BACKGROUND:Previous studies have confirmed that Wen-Shen-Tong-Du Decoction can promote the recovery of spinal cord injury by inhibiting pyroptosis of splenic B cells,promoting the phagocytosis of myelin debris by microvascular endothelial cells,affecting the migration and infiltration of microglia,promoting the recovery of damaged neurons,and decreasing neuronal apoptosis after spinal cord injury,but the mechanism of this is still not clear. OBJECTIVE:To investigate the effect of Wen-Shen-Tong-Du Decoction on the triggering receptor expressed on myeloid cells 2(TREM2)and PI3K/Akt signaling pathways in mice following spinal cord injury. METHODS:Thirty-six C57BL/6 mice were selected and randomly divided into a sham-operation group,a model group and a Wen-Shen-Tong-Du Decoction group,with 12 mice in each group.In the model and Wen-Shen-Tong-Du Decoction groups,mouse models of T10 spinal cord injury were prepared by the modified Allen's method.On the 1st day after modeling,the Wen-Shen-Tong-Du Decoction group was given Wen-Shen-Tong-Du Decoction by gavage,and the sham-operation group and the model group were given saline by gavage once a day for 28 days.During the drug administration period,mouse motor function was evaluated by Basso Mouse Scale score and inclined plane test.On the 7th and 28th days after modeling,hematoxylin-eosin staining was used to observe the histopathological changes in the spinal cord tissue of the mice;immunofluorescence double staining was used to detect the protein expression of ionized calcium binding adaptor molecule 1(IBA1)and TREM2;and western blot assay was used to detect the expression of TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,Bax and Caspase3 in spinal cord tissue. RESULTS AND CONCLUSION:Basso Mouse Scale scores and inclined plane test results indicated that the motor function of the mouse hindlimbs was declined after spinal cord injury,and Wen-Shen-Tong-Du Decoction significantly improved motor function in mice with spinal cord injury.Hematoxylin-eosin staining results revealed that Wen-Shen-Tong-Du Decoction significantly ameliorated the pathological structure of spinal cord tissue compared with the model group,manifesting as reduced degrees of dorsal white matter and neuronal atrophy,decreased cytoplasmic vacuolization,and reduced inflammatory cell infiltration.Immunofluorescence double staining results showed that on the 7th day after modeling,the protein expression of IBA1 and TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of IBA1 and TREM2 in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05);on the 28th day after modeling,the protein expression of TREM2 in the model group was lower than that in the sham-operation group(P＜0.05),and the protein expression of TREM2 in the spinal cord tissue of the mice in the Wen-Shen-Tong-Du Decoction group was higher than that in the model group(P＜0.05).Western blot results analysis demonstrated that on the 7th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,and Bcl2/Bax(P＜0.05),as well as a significant increase in p-Akt,Bax and p-Akt/Aktp-PI3K(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2,p-PI3K/PI3K,p-Akt/Ak,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax and Caspase3 protein expression(P＜0.05).On the 28th day after modeling,compared with the sham-operation group,the model group exhibited a significant reduction in TREM2,PI3K,p-PI3K,Akt,p-Akt,Bcl2 and Bcl2/Bax(P＜0.05),as well as a significant increase in Bax protein expression(P＜0.05);compared with the model group,the Wen-Shen-Tong-Du Decoction group showed a significant increase in TREM2,PI3K,Akt,p-Akt,Bcl2,and Bcl2/Bax(P＜0.05),as well as a significant decrease in Bax protein expression(P＜0.05).To conclude,Wen-Shen-Tong-Du Decoction may activate the PI3K/Akt signaling pathway by up-regulating the expression of TREM2 protein in microglia,and then inhibit neuronal apoptosis,thus exerting neuroprotective effects and promoting the repair of spinal cord injury.

Objective To explore the clinical characteristics of patients with diffuse large B-cell lymphoma (DLBCL) accompanied with KMT2D gene mutation and the impact of its co-mutated genes on prognosis. Methods Clinical data of 155 newly diagnosed DLBCL patients were obtained. The second-generation sequencing method was used to detect 475 hotspot genes, including KMT2D mutation. Patients were divided into the KMT2D mutation group and KMT2D wild-type group based on the presence or absence of KMT2D gene mutation. Clinical characteristics, differences in co-mutated genes, and survival differences between the two groups were compared. Results The frequency of KMT2D mutation was 31%, which is predominantly observed in elderly patients (P=0.07) and less in the double-expressor phenotype (P=0.07). Compared with the KMT2D wild-type group, KMT2D gene mutation was associated with higher co-mutation rates of CDKN2A (OR=2.82, P=0.01) and BCL2 (OR=3.84, P=0.016), while being mutually exclusive with MYC gene mutation (OR=0.11, P=0.013). In univariate survival analysis, no statistically significant difference in overall survival (OS) was found between the KMT2D mutation group and the wild-type group (P=0.54). Further analysis of the prognostic significance of KMT2D with other gene mutations indicated that patients with KMT2D^mutBTG2^mut had poorer OS than those with KMT2D^wt BTG2^mut (P=0.07) and KMT2D^wt BTG2^wt (P=0.05). On the contrary, patients with KMT2D^mut CD79B^mut had better OS than those with KMT2D^mut CD79B^wt (P=0.09), with no prognostic impact observed for other co-mutated genes. Multivariate Cox regression analysis revealed that Ann Arbor stages Ⅲ and Ⅳ (HR=2.751, 95%CI: 1.169-6.472, P=0.02), elevated LDH levels (HR=2.461, 95%CI: 1.396-4.337, P=0.002), Ki-67 index>80% (HR=1.875, 95%CI: 1.066-3.299, P=0.029), and KMT2D^mutBTG2^mut(HR=4.566, 95%CI: 1.348-15.471, P=0.015) were independent risk factors for OS in patients with DLBCL (P<0.05). Conclusion DLBCL patients with KMT2D mutation often have multiple gene mutations, among which patients with a co-mutated BTG2 gene have poor prognosis.

OBJECTIVE To evaluate the influence of gene polymorphism on plasma minimum concentration （cmin） of voriconazole （VRZ） in patients with invasive fungal infection. METHODS The Cochrane Library， Embase， PubMed， Web of Science， China Biomedical Literature Database， CNKI， VIP and Wanfang Data were searched for literature on the correlation between gene polymorphisms and cmin of VRZ from inception to April 2024. After screening the literature， extracting data， and evaluating the quality of the literature， meta-analysis was performed using R 4.3.2 software. RESULTS A total of 21 studies with 2 454 patients were included. The results of meta-analysis showed that the VRZ cmin of CYP2C19 IM and PM types was significantly higher than EM type， and the VRZ cmin of IM type was significantly lower than PM type （P＜0.01）. The VRZ cmin of CYP2C9 rs1057910 AA type was significantly higher than AC/CC type， and that of CYP3A5 rs776746 CC type was significantly higher than TT type （P＜0.01）. The VRZ cmin of POR rs10954732 GG type was significantly higher than GA and AA types， and that of POR rs1057868 CT type was significantly lower than TT type （P＜0.01）. The VRZ cmin of ABCB1 rs1045642 CC type was significantly higher than TT type （P＜0.05）. The VRZ cmin of NR1I2 rs2472677 CT type was significantly higher than TT type， and rs7643645 AA type was significantly higher than AG type （P＜0.05）. The VRZ cmin of ABCC2 rs717620 CC type was significantly lower than CT type and TT type， and the CT type was significantly lower than TT type （P＜0.01）. CONCLUSIONS Mutant alleles in CYP2C19， CYP2C9 rs1057910， CYP3A5 rs776746， POR rs10954732， ABCB1 rs1045642 and NR1I2 rs7643645 can lead to a decrease in VRZ plasma concentration， and mutant allele in ABCC2 rs717620 can lead to an increase in VRZ plasma concentration.

OBJECTIVE To evaluate the influence of gene polymorphism on plasma minimum concentration （cmin） of voriconazole （VRZ） in patients with invasive fungal infection. METHODS The Cochrane Library， Embase， PubMed， Web of Science， China Biomedical Literature Database， CNKI， VIP and Wanfang Data were searched for literature on the correlation between gene polymorphisms and cmin of VRZ from inception to April 2024. After screening the literature， extracting data， and evaluating the quality of the literature， meta-analysis was performed using R 4.3.2 software. RESULTS A total of 21 studies with 2 454 patients were included. The results of meta-analysis showed that the VRZ cmin of CYP2C19 IM and PM types was significantly higher than EM type， and the VRZ cmin of IM type was significantly lower than PM type （P＜0.01）. The VRZ cmin of CYP2C9 rs1057910 AA type was significantly higher than AC/CC type， and that of CYP3A5 rs776746 CC type was significantly higher than TT type （P＜0.01）. The VRZ cmin of POR rs10954732 GG type was significantly higher than GA and AA types， and that of POR rs1057868 CT type was significantly lower than TT type （P＜0.01）. The VRZ cmin of ABCB1 rs1045642 CC type was significantly higher than TT type （P＜0.05）. The VRZ cmin of NR1I2 rs2472677 CT type was significantly higher than TT type， and rs7643645 AA type was significantly higher than AG type （P＜0.05）. The VRZ cmin of ABCC2 rs717620 CC type was significantly lower than CT type and TT type， and the CT type was significantly lower than TT type （P＜0.01）. CONCLUSIONS Mutant alleles in CYP2C19， CYP2C9 rs1057910， CYP3A5 rs776746， POR rs10954732， ABCB1 rs1045642 and NR1I2 rs7643645 can lead to a decrease in VRZ plasma concentration， and mutant allele in ABCC2 rs717620 can lead to an increase in VRZ plasma concentration.

Objective To investigate the efficacy of leaflet augmentation technique to repair the recurrent mitral valve (MV) regurgitation after mitral repair in children. Methods A retrospective analysis was conducted on the clinical data of children who underwent redo MV repair for recurrent regurgitation after initial MV repair, using a leaflet augmentation technique combined with a standardized repair strategy at Fuwai Hospital, Chinese Academy of Medical Sciences, from 2018 to 2022. The pathological features of the MV, key intraoperative procedures, and short- to mid-term follow-up outcomes were analyzed. Results A total of 24 patients (12 male, 12 female) were included, with a median age of 37.6 (range, 16.5–120.0) months. The mean interval from the initial surgery was (24.9±17.0) months. All children had severe mitral regurgitation preoperatively. The cardiopulmonary bypass time was (150.1±49.5) min, and the aortic cross-clamp time was (94.0±24.2) min. There were no early postoperative deaths. During a mean follow-up of (20.3±9.1) months, 3 (12.5%) patients developed moderate or severe mitral regurgitation (2 severe, 1 moderate). One (4.2%) patient died during follow-up, and one (4.2%) patient underwent a second MV reoperation. The left ventricular end-diastolic diameter was significantly reduced postoperatively compared to preoperatively [ (43.5±8.6) mm vs. (35.8±7.8)mm, P<0.001]. Conclusion The leaflet augmentation technique combined with a standardized repair strategy can achieve satisfactory short- to mid-term outcomes for the redo mitral repair after previous MV repair. It can be considered a safe and feasible technical option for cases with complex valvular lesions and severe pathological changes.

Background::Carotid intima-media thickness (IMT) and diameter, stiffness, and wave reflections, are independent and important clinical biomarkers and risk predictors for cardiovascular diseases. The purpose of the present study was to establish nationwide reference values of carotid properties for healthy Chinese adults and to explore potential clinical determinants.Methods::A total of 3053 healthy Han Chinese adults (1922 women) aged 18-79 years were enrolled at 28 collaborating tertiary centers throughout China between April 2021 and July 2022. The real-time tracking of common carotid artery walls was achieved by the radio frequency (RF) ultrasound system. The IMT, diameter, compliance coefficient, β stiffness, local pulse wave velocity (PWV), local systolic blood pressure, augmented pressure (AP), and augmentation index (AIx) were then automatically measured and reported. Data were stratified by age groups and sex. The relationships between age and carotid property parameters were analyzed by Jonckheere-Terpstra test and simple linear regressions. The major clinical determinants of carotid properties were identified by Pearson’s correlation, multiple linear regression, and analyses of covariance.Results::All the parameters of carotid properties demonstrated significantly age-related trajectories. Women showed thinner IMT, smaller carotid diameter, larger AP, and AIx than men. The β stiffness and PWV were significantly higher in men than women before forties, but the differences reversed after that. The increase rate of carotid IMT (5.5 μm/year in women and 5.8 μm/year in men) and diameter (0.03 mm/year in both men and women) were similar between men and women. For the stiffness and wave reflections, women showed significantly larger age-related variations than men as demonstrated by steeper regression slopes (all P for age by sex interaction <0.05). The blood pressures, body mass index (BMI), and triglyceride levels were identified as major clinical determinants of carotid properties with adjustment of age and sex. Conclusions::The age- and sex-specific reference values of carotid properties measured by RF ultrasound for healthy Chinese adults were established. The blood pressures, BMI, and triglyceride levels should be considered for clinical application of corresponding reference values.

Background::The potential impact of pre-existing coronary artery stenosis (CAS) on acute pulmonary embolism (PE) episodes remains underexplored. This study aimed to investigate the association between pre-existing CAS and the elevation of high-sensitivity cardiac troponin I (hs-cTnI) levels in patients with PE.Methods::In this multicenter, prospective case-control study, 88 cases and 163 controls matched for age, sex, and study center were enrolled. Cases were patients with PE with elevated hs-cTnI. Controls were patients with PE with normal hs-cTnI. Coronary artery assessment utilized coronary computed tomographic angiography or invasive coronary angiography. CAS was defined as ≥50% stenosis of the lumen diameter in any coronary vessel >2.0 mm in diameter. Conditional logistic regression was used to evaluate the association between CAS and hs-cTnI elevation.Results::The percentage of CAS was higher in the case group compared to the control group (44.3% [39/88] vs. 30.1% [49/163]; P = 0.024). In multivariable conditional logistic regression model 1, CAS (adjusted odds ratio [OR], 2.680; 95% confidence interval [CI], 1.243–5.779), heart rate >75 beats/min (OR, 2.306; 95% CI, 1.056–5.036) and N-terminal pro-B type natriuretic peptide (NT-proBNP) >420 pg/mL (OR, 12.169; 95% CI, 4.792–30.900) were independently associated with elevated hs-cTnI. In model 2, right CAS (OR, 3.615; 95% CI, 1.467–8.909) and NT-proBNP >420 pg/mL (OR, 13.890; 95% CI, 5.288–36.484) were independently associated with elevated hs-cTnI. Conclusions::CAS was independently associated with myocardial injury in patients with PE. Vigilance towards CAS is warranted in patients with PE with elevated cardiac troponin levels.

Objective:Different methods were used to determine the dissolution of piroxicam patch,and the disso-lution results were evaluated,in order to select a determination method that could more accurately reflect the drug release process of piroxicam patch,so as to provide a reference for the scientific and accurate evaluation of drug quality.Methods:The liquid chromatography method for the detection of piroxicam was established,and the 24 hour dissolution curves of piroxicam patch were investigated by paddle over disk method,rotating cylinder method and vertical diffusion cell method,and the dissolution curves were compared by f1 difference factor method,f2 simi-larity factor method and Weibull model fitting,and the in vitro dissolution behavior of different methods was evalua-ted.Results:Piroxicam had a good linear relationship in the range of 1-150 μg·mL-1(r=1.000),the accura-cy was 100.9％(n=9),the precision was 1.7％(n=9),and the sample solution was stable within 72 hours.The results of the comparison of dissolution curves showed that the dissolution of piroxicam patch was more in line with the Weibull model.Under the same conditions of dissolution medium and temperature,there was little differ-ence between the paddle over disk method and rotating cylinder method,and there was a possibility of substitution for each other,and there were significant differences between the vertical diffusion cell method and the other two methods.Conclusion:The vertical diffusion cell method is more in line with the dissolution process of drugs in actual use,and provides more references for quality evaluation.

Objective To investigate the feasibility of establishing an animal model of rectovaginal fistula in rabbits by magnetic compression technique.Methods A magnetic device suitable for preparing rabbit rectovaginal fistula model was self-designed.Eight New Zealand female rabbits were used as experimental subjects.They were placed in a supine position after auricular intravenous anesthesia,and the magnets were placed on both sides of the rectovaginal septum through the vagina and anus,respectively,and the magnets were made to attract together.The operation time was recorded,the general state of the experimental rabbits was observed after operation,and the time of magnet discharge was recorded.The experimental rabbits were killed 1 week after operation to obtain rectovaginal fistula specimens,and the formation of rectovaginal fistula was observed by naked eye.Results The animal model of rectovaginal fistula was successfully established in 8 experimental rabbits.The operation process was smooth,with an average time of(1.63±0.70)minutes.The rabbits were generally in good condition after operation.The magnet was discharged from the body at(4.63±0.99)day after operation,and the rectovaginal fistula specimens were obtained 1 week after operation,and the rectovaginal fistula was well formed by naked eye observation.Conclusion The establishment of rabbit rectovaginal fistula model by magnetic compression technique has the advantages of simple operation and high success rate of model preparation.

Objectives:To propose a coronal imaging classification of neurofibromatosis type Ⅰ with dys-trophic upper thoracic scoliosis(DUTS-NF1),to verify its reliability and reproducibility,and to explore its clinical significance.Methods:We retrospectively analyzed the data of patients diagnosed with neurofibromato-sis type Ⅰ with dystrophic spinal scoliosis in the database of our hospital from June 2009 to December 2023.The patients whose main curve apex located in the upper thoracic vertebrae(T1-T5)were screen out and were classified according to the coronal scoliosis pattern on standing spinal X-rays:Type A,shoulder-neck type;Type B,distal thoracic compensatory curve type;Type C,trunk inclination type.The Cobb angle,upper thoracic kyphosis angle,clavicle angle(CA),T1 tilt,neck tilt(NT),head shift(HS),coronal balanced dis-tance(CBD),and deformity angular ratio(DAR)were measured and calculated for each type of patients.Three spine surgeons,who had been specially trained,independently performed two classifications according to the method.The results of the two classifications of the same observer were analyzed for reproducibility by apply-ing the Kappa value,and the results of the classification were analyzed for confidence between different ob-servers.Results:29 patients(7.9％)with DUTS-NF1 were identified from the 367 NF1 patients with dystrophic scoliosis,and the main Cobb angle was 78.7°±12.9°.The classification results of the designer were 16 patients of type A,8 of type B,and 5 of type C.The DAR of type B and type C was significantly higher than that of type A(20.6±2.2,20.0±3.0 vs 13.2±1.8,P＜0.001);Type C had more significant head and coronal shift distances than type A(HS:27.6±11.7mm vs 13.5±6.7mm,P＜0.001;CBD:34.8±20.5mm vs 13.9±10.9mm,P＜0.001);The T1 tilt of type C was significantly higher than that of type A(P＜0.05);The other imaging parameters were not statistically different between the three types(P＞0.05).174 times of classifications were performed by the 3 observers using the DUTS-NF1 coronal imaging classification method,including 96 classifications of type A,45 classifications of type B,and 33 classifications of type C.The intra-observer classification concordance rate was(82.57±8.44)％,with a Kappa value of 0.771-0.81,which was considered to be"Basically reliable";The inter-observer classification concordance rate was(84.19±8.65)％,with a Kappa value of 0.884-0.886,which was considered to be"Completely reliable".Conclusions:Based on the coronal imaging features,patients with DUTS-NF1 can be classified into three types of shoulder-neck type,distal thoracic compensatory curve type,and trunk inclination type.This classification system has satisfied reproducibility and reliability,which is helpful for assessing the coronal compensation of DUTS-NF1 patients,and thus guides the clinical diagnosis and treatment.