ObjectiveTo investigate microbial contamination status and distribution characteristics in laboratory animal barrier facilities, so as to provide a scientific basis for environmental quality control in barrier facilities. MethodsIn accordance with the national standard "Laboratory Animals—Environment and Housing Facilities" and the "Standard Operating Procedures" of the barrier facility, bacterial monitoring was performed on samples of air-settling bacteria, materials, and personnel gloves in the single-corridor barrier facility of the Animal Core Facility, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences (CEMCS). The monitoring data from January 2020 to December 2024 were collected, organized and statistically analyzed, and partial samples were subjected to species identification using PCR and sequencing methods. ResultsA total of 7 898 samples were collected from 2020 to 2024, including 3 175 air-settling bacteria samples, 3 353 material samples, and 1 370 glove samples. The overall compliance rate was 95.7% (7 559/7 898), among which the compliance rate of air-settling bacteria was 97.1% (3 084/3 175), that of materials was 93.2% (3 125/3 353), and that of personnel gloves was 98.5% (1 350/1 370). Over the five years, the compliance rates of all three types of monitored samples were above 90%. There were statistically significant differences in the compliance rates of air-settling bacteria and material samples among different quarters (P<0.05). Further investigation was conducted on samples collected from January to March 2024, and 190 bacterial strains were obtained through isolation and culture, including 126 strains from air-settling bacteria, 52 strains from materials, and 12 strains from personnel gloves. The strains were identified by PCR amplification and sequencing, and the 190 bacterial strains belonged to 9 genera and 20 species. Gram-positive bacteria accounted for the majority, with Staphylococcus as the dominant genus, accounting for 77.9% (148/190). ConclusionMicroorganisms carried by air, materials, and personnel gloves in barrier facilities are mainly Gram-positive bacteria. Regular monitoring of air-settling bacteria, materials, and personnel gloves in barrier facilities enables timely detection and control of potential risks during husbandry management and facility operation, which is of great significance for maintaining the sound operation of the barrier facility system and ensuring the quality of animal experiments.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

Objective:To investigate the survival outcomes and prognostic factors in patients undergoing radical resection for pancreatic body and tail cancer.Methods:A retrospective case series study was conducted on 992 patients who underwent radical resection for pancreatic body and tail cancer at the Pancreatic Center of the First Affiliated Hospital of Nanjing Medical University from January 2016 to June 2024. In this study, 577 (58.2%) were male and 415 (41.8%) were female,with an age of (65±9) years (range: 26 to 86 years). Follow-up continued until June 2024. Survival rates were estimated using the Kaplan-Meier method,and prognostic factors were identified using univariate and multivariate Cox proportional hazards models.Results:Among 992 patients,open surgery was the predominant approach (89.1%, 884/992), and radical antegrade modular pancreatosplenectomy (RAMPS) was performed in 317 patients (32.0%). Combined organ resection,venous resection,and arterial resection were performed in 23.5%, 9.3%,and 11.2% of patients,respectively. The rates of R0, R1-1 mm, and R1-direct resections were 49.8% (494/992),41.5% (412/992), and 8.7% (86/992),respectively. Stage ⅡB was the most common TNM stage (32.2%,319/992). A total of 801 patients (80.8%) received adjuvant chemotherapy. The median follow-up period was 32.0(8.8) months(range:3.2 to 105.3 months),during which 508 patients (51.2%) died. The overall median survival (OS) was 26.4 months,with 1-,3-, and 5-year survival rates of 79.0%,40.0%, and 29.0%, respectively. In the recent five years (from 2020 to 2024), the median OS improved significantly to 34.1 months compared to 20.0 months from 2016 to 2019 ( P<0.01). Histological subtype analysis showed that the median OS time was 26.7 months for pancreatic ductal adenocarcinoma (PDAC, n=855),58.9 months for invasive intraductal papillary mucinous carcinoma (IPMC, n=32),and 15.7 months for adenosquamous carcinoma of pancreas (ASCP, n=73) ( P=0.001). Among PDAC patients, adjuvant chemotherapy significantly improved survival (29.1 months vs. 14.4 months, P<0.01);in IPMC patients, adjuvant chemotherapy also extended survival (65.7 months vs. 58.9 months, P=0.047). Although ASCP patients receiving chemotherapy had a longer median OS time than those without (18.8 months vs. 8.9 months),the difference was not statistically significant ( P=0.151). Multivariate Cox regression analysis in PDAC patients indicated that adjuvant chemotherapy, R0 resection, T stage,N stage,and tumor differentiation were independent prognostic factors ( P<0.01). The median OS time by TNM stage was:not reached for stage ⅠA, 51.6 months for ⅠB, 25.5 months for ⅡA, 23.7 months for ⅡB, 23.0 months for Ⅲ, and 14.4 months for Ⅳ. The median OS time for R0,R1-1 mm,and R1-direct resections was 34.1,24.7,and 15.7 months,respectively ( P<0.01). Conclusion:Adjuvant chemotherapy,R0 resection,tumor stage,and differentiation are independent prognostic factors for pancreatic body and tail cancer.

BACKGROUND:Because of its anti-inflammatory and antioxidant activities,Apelin-13 plays an effective role in the treatment of common clinical diseases such as neuroinflammation,cardiovascular injury and pneumonia.However,there is no relevant basic research on whether Apelin-13 also has a good effect in the treatment of inflammatory bone loss. OBJECTIVE:To explore the therapeutic effect and mechanism of Apelin-13 on inflammatory bone loss,in order to find potential drugs for the treatment of inflammatory bone loss. METHODS:(1)In vitro experiment:RAW264.7 cells were divided into three groups:control group,lipopolysaccharide group and treatment group.The control group was only added with DMEM complete medium;lipopolysaccharide group was added with lipopolysaccharide(100 ng/mL)induced inflammation DMEM medium;and the treatment group was added with 10 nmol/L Apelin-13+lipopolysaccharide induced inflammation DMEM medium.Then,24 hours after lipopolysaccharide induced inflammation,western blot was used to detect the marker proteins inducible nitric oxide synthase and CD86 of M1 macrophages,and cell immunofluorescence was extracted to detect the expression of inducible nitric oxide synthase.Finally,the same amount of receptor activator of nuclear factor-κB ligand(RANKL;50 ng/ml)was added to the control group,lipopolysaccharide group and treatment group to induce osteoclasts.The results of osteoclast induction were evaluated by tartrate-resistant acid phosphatase staining and F-actin staining after 6 days of induction.(2)In vivo experiment:Eighteen male C57bl/6 mice were randomly divided into three groups:sham group,lipopolysaccharide group and treatment group.The sham group received intraperitoneal injection of 0.1 mL of PBS;the lipopolysaccharide group was injected with 0.1 mL of PBS diluent containing lipopolysaccharide(5 mg/kg);and the treatment group was injected with 0.1 mL of PBS diluent containing lipopolysaccharide(5 mg/kg)+Apelin-13(100 μg/kg).After 7 days of continuous intraperitoneal injection,the mice in each group were killed on the 8th day,and two femurs of each mouse were collected.Half of them were scanned by micro-CT and analyzed by bone mineral density,and the other half were stained by hematoxylin-eosin staining RESULTS AND CONCLUSION:(1)In vitro experiment:Western blot results showed that the expressions of inducible nitric oxide synthase and CD86 in the lipopolysaccharide group were significantly higher than those in the control group,and Apelin-13 could significantly inhibit the M1 polarization of macrophages induced by lipopolysaccharide.Cell immunofluorescence results also showed that the expression of inducible nitric oxide synthase in the treatment group was lower than that in the lipopolysaccharide group.Besides,tartrate-resistant acid phosphatase staining and F-actin staining results showed that Apelin-13 inhibited the abnormal activation and bone resorption of lipopolysaccharide induced osteoclasts.(2)In vivo experiment:The results of micro-CT showed that systemic inflammation led to significant bone loss in the distal femur,while Apelin-13 could significantly inhibit bone loss in vivo.Hematoxylin-eosin staining results also showed that Apelin-13 could effectively alleviate inflammation induced bone loss in the distal femur of mice.To conclude,Apelin-13 can alleviate bone loss induced by systemic inflammation by inhibiting M1 polarization of macrophages,inhibiting abnormal activation of osteoclasts and bone resorption.

Objective:To analyze the effect of the TOMO therapy on the exposure dose and volume of organs at risk(OAR)in patients with locally advanced non-small cell lung cancer(NSCLC),so as to analyze the TOMO's advantages.Methods:A total of ninety-eight patients with locally advanced NSCLC who received TOMO treatment at the General Hospital of PLA Southern Theatre Command from January 2019 to March 2024 were selected.The TOMO plan was designed for 54 patients,and the volumetric modulated arc therapy(VMAT)plan was designed for 44 patients.The effect of the two plans on the parameters of exposure dose in OAR was compared and analyzed.Results:The conformity index(CI)values of planning target volume(PTV)and planning gross tumor volume-T(PGTV-T)in the TOMO plan were respectively(0.769±0.012)and(0.756±0.011),which were higher than those in the VMAT plan.The homogeneity index(HI)value of PTV in the TOMO plan was(0.138±0.014),which was lower than that in the VMAT plan.The differences of the above indicators between TOMO plan and VMAT plan were statistically significant(t=4.457,6.993,7.245,P<0.05).In all NSCLC patients,the exposure volume(V5 Gy)of receiving 5Gy dose on whole lung and the V30 Gy on heart in OAR in the TOMO plan were respectively(45.251±1.652)％ and(21.002±1.265)％,which were better than those in the VMAT plan,with statistically significant differences(t=3.931,6.169,P<0.05).However,the V20 Gy of the whole lung in the VMAT plan was better than that in the TOMO plan,with statistically significant difference(t=4.346,P<0.05).In the left lung of NSCLC patients,the V20 Gy of the whole lung and the V30 Gy of the heart of OAR in the TOMO plan were respectively(24.278±1.456)％and(21.365±1.687)％,which were better than those in the VMAT plan,with statistically significant differences(t=9.140,4.992,P<0.05).The V40Gy of the heart in the VMAT plan was better than that in the TOMO plan,with statistically significant difference(t=1.422,P<0.05).In the right lung of NSCLC patients,the V50 Gy of the whole lung and the V40 Gy of the heart of the OAR of the TOMO plan were better than those of the VMAT plan,with statistically significant differences(t=7.460,6.201,P<0.05).There were no significant differences in the V20 Gy of the whole lung,V30 Gy of the heart,V50 Gy of the esophagus,and the maximum dose(Dmax)of spinal cord between the two plans(P>0.05).Conclusion:The conformity of PTV radiation of TOMO plan is the best in patients with locally advanced NSCLC,which is more suitable for the locally advanced NSCLC in right and left lungs.

Objective:To investigate the impact of body composition and inflammatory nutritional indicators on postoperative complications in patients with obstructive colorectal cancer,and to develop and validate a nomogram model.Methods:This is a retrospective case series study. The clinical data of 293 patients with obstructive colorectal cancer who were treated at the Department of Gastrointestinal Surgery,the Affiliated Hospital of Qingdao University,between January 2016 and January 2024,were retrospectively collected. The cohort included 182 males and 111 females,aged (65.0±12.1) years (range: 18 to 80 years). The dataset was randomly divided into a training group ( n=196) and a validation group ( n=97) with a 7∶3 ratio. Independent sample t test and multivariate logistic regression analysis were employed to identify independent risk factors associated with postoperative complications in patients with obstructive colorectal cancer. A preoperative nomogram model was subsequently developed for predicting postoperative complications,which was further validated using a validation cohort. Results:The training group comprised 119 males and 77 females,with 68 cases experiencing postoperative complications and 128 cases without complications. The validation group included 63 males and 34 females,with 30 cases experiencing postoperative complications and 67 cases without complications.Univariate analysis and multivariate analysis revealed that low skeletal muscle index ( OR=0.867,95% CI: 0.795 to 0.947),high visceral fat index ( OR=1.058,95% CI: 1.028 to 1.089),high systemic immune inflammation index ( OR=1.002, 95% CI: 1.000 to 1.003), low prognostic nutritional index ( OR=0.847,95% CI: 0.782 to 0.917),and preoperative anemia ( OR=2.714,95% CI: 1.161 to 6.344) were independent risk factors for postoperative complications (all P<0.05). A nomogram prediction model based on these five indicators was established. The area under the receiver operating characteristic (ROC) curve for the prediction model was 0.878 (95% CI: 0.829 to 0.928) in the training group and 0.849 (95% CI:0.767 to 0.930) in the validation group. Conclusions:The preoperative nomogram model,which incorporates inflammatory and nutritional indicators,demonstrates a good accuracy in predicting postoperative complications for patients with obstructive colorectal cancer. This model can effectively assist in guiding treatment decisions.

AIM:To establish a mouse model of chronic skin fibrosis by combining skin injury with bleomycin(BLM)induction.METHODS:Male SPF-grade BALB/c mice were randomly allocated into five groups(n=10 per group):control(Ctrl),high-dose BLM(BLM-H),medium-dose BLM(BLM-M),low-dose BLM(BLM-L),and BLM-control(BLM-Ctrl).A 6 mm full-thickness skin excision was performed on the dorsal region of mice,followed by subcuta-neous injections of BLM at four points around the wound.Mice in the Ctrl group were injected with saline,whereas the BLM-Ctrl group received injections without skin excision.The wound healing rates and times were assessed statistically.Histopathological alterations in wound tissues were examined using hematoxylin-eosin and Masson's trichrome staining.Enzyme-linked immunosorbent assay(ELISA)was employed to measure matrix metalloproteinases(MMPs),and Western blot analysis was conducted to detect collagen type I(COL I)and COL III expression.RESULTS:Compared to the Ctrl group,wound healing rates were significantly reduced(P<0.05 or P<0.01)and healing times significantly prolonged in BLM-H,BLM-M,and BLM-L groups.Histological analysis indicated significantly delayed epithelialization,thicker der-mis,increased collagen deposition,and heightened inflammatory infiltration in the BLM-H group relative to the Ctrl group(P<0.05 or P<0.01).ELISA revealed significantly elevated expression of MMP-2,MMP-3,and MMP-9 in the BLM-H group compared to controls(P<0.01).Western blot results demonstrated significantly increased COL I and COL III pro-tein levels in the BLM-H group compared to the Ctrl group(P<0.05 or P<0.01).CONCLUSION:A mouse model in-volving a 6 mm full-thickness dorsal skin excision combined with subcutaneous injections of BLM(5 mg/kg)at four perile-sional points daily for 21 consecutive days is suitable for investigating chronic skin fibrosis wounds.

Objective To observe the effectiveness and safety of DiaSphere embolized microsphere TACE for treating primary hepatocellular carcinoma(HCC).Methods Totally 188 patients with HCC were prospectively enrolled and randomly assigned to research group(n=93)and control group(n=95),who underwent TACE with DiaSphere embolized microspheres and Embosphere embolized microspheres,respectively.The incidence of TACE-related adverse events were recorded.The therapeutic efficacy 1 month after the first TACE,also 1 and 3 months after the last TACE,and liver functions 1 month after the first and last TACE were compared between groups.Results In research group,there were 69 cases underwent 1 time TACE,22 cases underwent 2 times and 2 cases underwent 3 times TACE,while in control group,there were 82 cases underwent 1 time and 13 cases underwent 2 times TACE,respectively.No statistical difference of the incidence of adverse events was found between groups(77.42%[72/93]vs.76.84%[73/95],P=1.000).One month after the first TACE,7 cases in research group and 11 cases in control group were lost to follow-up,respectively.One month after the last TACE,12 cases were lost to follow-up in both groups,and 3 months after the last TACE,28 cases were lost to follow-up in both groups.No significant difference of objective response rate nor disease control rate was found between groups at the above time points(all P＞0.05).One month after the first and last TACE,liver function indicators were not different between groups(all P＞0.05).Conclusion Both the short-term efficacy and safety of TACE with DiaSphere embolized microspheres for treating HCC were good.

Objective: To investigate the current status and influencing factors of quality of life among HIV/AIDS cases, so as to provide the basis for improving HIV/AIDS cases quality of life. Methods: From March to July 2024, HIV/AIDS cases under follow-up management at various community health service centers in Jinshan District, Shanghai Municipality, were selected as the survey subjects using a convenience sampling method. Demographic information and receiving antiretroviral therapy (ART) were collected through questionnaire surveys. Quality of life was assessed using the Chinese version of the World Health Organization Quality of Life Questionnaire for HIV brief version. A multiple linear regression model was employed to analyze the factors affecting quality of life. Results: A total of 179 HIV/AIDS cases were investigated, including 150 males (83.80%) and 29 females (16.20%), with a mean age of (47.00±12.90) years. The subjective self-evaluation score for the quality of life among HIV/AIDS cases was (13.87±2.84) points. The scores in the domains of physical, psychological, independence, social relationship, environment, and spiritual support/religion/personal beliefs were (14.77±2.64) (13.57±2.04) (13.86±2.04) (12.99±2.26) (13.58±1.98) (14.59±3.05) points, respectively. Multiple linear regression analysis revealed statistically significant associations (all P<0.05) between the following factors and quality of life domain scores: educational level (college degree or above, β' =0.162) and receiving ART (β' =-0.197) were associated with the subjective self-evaluation domain score; educational level (college degree or above, β' =0.186) and receiving ART (β' =-0.299) were associated with physical domain score; receiving ART (β' =-0.263) and symptoms related to sexually transmitted diseases (β' =-0.243) were associated with psychological domain score; occupation (retirees, β' =-0.191) and symptoms related to sexually transmitted diseases (β' =-0.220) were correlated with the independence domain score; annual household income per capita (≥30 000 yuan, β' =0.281) and receiving ART (β' =-0.299) were correlated with the social relationship domain score; educational level (college degree or above, β' =0.206) and receiving ART (β' =-0.285) were correlated with the environment domain score; and receiving ART (β' =-0.492) and duration since HIV confirmation (3 to <6 years, β' =0.233; ≥6 years, β' =0.161) were correlated with the spiritual support/religion/personal beliefs domain score. Conclusions The overall quality of life among HIV/AIDS cases in Jinshan District is relatively good, but the domains of psychological, independence, and social relationship were still room for improvement. It is mainly influenced by factors such as occupation, educational level, annual household income per capita, receiving ART, symptoms related to sexually transmitted diseases, and duration since HIV confirmation.

Objective:To investigate the influence of TGF-β1 on the malignant transformation of bystander cells after proton irradiation simulating space radiation, and its underlying mechanism.Methods:Normal human bronchial epithelial cells BEAS-2B were exposed to proton irradiation at 0, 0.2, 0.5, and 1.0 Gy to simulate space radiation. Supernatants from cell culture media were collected as a conditioned medium (CM) for treating bystander BEAS-2B cells. The enzyme-linked immunosorbent assay (ELISA) was employed to detect TGF-β1 levels within the CM. The soft agar colony formation assay was performed to assess the rate of malignant transformation of bystander cells. Immunofluorescence and Western blot techniques were utilized to examine the localization of β-arrestin1 in CM-treated bystander cells, with or without the TGF-β1 receptor inhibitor SB525334. The malignant transformation of bystander cells was assessed via soft agar colony formation assay under CM treatment, combined with either a TGF-β1 receptor inhibitor or β-arrestin1 knockdown. Additionally, mRNA and protein levels of epithelial-mesenchymal transition(EMT)-related genes (e.g., E-cadherin, N-cadherin, Fibronectin1, and Vimentin) were analyzed through qRT-PCR and Western blot, respectively.Results:Contrasting with the 0 Gy group, the proton irradiation groups exhibited a dose-dependent increase in TGF-β1 secretion after 24 h ( t=3.38, 8.32, 10.96, P<0.05), and a corresponding rise in the soft agar colony formation rate of CM-treated bystander cells ( t=5.04, 7.20, 10.78, P<0.05). Immunofluorescence and Western blot results indicated that with escalating doses, CM-treated bystander cells showed increased β-arrestin1 into nuclei ( t=7.57, 7.51, P<0.05), being stimulated by TGF-β1 and inhibited by SB525334. The SB525334 application or β-arrestin1 knockdown significantly inhibited the malignant transformation and EMT induced by proton irradiation in bystander cells. This inhibition further reduced the soft agar colony formation rate ( t=2.84, 3.39, P<0.05), and increased mRNA and protein levels of the E-cadherin gene in CM-treated bystander cells exposed to 1 Gy proton irradiation ( t=7.33, 5.38, P<0.05) while reducing the mRNA and protein levels of N-cadherin, Fibronectin1, and Vimentin genes ( t=4.37, 4.10, 5.29, 10.65, 5.15, 3.11, P<0.05). Conclusions:Proton irradiation simulating space radiation can enhance TGF-β1 secretion from lung epithelial cells, inducing β-arrestin1 into nuclei in bystander cells, thereby spurring the malignant transformation of cells. The TGF-β1/β-arrestin1 pathway plays a crucial role in this process.