Objective:To investigate the association of polymorphisms at the matrix metalloproteinase(MMP)-3-1612 position of the promotor region with the inflammatory response and oxidative stress in elderly patients with cerebral ischemic stroke.Methods:In this retrospective study, 129 elderly patients with cerebral infarction diagnosed and treated in our hospital between March 2019 and March 2021 were enrolled as the study group, and 110 healthy subjects were selected as the control group.Polymorphisms of the MMP-3-1612 position in the promotor region, the inflammatory response and oxidative stress were examined using appropriate parameters and the associations between them were analyzed. Results:Compared with the control group, the proportions of patients with hypertension, diabetes, and smoking history in the study group were significantly higher( χ2=16.05, 17.19, 14.19, all P<0.05), and the levels of fasting blood glucose, low-density lipoprotein, and homocysteine were also significantly higher( t=6.22, 3.64, 2.69, all P<0.05).Meanwhile, compared with patients carrying the MMP-3-5A/6A or the MMP-3-6A/6A genotype, the levels of serum inflammatory markers such as high mobility group box-1 protein(HMGB1), fractalkine(FKN), tumor necrosis factor-α(TNF-α), interleukin-1β(IL-1β)and interleukin-17(IL-17)in patients carrying the MMP-3 gene 5A/5A genotype were significantly higher(all P<0.05).In addition, the expression of serum oxidative stress-related molecules Kelch-like ECH-associated protein 1(Keap1), nuclear factor erythroid-2 related factor2(Nrf2), antioxidant response element(ARE), quinone oxidoreductase 1(NQO1), and heme oxygenase-1(HO-1)was also significantly increased(all P<0.05), but there was no difference in these markers between patients carrying the MMP-3-5A/6A genotype and patients carrying the MMP-3-6A/6A genotype( P>0.05).Patients carrying the 5A/5A genotype and the 6A/6A genotype exhibited only one 97 bp band and one 120 bp band, respectively, while the patients carrying the 5A/6A genotype exhibited two 97 bp bands and two 120 bp bands.There was no statistical difference in the number of patients carrying the 5A/6A genotype in the cerebral infarction group compared with the control group( P>0.05), and the number of patients carrying the 5A/5A genotype in the cerebral infarction group was higher than that in the control group(69% or 53.49% vs.35% or 31.82%, χ2=11.34, P<0.05).Polymorphisms of the MMP-3 gene had a positive correlation with the risk of stroke( r=0.25, P<0.05). MMP-3-1612 gene polymorphism( OR=7.21, 95% CI: 1.13-1.83, P=0.01), elevated blood glucose( OR=1.27, 95% CI: 1.18-2.06, P<0.001), high homocysteine( OR=1.05, 95% CI: 1.08-1.58, P<0.01), hypertension( OR=5.414, 95% CI: 1.140-4.46, P<0.01), elevated low-density lipoprotein( OR=4.03, 95% CI: 1.03-2.35, P=0.02), coronary heart disease( OR=1.17, 95% CI: 1.47-3.19, P<0.01)and diabetes( OR=8.52, 95% CI: 1.32-4.71, P<0.01)were risk factors for cerebral infarction. Conclusions:In elderly patients with cerebral infarction, polymorphisms of the MMP-3-1612 position in the promotor region is closely related to the risk of cerebral ischemic stroke, the inflammatory response and oxidative stress.MMP-3 gene polymorphisms are risk factors for stroke.

Objective:To analyze the risk factors and human papillomavirus (HPV) genotypes distribution in patients with condyloma acuminatum (CA) in two regions of Shandong province.Methods:From August 2019 to December 2020, an anonymous questionnaire survey of CA patients was conducted in three hospitals in Jinan City and Jining City, Shandong Province, and samples were collected for HPV typing. Multivariate binary logistic regression was used to analyze the risk factors of CA recurrence. HPV typing was detected by PCR-reverse dot blot hybridization.Results:A total of 653 questionnaires were collected, and the valid questionnaires accounted for 98.77% (645/653). Recurrence of the disease occurred in 174 patients, with a recurrence rate of 26.98%. Univariate analysis showed that there were statistically significant differences in the distribution of CA recurrence among residence time at current address, sexual frequency, genitalia cleaning, and knowledge of preventing HPV infection ( P<0.05). Multivariate binary logistic regression showed that knowing how to prevent HPV infection was a significant factor that influences CA recurrence. A total of 428 patients underwent HPV typing, and the positive detection rate of HPV was 98.60% (422/428). The top three positive rates were HPV6 (57.58%), HPV11 (36.49%) and HPV16 (11.37%). The main type of infection was low-risk HPV, accounting for 51.42% (217/422). Conclusions:CA patients have the phenomenon of "separation of knowledge and action" , so it is necessary to strengthen health education and behavioral intervention, guide the population to correctly treat sexual behavior, and improve self-prevention awareness and risk awareness.

Objective:To investigate the clinical, genetic, and clonality related aspects of individuals with Richter transformation (RT) .Methods:From January 2019 to December 2021, 18 RT patients with diagnoses at the First Affiliated Hospital of Nanjing Medical University (Pukou CLL center) were retrospectively examined. The immunoglobin heavy variable (IGHV) gene usage and IGHV-D-J rearrangement pattern of diagnosed CLL/SLL and transformed diffuse large B-cell lymphoma (DLBCL) were compared to determine the clonality relatedness. To investigate the risk factors of RT, Clinical and laboratory data from patients with newly diagnosed CLL/SLL and transformed DLBCL were gathered.Results:The median age of RT was 56.5 (41-75) years old. 17 patients transformed to DLBCL and 1 transformed to Hodgkin lymphoma (HL) . Of 17 individuals who had DLBCL transformation, 15 had CLL/SLL-related clonality and 2 had unrelated clonality. Next-generation sequencing (NGS) analysis of 11 paired initially diagnosed treatment-naive CLL/SLL and RT DLBCL found that EGR2、TP53 and NOTCH1 were among the most frequently mutated genes both in treatment-naive CLL/SLL and in RT DLBCL. In several cases, specific mutations were gained or lost throughout RT, indicating clonal evolution. Among 10 patients before exposure to BTK inhibitors before RT, four patients acquired BTK mutation. The aforementioned mutations should be considered high-risk variables for transformation; in addition, TP53 and EGR2 mutations could be linked to a poor prognosis following RT in patients receiving a cocktail of new medicines.Conclusion:Most RT DLBCL patients in our center are clonality related (15/17, 88.2% ) and we recommend all qualified centers to evaluate clonality relatedness of RT DLBCL patients. There was some variability in the mutational landscape between DLBCL that had undergone a transformation and initially diagnosed, treatment-naive CLL/SLL. The underlying molecular mechanism of RT needs more research.

Objective:To explore the effects of cluster intervention guided by key points of control on cleaning quality of reused surgical instruments, and provide new clinical ideas for improving the cleaning quality of reused surgical instruments.Methods:The surgical instruments used and sent to the Central Sterile Supply Department (CSSD) at the First Affiliated Hospital of Zhengzhou University were selected. The 224 samples handled according to traditional device processing procedures (between January and May 2019) were included into the control group, while 224 samples handled with cluster intervention guided by key points of control (from June to October 2019) were included into the observation group. The cleaning quality of surgical instruments was compared between the two groups.Results:The cleaning qualification rate of reused surgical instruments was affected by multiple factors such as hospital level, management model, staffing, supervision and management, equipment, methods, and cleaning time. The cleaning qualification rate of the observation group was 98.21% (220/224) , which was higher than 91.52% (205/224) of the control group, and the difference was statistically significant ( P<0.05) . Conclusions:The cluster intervention strategy guided by key points of control can effectively improve the cleaning quality of reused surgical instruments.

Objective To investigate the effect of different forbidden drink schemes on anesthesia induction and postoperative nausea and vomiting during pediatric interventional heart surgery.Methods One hundred and twenty pediatric patients underwent cardiac interventional procedures under general anesthesia were randomized into group A,B and C,with 40 patients in each group.Patients in cach group were fasted for 8 h preoperatively.Water was prohibited for patients in group A for 6 h preoperatively.Patients in groups B and C orally took 10％ glucose solution and a multivitamin drink (Outfast) at 2 h preoperatively,respectively.Nausea and vomiting after anesthesia induction were recorded for 24 h postoperatively.Results The sedation and mask acceptance scores were significantly higher in group B and C than those in group A,and were significantly higher in group C than those in group B (P ＜ 0.05,resoectively).Following anesthesia induction,MAP was significantly higher in group B and C than that in group A (P ＜ 0.05,resoectively).Both the severity and incidence of postoperative nausea and vomiting were higher in group B and C than those in group A,and was lower in group C than that in group B (P ＜ 0.05,resoectively).Conclusions Taking clear water orally 2 hours before surgery can decrease the restlessness of pediatric interventional heart surgery during anesthesia induction period,with stable smooth hemodynamics,reducing the degree of PONV.

AIM: To investigate the effect of ligustrazine (Lig) on cerebral injury in LPS-induced septic shock rats and to explore the underlying mechanism.METHODS: Wistar rats (n =48) were randomly divided into control group, LPS group and LPS +Lig treatment group.The rats in LPS group were randomly divided into 2 subgroups at time points of 6 h and 12 h.After ligustrazine treatment, the venous blood was collected by removal of eyeballs to detect the con-centration of neuron-specific enolase (NSE) using ELISA.The nitric oxide (NO) concentration in the homogenate of brain tissues was examined.The apoptosis in the hippocampus was analyzed by TUNEL staining.The protein expression of Bax and Bcl-2 was determined by Western blot.RESULTS: Ligustrazine inhibited the elevation of NSE and NO concentrations in LPS-induced septic shock rats.Furthermore, ligustrazine administration also attenuated LPS-induced increase in Bax ex-pression and decrease in Bcl-2 expression.CONCLUSION: Ligustrazine decreases the concentration of NSE and NO, and attenuates cerebral injury in LPS-induced septic shock rats.These effects may be related to the regulation of Bax and Bcl-2 expression.

Aim To study the influence of Si-Wu De-coction (SWD ) and its active components on cyto-chrome P450 activity and mRNA expression in rats in order to provide an experimental basis for compatibility of SWD.Methods SWD and its active components were intragastrically administrated for seven days,the doses of SWD was 10 g · kg -1 · d -1 ,the doses of fructose,ferulic acid,ligustrazine,peoniflorin were 0.334,0.002,0.011 and 0.022 g·kg -1 ·d -1 ,re-spectively.After administration for seven days,rats were executed,and liver microsomes were prepared. The effects of SWD and its active components on cyto-chrome P450 in rats were investigated by hybrid probe and liver microsomes incubation method.The level of mRNA expression in liver was detected by real-time quantitative polymerase chain reaction using specific target primers for CYP450 genes.The level of protein expression of CYP2B1 was detected by Western blot. Results Compared with the control group,fructose significantly decreased the activity of CYP1A2, CYP2B6,CYP2C9,CYP2D6;ferulic acid significantly decreased the activity of CYP2C9,CYP2B6;ligus-trazine significantly decreased the activity of CYP1A2, CYP2C9,CYP2B6;peoniflorin significantly decreased the activity of CYP2D6,CYP2B6;fructose,ferulic acid,peoniflorin inhibited the mRNA expression of CYP2B1;fructose,ferulic acid,ligustrazine and peon-iflorin also inhibit the protein expression of CYP2B1. Conclusion Fructose,ferulic acid,peoniflorin inhib-it the activity of CYP2B1,decrease the expression lev-els of mRNA and protein of CYP2B1.

BACKGROUND:Endoplasmic reticulum stress participates in the occurrence and development of many diseases, such as atherosclerosis, diabetes, and Alzheimer’s disease. GRP78 is a marker of endoplasmic reticulum stress. The expression of GRP78 reflects the degree of endoplasmic reticulum stress.
OBJECTIVE:To investigate the effect of cyclic stretch on GRP78 expression of L6 rat myoblasts, and to identify the relationship between cyclic stretch and endoplasmic reticulum stress.
METHODS:In vitro culture-tensile stimulation models of myoblasts of L6 rats were established successful y. The expression of GRP78 of myoblasts exposed to cyclic stretch was determined by reverse transcription-PCR and western blot assay. Stretch groups were subjected to 15%surface elongation at a frequency of 10 cycles per minute, over a period of 1, 6, 12 and 24 hours. cells were simultaneously seeded on a plate in the control and experimental groups with no stimulation.
RESULTS AND CONCLUSION:The expression of GRP78 mRNA was continuously elevated over time after stretched treatment, and significant differences were detected as compared with the control group (P<0.05). GRP78 protein expression began to increase at 1 hour after stretched treatment, was significantly increased at 6 hours, peaked at 24 hours, and significant differences were visible as compared with the control group (P<0.05). In conclusion, cyclic stretch induced the occurrence of endoplasmic reticulum stress, which was enhanced with prolonged time. However, prolonged stretch caused severe endoplasmic reticulum stress and leaded to apoptosis of myoblasts.

Objective To investigate the mechanism of treatment of granulocyte colony-stimulating factor(rhG-CSF),recombinant human interleukin-11(rhIL-11)and recombinant human interleukin-2 (rhIL-2)on hematopoietic injuries induced by 4.5 Gy60 Coγ-ray irradiation in beagles,and to provide experimental evidence for the clinical treatment of extremely severe myeloid acute radiation sickness (ARS).Methods Sixteen beagle dogs were given 4.5 Gy60 Co γ-ray total body irradiation(TBI),then randomly assigned into irradiation control group,supportive care group or cytokines+supportive care (abbreviated as cytokines)group.In addition to supportive care,rhG-CSF,rhlL-11 and rhIL-2 were administered subcutaneously to treat dogs in cytokines group.The percentage of CD34+cells,cell cycle and apoptosis of nucleated cells in peripheral blood were examined by Flow cytometry.Results After 4.5 Gy 60 Co γ-ray irradiation,the CD34+cells in peripheral blood declined obviously(61.3%and 52.1% of baseline for irradiation control and supportive care group separately).The cell proportion of nucleated cells in Go/G1 phase was increased notably(99.27% and 99.49% respectively).The rate of apoptosis(26.93% and 21.29% separately)and necrosis(3.27% and 4.14%,respectively)of nucleated cells were elevated significantly when compared with values before irradiation(P<0.05) 1 d post irradiation.When beagles were treated with cytokines and supportive care,the CD34+cells in peripheral blood were markedly increased(135.6% of baseline).The effect of G0/G1 phase blockage of nucleated cells became more serious(99.71%).The rate of apoptosis(5.66%)and necrosis(1.60%)of nucleated cells were significantly lower than that of irradiation control and supportive care groups 1 d after exposure.Conclusions Cytokines maybe mobilize CD34+cells in bone marrow to peripheral blood,indce cell cycle block at G0/G1 phase and reduce apoptosis,and eventually cure hematopoieticinjuries induced by irradiation.

Objectivc To observe the therapeutic effects of combined cytokines on hematopoietic injuries induced by 4.5 Gy60 Co γ-rays irradiation in beagles,and to provide experimental evidences for the clinical treatment of extremely severe myeloid acute radiation sickness(ARS).Methods 16 beagles were given 4.5 Gy60 Co γ-rays total body irradiation,and then randomly assigned into irradiation control group,supportive care group and cytokines group.In addition to supportive care,recombinant human granulocyte colony-stimulating factor (rhG-CSF),recombinant human interleukin-11(rhIL-11)and recombinant human interleukin-2(rhIL-2)were administered subcutaneouly to dogs in cytokines group.Peripheral blood hemogram was examined once every two days.Bone marrow and peripheral blood were collected to proceed colony cultivation 4 d pre-irradiation and 1 and 45 d post-irradiation.Conventional histopathological sections of sternum were prepared to observe the histomorphology changes. Results After irradiation,the population of all kinds of cells in peripheral blood declined sharply.WBC nadir Was elevated(1.04×109/L,but 0.28×109/L and 0.68×109/L for the irradiation control group and the supportive care group separately),the duration of thrombocytopenia was shortened (24 days,but 33 days for the supportive care groug) and red blood cell counts were maintained in the range of normal values after cytokincs treatment in combination.The colony forming efficiency of haemopoietic stem cells(HSCs)in bone marrow and peripheral blood decreased obviously 1 d post irradiation,but recovered to the level of that before irradiation 45 d post irradiation after supportive care and cytokines treatment.Hematopoietic cells disappeared in bone marrow of animals in irradiation control group,but hematopoietic functions were recovered after cytokines were administrated.Conclusions RhG-CSF.rhIL-11 and rhIL-2 used in combination could elevate WBC nadir,accelerate the recovery of leukocytes,platelets and red blood cells and promote the proliferation,differentiation and maturity of HSPCs left in the body after 4.5 Gy γ-rays total body irradiation,eventually restore the hematopoietic function.Hence,combination of rhG-CSF,rhIL-11 and rhIL-2 could serve as better therapeutic strategy to treat extremely severe myeloid ARS.