Objective To investigate the therapeutic effect of chimeric antigen receptor(CAR)T cells on myocardial infarction(MI)and observe the impact of different administration routes on CAR-T cell cardiac toxicity.Methods Twenty-four SCID Beige immunodeficient mice,which successfully established a myocardial infarction model,were randomly divided into Hank's balanced salt solution(HBSS)group,CAR-TIM group,CAR-TIV group,and CAR-TIMIV group(n=6 for each group).In addition,a Sham group(n=6)was set up.The Sham group,HBSS group,CAR-TIM group,and CAR-TIMIV group were injected with HBSS or CAR-T cells via intramyocardial injection on the 7th day after modeling.The Sham group,HBSS group,CAR-TIV group,and CAR-TIMIV group were injected with HBSS or CAR-T cells via tail vein injection on the 7th day and 14th day after modeling.After 28 days of modeling,the electrical physiological indicators of the mice were observed,and the myocardial tissues were subjected to Masson staining to calculate the area of myocardial infarction.Results Compared with the Sham group,the HBSS group had significant increases in myocardial infarction size and incidence of arrhythmia(P＜0.05).Compared with HBSS group,different routes of CAR-T cell therapy significantly reduced the area of myocardial infarction(all P＜0.05)and significantly increased the incidence of arrhythmia(all P＜0.05).There was no significant difference in the effect of CAR-TIV and CAR-TIM groups on the area of myocardial infarction and the incidence of arrhythmia.Compared with the CAR-TIV group,the area of myocardial infarction significantly reduced in the CAR-TIMIV group(P＜0.05),with no significant difference in the incidence of arrhythmia between the two groups.Conclusions Intravenous and local myocardial injection of CAR-T cells can effectively reduce the myocardial infarction area but increase the incidence of arrhythmia.The mechanism needs further study.

Objective:To investigate the diagnostic value of urine pH, serum uric acid and related clinical indicators in the diagnosis of urinary infection stones, and to construct a prediction nomogram.Methods:The clinical data of 432 patients with urinary calculi admitted to Xuzhou Central Hospital from August 2018 to November 2023 were retrospectively analyzed. The study included 289 males and 143 females, with an average age of (52.72±13.46) years old. Among the patients, there were 98 cases of hypertension, 67 cases of diabetes, and 100 cases of recurrent calculi. Kidney stones were present in 152 cases, ureteral stones in 242 cases, and bladder stones in 38 cases. Urine bacterial culture yielded positive results in 97 cases. According to the results of postoperative stone composition analysis, the two groups were categorized as infection and no-infection stone groups, and the differences in general data between the two groups were compared. Univariate and multivariate logistic regression analysis were conducted to assess the diagnostic value of urine pH, serum uric acid, and related clinical indicators for urinary infection stones. Receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to evaluate the clinical significance of urine pH, serum uric acid, and combined indexes in preoperatively diagnosing urinary infection stones, as well as constructing a nomogram prediction model.Results:There were 127 cases of infection stones and 305 cases of no-infection stones. The infection stone group exhibited a higher urine pH value [7.0(6.5, 7.5) vs. 6.0(5.5, 6.5), P<0.001], lower serum uric acid levels [(301.38±70.12) vs. (358.88±88.99) μmol/L, P<0.001], a higher proportion of females [55.1%(70/127) vs. 23.9%(73/305), P<0.001], younger age [(48.36±14.83)vs. (53.12±12.61)years old, P<0.001], a higher proportion of recurrence stones [34.6 %(44/127) vs. 18.4%(56/305), P<0.001], and a higher rate of positive urine bacteria culture[29.9%(38/127)vs. 19.3%(59/305), P=0.016]and nitrite test results [18.9%(24/127)vs. 6.3%(19/305), P <0.001]. Univariate logistic regression analysis revealed that urine pH value, serum uric acid levels, gender, age, recurrent stones, urine bacterial culture, and urine nitrite were associated with urinary infection stones ( P< 0.05). Multivariate logistic regression analysis revealed that urine pH value ( OR= 4.836, 95% CI 3.342-6.997), female gender( OR=2.320, 95% CI 1.286-4.186), recurrent stones ( OR=2.225, 95% CI 1.208-4.101), positive urine bacterial culture ( OR=2.061, 95% CI 1.094-3.883), serum uric acid ( OR=0.992, 95% CI 0.949-0.989), age ( OR=0.969, 95% CI 0.949-0.990) were independent risk factors for urinary infection stones ( P<0.05). The combined diagnostic value of six indicators was the highest, with an AUC of 0.874 (95% CI 0.837-0.911). Following this, urine pH exhibited an AUC of 0.818 (95% CI 0.778-0.858), while serum uric acid had an AUC of 0.704 (95% CI 0.652-0.756). The nomogram model was successfully constructed based on the six indicators. The mean AUC of the ROC curve after 1 000 resamples of the Bootstrap method was 0.864 (95% CI 0.828-0.900), and the calibration curve showed that the predicted curve fit the ideal curve well, with a mean absolute error of 0.005 and a Hosmer-Lemeshow test of P>0.05. Clinical decision curve analysis (DCA) showed that the model had a higher net clinical benefit when the model had a threshold probability value≥0.01. Conclusions:Urine pH and serum uric acid are closely related to urinary infection stones. A nomogram model combining these factors with gender, age, recurrent stones, and urine culture results can effectively predict the probability of infection-related stones, providing significant clinical value.

Objective:To investigate the diagnostic value of urine pH, serum uric acid and related clinical indicators in the diagnosis of urinary infection stones, and to construct a prediction nomogram.Methods:The clinical data of 432 patients with urinary calculi admitted to Xuzhou Central Hospital from August 2018 to November 2023 were retrospectively analyzed. The study included 289 males and 143 females, with an average age of (52.72±13.46) years old. Among the patients, there were 98 cases of hypertension, 67 cases of diabetes, and 100 cases of recurrent calculi. Kidney stones were present in 152 cases, ureteral stones in 242 cases, and bladder stones in 38 cases. Urine bacterial culture yielded positive results in 97 cases. According to the results of postoperative stone composition analysis, the two groups were categorized as infection and no-infection stone groups, and the differences in general data between the two groups were compared. Univariate and multivariate logistic regression analysis were conducted to assess the diagnostic value of urine pH, serum uric acid, and related clinical indicators for urinary infection stones. Receiver operating characteristic (ROC) curve and area under curve (AUC) were utilized to evaluate the clinical significance of urine pH, serum uric acid, and combined indexes in preoperatively diagnosing urinary infection stones, as well as constructing a nomogram prediction model.Results:There were 127 cases of infection stones and 305 cases of no-infection stones. The infection stone group exhibited a higher urine pH value [7.0(6.5, 7.5) vs. 6.0(5.5, 6.5), P<0.001], lower serum uric acid levels [(301.38±70.12) vs. (358.88±88.99) μmol/L, P<0.001], a higher proportion of females [55.1%(70/127) vs. 23.9%(73/305), P<0.001], younger age [(48.36±14.83)vs. (53.12±12.61)years old, P<0.001], a higher proportion of recurrence stones [34.6 %(44/127) vs. 18.4%(56/305), P<0.001], and a higher rate of positive urine bacteria culture[29.9%(38/127)vs. 19.3%(59/305), P=0.016]and nitrite test results [18.9%(24/127)vs. 6.3%(19/305), P <0.001]. Univariate logistic regression analysis revealed that urine pH value, serum uric acid levels, gender, age, recurrent stones, urine bacterial culture, and urine nitrite were associated with urinary infection stones ( P< 0.05). Multivariate logistic regression analysis revealed that urine pH value ( OR= 4.836, 95% CI 3.342-6.997), female gender( OR=2.320, 95% CI 1.286-4.186), recurrent stones ( OR=2.225, 95% CI 1.208-4.101), positive urine bacterial culture ( OR=2.061, 95% CI 1.094-3.883), serum uric acid ( OR=0.992, 95% CI 0.949-0.989), age ( OR=0.969, 95% CI 0.949-0.990) were independent risk factors for urinary infection stones ( P<0.05). The combined diagnostic value of six indicators was the highest, with an AUC of 0.874 (95% CI 0.837-0.911). Following this, urine pH exhibited an AUC of 0.818 (95% CI 0.778-0.858), while serum uric acid had an AUC of 0.704 (95% CI 0.652-0.756). The nomogram model was successfully constructed based on the six indicators. The mean AUC of the ROC curve after 1 000 resamples of the Bootstrap method was 0.864 (95% CI 0.828-0.900), and the calibration curve showed that the predicted curve fit the ideal curve well, with a mean absolute error of 0.005 and a Hosmer-Lemeshow test of P>0.05. Clinical decision curve analysis (DCA) showed that the model had a higher net clinical benefit when the model had a threshold probability value≥0.01. Conclusions:Urine pH and serum uric acid are closely related to urinary infection stones. A nomogram model combining these factors with gender, age, recurrent stones, and urine culture results can effectively predict the probability of infection-related stones, providing significant clinical value.

Background::Exercise, as the cornerstone of pulmonary rehabilitation, is recommended to chronic obstructive pulmonary disease (COPD) patients. The underlying molecular basis and metabolic process were not fully elucidated.Methods::Sprague-Dawley rats were classified into five groups: non-COPD/rest ( n = 8), non-COPD/exercise ( n = 7), COPD/rest ( n = 7), COPD/medium exercise ( n = 10), and COPD/intensive exercise ( n = 10). COPD animals were exposed to cigarette smoke and lipopolysaccharide instillation for 90 days, while the non-COPD control animals were exposed to room air. Non-COPD/exercise and COPD/medium exercise animals were trained on a treadmill at a decline of 5° and a speed of 15 m/min while animals in the COPD/intensive exercise group were trained at a decline of 5° and a speed of 18 m/min. After eight weeks of exercise/rest, we used ultrasonography, immunohistochemistry, transmission electron microscopy, oxidative capacity of mitochondria, airflow-assisted desorption electrospray ionization-mass spectrometry imaging (AFADESI-MSI), and transcriptomics analyses to assess rectal femoris (RF). Results::At the end of 90 days, COPD rats’ weight gain was smaller than control by 59.48 ± 15.33 g ( P = 0.0005). The oxidative muscle fibers proportion was lower ( P < 0.0001). At the end of additional eight weeks of exercise/rest, compared to COPD/rest, COPD/medium exercise group showed advantages in weight gain, femoral artery peak flow velocity (Δ58.22 mm/s, 95% CI: 13.85-102.60 mm/s, P = 0.0104), RF diameters (Δ0.16 mm, 95% CI: 0.04-0.28 mm, P = 0.0093), myofibrils diameter (Δ0.06 μm, 95% CI: 0.02-0.10 μm, P = 0.006), oxidative muscle fiber percentage (Δ4.84%, 95% CI: 0.15-9.53%, P = 0.0434), mitochondria oxidative phosphorylate capacity ( P < 0.0001). Biomolecules spatial distribution in situ and bioinformatic analyses of transcriptomics suggested COPD-related alteration in metabolites and gene expression, which can be impacted by exercise. Conclusion::COPD rat model had multi-level structure and function impairment, which can be mitigated by exercise.

Heart failure with preserved ejection fraction (HFpEF) displays normal or near-normal left ventricular ejection fraction, diastolic dysfunction, cardiac hypertrophy, and poor exercise capacity. Berberine, an isoquinoline alkaloid, possesses cardiovascular benefits. Adult male mice were assigned to chow or high-fat diet with L-NAME ("two-hit" model) for 15 weeks. Diastolic function was assessed using echocardiography and noninvasive Doppler technique. Myocardial morphology, mitochondrial ultrastructure, and cardiomyocyte mechanical properties were evaluated. Proteomics analysis, autophagic flux, and intracellular Ca²⁺ were also assessed in chow and HFpEF mice. The results show exercise intolerance and cardiac diastolic dysfunction in "two-hit"-induced HFpEF model, in which unfavorable geometric changes such as increased cell size, interstitial fibrosis, and mitochondrial swelling occurred in the myocardium. Diastolic dysfunction was indicated by the elevated E value, mitral E/A ratio, and E/e' ratio, decreased e' value and maximal velocity of re-lengthening (-dL/dt), and prolonged re-lengthening in HFpEF mice. The effects of these processes were alleviated by berberine. Moreover, berberine ameliorated autophagic flux, alleviated Drp1 mitochondrial localization, mitochondrial Ca²⁺ overload and fragmentation, and promoted intracellular Ca²⁺ reuptake into sarcoplasmic reticulum by regulating phospholamban and SERCA2a. Finally, berberine alleviated diastolic dysfunction in "two-hit" diet-induced HFpEF model possibly because of the promotion of autophagic flux, inhibition of mitochondrial fragmentation, and cytosolic Ca²⁺ overload.
Male ; Mice ; Animals ; Heart Failure/drug therapy* ; Stroke Volume/physiology* ; Ventricular Function, Left/physiology* ; Berberine/therapeutic use* ; Disease Models, Animal ; Mitochondrial Dynamics ; Myocardium ; Homeostasis

Objective:To analyze the influence of comprehensive rehabilitation on postoperative functions in the elderly patients with femoral intertrochanteric fracture.Methods:From June 2015 to June 2019, 144 elderly patients were treated at Department of Orthopedics, China-Japan Friendship Hospital for femoral intertrochanteric fractures by internal fixation with proximal femoral nail anti-rotation (PFNA). Of them, 65 received comprehensive rehabilitation, including intervention measures for details, prevention and management of comorbidities and complications and active exercise of the injured limb, while 79 conventional rehabilitation. In the comprehensive rehabilitation group, there were 22 males and 43 females with an age of (76.6±6.7) years, and 18 cases of type 31-A1, 35 cases of type 31-A2 and 12 cases of type 31-A3 by the AO type. In the control group, there were 23 males and 56 females with an age of (75.2±7.0) years, and 25 cases of type 31-A1, 39 cases of type 31-A2 and 15 cases of type 31-A3 by the AO type. The 2 groups were compared in terms of visual analog scale (VAS), Harris hip score, Barthel index, postoperative ambulation time and complications at 6 months after operation.Results:The 2 groups were comparable because there was no significant difference between them in the preoperative or intraoperative general data ( P>0.05). The comprehensive rehabilitation group had a significantly lower VAS score (1.5±1.0), a significantly higher Harris hip score(83.9±5.4), a significantly higher Barthel index (81.6±5.4), significantly shorter postoperative ambulation time [(2.6±1.0) d], and a significantly lower incidence of complications [4.6% (3/65)] than the control group did [1.9±1.2, 80.2±7.9, 78.2±7.9, (3.2±1.4) d, 16.5%(13/79), respectively] (all P< 0.05). Conclusion:For elderly patients with femoral intertrochanteric fracture, comprehensive rehabilitation can significantly reduce complications, promote functional recovery of the hip, and speed up recovery of capabilities of daily living compared with conventional rehabilitation.

Chemical modification of DNA bases in recent years has been one of the hot areas of life science research. DNA methylation is a common epigenetic phenomenon and can change the genetic performance without changing the DNA sequence. Various stress factors can induce the variation of DNA methylation in plants, but the response mechanism is still unknown. In this paper, the progress of DNA methylation in plants was reviewed. In combination with the researchconclusions of our own research group, the DNA methylation variation induced by 7Li ion beam and gamma ray was reported to provide a basis for DNA methylation, which may be involved in the phenotypic plasticity of plants.
DNA Methylation ; Epigenesis, Genetic ; Epigenomics ; Plants ; genetics