Background China is a big country in the production and use of antibiotics. The abuse of antibiotics enables bacteria in water environment to acquire resistance, and promotes the generation and spread of antibiotics resistance genes (ARGs). The problem of antibiotic-resistant bacteria is increasingly serious and has become a public security issue of global concern. Water environment is a huge reservoir of antibiotics and ARGs. It is of great significance to study the pollution of antibiotics and ARGs in water to protect water sources and optimize the biosecurity of drinking water. Objective To evaluate the detection of antibiotics and ARGs in typical water sources, and to explore the relationship between antibiotics and ARGs. Methods Water samples were collected in Heilongjiang, Liaoning, and Hubei provinces during the wet season (from August to October) in 2020. Ten water samples were collected from each of the three places, and a total of 30 water samples were collected in this study. Five kinds of antibiotics, including macrolides, quinolones, sulfonamides, tetracycline, and β-lactam, were detected by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The integron (Intl1), 16S rRNA, and 6 kinds of ARGs were detected by quantitative real-time PCR (qPCR). The ARGs include one macrolide ARGs (ermB), one β-lactam ARGs (bla_TEM), two tetracycline ARGs (tetC, tetQ), and two sulfonamide ARGs (sul1, sul2). Results The types of detected antibiotics varied by the three regions, and the concentration ranges of the same antibiotics varied by the three regions (P<0.05). The concentration ranges of selected five kinds of antibiotics were 0.11-418.80 ng·L⁻¹ in region A, 0.12-23.23 ng·L⁻¹ in region B, and 4.69-285.75 ng·L⁻¹ in region C, respectively. The detection rates of all six ARGs were 100%. The absolute abundance of ARGs in region A ranged from 22.56 to 94355.91 copies·mL⁻¹, that in region B ranged from 27.99 to 80584.32 copies·mL⁻¹, and that in region C ranged from 41.99 to 111068.19 copies·mL⁻¹. The absolute abundance of bla_TEM was higher among the ARGs, followed by sul1 and sul2. In addition, the absolute abundance of Intl1 was also at a high level. The results of correlation analysis showed that the abundance of ARGs was positively correlated with each other. There was no correlation between specific antibiotics and corresponding ARGs. There was a positive correlation between Intl1 and sul1 or sul2 (P<0.05). Conclusion The types and concentrations of antibiotics and the abundance of ARGs in source water vary greatly in the study areas. The association between antibiotics and ARGs is uncertain. Intl1 may play an important role in the horizontal transfer of sulfonamide resistance genes.

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

Objective: To evaluate the value of MRI-T₂WI texture analysis in the differentiation of atypical medulloblastoma and ependymoma of the fourth ventricle. Methods: Preoperative MRI data of 36 cases of fourth ventricle tumor (19 cases of medulloblastoma and 17 cases of ependymoma) confirmed by the Central Theater General Hospital of the Chinese People′s Liberation Army were retrospectively analyzed. Manually sketch areas of interest (ROI) were made using texture analysis software to get histogram parameters, including mean, median, standard deviation, skewness, kurtosis, maximum, minimum, heterogeneity, entropy, the 5th percentile (T₂WI_5th), the 10th percentile (T₂WI_10th), the 25th percentile (T₂WI_25th), the 50th percentile (T₂WI_50th), the 75th percentile(T₂WI_75th), the 95th percentile(T₂WI_95th). Independent sample t test or mann-whitney U test was used for statistical analysis of each parameter value between the two groups. Logistic regression analysis was used to perform multiparameter joint analysis on meaningful parameters. The area under the curve (AUC) was obtained by using the subject operating characteristic (ROC) curve to determine the threshold and diagnostic efficacy for distinguishing the two group. Results: The mean, median, T₂WI_5th, T₂WI_10th, T₂WI_25th, T₂WI_50th, T₂WI₇5th values of the medulloblastoma group were smaller than those of the ependymoma group, and difference was statistically significant (P<0.05). The T₂WI_5th had the best diagnostic performance. When the critical value was 1 343, the diagnostic specificity was 75.0% and the sensitivity was 92.9%. Logistic regression was used to predict the joint analysis of probability parameters. T₂WI_5th+T₂WI_10th had the best performance, and AUC was 0.928. When the critical value was 0.75, the diagnostic specificity was 75.0% and the sensitivity was 100.0%. Conclusions MRI-T₂WI texture analysis can provide quantitative information for preoperative diagnosis of atypical medulloblastoma and ependymoma and improve the accuracy of preoperative diagnosis, which has obvious clinical value.

Objective To investigate the correlation between intraoperative ultrasonographic features and expression of immunohistochemical markers in patients with glioma.Methods Totally 116 patients with glioma confirmed pathologically were collected.Ultrasonic features were observed,including the main site of the tumor,maximum diameter,border,cystic degeneration,calcification,the degree of peritumoral edema and CDFI blood flow classification,and the correlation between ultrasonographic features and immunohistochemical results such as Ki-67 and isocitrate dehydrogenase 1 (IDH1) was analyzed.Results Univariate analysis showed that the border,peritumoral edema and CDFI blood flow were significantly different between negative and positive Ki-67 expression patients (P＜ 0.01).The border,cystic degeneration and peritumoral edema were distinct between negative and positive IDH1 patients (P＜0.01).Multivariate analysis showed that gliomas with clear border,high degree of peritumoral edema and rich CDFI blood flow tended to show positive Ki-67 expression,while those with vague border,low degree of peritumoral edema were frequently accompanied by positive IDH1 expression.Conclusion The border of gliomas,peritumoral edema and blood flow showed on ultrasonography may predict the expression of Ki-67 and IDH1.It is of great significance for preliminary evaluation on biological behaviors and prognosis of the tumors before surgical operation.

Objective To study the delayed gastric emptying for patients underwent pylorus-preserving pancreaticoduodenectomy and standard Whipple procedure.Methods Clinical data of 401 consecutive patients who underwent standard Whipple procedure/pylorus-preserving pancreaticoduodenectomy between January 2012 and July 2016 in the First Affiliated Hospital of Harbin Medical University were retrospectively collected and analyzed.Using the independent-samples t test,x2 test or Fisher's exact test,Mann-Whitney test and other statistical methods to compare the postoperative complications between pylorus-preserving pancreaticoduodenectomy and standard Whipple procedure group.Results Compare with standard Whipple procedure group,delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy occurred in 8 of 35 patients (22.9％),obviously higher than it after standard Whipple procedure occurred in 40 of 366 patients (10.9％) (P =0.038).Other postoperative complications were not significantly different (P ≥ 0.05).Each level of delayed gastric emptying after pyloruspreserving pancreaticoduodenectomy and standard Whipple procedure were not significantly different (P ≥ 0.05),but the average recovery time of delayed gastric emptying after pylorus-preserving pancreaticoduodenectomy (12.13 ± 3.09) d was obviously shorter than it after standard Whipple procedure (17.28 ± 9.63) d (P =0.009).Conclusions Pylorus-preserving pancreaticoduodenectomy increases the risk of delayed gastric emptying,but it does not increase severity delayed gastric emnptying by each level.The recovery time of delayed gastric after pyloruspreserving pancreaticoduodenectomy is shorter.

Objective: To study the prognostic factors of delayed gastric emptying(DGE) after pancreaticoduodenectomy(PD) and construct a prognostic predictive model for clinical application. Methods: Clinic data of 401 consecutive patients who underwent PD between January 2012 and July 2016 in the First Affiliated Hospital of Harbin Medical University were retrospectively collected and analyzed. The patients were randomly selected to modeling group(n=299) and validation group(n=102) at a ratio of 3∶1. The data of modeling group were subjected to univariate and multivariate analysis for prognostic factors and to construct a prognostic predictive model of DGE after PD. The data of validation group were applied to test the prognostic predictive model. Results: DGE after PD occurred in 35 of 299 patients(11.7%) in the modeling group. The multivariate analysis of the modeling group showed that upper abdominal operation history(χ²=6.533, P=0.011), diabetes mellitus(χ²=17.872, P=0.000), preoperative hemoglobin <90 g/L(χ²=14.608, P=0.000) and pylorus-preserving pancreaticoduodenectomy(PPPD)(χ²=8.811, P=0.003) were associated with DGE after PD independently. A prognostic predictive model of DGE after PD was constructed based on these factors and successfully tested. The area under the receiver operating characteristic(ROC) curve was 0.761(95%CI: 0.666-0.856) of the modeling group and 0.750(95% CI: 0.577-0.923) of the validation group. Conclusions Upper abdominal operation history, diabetes mellitus, preoperative hemoglobin<90 g/L and PPPD are associated with DGE after PD independently. The preoperative assessment of a patient′s prognostic for DGE after PD is feasible. The model is a valid tool to take precautions against DGE after PD.

Objective To investigate the effects and value of enhance recovery after surgery (ERAS) application in patients with hepatocellular carcinoma underwent liver resection.Methods One hundred and seventy-two patients with hepatocellular carcinoma underwent liver resection in the first affiliated hospital of Harbin medical university from June 2013 to June 2015,ERAS group (92 cases) and control group (80 cases) were retrospectively studied.Laboratory indicators (ALT,AST,TBIL,ALB,PA,lymphocyte count),postoperative complications,postoperative hospitalization days and total hospitalization expenses were compared between two groups.Results For postoperative liver functional indicators (ALT,AST,TBIL),ERAS group Day 1 and Day 7 were respectively (216.3±141.7) U/Land (70.1 ±29.4) U/L,(184.0±155.8) U/Land (39.1 ±17.5) U/L,(22.4± 8.7) μmol/L and (20.0 ± 7.5) μmol/L,control group were respectively (304.5 ± 226.2) U/L and (83.9 ± 48.5) U/L,(294.1 273.0) U/L and (49.2 ±33.8) U/L,(26.9 ±15.6) μmol/L and (24.6 ± 10.8) μmol/L,the difference between two groups was statistically significant (F =9.33,9.84,9.26,P ＜ 0.05).For postoperative nutritional indicators (ALB,PA),ERAS group Day 7 were respectively (35.3 ± 4.4) g/Land (136.3 ±34.1) mg/L,control group were respectively (33.6 ±4.2) g/L and (108.0 ± 32.5) mg/L,the difference was statistically significant (F =4.97,4.54,P ＜ 0.05).For postoperative immune indicators (lymphocyte count),ERAS group Day 1 and Day 7 were respectively (0.9 ±0.3) × 109/L and (1.5 ± O.5) × 109/L,control group were respectively (0.7 ± 0.3) × 109/L and (1.3 ± 0.5) × 109/L,the difference was statistically significant (F =7.37,P ＜ 0.05).For postoperative complications (hemorrhage,bile fistula,hepatic dysfunction,infection) were no statistically significant differences (P ＞ 0.05),however,ascites had statistically significant difference (x2 =7.609,P ＜ 0.05).Off bed time,postoperative exhaust time,postoperative hospitalization time and total hospitalization expense of ERAS group were respectively (1.7 ± 0.5) days,(2.3 ± 0.6) days,(9.8 ± 2.3) days,(4.6 ± O.9) × 104 RMB,control group were respectively (3.0 ± 0.7) days,(3.4 ± 0.8) days,(17.6 ± 5.8) days,(6.3 ± 2.1) × 104 RMB,the difference was statistically significant (t =13.032,10.937,11.371,7.118,P ＜ 0.05).Conclusions Application of ERAS in patients with HCC underwent liver resection is safe and effective.ERAS effectively reduce stress reaction of patients,promote the recovery of liver function,improve the postoperative immune and nutrition status,shorter postoperative hospitalization time,and reduce the total cost of hospitalization.

Objective To discriminate whether chemical compounds are micronuclei-inducing by counting the ratio of bone marrow micronucleus polychromatic erythrocytes ( MNPCE) dyed with a single fluorescence reagent ( acriding organe, AO) by single-laser flow cytometry.Methods Treating male KM mice and SD rat with cyclophosphamide ( CP) respectively, and counting their frequencies of micronucleated polychromatic erythrocytes ( MNPCE) as well as frequencies of micronucleated normochromatic erythrocytes ( MNNCE ) in bone marrow by AO and a single_laser flow cytometer (FCM), comparing and analyzing the results from different methods.Results The results showed that, along with increasing dose of CP, the ratio of MNPCE also corresponding increase, suggesting significant quantative-efficiency correlation.MNPCE were also counted manually by fluorescence microscopy, and the results showed no significant difference with that by flow cytometry.Conclusions AO_FCM fully automated detection method for the detection of MNPCE and MNNCE in mice and rat bone marrow micronucleus rate is reliable.

To study the umbilical cord mesenchymal stem cells impact of inflammatory factors in rheumatoid arthritis patients.Methods:94 cases of patients with RA hospitalized in our department from April 2011 to December 2012 were treated with umbilical cord mesenchymal stem cells (MSCs) UC,during which the cell therapy scholastic ethics was committed approvally and patients′informed consents were separately signed .94 patients were directly intravenous infusion with 40 ml UC-MSCs ( 4×107 cells/ml),including 57 cases with two UC-MSCs therapy.We used multifunctional flow lattice Luminex 200 analysis to detect contents of 13 kinds of factors in serum such as TNF alpha,IFN-gamma,IL-1β,IL-4,IL-6,IL-8,IL-10,ie,and detected CPR,ESR,assessment DAS28,HAQ,and ARA.Follow-up treatments were performed after 1 week,3 months,6 months ( two cells treatment of 60 cases).Results:①DAS28,HAQ grading standards,were decreased (P<0.01) in 3 months and 6 months before the patients treatment ,2 times than one continue treatment decreased ( P<0.01 );the ESR and CRP in 1 week dropped significantly after treatment ( P<0.01),3 months,6 months before the treatment also decreased (P<0.05).②IL-6,TNF alpha were in falling levels after 1 week,3 months and 6 months treatment ,( P<0.05 ).Conclusion: We proved the inflammatory factors directly related with clinical indicators and symptoms of RA patients .94 cases of patients with other inflammatory factor (IL-17,IL-4,IL-10,etc.) also had some change,we still needed further observation.According to drug rheumatism guide at the same time , collaborative using with UC-MSCs could make RA patients improve local and systemic inflammatory response ,prevent disease progression.

BACKGROUND:Rheumatoid arthritis is an autoimmune disease, and traditional treatment methods are difficult to effectively solve the patient's lack of immune tolerance mechanisms. With the development of stem cel s in regenerative medicine, stem cel therapy has become a hot spot in the treatment of autoimmune diseases.
Currently, studies on cel transplantation for the treatment of rheumatoid arthritis are rarely reported.
OBJECTIVE:To study the influence of umbilical cord mesenchymal stem cel therapy on the changes of Th1/Th2 and Treg in rheumatoid arthritis patients, thereby seeking new therapies for rheumatoid arthritis.
METHODS:We selected 180 cases of rheumatoid arthritis, including 27 patients as control group undergoing non-steroidal anti-inflammatory drugs and anti-rheumatic drugs and 153 patients as cel treatment group undergoing intravenous infusion of 40 mL umbilical cord mesenchymal stem cel s at a density of 4×107. Dosing regimen was same in the two groups. The 76 of 153 patients accepted second cel therapy at 3-4 months after the first cel therapy. After fol ow-up of 3 and 6 months, clinical effectiveness evaluation (DAS28, HAQ, ACR20), rheumatoid factor, anti-CCP antibodies, T cel subsets, Th cytokine were detected;for patients with second cel therapy, T cel subsets and Treg were detected at 8 months after treatment.
RESULTS AND CONCLUSION:(1) At 3 months after treatment, the DAS28, HAQ and ACR20 scores were significantly lower in the cel treatment group than the control group (P<0.01). (2) At 3 and 6 months after cel therapy, the DAS28 and HAQ scores were significantly decreased in the cel treatment group (P<0.01), and these scores were decreased continuously after second cel therapy (P<0.01). (3) Interferon-γlevel in cel s did not change obviously at 3-6 months after treatment, but the interleukin-4 level was gradual y increased at 6 months after treatment (P<0.05). (4) The number of Treg cel s was significantly increased at 3-6 months after treatment (P<0.01), which was closely related to ACR, especial y ACR70 percentage (P<0.05);the ratio of CD4+Treg was increased significantly at 3 months after treatment (P<0.05), and this increasing trend was also maintained at 6 and 8 months after treatment, but there was no significant difference (P>0.05). (5) B cel levels were significantly decreased at 6 months after treatment (P>0.05);the rheumatoid factor value was significantly decreased at 3-6 months after treatment (P<0.05). (6) There was no change in anti-CCP antibody and interleukin-17 levels at 3-6 months after treatment. These findings indicate that after treatment with umbilical cord mesenchymal stem cel s, the Th1/Th2 tends to balance and Treg level is elevated in rheumatoid arthritis patients, which are directly related to clinical trials and symptomatic relief. Therefore, standard rheumatism medication combined with umbilical cord mesenchymal stem cel transplantation can improve immune network effects, adjust the immune tolerance and prevent il ness progress in rheumatoid arthritis patients.