Multiple myeloma(MM)is a systemic malignancy of plasma cells.Nowadays,the basic research on MM is flourishing with the continuous optimization and innovation of mouse models of MM.Heterologous mouse models of MM established with human-derived cells and immunodeficient mice have been applied in assessing drug efficacy,exploring drug resistance mechanisms,and observing tumor-bone marrow microenvironment interactions.In the last decades,the homologous mouse models of MM established with murine-derived cells or gene-editing technologies have been widely used in the research on the pathogenesis and drug development.Additionally,the stable modeling of targeted organ injury will be a key problem to be tackled in this field.This review summarizes the characteristics and application progress of mouse models of MM.
Humans ; Animals ; Mice ; Multiple Myeloma/pathology* ; Bone Marrow/pathology* ; Disease Models, Animal ; Drug Resistance ; Tumor Microenvironment

Objective: To investigate the association between peripheral blood mitochondrial DNA copy number (mtDNAcn) and incident risk of liver cancer. Methods: At the baseline of Dongfeng-Tongji (DFTJ) cohort, 27 009 retirees were recruited from Dongfeng Motor Corporation in 2008. After excluding people without baseline DNA, with current malignant tumor and loss of follow-up, 1 173 participants were randomly selected into a sub-cohort by age-and gender-stratified sampling method at a proportion of 5% among all retirees. A total of 154 incident liver cancer cases identified from the cohort before December 31, 2018 (4 cases had been selected into the sub-cohort) were selected to form the case cohort of liver cancer. For the above 1 323 participants, their baseline levels of mtDNAcn in peripheral blood cells were measured by using quantitative real-time PCR method. The restricted cubic spline analysis was used to fit the shape of the association between baseline mtDNAcn and incident risk of liver cancer. The weighted Cox proportional hazards model was used to estimate the hazard ratio (HR) and 95%CI. Results: In this case-cohort study, the median follow-up time was 10.3 years. The restricted cubic spline analysis indicated that the relationship between peripheral blood mtDNAcn and incident risk of liver cancer followed a U-shaped pattern (P_non-linear<0.05). All case-cohort population were divided into four subgroups by sex-specific quartiles of mtDNAcn levels among sub-cohort participants, when compared to participants in the Q₂ subgroup of mtDNAcn, those in the Q₁ subgroup (HR=2.00,95%CI:1.08-3.70) and Q₄ subgroup (HR=4.11,95%CI:2.32-7.26) both had a significantly elevated risk of liver cancer, while those in the Q₃ subgroup (HR=1.05,95%CI:0.54-2.05) had not. There were no significant multiply interaction effects of aging, gender, tobacco smoking, alcohol drinking and history of chronic hepatitis on the above association (P_interaction>0.05). Conclusion: Both extremely low and high baseline level of mtDNAcn in peripheral blood cells are associated with an increased risk of incident liver cancer, but the underlying mechanisms need to be further clarified.
Cohort Studies ; DNA Copy Number Variations ; DNA, Mitochondrial/genetics* ; Female ; Humans ; Liver Neoplasms/genetics* ; Male ; Mitochondria

OBJECTIVE: To observe the impacts of electroacupuncture (EA) on neurological function, the pathological morphology in brain tissue, apoptosis level and the protein expressions of apoptosis-related cytochrome C (Cyt-C) and cysteine aspartic acid protease-9 (Caspase-9) in the rats with traumatic brain injury (TBI) and explore the potential mechanism of EA in treatment of TBI. METHODS: A total of 70 clean-grade SD mice were randomized into a blank group (8 rats), a sham-operation group (8 rats), a model group (27 rats) and an EA group (27 rats). In terms of interventions of 3, 7 and 14 days, 3 subgroups were divided in the model group and the EA group successively, 9 rats in each subgroup. The modified Feeney free-fall percussion method was adopted to establish TBI models of rats. In the sham-operation group, only the skull was exposed and drilled and no free-fall percussion was exerted. One day after modeling, EA was given in the rats of EA group at "Shuigou" (GV 26), "Baihui" (GV 20) and "Neiguan" (PC 6) and "Zusanli" (ST 36) on the affected side, with intermittent wave, 2 Hz in frequency, once daily, 10 min each time, for 3, 7 and 14 days successively. Separately, on the day 3, 7 and 14 of intervention, the modified neurological severity scale (mNSS) was used to evaluate the degree of neurological function injury in the rats, HE staining and Nissl staining were to observe the pathological and morphological changes in brain tissue, TUNEL method was to observe the level of apoptosis in brain tissue and immunohistochemistry (IHC) method and Western blot were to determine the protein expressions of Cyt-C and Caspase-9 in brain tissue. RESULTS: Compared with the sham-operation group, on the day 3, 7 and 14 of intervention, mNSS scores were increased obviously in the rats of the model group respectively (<0.01). Compared with the model group, on the day 3, 7 and 14 of intervention, mNSS scores were reduced in the rats of the EA group respectively (<0.05). On day 3 of intervention, in brain injury region of the rats in the model group and the EA group, gross tissue necrosis, nuclear fragmentation, consolidation and obvious vacuolar changes, reduced Nissl bodies and scattered arrangement were found. On day 7 and 14 of intervention, in the model group and the EA group, the new connective tissue filling and normal cells were visible and Nissl bodies increased. The overall repair and Nissl body quantity in the EA group were better than the model group. Compared with the sham-operation group, on day 3, 7 and 14 of intervention, the numbers of apoptotic cells were increased obviously in the model group (<0.01) and they were reduced in the EA group as compared with the model group (<0.05). Compared with the sham-operation group, on day 3, 7 and 14 of intervention, the protein expressions of Cyt-C and Caspase-9 in damaged brain tissue were all increased obviously in the model group (<0.01) and they were all reduced in the EA group as compared with the model group successively (<0.05). CONCLUSION Electroacupuncture remarkably improves the condition in the neurological function injury and reduces apoptosis degree in TBI model rats, which is likely related to the down-regulation of the protein expressions of Cyt-C and Caspase-9 in damaged brain tissue and further to bring the impacts on mitochondria mediated apoptosis process.
Animals ; Apoptosis ; Brain Injuries, Traumatic ; therapy ; Caspase 9 ; metabolism ; Cytochromes c ; metabolism ; Electroacupuncture ; Random Allocation ; Rats ; Rats, Sprague-Dawley

BACKGROUND: Currently, there are no drugs that have been proven to be effective against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Because of its broad antiviral activity, interferon (IFN) should be evaluated as a potential therapeutic agent for treatment of coronavirus disease 2019 (COVID-19), especially while COVID-19-specific therapies are still under development. METHODS: Confirmed COVID-19 patients hospitalized in the First Affiliated Hospital, School of Medicine, Zhejiang University in Hangzhou, China, from January 19 to February 19, 2020 were enrolled in a retrospective study. The patients were separated into an IFN group and a control group according to whether they received initial IFN-α2b inhalation treatment after admission. Propensity-score matching was used to balance the confounding factors. RESULTS: A total of 104 confirmed COVID-19 patients, 68 in the IFN group and 36 in the control group, were enrolled. Less hypertension (27.9% vs. 55.6%, P=0.006), dyspnea (8.8% vs. 25.0%, P=0.025), or diarrhea (4.4% vs. 19.4%, P=0.030) was observed in the IFN group. Lower levels of albumin and C-reactive protein and higher level of sodium were observed in the IFN group. Glucocorticoid dosage was lower in the IFN group (median, 40 vs. 80 mg/d, P=0.025). Compared to the control group, fewer patients in the IFN group were ventilated (13.2% vs. 33.3%, P=0.015) and admitted to intensive care unit (ICU) (16.2% vs. 44.4%, P=0.002). There were also fewer critical patients in the IFN group (7.4% vs. 25.0%, P=0.017) upon admission. Although complications during admission process were comparable between groups, the discharge rate (85.3% vs. 66.7%, P=0.027) was higher and the hospitalization time (16 vs. 21 d, P=0.015) was shorter in the IFN group. When other confounding factors were not considered, virus shedding time (10 vs. 13 d, P=0.014) was also shorter in the IFN group. However, when the influence of other factors was eliminated using propensity score matching, virus shedding time was not significantly shorter than that of the control group (12 vs. 15 d, P=0.206). CONCLUSIONS IFN-α2b spray inhalation did not shorten virus shedding time of SARS-CoV-2 in hospitalized patients.
Albumins/analysis* ; Antiviral Agents/administration & dosage* ; Betacoronavirus ; C-Reactive Protein/analysis* ; COVID-19 ; Case-Control Studies ; China ; Coronavirus Infections/drug therapy* ; Glucocorticoids/pharmacology* ; Hospitalization ; Humans ; Interferon alpha-2/administration & dosage* ; Nasal Sprays ; Pandemics ; Pneumonia, Viral/drug therapy* ; Propensity Score ; Retrospective Studies ; SARS-CoV-2 ; Sodium/blood* ; Virus Shedding/drug effects* ; COVID-19 Drug Treatment

OBJECTIVETo study the association of human epidermal growth factor receptor family molecules expression in gastric cancer tissues with the prognosis of patients with gastric cancer.

METHODSClinical data of 161 patients with gastric cancer undergoing gastrectomy in Jiangsu Cancer Hospital between January 2006 and January 2007 were analyzed retrospectively. The expression of HER1, HER2, HER3 and HER4 was detected by immunohistochemistry. Association of the expression of HER family with the prognosis of patients was examined. Kaplan-Meier method was used to analyze the survival.

RESULTSHigh expression rates of HER1, HER2, HER3 and HER4 were 46.0% (74/161), 10.6% (17/161),55.9% (90/161) and 68.3% (110/161) respectively. Univariate analysis revealed that high expression of HER3 was associated with tumor invasion depth, lymph node metastasis, stage, neurovascular invasion, and overall 4-year survival. High expression of HER4 was associated with tumor distant metastasis and stage. High co-expression of HER2 and HER3 was associated with overall 4-year survival (P=0.023). Multivariate analysis revealed that high expression of HER3 and stage were prognostic independent factors.

CONCLUSIONUp-regulated expression of HER3 is associated with the poor prognosis in gastric cancer patients.

Adult ; Aged ; Aged, 80 and over ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; Middle Aged ; Prognosis ; Receptor, Epidermal Growth Factor ; metabolism ; Receptor, ErbB-2 ; metabolism ; Receptor, ErbB-3 ; metabolism ; Receptor, ErbB-4 ; Retrospective Studies ; Stomach Neoplasms ; metabolism ; pathology

BACKGROUNDPomegranate (punica granatum) belongs to the family Punicaceae, and its peel has been used as a traditional Chinese medicine because of its efficacy in restraining intestine, promoting hemostasis, and killing parasites. Pomegranate peel has been reported to possess wound-healing properties which are mainly attributed to its polyphenol extracts. The purpose of this study was to investigate the effect of pomegranate peel polyphenols (PPP) gel on cutaneous wound healing in diabetic rats.

METHODSAlloxan-induced diabetic rats were given incisional wounds on each side of the mid-back and then treated daily with PPP gel (polyphenol mass fraction = 30%) post-wounding. Rats were sacrificed on days 4, 7, 14, and 21 post-wounding to assess the rates of wound closure, histological characteristics; and to detect the contents of hydroxyproline, production of nitric oxide (NO), and activities of NO synthase (NOS), as well as the expressions of transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) in wound tissue.

RESULTSWound closure was significantly shortened when PPP gel was applied to the wounds of diabetic rats. Histological examination showed the ability of PPP gel to increase fibroblast infiltration, collagen regeneration, vascularization, and epithelialization in the wound area of diabetic rats. In addition, PPP gel-treated diabetic rats showed increased contents of hydroxyproline, production of NO, and activities of NOS and increased expressions of TGF-β1, VEGF, and EGF in wound tissues.

CONCLUSIONPPP gel may be a beneficial method for treating wound disorders associated with diabetes.

Alloxan ; Animals ; Diabetes Mellitus, Experimental ; pathology ; physiopathology ; Female ; Gels ; Hydroxyproline ; analysis ; Male ; Nitric Oxide ; biosynthesis ; Polyphenols ; pharmacology ; Punicaceae ; Rats ; Rats, Wistar ; Transforming Growth Factor beta1 ; physiology ; Vascular Endothelial Growth Factor A ; physiology ; Wound Healing ; drug effects

Objective To investigate 12 general hospitals operating room infection management of in Harbin city,analyze current hospital operating room infection control factors,and to improve the operating room health care quality,increase patient safety and security.Methods Harbin Heading nurses in the operating room of six three and six two general hospitals were selected as the object of study ; using questionnaires to explore the operating room risk factors for infection.Results Overall operation number in six two general hospital was 3 211 in one year,and 163 operations occurred hospital infection,19 operations occurred operation room infection; overall operation number in six three hospital was 7 592 one year,hospital and operation room infection number were 1339 and 11,respectively.Factors influencing operation infection were as following:hand hygiene of the staff,sterilization and isolation of equipment,environment of operation room,and layout and workflow.Conclusions Operating room infection control management should be strengthened in hand hygiene,disinfection and sterilization isolation,environment,layout and work flow,which can effectively reduce the incidence of infection in the operating room number.

OBJECTIVEDuring 2003-2005, an outbreak of meningitis due to Neisseria meningitidis serogroup C occurred in China. With the aim to find strain clues result in the final epidemics, the ancestral strain 053442, a clinical isolate, and a carrier strain 053426 with different gene type were analyzed.

METHODSClinical strain 053442 and carrier strain 053426 were cultured on GC agar plates under the same condition. Two-dimensional electrophoresis was performed using the pH 3-10 nonlinear IPG strips of 24 cm length, and all the protein spots were identified by matrix-assisted laser desorption/ionization time of flight spectrometry.

RESULTS502 and 380 protein spots were identified in 053426 and 053442 respectively, relating to 266 and 202 different genes covering a wide range of cellular functions. The express volume and number of proteins involved in energy metabolism, protein synthesis and amino acid biosynthesis in 053426 were higher than in 053442. Virulence factor Opa, Opc and a series of proteins involved in pilus assembly and retraction were identified in 053442, which appear to be of primary importance in colonization and invasion of human cells. Compared to 053442, virulence protein species were less in 053426, with lower express volumes too. No Opa and Opc were detected in 053426.

CONCLUSIONSThe different protein expression profiles of the clinical strain 053442 and carrier strain 053426 in the present study provide some clues of the different pathogenicity of the two strains, which may account for result in the final epidemics.

Bacterial Proteins ; analysis ; Bacterial Typing Techniques ; China ; epidemiology ; Disease Outbreaks ; Electrophoresis, Gel, Two-Dimensional ; Humans ; Meningitis, Meningococcal ; cerebrospinal fluid ; epidemiology ; microbiology ; Neisseria meningitidis, Serogroup C ; classification ; isolation & purification ; Proteome ; analysis ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization

Objective To understand human rhinovirus (HRV) etiology of acute lower respiratory tract infection (ALRTI) in children in Shanghai area and establish a nested reverse transcription- polymerase chain reaction (nested RT-PCR) assay.Methods Three hundred and forty-two naso- pharyngeal secretion (NPS) samples from ALRTI cases who were hospitalized were collected during January 2005—December 2005.Nested RT-PCR techniques were used to detect HRV-specific RNA.The PCR products were sequenced and data of nucleotides were analyzed.The proportion of HRV infection in children with ALRTI,the distribution of gender,age and season,and clinical char- acteristics were also investigated.Results Forty-six (13.5%) of 342 samples were HRV positive detected by nested RT-PCR.The sequences of 15 positive samples shared high homology of 83%- 97% with HRV sequence in GenBank.Within the 15 positive samples,nucleotide homology varied from 64.4% to 98.4%,and the ratio of genetic variation was from 1.6% to 48.3%./00.These 15 ampli- cons attribute to the two branches of HRV cladogram.The sequences of 15 amplieons were highly varied,in which single nucleotide mutation and several nearby nueleotides mutations were found. Ribonucleotide deletion and insertion in the nucleotide sequence was also found.HRV positive sam- ples were detected in 33 boys and 13 girls,respectively.The ratio of infection cases between boys and girls was 2.5:1.Of 46 HRV infected cases,27 (58.7%) were less than 12 months of age and 38 (82.6%) were less than 3 years old.HRV infected ALRTI occured all the year round and peaked from March to May.Of the patients whose NPS samples were HRV positive detected by nested RT-PCR,45 patients were diagnosed with bronchopneumonia and 1 was diagnosed with asthmatic bronchitis.Fever of most patients was moderate.The peripheral blood leukocyte counts in thirty-nine (84.8%) patients were less than 10?10~9/L.Neutrophil percentages in thirty-seven (80.4%) patients were less than 0.50.C-reactive protein of thirty-six (78.3%) patients were less than 8 mg/L. All of these features were the characteristics of viral pneumonia.The complications were not common and conditions of most patients were not severe.All the children were cured.Conclusions This nes- ted RT-PCR technique is highly specific,rapid and convenient for the detection of HRV RNA in NPS of patients with ALRTI and the genome of HRV viruses is highly variable.The incidence of HRV infection predominates in children in Shanghai area.ALRTI of HRV is short of specificity and condi- tions of most patients are not severe and their prognoses are fine.

BACKGROUNDThe influences of genomic background are confirmed in more diseases. Immunologic tolerance after intrauterine infection of hepatitis B virus is considered to occur in T cells. Cytokines work effectively in eliminating virus by immune system after hepatitis B virus infection. To explore the relationship between cytokines (tumor necrosis factor-alpha, interferon-gamma, interleukin-4 and interleukin-10), which expressed abnormal quantity in the peripheral blood to intrauterine hepatitis B virus infectious children, gene single nucleotide polymorphism (SNP) and susceptibility to hepatitis B virus intrauterine infection.

METHODSThis is a cross sectional study of molecular clinical epidemiology. The subjects in this study were selected from outpatients of hepatitis B vaccine follow-up special clinics of our hospital in the period. According to intrant criteria, the high risk children of hepatitis B virus (HBV) intrauterine infection were divided into immune failure group (group I); and immune effective group (group II) and non high risk children belonged to the control group. Four gene SNP sites of TNF-alpha -238, IFN-gamma +874, IL-4 -590 and IL-10 -1082 were determined by real-time quantitative fluorescent polymerase chain reaction (PCR).

RESULTSThe significant differences of TNF-alpha -238 A allele frequency were found between group I and group II (chi(2) = 6.797, P < 0.05) and between group I and the control group (chi(2) = 9.513, P < 0.05). No evident differences of TNF-alpha -238 A were found between group II and control group (chi(2) = 0.047, P > 0.05); the significant differences of IFN-gamma +874 A allele frequency were found between group I and group II (chi(2) = 7.238, P < 0.05), and between group I and the control group (chi(2) = 5.199, P < 0.05). No evident differences were found between group II and the control group (chi(2) = 0.602, P > 0.05); the significant differences of IL-4 -590 C/T allele frequency were not found between group I and group II (chi(2) = 0.632, P > 0.05), also group I and the control group (chi(2) = 0.584, P > 0.05), and the group II and the control group (chi(2) = 0.004, P > 0.05) respectively; The significant differences of IL-10 -1082 G allele frequency were found between group II and group I (chi(2) = 10.359, P < 0.001), and between group II and the controls (chi(2) = 35.418, P < 0.001), but the significant differences were not found between group I and the control group (chi(2) = 1.759, P > 0.05).

CONCLUSIONSThis study suggested the possibility that the TNF-alpha -238 A allele and IFN-gamma +874 A allele were associated with HBV intrauterine infection. There was no evident relationship between IL-4 -590 C/T allele SNP and susceptibility to HBV intrauterine infection, but the IL-10 -1082 G allele was associated with preventive efficacy to HBV intrauterine infection.

Cross-Sectional Studies ; Cytokines ; genetics ; Female ; Genetic Predisposition to Disease ; Genotype ; Hepatitis B ; genetics ; transmission ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical ; Interferon-gamma ; genetics ; Interleukin-10 ; genetics ; Interleukin-4 ; genetics ; Male ; Pregnancy ; Tumor Necrosis Factor-alpha ; genetics