The objective of this study was to evaluate the toxicity and safety of novel Mycobacterium tuberculosis fusion strain protein derivatives,referred to as B/R strain active proteins.In cellular experiments,RAW264.7 cells were treated with each vaccine preparation,and apoptosis rates were measured.In subsequent animal experiments,C57BL/6 mice were immunized via subcutaneous injection,and their survival and body weight changes were monitored and recorded at 2,4,8,12,and 16 weeks.The lungs and spleens were harvested to calculate organ coefficients,and pathological examinations were conducted.At the eighth week of immunization,the mice were infected with high concentrations of BCG,and pathological changes in the lungs and spleens were observed 4 weeks post-infection.The apoptosis rate at 6 hours was significantly higher in the experimental group than the PBS group(P<0.05).At 12 and 24 hours,the apoptosis rate in the experimental group remained higher than that in the PBS group,although this difference was not statistically significant.After immunization,mice in all four groups exhibited normal growth patterns,as indicated by stable body weight changes.At 4 and 12 weeks post-immunization,the lung coefficients in the protein group were significantly higher than those in the PBS group at the same time points.Additionally,the lung coefficients in the BCG group were significantly elevated across all time periods(P<0.05).The spleen coefficients in the protein and BCG groups were significantly higher than those in the PBS group at 2,4,8,12,and 16 weeks,whereas the ICD B/R group showed higher spleen coefficients than the PBS group only at week 8(P<0.05).Pathological examination revealed normal lung and spleen tissues in the PBS group.However,during the 2-8 weeks immunization period,lung and spleen tissues in all experimental groups exhibited varying degrees of damage,which gradually diminished by 12-16 weeks.Notably,no tuberculosis nodules were observed in any experimental group.After infection with high concentrations of BCG,no overt pathological changes were observed on the surfaces of the lungs and spleens in any group.Microscopic examination revealed less severe pathological changes in the lungs and spleens of mice in the experimental groups than the PBS group.Furthermore,no statistically significant differences were observed between the protein group and the BCG group.Our findings suggested that the B/R strain active proteins'toxicity and safety profiles were comparable to those of BCG,and showed immunoprotective effects.This study provides an experimental foundation for the development of a novel tuberculosis vaccine.

Objective:To establish a mouse model of liver cancer resistant to PD-1 monoclonal antibody and analyze the changes in its metabolomics to explore the potential mechanism of drug resistance.Methods:BALB/c mice were randomly divided into control and treatment groups after being loaded with tumor,and a normal group was additionally set up.The normal and control groups were injected with saline,and the treatment group was injected with PD-1 monoclonal antibody,after which the mice in the treatment group were screened for drug resistant and response groups.Observed the drug-resistant situation,body mass,tumor growth and survival rate of mice in each group,calculate the spleen index.The pathological features of tumor tissues were observed by HE staining method.Serum metabolites were detected by non-targeted metabolomics.Finally,a bivariate Pearson correlation analysis was conducted between the differential serum metabolites and tumor size.Results:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established,and the drug resistance rate of the mice was 50％.Compared with the normal and response groups,mice in the resistant group showed an increase in body weight,a significant increase in tumor volume,a decrease in survival rate,and a significant increase in splenic index.There was less lymphocyte infiltration in the tumor tissue.Metabolomics analysis showed that the serum levels of glutamic acid and aspartic acid increased and malic acid decreased in the resistant mice compared with the response group,and these changes were closely related to the arginine biosynthesis pathway.Conclusions:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established.The changes in its peripheral serum metabolomics mainly involve arginine metabolism and the related changes of aspartate,malate and glutamate.

Objective:To compare the efficacy of active warming versus conventional warming during the perioperative period of robotic-assisted total hip arthroplasty (THA) for femoral neck fracture in elderly patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 312 elderly patients with femoral neck fracture who underwent robot-assisted THA at Second Affiliated Hospital of Xi ′an Jiaotong University from January 2024 to January 2025, including 196 males and 116 females, aged 65-89 years [(77.0±7.3)years]. Among them, 156 patients received standardized thermal management (active warming group), involving the administration of pre-warmed intravenous fluids and use of an inflatable warming blanket preoperatively, combined application of a forced-air warming system and warmed fluids intraoperatively, and transfer to a temperature-controlled ward combined with a foot circulatory compression device postoperatively. The other 156 patients received conventional warming with cotton quilts (conventional warming group), involving no administration of pre-warmed intravenous fluids preoperatively, use of warmed fluids intraoperatively, and transfer to a standard ward without the use of a foot circulatory compression device postoperatively. Core body temperature was compared between the two groups at 30 minutes preoperatively, 30 minutes intraoperatively, immediately postoperatively, and at 1 hour, 1 day, 5 days, and 7 days postoperatively. Changes in the coagulation function, including prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), and the inflammatory marker C-reactive protein (CRP) were assessed at 1 day preoperatively and at 1, 5, and 7 days postoperatively. Length of hospital stay and incidence of postoperative complications (incision infection, deep vein thrombosis, cardiac complications, and unplanned reoperations) were also recorded. Results:The core body temperature at 30 minutes intraoperatively, immediately postoperatively and at 1 hour postoperatively was (36.77±0.17)℃, (36.29±0.14)℃, and (36.35±0.14)℃ in the active warming group, significantly higher than (36.12±0.27)℃, (35.49±0.25)℃, and (35.67±0.29)℃ in the conventional warming group ( P<0.01). No significant differences in body temperature were observed between the two groups at 30 minutes preoperatively, at 1, 5, or 7 days postoperatively ( P>0.05). At 1 day postoperatively, the PT, TT and APTT were (8.5±1.3)seconds, (10.0±0.9)seconds and (24.8±2.3)seconds, significantly lower than (9.7±1.3)seconds, (12.1±1.5)seconds and (29.2±2.7)seconds in the conventional warming group ( P<0.01). There were no significant differences in PT, TT, APTT or CRP levels between the two groups at 1 day preoperatively or at 5 and 7 days postoperatively ( P>0.05). The CRP level at 1 day postoperatively was (8.0±3.0)mg/L in the active warming group, significantly lower than (13.5±3.2)mg/L in the conventional warming group ( P<0.05). There were no significant differences in CRP between the two groups at 1 day preoperatively or at 5 and 7 days postoperatively ( P>0.05). The average length of hospital stay was (12.2±1.4)days in the active warming group, significantly shorter than (14.9±1.4)days in the conventional warming group ( P<0.01). The perioperative complication rate was 6.4% (10/156) in the active warming group, significantly lower than 17.9% (28/156) in the conventional warming group ( P<0.01). Conclusion:For elderly patients with femoral neck fracture operated via robot-assisted THA, active warming during the perioperative period can more effectively maintain intraoperative normothermia, improve early postoperative coagulation function, reduce inflammatory response, shorten the length of hospital stay, and decrease complication rate when compared with conventional warming.

Objective:To explore the effects of medication interval on the quality of split-dose bowel preparation and analyze the independent risk factors affecting the quality of bowel preparation.Methods:This pilot study involved two centers. Adult outpatients who underwent screening, surveillance, and diagnostic colonoscopy in the First Affiliated Hospital of Naval Medical University ( n=46) and the Fifth Hospital of Zhangjiakou ( n=20) between April and June 2023 were enrolled. Bowel preparation was conducted based on the guideline. Patients were divided into the short-interval group (4-<10 hours, n=45) and the long-interval group (10-16 hours, n=21) based on the time between the two administrations of polyethylene glycol during bowel preparation. Differences in terms of patient-reported outcome measurements (patient-reported willingness to repeat the bowel preparation regimen, satisfaction with bowel preparation, satisfaction with sleep), defecation frequency, Boston bowel preparation scale scores, bowel preparation bubble scores, bowel preparation qualified rates, polyp detection rates and incidence of adverse events were compared. Relevant factors influencing bowel preparation quality were analyzed by univariate logistic regression. Results:There were no significant differences in patient-reported willingness to repeat the bowel preparation regimen [88.9% (40/45) VS 85.7% (18/21), χ2<0.001, P>0.999], the satisfaction with bowel preparation [65.9% (29/45) VS 57.1% (12/21), χ2=0.469, P=0.493], or the satisfaction with sleep quality [35.6% (16/45) VS 28.6% (6/21), χ2=0.314, P=0.575] between the short-interval and long-interval groups. Similarly, no significant differences were observed between the groups in defecation frequency (11.3±4.8 VS 10.2±4.4, t=0.861, P=0.395), Boston bowel preparation scale scores (8.2±1.4 scores VS 7.9±1.2 scores, t=1.024, P=0.311), bowel preparation bubble scores (8.6±1.0 scores VS 8.4±1.5 scores, t=0.672, P=0.506), bowel preparation qualified rates [88.9% (40/45) VS 90.5% (19/21), χ2<0.001, P>0.999], polyp detection rates [33.3% (15/45) VS 47.6% (10/21), χ2=1.242, P=0.265], or incidence of adverse events [24.4% (11/45) VS 14.3% (3/21), χ2=0.381, P=0.537]. Univariate logistic analysis suggested that a low-fiber diet ( OR=8.100, 95% CI:1.400-46.849, P=0.019) was an influencing factor for qualified bowel preparation. Conclusion:Medication interval of the two doses of polyethylene glycol in a split-dose bowel preparation regimen for colonoscopy has no significant impact on bowel preparation quality. Notably, preoperative low-fiber diet emerges as an independent protective factor for qualified bowel preparation.

Objective To investigate the coagulation effect of a cold atmospheric plasma(CAP)jet device with helium as the working gas and to study its coagulation mechanism preliminarily.Methods A CAP jet device treatment group,a helium airflow treatment group,a hot air treatment group(60℃)and a natural coagulation group were formed according to the treatment modes of the blood samples,with 10 μL of blood samples involved in each group,in order to validate the coagulation effect of the CAP jet device in vitro;the coagulation mechanism of the CAP jet device was explored by its application to the treatment of anticoagulated whole blood,platelet-rich plasma and platelet-depleted plasma;the coagulation effect of the CAP jet device in vivo was verified with a mouse liver punctate hemorrhage model and a rabbit mesenteric hemorrhage model.Results The CAP jet device can significantly accelerate the coagulation of anticoagulated blood droplets,and the coagulation time of anticoagulated blood droplets in the CAP jet device-treated group was shortened from 28 min in the natural coagulation group to(23±1.56)s,with the difference statistically significant(P<0.05),and the CAP jet device treatment group gained advantages significantly over the helium airflow treatment group(P<0.05)and the hot air(60℃)treatment group(P<0.05)in coagulation-promoting effect;the procoagulant effect of the CAP jet device rose with the increase of platelet content in blood droplets,and the coagulation effect of platelet-rich blood droplets was significantly better than that of whole blood(P<0.05),while no coagulation was observed in platelet-poor droplets.The CAP jet device could rapidly stop hemostasis of punctate hemorrhage in mouse liver and mesenteric hemorrhage in rabbits without delayed hemorrhage occurring within 10 min,and no obvious structural abnormality of the liver and thermal damage of the tissue were found microscopically.Conclusion The CAP jet device plays procoagulant and hemostatic effects in vivo and in vitro,and its effect is not dependent on temperature and airflow evaporation effects and is considered to be related to platelet activation,with low thermal damage to living tissue.[Chinese Medical Equipment Journal,2025,46(6):20-27]

Objective:To establish a mouse model of liver cancer resistant to PD-1 monoclonal antibody and analyze the changes in its metabolomics to explore the potential mechanism of drug resistance.Methods:BALB/c mice were randomly divided into control and treatment groups after being loaded with tumor,and a normal group was additionally set up.The normal and control groups were injected with saline,and the treatment group was injected with PD-1 monoclonal antibody,after which the mice in the treatment group were screened for drug resistant and response groups.Observed the drug-resistant situation,body mass,tumor growth and survival rate of mice in each group,calculate the spleen index.The pathological features of tumor tissues were observed by HE staining method.Serum metabolites were detected by non-targeted metabolomics.Finally,a bivariate Pearson correlation analysis was conducted between the differential serum metabolites and tumor size.Results:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established,and the drug resistance rate of the mice was 50％.Compared with the normal and response groups,mice in the resistant group showed an increase in body weight,a significant increase in tumor volume,a decrease in survival rate,and a significant increase in splenic index.There was less lymphocyte infiltration in the tumor tissue.Metabolomics analysis showed that the serum levels of glutamic acid and aspartic acid increased and malic acid decreased in the resistant mice compared with the response group,and these changes were closely related to the arginine biosynthesis pathway.Conclusions:The tumor-bearing mouse model with PD-1 monoclonal antibody resistance was successfully established.The changes in its peripheral serum metabolomics mainly involve arginine metabolism and the related changes of aspartate,malate and glutamate.

Objective To investigate the coagulation effect of a cold atmospheric plasma(CAP)jet device with helium as the working gas and to study its coagulation mechanism preliminarily.Methods A CAP jet device treatment group,a helium airflow treatment group,a hot air treatment group(60℃)and a natural coagulation group were formed according to the treatment modes of the blood samples,with 10 μL of blood samples involved in each group,in order to validate the coagulation effect of the CAP jet device in vitro;the coagulation mechanism of the CAP jet device was explored by its application to the treatment of anticoagulated whole blood,platelet-rich plasma and platelet-depleted plasma;the coagulation effect of the CAP jet device in vivo was verified with a mouse liver punctate hemorrhage model and a rabbit mesenteric hemorrhage model.Results The CAP jet device can significantly accelerate the coagulation of anticoagulated blood droplets,and the coagulation time of anticoagulated blood droplets in the CAP jet device-treated group was shortened from 28 min in the natural coagulation group to(23±1.56)s,with the difference statistically significant(P<0.05),and the CAP jet device treatment group gained advantages significantly over the helium airflow treatment group(P<0.05)and the hot air(60℃)treatment group(P<0.05)in coagulation-promoting effect;the procoagulant effect of the CAP jet device rose with the increase of platelet content in blood droplets,and the coagulation effect of platelet-rich blood droplets was significantly better than that of whole blood(P<0.05),while no coagulation was observed in platelet-poor droplets.The CAP jet device could rapidly stop hemostasis of punctate hemorrhage in mouse liver and mesenteric hemorrhage in rabbits without delayed hemorrhage occurring within 10 min,and no obvious structural abnormality of the liver and thermal damage of the tissue were found microscopically.Conclusion The CAP jet device plays procoagulant and hemostatic effects in vivo and in vitro,and its effect is not dependent on temperature and airflow evaporation effects and is considered to be related to platelet activation,with low thermal damage to living tissue.[Chinese Medical Equipment Journal,2025,46(6):20-27]

Objective To establish a ultra-high performance liquid chromatography-tandem mass spectrometer(UPLC-MS/MS)method for determining the concentration of sotagliflozin in rat plasma and apply it to pharmacokinetic studies in rats.Methods Electrospray negative ion multi-reaction ion detection was used.Chromatographic column:EXT-C18(2.1 mm × 100.0 mm,2.7 μm);column temperature:45 ℃;mobile phase:5 mmol·L-1 ammonium acetate aqueous solution-acetonitrile;flow rate:0.35 mL·min-1;ion pairs:sotagliflozin m/z 483.3→315.1,dapagliflozin m/z 467.4→329.2;injection volume:6 μL,plasma samples were processed using methyl tert-butyl ether liquid-liquid extraction.Six male SD rats were administered a single oral dose of sogliflozin at 40 mg·kg-1,and detected the concentration of sogliflozin in plasma.Pharmacokinetic parameters were calculated using Drug And Statistics(DAS)2.1.1.Results Sotagliflozin showed good linearity within the range of 5-2 000 ng·mL-1,with intra-day and inter-day precision both less than 15％.The recovery rate,matrix effect,and stability were all within the specified range.Pharmacokinetic parameters:Cmax was(3 716.67±568.28)ng·mL-1,tmax was(1.00±0.32)h,t1/2 was(2.28±0.45)h,AUC0-t was(1.70 × 104±2 075.87)ng·mL-1·h.Conclusion This study established a method for determining the concentration of sotagliflozin in rat plasma,which is characterized by high sensitivity,rapid detection,and good repeatability.It is suitable for the determination of sotagliflozin concentration in plasma and pharmacokinetic studies.

Objective:To compare the efficacy of active warming versus conventional warming during the perioperative period of robotic-assisted total hip arthroplasty (THA) for femoral neck fracture in elderly patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 312 elderly patients with femoral neck fracture who underwent robot-assisted THA at Second Affiliated Hospital of Xi ′an Jiaotong University from January 2024 to January 2025, including 196 males and 116 females, aged 65-89 years [(77.0±7.3)years]. Among them, 156 patients received standardized thermal management (active warming group), involving the administration of pre-warmed intravenous fluids and use of an inflatable warming blanket preoperatively, combined application of a forced-air warming system and warmed fluids intraoperatively, and transfer to a temperature-controlled ward combined with a foot circulatory compression device postoperatively. The other 156 patients received conventional warming with cotton quilts (conventional warming group), involving no administration of pre-warmed intravenous fluids preoperatively, use of warmed fluids intraoperatively, and transfer to a standard ward without the use of a foot circulatory compression device postoperatively. Core body temperature was compared between the two groups at 30 minutes preoperatively, 30 minutes intraoperatively, immediately postoperatively, and at 1 hour, 1 day, 5 days, and 7 days postoperatively. Changes in the coagulation function, including prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT), and the inflammatory marker C-reactive protein (CRP) were assessed at 1 day preoperatively and at 1, 5, and 7 days postoperatively. Length of hospital stay and incidence of postoperative complications (incision infection, deep vein thrombosis, cardiac complications, and unplanned reoperations) were also recorded. Results:The core body temperature at 30 minutes intraoperatively, immediately postoperatively and at 1 hour postoperatively was (36.77±0.17)℃, (36.29±0.14)℃, and (36.35±0.14)℃ in the active warming group, significantly higher than (36.12±0.27)℃, (35.49±0.25)℃, and (35.67±0.29)℃ in the conventional warming group ( P<0.01). No significant differences in body temperature were observed between the two groups at 30 minutes preoperatively, at 1, 5, or 7 days postoperatively ( P>0.05). At 1 day postoperatively, the PT, TT and APTT were (8.5±1.3)seconds, (10.0±0.9)seconds and (24.8±2.3)seconds, significantly lower than (9.7±1.3)seconds, (12.1±1.5)seconds and (29.2±2.7)seconds in the conventional warming group ( P<0.01). There were no significant differences in PT, TT, APTT or CRP levels between the two groups at 1 day preoperatively or at 5 and 7 days postoperatively ( P>0.05). The CRP level at 1 day postoperatively was (8.0±3.0)mg/L in the active warming group, significantly lower than (13.5±3.2)mg/L in the conventional warming group ( P<0.05). There were no significant differences in CRP between the two groups at 1 day preoperatively or at 5 and 7 days postoperatively ( P>0.05). The average length of hospital stay was (12.2±1.4)days in the active warming group, significantly shorter than (14.9±1.4)days in the conventional warming group ( P<0.01). The perioperative complication rate was 6.4% (10/156) in the active warming group, significantly lower than 17.9% (28/156) in the conventional warming group ( P<0.01). Conclusion:For elderly patients with femoral neck fracture operated via robot-assisted THA, active warming during the perioperative period can more effectively maintain intraoperative normothermia, improve early postoperative coagulation function, reduce inflammatory response, shorten the length of hospital stay, and decrease complication rate when compared with conventional warming.

Objective:To explore the effects of medication interval on the quality of split-dose bowel preparation and analyze the independent risk factors affecting the quality of bowel preparation.Methods:This pilot study involved two centers. Adult outpatients who underwent screening, surveillance, and diagnostic colonoscopy in the First Affiliated Hospital of Naval Medical University ( n=46) and the Fifth Hospital of Zhangjiakou ( n=20) between April and June 2023 were enrolled. Bowel preparation was conducted based on the guideline. Patients were divided into the short-interval group (4-<10 hours, n=45) and the long-interval group (10-16 hours, n=21) based on the time between the two administrations of polyethylene glycol during bowel preparation. Differences in terms of patient-reported outcome measurements (patient-reported willingness to repeat the bowel preparation regimen, satisfaction with bowel preparation, satisfaction with sleep), defecation frequency, Boston bowel preparation scale scores, bowel preparation bubble scores, bowel preparation qualified rates, polyp detection rates and incidence of adverse events were compared. Relevant factors influencing bowel preparation quality were analyzed by univariate logistic regression. Results:There were no significant differences in patient-reported willingness to repeat the bowel preparation regimen [88.9% (40/45) VS 85.7% (18/21), χ2<0.001, P>0.999], the satisfaction with bowel preparation [65.9% (29/45) VS 57.1% (12/21), χ2=0.469, P=0.493], or the satisfaction with sleep quality [35.6% (16/45) VS 28.6% (6/21), χ2=0.314, P=0.575] between the short-interval and long-interval groups. Similarly, no significant differences were observed between the groups in defecation frequency (11.3±4.8 VS 10.2±4.4, t=0.861, P=0.395), Boston bowel preparation scale scores (8.2±1.4 scores VS 7.9±1.2 scores, t=1.024, P=0.311), bowel preparation bubble scores (8.6±1.0 scores VS 8.4±1.5 scores, t=0.672, P=0.506), bowel preparation qualified rates [88.9% (40/45) VS 90.5% (19/21), χ2<0.001, P>0.999], polyp detection rates [33.3% (15/45) VS 47.6% (10/21), χ2=1.242, P=0.265], or incidence of adverse events [24.4% (11/45) VS 14.3% (3/21), χ2=0.381, P=0.537]. Univariate logistic analysis suggested that a low-fiber diet ( OR=8.100, 95% CI:1.400-46.849, P=0.019) was an influencing factor for qualified bowel preparation. Conclusion:Medication interval of the two doses of polyethylene glycol in a split-dose bowel preparation regimen for colonoscopy has no significant impact on bowel preparation quality. Notably, preoperative low-fiber diet emerges as an independent protective factor for qualified bowel preparation.