Objective Explore differences in the cognitive abilities of socially different Labradors.Methods The dog mentality assessment(DMA)test created by the Swedish Working Dog Association was modified to employ 12 behavioral variables from five subtests of the DMA test,social contact,play Ⅰ,distance-play,ghosts and play Ⅱ,to assess sociability of the dogs.In accordance with the scoring criteria,49 labradors provided by the China Guide Dog Training Centre in Dalian were scored on the social behavioral variables and classified into high(n=15)and low(n=34)sociability groups by cluster analysis.A new system to test canine cognitive ability was developed using the dog cognitive development battery,which tests various domains of cognitive ability such as social cue use,unsolvable task,inhibitory control,cognitive flexibility,working memory,and multistep problem solving task.The dogs'behavioral performance and duration of the test were also recorded.Statistical analysis was performed to determine assess differences in the cognitive abilities of socially diverse dogs.Results Dogs in the high and low social subgroups differed significantly in behavioral variables of the unsolvable task,inhibitory control test,and multistep problem solving task.In the unsolvable task,dogs in the high social group looked at people for significantly longer than dogs in the low social grouping(P=0.008)and looked at people with significantly less latency time than dogs in the low social group(P=0.0001).In the inhibitory control,dogs in the high social group chose significantly more correctly than dogs in the low social group(P=0.034)and chose for significantly less time than dogs in the low social group(P=0.039).In the multistep problem solving task,for dogs in the high social group.successfully completed number of stakes was significantly higher than for dogs in the low social group(P=0.044).The percentage of operation pale time was significantly lower than for dogs in the low social group(P=0.05).The average latency time to solve the bone task was significantly higher than for dogs in the low social group(P=0.037).Moreover,the percentage of operation bone time was significantly lower than for dogs in the low social group(P=0.038).In tests involving a manipulable apparatus,dogs in the high social group spent more time looking at people than dogs in the low social group and less time manipulating the apparatus than dogs in the low subgroup,but no statistically significant differences were observed(P＞0.05).Conclusions Highly sociable labradors have a greater cognitive ability,they are more able to suppress impulses during tests,more able to complete the multistep problem solving task,and more inclined to change strategies to seek new cues from people rather than obsessing over manipulating the apparatus when they are unable to solve a problem.

Objective To analyze the characteristics of hepatitis B infection time in Baqiao Distract of Xian City, predict the incidence trend of hepatitis B in the next years with ARIMA model, and provide theoretical guidance for the adjustment of hepatitis B prevention and control strategies. Methods A total of 7173 cases of hepatitis B in our hospital from 2018 to 2023 were collected as subjects,the annual percentage of change (APC) was used to analyze the characteristics of time of hepatitis B infection in the next years, and the ARIMA optimal model was used to predict the incidence rate in 2024. Results The gross incidence of hepatitis B in Baqiao Distract of Xian City from 2018 to 2023 was 51.30 per 100 000, and the standardized incidence rate was 42.11 per 100 000. The six-year incidence rate showed an upward trend (APC=8.71%,95% CI：3.29% -9.61% , P<0.05). Chi square results showed that the standardized incidence rate of hepatitis B in men is 1.51 times than women, and the incidence rate of hepatitis B in the 30-45 age group was the highest. The prediction results showed that the number of hepatitis B cases in 2024 was 1590, which was 1.91% lower than that in 2023 (1621 cases). Conclusion The infection of hepatitis B is on the rise in Baqiao Distract of Xian City, ARIMA can be used to predict this kind of infectious disease and provide scientific guidance for the prevention of this disease.

Objective To construct and identify a patient-derived organoid model,and to investigate the sensitivity of chemotherapy drugs using this model.Methods Pancreatic cancer cells were obtained from the surgical specimens of two female patients with a confirmed diagnosis of pancreatic cancer after tumor tissue digestion,and then the cells were inoculated into a culture dish using matrigel for three-dimensional culture.Paraffin sections were prepared for HE staining and immunohistochemical staining and were compared with the parent tumor tissue to determine whether the histopathological features of the tumor in vivo were preserved.The pancreatic cancer organoids were treated with seven chemotherapy drugs at different concentrations;Cell Titer-Glo?3D reagent was used to measure cell viability,and the results of drug sensitivity were analyzed.Results Two patient-derived pancreatic cancer organoids were successfully constructed,and HE staining and immunohistochemical staining showed that the pancreatic cancer organoids had consistent histopathological features with the tumors of the corresponding patient.Both pancreatic cancer organoids were more sensitive to gemcitabine monotherapy and the combination of oxaliplatin+SN38+fluorouracil,and patient 1 was more sensitive than patient 2.There were individual differences in the response to drugs between the organoids from different patients.Conclusion The pancreatic cancer organoid model successfully constructed in this study can reflect the histological classification of parent pancreatic tumors and can be used for in vitro chemotherapy drug sensitivity test,which is expected to provide a reference for clinical medication.

Objective To explore the establishment of a prognostic model based on machine learning algorithm to predict primary graft dysfunction(PGD)in patients with idiopathic pulmonary fibrosis(IPF)after lung transplantation.Methods Clinical data of 226 IPF patients who underwent lung transplantation were retrospectively analyzed.All patients were randomly divided into the training and test sets at a ratio of 7∶3.Using regularized logistic regression,random forest,support vector machine and artificial neural network,the prognostic model was established through variable screening,model establishment and model optimization.The performance of this prognostic model was assessed by the area under the receiver operating characteristic curve(AUC),positive predictive value,negative predictive value and accuracy.Results Sixteen key features were selected for model establishment.The AUC of the four prognostic models all exceeded 0.7.DeLong and McNemar tests found no significant difference in the performance among different models(both P＞0.05).Conclusions Based on four machine learning algorithms,the prognostic model for grade 3 PGD after lung transplantation is preliminarily established.The overall prediction performance of each model is similar,which may predict the risk of grade 3 PGD in IPF patients after lung transplantation.

Objective:To explore the genetic basis for a child with pachygyria.Methods:A proband who had visited Qinzhou Maternal and Child Health Care Hospital for pachygyria and mental retardation in June 2020 was selected as the study subject. Clinical data was collected. The child was subjected to whole exome sequencing (WES), and candidate variant was verified by Sanger sequencing. This study was approved by the Qinzhou Maternal and Child Health Care Hospital (Ethics No. 20220710).Results:The proband, a 4-year-old and 6-month-old female, was clinically diagnosed with megagyrus deformity. WES revealed that she has harbored compound heterozygous variants of the ADGRG1 gene, namely c. 781G>T (p.E261*) in exon 6 and c. 1369A>C (p.S457R) in exon 11, which were verified by Sanger sequencing to be derived from her mother and father, respectively. Her younger sister was also heterozygous for the c. 1369A>C (p.S457R) variant. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were rated as likely pathogenic (PVS1+ PM2_ Supporting; PM1+ PM2_Supporting+ PM3+ PP3). Conclusion:The c. 781G>T (p.E261*) and c. 1369A>C (p.S457R) compound heterozygous variants of the ADGRG1 gene probably underlay the pachygyria malformation in this child.

Succinic acid is an important C4 platform chemical that is widely used in food, chemical, medicine sectors. The bottleneck of fermentative production of succinic acid by engineered Escherichia coli is the imbalance of intracellular cofactors, which often leads to accumulation of by-products, lower yield and low productivity. Stoichiometric analysis indicated that an efficient production of succinic acid by E. coli FMME-N-26 under micro-aeration conditions might be achieved when the TCA cycle provides enough ATP and NADH for the r-TCA pathway. In order to promote succinic acid production, a serial of metabolic engineering strategies include reducing ATP consumption, strengthening ATP synthesis, blocking NADH competitive pathway and constructing NADH complementary pathway were developed. As result, an engineered E. coli FW-17 capable of producing 139.52 g/L succinic acid and 1.40 g/L acetic acid in 5 L fermenter, which were 17.81% higher and 67.59% lower than that of the control strain, was developed. Further scale-up experiments were carried out in a 1 000 L fermenter, and the titer of succinic acid and acetic acid were 140.2 g/L and 1.38 g/L, respectively.
Escherichia coli/genetics* ; NAD ; Succinic Acid ; Acetic Acid ; Adenosine Triphosphate

Purpose: Cavernous nerve injury induced erectile dysfunction (ED) is a refractory complication with high incidence in person under radical prostatectomy. Studies have shown that relaxin-2 (RLX-2) plays a vital role of endothelial protection, vasodilation, anti-fibrosis and neuroprotection in a variety of diseases. However, whether penile cavernous erection can benefit from RLX-2 remains unknown. The purpose of the experiment was to explore the effects of RLX-2 on ED in the rat suffering with bilateral cavernous nerve injury (BCNI). Materials and Methods: The rats were divided into three groups: Sham group was underwent sham operation, BCNI+RLX group or BCNI group was underwent bilateral cavernous nerve crush and then randomly treated with RLX-2 (0.4 mg/kg/d) or saline by continuous administration using a subcutaneously implanted micro pump for 4 weeks respectively. Then, erectile function was evaluated by electrical stimulation of cavernous nerves. Cavernous nerves and penile tissues and were collected for histological evaluation. Results: Erectile function of rats with BCNI was partially improved after RLX-2 treatment. The BCNI group had lower expression of relaxin family peptide receptor (RXFP) 1, p-AKT/AKT, p-eNOS/eNOS ratios than sham operation rats, but RLX-2 could partially reversed these changes. Histologically, the BCNI+RLX group had a significant effect on preservation of neurofilament, neuronal glial antigen 2 of penile tissue and nNOS of cavernous nerves when compared with BCNI group. RLX-2 could inhibited the lever of BCNI induced corporal fibrosis and apoptosis via regulating TGFβ1-Smad2/3-CTGF pathway and the expression of Bax/Bcl-2 ratio, caspase3. Conclusions RLX-2 could improve erectile function of BCNI rats by protecting cavernous nerve and endothelial function and suppressing corporal fibrosis and apoptosis via RXFP1 and AKT/eNOS pathway. Our findings may provide a promising treatment for refractory BCNI induced ED.

Purpose: To determine whether microRNA could be a therapy target of erectile dysfunction (ED) and the underlying mechanisms. Materials and Methods: Eight-week-old fasting male SD rats were intraperitoneally injected with streptozotocin to construct diabetic rat models. Diabetic ED rats were treated with miRNA-92a inhibitor. The cavernous nerves were electrically stimulated to measure the intracavernous pressure and mean arterial pressure of rats in each group. After the detection, the penile cavernous tissues are properly stored for subsequent experiments. Rat aortic endothelial cells were used in in vitro studies. Results: The expression of miR-92a was significantly increased in the corpus cavernosum of Streptozocin (STZ)-induced diabetic rats and injection of miR-92a antagomir into the corpus cavernosum of diabetic rats significantly increased eNOS/NO/ cGMP signaling pathway activities, cavernous endothelial cell proliferation, endothelial cell-cell junction protein expression and decreased the levels of oxidative stress. These changes restored erectile function in STZ-induced diabetic rats. Moreover, in vitro study demonstrated that the miR-92a expression increased significantly in endothelial cells treated with high glucose, inhibiting AMPK/eNOS and AMPK/Nrf2/HO-1 signaling pathways in rat aortic endothelial cells via targeting Prkaa2, causing endothelial dysfunction and overactive oxidative stress, miR-92a inhibitor can improve the above parameters. Conclusions miRNA-92a inhibitor could exert an inhibition role on oxidative stress and endothelial dysfunction to improve diabetic ED effectively.

Objective:To compare the effect of extracorporeal membrane oxygenation(ECMO)on pulmonary transplantation(LTx)in patients with idiopathic pulmonary fibrosis(IPF)complicated with pulmonary hypertension(PH).Methods:From January 2017 to December 2020, clinical data were retrospectively reviewed for 112 IPF patients complicated with PH undergoing LTx assisted by venous ECMO(VV-ECMO group, n=68)or venous arterial ECMO(VA-ECMO group, n=44). Gender, age, mechanical ventilation time, oxygenation index, cold ischemic time, preoperative gender, age, smoking history, PO 2, PCO 2, PH degree, NYHA cardiac function grade, right cardiac function, ejection fraction(EF)and complications(hypertension & diabetes)of two groups were compared. Intraoperative approach, operative duration, ECMO transfer time, blood loss, blood transfusion, urine volume, postoperative blood transfusion, mechanical ventilation time, ICU stay time, re-thoracotomy, pulmonary infection, primary graft dysfunction(PGD)and renal insufficiency were recorded. And the effects of two different diversion modes on early postoperative complications and short-term outcomes of LTx were further analyzed by multiple factors. Cox proportional risk model was employed for comparing VV-ECMO and VA-ECMO flow patterns with factors related to recipient survival after transplantation. Results:The preoperative PO 2 of 58.3(51.3, 72.0)mmHg was significantly lower in VV-ECMO bypass group than that of 73.2(63.3, 96.8)mmHg in VA-ECMO group and the difference was statistically significant( P<0.006). Compared with VV-ECMO group, 24(54.5%), 15(34.1%)and 22(50.0%)had NYHA class Ⅲ, severe PH and preoperative right heart enlargement in VA-ECMO group respectively and the differences were statistically significant compared with 17(25.0%), 6(8.8%)and 16(23.5%)in VV-ECMO group( P<0.05 for all). No significant inter-group differences existed in postoperative PGD, postoperative mechanical ventilation time(≥3 d), pulmonary infection, postoperative thoracotomy ratio, postoperative renal insufficiency, ICU stay, hospital stay and other aspects( P>0.05). And 6-month postoperative survival rates of VV-ECMO and VA-ECMO groups were 80.9% and 61.4%, respectively and no significant inter-group difference existed in short-term survival rate(6 months)after adjustment by multivariate Cox regression model( P>0.05). Multivariate statistics indicated that the risk of delayed postoperative withdrawal was 14.452-fold higher in VV-ECMO group than in VA-ECMO group and the inter-group difference was statistically significant(95% CI: 2.448-85.323, P=0.03). Conclusions:No differences exist in postoperative complications or short-term survival rate between IPF recipients with mild PH on VV-ECMO mode and IPF recipients with severe PH on VA-ECMO mode. VV-ECMO flow reversal can delay the transplant back-off time.

Objective:To provide consistent data basis for the application of reference intervals for children blood cell analysis in different testing systems.Methods:According to the requirements of American Institute for Clinical and Laboratory Standardization (CLSI) EP9-A3 document, 45 samples were collected and Sysmex XN20-A1 were used as reference system. Beckman DxH800, Siemens ADVIA 2120i, and Mindray BC5310 were comparison systems. Complete blood count and leukocyte classification were performed by four systems. The outliers of the detection results were tested by the generalized extreme student deviate (ESD) method. An optimal regression model was selected by scatter diagram, deviation diagram and frequency distribution diagram, which was used to fit the regression equation and calculate the deviation at the medical decision level and reference interval. The acceptable range for blood count deviation was cited from the Analytical Quality Specifications for Routine Tests in Clinical Hematology. The acceptable range for leukocyte classification was based on the EQA program of Royal College of Pathologists of Australasia (RCPA).Results:After the outliers were deleted, the scatter plot showed a linear relationship between the reference system and the three comparison systems. The deviation plot showed that the differences were variable. Deming regression or Passing-Bablok regression was selected according to the data distribution. The determination coefficient R2 of reference system and three comparison systems ranged from 0.95 to 0.99 in blood count and leukocyte classification. At the upper and lower limits of the reference interval, the deviations between XN-20A1 and ADVIA 2120 system were all acceptable, except for MONO# at 0.12×10 9/L. The deviations of all parameters at medical decision level were within acceptable ranges. The lower limit of PLT is partially unacceptable at the level of medical decision related to treatment and prognosis. Conclusions:The results of complete blood count and leukocyte classification in reference system and the comparison system had good consistency within the children′s reference interval. Our study provided a scientific basis for the feasibility of adopting a unified reference interval for different detection systems.