Objective To evaluate the diagnostic efficacy of metagenomic next-generation sequencing(mNGS)in detecting pathogens causing secondary infections in maintenance hemodialysis(MHD)patients,providing evidence for clinical implementation.Methods Sixty-five MHD patients with suspected secondary infections admitted to the blood purification treatment center of Tianjin University Tianjin Hospital from October 2022 to March 2024 were selected as the research subjects.All enrolled patients underwent routine laboratory examinations and imaging tests,the peripheral blood,sputum,bronchoalveolar lavage fluid(BALF),urine,feces,pleural effusion,and peritoneal effusion were collected for mNGS and traditional isolation and culture respectively.The infection status of MHD patients was analyzed.Compare the sensitivity,specificity,diagnostic accuracy,positive predictive value,negative predictive value,pathogen detection rate,and detection cycle across the two etiological diagnostic methods.Results Among the enrolled patients,11 were excluded from infection after comprehensive analysis and diagnostic treatment,and 54 were definitively diagnosed with MHD-associated secondary infections,including 20 cases of respiratory system infection(accounting for 37.04%),18 cases of bloodstream infection(33.33%),13 cases of urinary system infection(24.07%),2 cases of pleurisy(3.71%),and 1 case of peritonitis(1.85%).Among these infected cases,there were 12 cases of single bacterial infection,6 cases of single fungal infection,3 cases of atypical pathogen infection,and 33 cases of overlapping infections detected.The most common pathogens in respiratory infections,bloodstream infections,and urinary tract infections were Klebsiella pneumoniae,Staphylococcus aureus,and Escherichia coli respectively.Through mNGS,6 additional cases of Pneumocystispneumonia,3 cases of pulmonary Aspergillosis,3 cases of pulmonary tuberculosis,and 1 case of fungal pleurisy were successfully detected.A total of 25 patients had their medication adjusted based on the mNGS results,among whom 18 were discharged after improvement with treatment.The most common pattern of mixed infection was bacteria+fungi(16 cases),followed by bacteria+bacteria(9 cases),bacteria+fungi+atypical pathogens(4 cases),bacteria+atypical pathogens(3 cases),and fungi+fungi(1 case)in overlapping infections.The positive detection rate of overlapping infections by mNGS was significantly higher than that by traditional isolation and culture[78.79%(26/33)vs.12.12%(4/33),P<0.05].The sensitivity of mNGS in diagnosing pathogenic infections was significantly higher than that of traditional isolation and culture(overall diagnostic efficacy:96.30%vs.59.26%,precise diagnostic efficacy:95.35%vs.35.29%,both P<0.05).However,the specificity of the overall diagnostic efficacy of traditional isolation and culture was significantly higher than that of mNGS(100.00%vs.81.82%,P<0.05),the diagnostic coincidence rate,accuracy rate of single pathogen detection,and accuracy rate of overlapping pathogen detection of mNGS were all significantly higher than those of traditional isolation and culture(diagnostic coincidence rate of overall diagnostic efficacy:93.85%vs.66.15%,diagnostic coincidence rate of precise diagnostic efficacy:76.92%vs.35.38%,accuracy rate of single pathogen detection:80.95%vs.52.38%,accuracy rate of overlapping pathogen detection:66.67%vs.0,all P<0.05).The detection cycle of mNGS was significantly shorter than that of traditional isolation and culture[hours:27(26,29)vs.70(28,114),P<0.05].Conclusion mNGS can provide accurate and rapid etiological diagnosis for secondary infections in MHD patients,bringing benefits to precise diagnosis and targeted drug therapy.

OBJECTIVE: To investigate the effectiveness of tibial transverse transport (TTT) in treating Wagner grade 3-4 type 2 diabetic foot ulcers and analyze dynamic changes in immunoglobulin levels. METHODS: The clinical data of 68 patients with Wagner grade 3-4 type 2 diabetic foot ulcers treated with TTT between May 2022 and September 2023 was retrospectively analyzed. The cohort included 49 males and 19 females, aged 44-91 years (mean, 67.3 years), with 40 Wagner grade 3 and 28 grade 4 ulcers. The duration of type 2 diabetes ranged from 5 to 23 years, with an average of 10 years. The number of wound healing cases, healing time, amputation cases, death cases, and complications were observed and recorded. Serum samples were collected at 6 key time points [1 day before TTT and 3 days, 7 days (the first day of upward transverse transfer), 14 days (the first day of downward transverse transfer), 21 days (the first day after the end of transfer), 36 days (the first day after the removal of the transfer device)], and the serum immunoglobulin levels were detected by flow cytometry including immunoglobulin G (IgG), IgA, IgM, IgE, complement C3 (C3), C4, immunoglobulin light chain κ (KAP), immunoglobulin light chain λ (LAM). RESULTS: All the 68 patients were followed up 6 months. Postoperative pin tract infection occurred in 3 cases and incision infection in 2 cases. Amputation occurred in 5 patients (7.4%) at 59-103 days after operation, and 8 patients (11.8%) died at 49-77 days after operation; the wounds of the remaining 55 patients (80.9%) healed in 48-135 days, with an average of 80 days. There was no recurrence of ulcer, peri-osteotomy fracture, or local skin necrosis during follow-up. The serum immunoglobulin levels of 55 patients with wound healing showed that the levels of IgG and IgM decreased significantly on the 3rd and 7th day after operation compared with those before operation ( P<0.05), and gradually returned to the levels before operation after 14 days, and reached the peak on the 36th day. IgA levels continued to decrease with time, and there were significant differences at all time points when compared with those before operation ( P<0.05). The level of IgE significantly decreased at 21 days after operation compared with that before operation ( P<0.05), while it was higher at other time points than that before operation, but the difference was not significant ( P>0.05). The level of C3 showed a clear treatment-related increase, which was significantly higher on the 7th, 14th, and 21st days after operation than that before operation ( P<0.05), and the peak appeared on the 14th day. The change trend of C4 level was basically synchronous with that of C3, but the amplitude was smaller, and the difference was significant at 7 and 14 days after operation compared with that before operation ( P<0.05). There was no significant difference in KAP/LAM between different time points before and after operation ( P>0.05). CONCLUSION TTT can accelerate wound healing, effectively treat diabetic foot ulcer, and reduce amputation rate, and has definite effectiveness. The potential mechanisms of TTT in the treatment of diabetic foot ulcers include the dynamic regulation of IgG, IgA, IgM, and IgE levels to balance the process of inflammation and repair, and the periodic increase of C3 and C4 levels may promote tissue cleaning, angiogenesis, and anti-infection defense.
Humans ; Male ; Female ; Middle Aged ; Aged ; Diabetic Foot/immunology* ; Wound Healing ; Adult ; Retrospective Studies ; Aged, 80 and over ; Treatment Outcome ; Tibia/transplantation* ; Diabetes Mellitus, Type 2/complications* ; Amputation, Surgical ; Immunoglobulins/blood* ; Immunoglobulin G/blood*

In recent years,the combined application of targeted-immunotherapy has become a recommended treatment option for advanced renal cell carcinoma in various guidelines.However,although this strategy has significant therapeutic effects and survival advantages,it is associated with a variety of adverse reactions that cannot be ignored.Therefore,how to effectively manage adverse reactions and ensure the treatment safety has become one of the core issues.This article systematically reviews the adverse effects and management strategies,discusses the early identification of adverse reactions,monitoring methods,the design of individualized treatment plans and future development,aiming to provide practical safety management guidance and explore the direction of future development.

Objective:To investigate the effect of oxidized-low density lipoprotein (ox-LDL) on contrast-induced renal tubular epithelial cell apoptosis and its mechanism.Methods:Human renal proximal tubular epithelial HK-2 cells were cultured in vitro and divided into four groups using the random number table method, including a control group, an ox-LDL group (50 μg/ml ox-LDL), an iohexol group (100 mg I/ml iohexol) and an ox-LDL+iohexol group (50 μg/ml ox-LDL+100 mg I/ml iohexol). Apoptosis rates were detected using the in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay. Western blotting was used to detect the level of apoptosis by evaluating the presence of cleaved cysteine aspartic acid specific protease-3 (cleaved Caspase-3) protein. Mitochondrial membrane potential was detected using the JC-1 method. Mitochondrial/cytoplasmic cytochrome C (Cyt C) levels were detected by Western blotting to assess mitochondrial damage. Western blotting was used to detect the levels of the mitochondrial fission-related dynamin-related protein 1 (Drp1) and the mitochondrial fusion-related optic atrophy protein 1 (OPA1) to evaluate mitochondrial fusion/fission. Independent sample t test and one-way analysis of variance were used for data analysis. Results:The apoptosis rate [(30.12±3.19)%] and the relative expression of cleaved Caspase-3 protein (0.34±0.07) in the iohexol group were higher than those in the control group [(4.77±1.68)%, 0.23±0.05] ( P<0.05, 0.01). The apoptosis rate [(48.81±4.96)%] and the relative expression of cleaved Caspase-3 protein (0.53±0.05) in the ox-LDL+iohexol group were higher than those in the iohexol group (both P<0.01). The mitochondrial membrane potential (1.61±0.15) and mitochondrial/cytoplasmic Cyt C ratio (1.09±0.14) in the iohexol group were lower than those in the control group (6.15±0.52 and 3.09±0.45) (both P<0.01). The mitochondrial membrane potential (0.27±0.01) and the mitochondrial/cytoplasmic Cyt C ratio (0.24±0.04) in the ox-LDL+iohexol group were lower than those in the iohexol group (both P<0.01). The relative expression of Drp1 protein in the iohexol group (0.49±0.05) was higher than that in the control group (0.29±0.03), the relative expression of long OPA1 protein (0.24±0.03) was lower than that of the control group (0.40±0.03) (both P<0.01). The relative expression of Drp1 protein in the ox-LDL+iohexol group (0.64±0.02) was higher than that in the iohexol group, the relative expression of long OPA1 protein (0.07±0.02) was lower than that in the iohexol group (both P<0.01). Conclusions:ox-LDL can exacerbate contrast-induced renal tubular epithelial cell apoptosis, and its mechanism may be due to an imbalance in mitochondrial fusion and division caused by the contrast agent, leading to the increase mitochondrial damage.

Objective:To investigate the impact of geometric morphology and hemodynamic characteristics at the carotid bifurcation on the formation of ulcerated plaques based on CT angiography(CTA).Methods:This was a cross-sectional study. The clinical and imaging data of 71 patients with carotid bifurcation atherosclerotic plaques (stenosis≥50%) confirmed by cranial and cervical CTA at Tianjin TEDA Hospital from July 2020 to October 2023 were retrospectively analyzed. Patients were divided into an ulcerated plaque group (32 cases) and a non-ulcerated plaque group (39 cases) based on plaque ulceration status. The CTA technique was used to assess the geometric parameters of the carotid bifurcation [such as the bifurcation angle, the angle between the common carotid artery and internal carotid artery (CCA-ICA), the proximal curvature angle of the internal carotid artery (ICA), and the ratio of the maximum area at the carotid bifurcation to the initial area of the carotid artery (CCAMAX/CCA)] and plaque characteristic parameters [such as plaque area at the site of stenosis, maximum wall thickness, remodeling ratio, eccentricity index, and presence of calcification within plaques]. Quantitative analysis of hemodynamic parameters in the plaque region was performed using finite-element analysis software, including time-averaged wall shear stress (TAWSS), transverse wall shear stress (transWSS), relative residence time (RRT), and oscillatory shear index (OSI). Comparisons of parameters between the two groups were conducted using the Mann-Whitney U test or χ2 test, and multivariate logistic regression analysis was employed to identify independent geometric and plaque characteristic factors influencing the formation of ulcerated plaques. A combined model incorporating hemodynamic, geometric, and plaque characteristic parameters was developed, and the efficacy of this combined model in predicting ulceration formation at the carotid bifurcation was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Results:The bifurcation angle, CCA-ICA angle, proximal ICA curvature angle, CCAMAX/CCA ratio, presence of calcification within plaques, plaque area at the site of stenosis, and maximum wall thickness exhibited statistically significant differences between the ulcerated plaque group and the non-ulcerated plaque group ( P<0.05). Logistic regression analysis showed that CCAMAX/CCA ( OR=6.452, 95% CI 1.541-27.015, P=0.011) and plaque area at the site of stenosis ( OR=1.048, 95% CI 1.015-1.124, P=0.011) were independent factors influencing the formation of ulcerated plaques at the carotid bifurcation. The maximum and mean values of RRT and OSI in the ulcerated plaque group were significantly higher than those in the non-ulcerated group ( P<0.05), while the maximum and mean values of transWSS and TAWSS were lower in the ulcerated group compared to the non-ulcerated group ( P<0.05). The AUC for the combined model predicting ulceration formation at the carotid bifurcation was 0.926. Conclusions:The CCAMAX/CCA ratio and plaque area at the site of stenosis at the carotid bifurcation are independent factors influencing the formation of ulcerated plaques. A model that combines geometric morphology and hemodynamic parameters can more effectively diagnose the formation of ulcerated plaques at the carotid bifurcation.

Objective:To evaluate the advantages and short-term clinical effects of totally robotic Nissen 360° fundoplication compared with laparoscopic surgery.Methods:A retrospective analysis was conducted on data of 110 patients undergoing Nissen 360° fundoplication at the Second Department of General Surgery, Yan'an Hospital Affiliated to Kunming Medical University from Aug 2023 to Aug 2024. Among them, 50 cases underwent totally robotic fundoplication, and 60 cases underwent laparoscopic fundoplication. By comparing and analyzing the fatigue level of the primary surgeon during the operations, postoperative incisional pain in patients, swallowing function recovery and the time to resume a normal solid-food diet within 3 months post-surgery, the advantages of totally robotic surgery were evaluated. Additionally, by examining the postoperative recovery of reflux symptoms, postoperative patient comfort, and satisfaction levels in both groups, the short-term clinical outcomes of totally robotic surgery were assessed.Results:Both groups of patients successfully completed the surgeries without any intraoperative or postoperative complications occurring. The fatigue score of the primary surgeon in the totally robotic group was significantly better than that in the laparoscopic group[ (2.34±1.38) vs. (2.89±1.51), t=1.385, P<0.01]. The time taken to resume a normal solid-food diet postoperatively in the totally robotic group was significantly shorter than that in the laparoscopic group[ (27.90±6.77) d vs. (40.78±13.60) d, t =5.765, P<0.01]. Moreover, the postoperative pain comfort level was better in the robotic group than in the laparoscopic group [(1.65±0.72) points vs. (2.23±0.59) points, t=3.742, P<0.01]. Within 12 months postoperatively, the GERD-Q scores in the totally robotic group decreased significantly, and reflux symptoms disappeared, comparable to that in the laparoscopic group. Conclusions:The totally robotic Nissen 360° fundoplication leads to lower fatigue levels for the surgeon. Patients experience significant advantages in terms of postoperative pain perception and dietary recovery. Additionally, it demonstrates excellent postoperative anti-reflux efficacy, high patient comfort, and the surgery is safe and reliable.

In recent years,the combined application of targeted-immunotherapy has become a recommended treatment option for advanced renal cell carcinoma in various guidelines.However,although this strategy has significant therapeutic effects and survival advantages,it is associated with a variety of adverse reactions that cannot be ignored.Therefore,how to effectively manage adverse reactions and ensure the treatment safety has become one of the core issues.This article systematically reviews the adverse effects and management strategies,discusses the early identification of adverse reactions,monitoring methods,the design of individualized treatment plans and future development,aiming to provide practical safety management guidance and explore the direction of future development.

Objective:To investigate the impact of geometric morphology and hemodynamic characteristics at the carotid bifurcation on the formation of ulcerated plaques based on CT angiography(CTA).Methods:This was a cross-sectional study. The clinical and imaging data of 71 patients with carotid bifurcation atherosclerotic plaques (stenosis≥50%) confirmed by cranial and cervical CTA at Tianjin TEDA Hospital from July 2020 to October 2023 were retrospectively analyzed. Patients were divided into an ulcerated plaque group (32 cases) and a non-ulcerated plaque group (39 cases) based on plaque ulceration status. The CTA technique was used to assess the geometric parameters of the carotid bifurcation [such as the bifurcation angle, the angle between the common carotid artery and internal carotid artery (CCA-ICA), the proximal curvature angle of the internal carotid artery (ICA), and the ratio of the maximum area at the carotid bifurcation to the initial area of the carotid artery (CCAMAX/CCA)] and plaque characteristic parameters [such as plaque area at the site of stenosis, maximum wall thickness, remodeling ratio, eccentricity index, and presence of calcification within plaques]. Quantitative analysis of hemodynamic parameters in the plaque region was performed using finite-element analysis software, including time-averaged wall shear stress (TAWSS), transverse wall shear stress (transWSS), relative residence time (RRT), and oscillatory shear index (OSI). Comparisons of parameters between the two groups were conducted using the Mann-Whitney U test or χ2 test, and multivariate logistic regression analysis was employed to identify independent geometric and plaque characteristic factors influencing the formation of ulcerated plaques. A combined model incorporating hemodynamic, geometric, and plaque characteristic parameters was developed, and the efficacy of this combined model in predicting ulceration formation at the carotid bifurcation was evaluated using receiver operating characteristic curves and the area under the curve (AUC). Results:The bifurcation angle, CCA-ICA angle, proximal ICA curvature angle, CCAMAX/CCA ratio, presence of calcification within plaques, plaque area at the site of stenosis, and maximum wall thickness exhibited statistically significant differences between the ulcerated plaque group and the non-ulcerated plaque group ( P<0.05). Logistic regression analysis showed that CCAMAX/CCA ( OR=6.452, 95% CI 1.541-27.015, P=0.011) and plaque area at the site of stenosis ( OR=1.048, 95% CI 1.015-1.124, P=0.011) were independent factors influencing the formation of ulcerated plaques at the carotid bifurcation. The maximum and mean values of RRT and OSI in the ulcerated plaque group were significantly higher than those in the non-ulcerated group ( P<0.05), while the maximum and mean values of transWSS and TAWSS were lower in the ulcerated group compared to the non-ulcerated group ( P<0.05). The AUC for the combined model predicting ulceration formation at the carotid bifurcation was 0.926. Conclusions:The CCAMAX/CCA ratio and plaque area at the site of stenosis at the carotid bifurcation are independent factors influencing the formation of ulcerated plaques. A model that combines geometric morphology and hemodynamic parameters can more effectively diagnose the formation of ulcerated plaques at the carotid bifurcation.

Objective To evaluate the diagnostic efficacy of metagenomic next-generation sequencing(mNGS)in detecting pathogens causing secondary infections in maintenance hemodialysis(MHD)patients,providing evidence for clinical implementation.Methods Sixty-five MHD patients with suspected secondary infections admitted to the blood purification treatment center of Tianjin University Tianjin Hospital from October 2022 to March 2024 were selected as the research subjects.All enrolled patients underwent routine laboratory examinations and imaging tests,the peripheral blood,sputum,bronchoalveolar lavage fluid(BALF),urine,feces,pleural effusion,and peritoneal effusion were collected for mNGS and traditional isolation and culture respectively.The infection status of MHD patients was analyzed.Compare the sensitivity,specificity,diagnostic accuracy,positive predictive value,negative predictive value,pathogen detection rate,and detection cycle across the two etiological diagnostic methods.Results Among the enrolled patients,11 were excluded from infection after comprehensive analysis and diagnostic treatment,and 54 were definitively diagnosed with MHD-associated secondary infections,including 20 cases of respiratory system infection(accounting for 37.04%),18 cases of bloodstream infection(33.33%),13 cases of urinary system infection(24.07%),2 cases of pleurisy(3.71%),and 1 case of peritonitis(1.85%).Among these infected cases,there were 12 cases of single bacterial infection,6 cases of single fungal infection,3 cases of atypical pathogen infection,and 33 cases of overlapping infections detected.The most common pathogens in respiratory infections,bloodstream infections,and urinary tract infections were Klebsiella pneumoniae,Staphylococcus aureus,and Escherichia coli respectively.Through mNGS,6 additional cases of Pneumocystispneumonia,3 cases of pulmonary Aspergillosis,3 cases of pulmonary tuberculosis,and 1 case of fungal pleurisy were successfully detected.A total of 25 patients had their medication adjusted based on the mNGS results,among whom 18 were discharged after improvement with treatment.The most common pattern of mixed infection was bacteria+fungi(16 cases),followed by bacteria+bacteria(9 cases),bacteria+fungi+atypical pathogens(4 cases),bacteria+atypical pathogens(3 cases),and fungi+fungi(1 case)in overlapping infections.The positive detection rate of overlapping infections by mNGS was significantly higher than that by traditional isolation and culture[78.79%(26/33)vs.12.12%(4/33),P<0.05].The sensitivity of mNGS in diagnosing pathogenic infections was significantly higher than that of traditional isolation and culture(overall diagnostic efficacy:96.30%vs.59.26%,precise diagnostic efficacy:95.35%vs.35.29%,both P<0.05).However,the specificity of the overall diagnostic efficacy of traditional isolation and culture was significantly higher than that of mNGS(100.00%vs.81.82%,P<0.05),the diagnostic coincidence rate,accuracy rate of single pathogen detection,and accuracy rate of overlapping pathogen detection of mNGS were all significantly higher than those of traditional isolation and culture(diagnostic coincidence rate of overall diagnostic efficacy:93.85%vs.66.15%,diagnostic coincidence rate of precise diagnostic efficacy:76.92%vs.35.38%,accuracy rate of single pathogen detection:80.95%vs.52.38%,accuracy rate of overlapping pathogen detection:66.67%vs.0,all P<0.05).The detection cycle of mNGS was significantly shorter than that of traditional isolation and culture[hours:27(26,29)vs.70(28,114),P<0.05].Conclusion mNGS can provide accurate and rapid etiological diagnosis for secondary infections in MHD patients,bringing benefits to precise diagnosis and targeted drug therapy.

Objective:To evaluate the advantages and short-term clinical effects of totally robotic Nissen 360° fundoplication compared with laparoscopic surgery.Methods:A retrospective analysis was conducted on data of 110 patients undergoing Nissen 360° fundoplication at the Second Department of General Surgery, Yan'an Hospital Affiliated to Kunming Medical University from Aug 2023 to Aug 2024. Among them, 50 cases underwent totally robotic fundoplication, and 60 cases underwent laparoscopic fundoplication. By comparing and analyzing the fatigue level of the primary surgeon during the operations, postoperative incisional pain in patients, swallowing function recovery and the time to resume a normal solid-food diet within 3 months post-surgery, the advantages of totally robotic surgery were evaluated. Additionally, by examining the postoperative recovery of reflux symptoms, postoperative patient comfort, and satisfaction levels in both groups, the short-term clinical outcomes of totally robotic surgery were assessed.Results:Both groups of patients successfully completed the surgeries without any intraoperative or postoperative complications occurring. The fatigue score of the primary surgeon in the totally robotic group was significantly better than that in the laparoscopic group[ (2.34±1.38) vs. (2.89±1.51), t=1.385, P<0.01]. The time taken to resume a normal solid-food diet postoperatively in the totally robotic group was significantly shorter than that in the laparoscopic group[ (27.90±6.77) d vs. (40.78±13.60) d, t =5.765, P<0.01]. Moreover, the postoperative pain comfort level was better in the robotic group than in the laparoscopic group [(1.65±0.72) points vs. (2.23±0.59) points, t=3.742, P<0.01]. Within 12 months postoperatively, the GERD-Q scores in the totally robotic group decreased significantly, and reflux symptoms disappeared, comparable to that in the laparoscopic group. Conclusions:The totally robotic Nissen 360° fundoplication leads to lower fatigue levels for the surgeon. Patients experience significant advantages in terms of postoperative pain perception and dietary recovery. Additionally, it demonstrates excellent postoperative anti-reflux efficacy, high patient comfort, and the surgery is safe and reliable.