Prediction of potential suitable habitats of Haemphysalis concinna in Heilongjiang Province based on the maximum entropy model / 中国血吸虫病防治杂志

Objective To predict the potential suitable habitat of Haemaphysalis concinna in Heilongjiang Province under different climatic scenarios. Methods The geographic locations of ticks in Heilongjiang Province from 1980 to 2022 were captured from literature review and field ticks monitoring data from Harbin Center for Disease Control and Prevention in Heilongjiang Province, and the tick distribution sites with spatial correlations were removed using the software ArcGIS 10.2. The environment data under historical climatic scenarios from 1970 to 2000 and the climatic shared socioeconomic pathways (SSP) 126 scenario model from 2021 to 2040 and from 2041 to 2060 were downloaded from the WorldClim website, and the elevation (1 km, 2010), population (1 km grid population dataset of China, 2010) and annual vegetation index (1 km, 2010) data were downloaded from the Resource and Environmental Science and Data Center, Institute of Geographical Sciences and Natural Resources, Chinese Academy of Sciences. The contribution of environmental factors to H. concinna distribution was evaluated and environmental variables were screened using the software MaxEnt 3.4.1 and R package 4.1.0, and the areas of suitable habitats of H. concinna and changes in center of gravity were analyzed using the maximum entropy model in Heilongjiang Province under different climatic scenarios. In addition, the accuracy of the maximum entropy model for prediction of H. concinna distribution was assessed using the area under curve (AUC) of the receiver operating characteristic curve. Results A total of 79 H. concinna distribution sites and 24 environmental variables were collected, and 70 H. concinna distribution sites and 9 environmental factors that contributed to distribution of the potential suitable habitats of H. concinna in Heilongjiang Province were screened. The three most significant contributing factors included precipitation seasonality, annual precipitation, and mean temperature of the driest quarter, with cumulative contributions of 60.7%. The total area of suitable habitats of H. concinna was 29.05 × 104 km2 in Heilongjiang Province under historical climatic scenarios, with the center of gravity of suitable habitats located at (47.31° N, 129.16° E), while the total area of suitable habitats of H. concinna reduced by 0.97 × 104 km2 in Heilongjiang Province under the climatic SSP126 scenario from 2041 to 2060, with the center of gravity shifting to (47.70° N, 129.28° E). Conclusions The distribution of suitable habitats of H. concinna strongly correlates with temperature and humidity in Heilongjiang Province. The total area of potential suitable habitats of H. concinna may appear a tendency towards a decline with climatic changes in Heilongjiang Province, and high-, medium- and low-suitable habitats may shift.

Study on the correlation of integr in associated protein and disease activity and bone destruction in patients with rheumatoid arthritis / 中华风湿病学杂志

Objective:To analyze the serum levels of integrin-associated proteins (CD47) in patients with rheumatoid arthritis (RA), and to explore its association with disease activity and bone destruction in RA.Methods:Serum and clinical data were collected from 65 RA patients and 25 healthy subjects. RA patients were grouped into low, moderate, and high bone erosion groups according to 7-joint ultrasonography score (US7). The levels of serum CD47, thrombospondin-1 (TSP-1) and receptor activator of nuclear factor-κB ligand (RANKL) were measured by enzyme-linked immunosorbnent assay (ELISA) in patients with RA and healthy subjects. The statistical analysis was carried out with independent t-test, analysis of variance, nonparametric rank sum test, pearson or Spearman correlation and logistic regression. Results:① The Serum levels of CD47, TSP-1, and RANKL were higher in the RA group than in the healthy controls ( P<0.01). ② In RA patients, serum CD47 level was positively correlated with disease course ( r=0.301, P<0.05), C-reactionprotein (CRP)( r=0.316, P<0.05), number of tender joints (TJC) ( r=0.254, P<0.05), number of swollen joints (SJC) ( r=0.316, P<0.05), disease activity score in 28 joints (DAS28) ( r=0.255, P<0.05), RANKL ( r=0.252, P<0.05) and TSP-1 ( r=0.260, P<0.05). Serum TSP-1 level was positively correlated with CRP ( r=0.299, P<0.05), TJC ( r=0.335, P<0.01), DAS28 ( r=0.315, P<0.05), RANKL ( r=0.305, P<0.05). ③ The disease course [ OR(95% CI)=1.048(1.033, 1.017)] and TSP-1 [ OR(95% CI)=1.013(1.000, 1.026)] were independently relevant factors affecting bone destruction. Conclusion:CD47 levels is significantly higher in RA patients than in healthy controls, and is associated with disease activity and bone destruction. CD47 may be involved in the bone destruction process of RA by acting on TSP-1.

Relationship between recovery of urinary continence after laparoscopic radical prostatectomy and preoperative/postoperative membranous urethral length / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the relationship between recovery of urinary continence after laparoscopic radical prostatectomy (LRP) and preoperative/postoperative membranous urethral length (MUL) on magnetic resonance imaging.@*METHODS@#We retrospectively analyzed 69 patients with pathologic confirmed prostate carcinoma who underwent laparoscopic radical prostatectomy. Preoperative MUL was defined as the distance from the apex of prostate to the level of the urethra at penile bulb on the coronal image. Postoperative MUL was defined as the distance from the bladder neck to the level of the urethra at the penile bulb on the coronal image. MUL-retained rate was defined as the percentage of postoperative MUL to preoperative MUL. All patients received extraperitoneal LRP. Patients reported freedom from using safety pad (0 pad/d) were defined as urinary continence. Multivariate Logistic regression analyses were used to identify independent predictors of early continence recovery after LRP. Kaplan-Meier analyses and log-rank test were used to compare time to continence recovery between the groups.@*RESULTS@#For all the 69 patients, the average age was (71.4±8.6) years. The prostate specific antigen before biopsy was (23.40±30.31) μg/L, and the mean preoperative prostatic volume by magnetic resonance imaging was (39.48±22.73) mL. The mean preoperative MUL was (13.0±3.3) mm, the mean postoperative MUL was (12.3±3.4) mm, and the mean MUL-retained rate was 93.9%±6.2%. The continence rate for all the patients after LRP was 57.9% and 97.1% in three months and one year, respectively. The patients achieving early continence recovery had significant smaller prostatic volume (P=0.028), longer preoperative MUL and postoperative MUL (P < 0.001). Multivariate Logistic regression analyses revealed postoperative MUL (P < 0.001) were predictors of continence recovery after LRP. Kaplan-Meier analyses and Log-rank test revealed that preoperative MUL (≥14 mm vs. < 14 mm, P < 0.001) and postoperative MUL (≥13 mm vs. < 13 mm, P < 0.001), MUL-retained rate (< 94% vs. ≥94%, P < 0.001) were all significantly associated with continence recovery.@*CONCLUSION@#Post-operative MUL was independently predictors of early continence recovery after LRP. Preoperative MUL, postoperative MUL and MUL retained rate were significantly associated with recovery of urinary continence.

CAS9 is a genome mutator by directly disrupting DNA-PK dependent DNA repair pathway

With its high efficiency for site-specific genome editing and easy manipulation, the clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR associated protein 9 (CAS9) system has become the most widely used gene editing technology in biomedical research. In addition, significant progress has been made for the clinical development of CRISPR/CAS9 based gene therapies of human diseases, several of which are entering clinical trials. Here we report that CAS9 protein can function as a genome mutator independent of any exogenous guide RNA (gRNA) in human cells, promoting genomic DNA double-stranded break (DSB) damage and genomic instability. CAS9 interacts with the KU86 subunit of the DNA-dependent protein kinase (DNA-PK) complex and disrupts the interaction between KU86 and its kinase subunit, leading to defective DNA-PK-dependent repair of DNA DSB damage via non-homologous end-joining (NHEJ) pathway. XCAS9 is a CAS9 variant with potentially higher fidelity and broader compatibility, and dCAS9 is a CAS9 variant without nuclease activity. We show that XCAS9 and dCAS9 also interact with KU86 and disrupt DNA DSB repair. Considering the critical roles of DNA-PK in maintaining genomic stability and the pleiotropic impact of DNA DSB damage responses on cellular proliferation and survival, our findings caution the interpretation of data involving CRISPR/CAS9-based gene editing and raise serious safety concerns of CRISPR/CAS9 system in clinical application.

CAS9 is a genome mutator by directly disrupting DNA-PK dependent DNA repair pathway

With its high efficiency for site-specific genome editing and easy manipulation, the clustered regularly interspaced short palindromic repeats (CRISPR)/ CRISPR associated protein 9 (CAS9) system has become the most widely used gene editing technology in biomedical research. In addition, significant progress has been made for the clinical development of CRISPR/CAS9 based gene therapies of human diseases, several of which are entering clinical trials. Here we report that CAS9 protein can function as a genome mutator independent of any exogenous guide RNA (gRNA) in human cells, promoting genomic DNA double-stranded break (DSB) damage and genomic instability. CAS9 interacts with the KU86 subunit of the DNA-dependent protein kinase (DNA-PK) complex and disrupts the interaction between KU86 and its kinase subunit, leading to defective DNA-PK-dependent repair of DNA DSB damage via non-homologous end-joining (NHEJ) pathway. XCAS9 is a CAS9 variant with potentially higher fidelity and broader compatibility, and dCAS9 is a CAS9 variant without nuclease activity. We show that XCAS9 and dCAS9 also interact with KU86 and disrupt DNA DSB repair. Considering the critical roles of DNA-PK in maintaining genomic stability and the pleiotropic impact of DNA DSB damage responses on cellular proliferation and survival, our findings caution the interpretation of data involving CRISPR/CAS9-based gene editing and raise serious safety concerns of CRISPR/CAS9 system in clinical application.

The computer-aided design and manufacturing of individualized miniscrew surgical guides based on a high-precision three-dimensional integrated digital maxillodental model / 中国组织工程研究

BACKGROUND: Surgical guides designed based on a three-dimensional cone-beam CT (CBCT) model have been reported. However, CBCT cannot remodel fine soft tissue such as gums, and it can only be used to design a simple dental retainer with relatively poor stability. OBJECTIVE: To establish a high-precision three-dimensional (3D) integrated maxillodental model by matching CBCT model with 3D digital maxillodental model using 3D automatic registration method, based on which, we designed and manufactured individualized miniscrew surgical guides. METHODS: CBCT maxillodental models and laser-scanned dentition models obtained from six malocclusion cases were matched and overlapped using the 3D automatic registration method to fabricate the 3D integrated maxillodental model. Then, we accurately positioned and virtually implanted a micro-implant into the 3D integrated maxillodental model. Subsequently we prepared a high-precision individualized resin surgical guide by rapid prototyping technology. The inner diameter of the guide track was detected by a vernier caliper. Patients tried on the resin surgical guide, and then occlusion condition, guide seating and retention were detected. RESULTS AND CONCLUSION: Due to the high-precision registration of the model, all the resin surgical guide plates were suitable. The plate retention was enhanced after tooth clinching, and all the patients felt comfort when wearing the surgical guide plate, with no compression or other discomforts. The inner diameter of the guide track was (1.79±0.23) mm, and the measurement error was not statistically significant (P >0.05). These findings demonstrate that the high-precision surgical guide plate based on the high-precision 3D integrated model can provide the foundation for further investigations on the clinical application of surgical guides.

Effect of CD3+, CD4+, CD8+ T lymphocytes and CD19+ B lymphocytes on the pathogenesis of acute respiratory distress syndrome / 中华急诊医学杂志

Objective To investigate the roles of CD3+,CD4+,CD8+T lymphocytes and CD19+B lymphocytes on the pathogenesis of acute respiratory distress syndrome(ARDS).Methods According to Berlin definition Of ARDS in 2012,34 patients with ARDS admitted in the Department of ICU of Central Hospital of Baoji from January,2016 to January,2017 were enrolled in this study as study group(ARDS group).At the same time,22 healthy subjects were recruited as control group.Clinical data of ARDS patients were collected,and the survivors were followed up.The ARDS patients were divided into moderate group(n=20) and severe group (n=14) according to clinical settings on the first day after diagnosis of ARDS and Berlin Definition of ARDS in 2012,and at the same time they were also dividedinto two groups according to the outcome followed up for 28 days:non-survival group(n=14) and survival group(n =20).Sample of 3 mL peripheral venous blood of ARDS patients was collected on an empty stomach in the early morning on the first day after diagnosis of ARDS and the blood samples of healthy subjects were also collected on the first day to measure the level of CD3+,CD4+,CD8+T cells and CD19+ B cell in peripheral venous blood by flow cytometry.Comparison of CD3+,CD4+,CD8+ T cells and CD 19+ B cell numbers were carried out between ARDS group and control group on the first day after diagnosis of ARDS,and between moderate group and severe group as well as between survival group and nonsurvival group.The risk factors associated with ARDS were analyzed using logistic regression analysis.Results On the first day after diagnosis of ARDS,there were significant differences in serum Lac and pre-albumin between survival group and non-survival group(P＜0.05).The numbers of CD3+,CD4+T cells and CD19+B cell of peripheral venous serum in ARDS group were significantly lower than those in control group(P＜0.05),while there was no significant difference in CD8+ T cell number between ARDS group and control group (P＞0.05).There were statistically significant differences in numbers of CD3+,CD4+,CD8+T cells and CD19+B cell between moderate group and severe group and as well as between survival group and non-survival group(P＜0.05).Logistic regression analysis showed that CD19+B cell (OR=0.614,95％CI:0.416-0.907,P=0.014) level on the first day after diagnosis of ARDS was related with the risk of prognosis of ARDS.The ROC of CD19+B cell had area under curve(AUC) of 0.907,and the cut-off value of CD19+B cell in the survival followed up for 28 day's was 12.59％.Conclusions CD3+,CD4+,CD8+T cells and CD19+B cell level of peripheral venous serum in ARDS patients can be helpful for the assess of ARDS severity of patients in the early stage,and for prognosis judgment,especially CD 19+B cell is more remarkable.

Generation of a new strain of NOD/SCID/IL2Rγ mice with targeted disruption of Prkdc and IL2Rγ genes using CRISPR/Cas9 system / 南方医科大学学报

<p><b>OBJECTIVE</b>The NOD/SCID/IL2Rγ (NSG) mouse strain is the most widely used immunodeficient strain for xenograft transplantation. However, the existing SCID mutation is a spontaneous mutation of the Prkdc gene, which leads to leaky T cell developmental block and difficulty in genotyping. It is therefore important to develop a new strain of NSG mice with targeted disruption of Prkdc and IL2Rγ genes.</p><p><b>METHODS</b>Targeted disruption of Prkdc and IL2Rγ genes was achieved using the CRISPR/Cas9 system. By intercrossing the knockout and NOD mice, we obtained a novel strain of NOD/SCID/IL2Rγ(NSG) mice, denoted as cNSG (Chinese NSG) mice.</p><p><b>RESULTS</b>In addition to the NOD mutation, cNSG mice exhibited a complete absence of T cells, B cells and NK cells. cNSG mice allowed more efficient engraftment of human cancer cells than the commonly used immunodeficient nude mice.</p><p><b>CONCLUSION</b>cNSG mice will provide an important xenotransplantation model for biomedical research.</p>

Application value of magnetic resonance diffusion weighted imaging technology in identification of rabbit pancreatic tumor model / 重庆医学

Objective To explore the application value of magnetic resonance molecular functional imaging diffusion weighted imaging(DWI) in the identification of pancreatic carcinoma and mass-type pancreatitis of animal model.Methods Each 8 cases of laboratory pancreatic head transplantation tumor model,chronic mass-type pancreatitis model and normal rabbits were selected and performed the MR DWI molecular functional imaging,the b values were 333,667,1 000 s/mm2 respectively.The apparent diffusion coefficients(ADC) of pancreatic carcinoma model,mass-type pancreatitis model and normal pancreas under different b values were observed.Then the change situation of ADC values of pancreatic carcinoma model,mass-type pancreatitis model and normal pancreas under different b values and difference of ADC(DADC) was analyzed.Moreover the differences in molecular diffusion,tissue perfusion among various groups were observed.Results Throughout the study period,the mortality rate of pancreatic head transplantation tumor model was 50%;the mass-type pancreatitis model and 8 normal rabbits were normally survival.The ADC value of pancreatic carcinoma under the same b value was significantly lower than that of chronic inflammation and normal pancreas area.The ADC value in each group was decreased with the increase of b value,and there was significant difference in ADC value when the b value was 333 s/mm2(F=6.662,P=0.014),in the pairwise comparison among groups,the difference between pancreatic cancer and pancreatitis (t=6.773,P=0.003) and between pancreatic cancer and normal pancreas(t=5.883,P=0.016) had statistical significance (P<0.05).The b value was increased,DADC was smaller,the difference change of DADC between pancreatic cancer area and chronic pancreatitis mass area,between pancreatic cancer area and normal pancreatic head area had statistical significance (P<0.05).Conclusion Rationally selecting the molecular functional imaging DWI technology of b value can better distinguish pancreatic cancer from mass-type pancreatitis,which may be promoted and applied in the evaluation of animal pancreatic head cancer model.

VX-2 tissue orthotopic implantation versus panc-1 cell suspension orthotopic implantation in establishing a rabbit model of pancreatic cancer / 医学研究生学报

Objective Few reports are seen on the methods of establishing the rabbit model of pancreatic cancer .This study was to compare the effect of Panc-1 cell suspension orthotopic implantation with that of VX-2 tissue orthotopic implantation in construc-ting the rabbit model of pancreatic cancer . Methods Using the random number table method , we divided 30 healthy rabbits into a tissue suspension group ( n=15) and a cell suspension group ( n=15) , VX-2 tissue suspension employed for in-situ implanting in the former group and panc-1 cell suspension utilized in the latter .Then we evaluated the two modeling methods by B-ultrasonography , 3.0T MRI, and CT. Results In the third week after modeling , transpla-ntive metastasis of lots of tumor tissues was observed in the duode-num, colon, appendix, and peritoneal wall in 5 rabbits of the tissue suspension group , but only in the greater omentum of 3 rabbits in the cell suspension group , with high signals of MR T 2 in the posterior gastric body .One case of duodenal metastasis was seen in the cell suspension group , with slightly high signals of MR LAVA in the posterior gastric body .The model of pancreatic cancer was successfully established in all the 15 rabbits of the tissue suspension group , but only in 3 of the cell suspension group .The success rate of tumor im-planting at 3 and 4 weeks was significantly higher in the former ( 46.66%and 100%) than in the latter group ( 6.67%and 20.00%) (P<0.05). Conclusion VX-2 tissue orthotopic implantation is a more feasible and convenient method than Panc -1 cell suspension orthotopic implantation for establishing the rabbit model of pancreatic cancer .

Quality of life and major dimensions of health status among the elderly in the central and western poor areas of China / 中华流行病学杂志

Objective To analyze the quality of life and the main dimensions of health status among the elderly living in the central and westem poor areas of China.Methods Cluster sampling was used and 1145 elderly aged above 60 were sampled from 4 provinces in western areas of China.Economic status,performance of health,self reported situation and satisfaction on health were investigated.We conducted comparative dimensions of health analysis across age and gender.Results Among the elderly,58.6％ of them had monthly income less than 250 Yuan RMB and 14.1％ of them with monthly income between 250-400 Yuan RMB.As for the sources of income,50.1％ of the elderly relied on their children while 43.7％ of them supported themselves.Among the elderly aged 60-,70-and 80-,68.54％,54.63％ and 38.46％ of them had no difficulty in mobility while 75.73％,68.52％ and 53.85％ had no difficulty taking care of themselves,67.98％,56.02％ and 35.90％ of them had no difficulty in managing daily activities,55.51％,51.39％ and 38.46％ of them had no pain or discomfort and 69.66％,59.26％,51.28％ of them did not show any signs on anxiety or depression.Men aged over 80 had better status than women,however,there was no significant difference for the age groups 60-or 70-on the mobility and self-care between genders.37.98％,31.02％ and 28.21％ of the elderly in the age groups 60-,70-or 80-,self-reported to have had good health,with males more than females (P＜0.05).76.74％,75.00％ and 79.49％ of the 60-,70-or 80-elderly groups self-reported having satisfactory life style.The aged 60-elderly did not show significant gender difference on self-reported satisfaction with life but the male elderly aged 70 and above reported having more satisfied life than the females (P＜0.05).Factors as marriage status,gender,chronic disease,ability of mobility and daily activities played positive promotion roles on health status of the elderly.Conclusion Sources of income was limited among the elderly.The overall self-reported health status was poor but males were more likely to show positive results on self-assessment.Proportions of health-related quality of life indicators among elderly declined with age,and the performance of life function of the elderly women were inferior to men.Elderly living in the rural areas presented a higher proportion on ‘satisfaction of life'.