exogenous gene insertion. In recent years, genetic modification technologies have been successfully applied to bacteria, yeast, human cells, fruit fly, zebra fish, mouse, rat, livestock, cynomolgus monkey, Arabidopsis, rice, tobacco, maize, sorghum, wheat, barley and other organisms, showing its enormous advantage in gene editing field. Especially, the newly developed CRISPR-Cas9 system arose more attention because of its low cost, high effectiveness, simplicity and easiness. We reviewed the principles and the latest research progress of these three technologies, as well as prospect of future research and applications.
Animals ; CRISPR-Cas Systems ; DNA Breaks, Double-Stranded ; Endonucleases ; Genetic Engineering ; methods ; Humans ; Mutagenesis, Insertional ; Mutagenesis, Site-Directed ; Plants ; Zinc Fingers

Objective To study the anti-tumor effect and mechanism of bortezomib in primary acute leukemia cells from elderly patients.Methods Primary acute leukemia cells were treated with bortezomib 50-5000 nmol/L for 24-48 h,cell proliferation was analysed by MTT assay; apoptosis of primary acute leukemia cells was observed by fluorescence microscopy and flow cytometry; protein expression of bcl-2 and Bax was detected by Western blot.Results The cell viability was 90 ％ and 70 ％ when leukemia cells were treated with 50 and 5000 nmol/L bortezomib for 24 h,respectively.Meanwhile,cells showed (10.2±2.3) ％ and (13.3±3.3) ％ apoptosis.With prolonged treatment for 48 h,cell viability decreased to 86 ％ and 60 ％,respectively,while the apoptosis rates were increased to(18.4±3.9) ％ and(20.7±3.7) ％.Compared to the control group 0 nmol/L bortezomib,the differences were statistically significant (F =53.76,F =7.74,F =54.49,F =16.94,all P values ＜ 0.05).With the increase of bortezomib concentration,the bcl-2 protein expression was decreased,while Bax was up-regulated.Conclusion Bortezomib can inhibit primary leukemia cells from elderly patients proliferation and induce apoptosis.The mechanism may be associated with the changes in bcl-2 family protein expression.