Objective To investigate the relationship of compression area, time and weight as risky factors with local injury and systemic pathophysiological responses in rats so as to establish repeatable experimental model of crush syndrome. Methods A total of 144 male SD rats were divided into two groups, ie, mortality investigation group and biochemical indicator investigation group. Every group included the same 18 subgroups based on 18 kinds of combination with different levels of compression area (the right or both hind limbs), time (4, 6, 8 hours) and weight (2, 3, 4 kg). The circumference of the compressed hind limbs of all rats were measured and serum potassium (K+), serum creatine phosphokinase (CK), creatinine and carbamide were measured too before compression and three hours after decompression. Incidence of myoglobinuria of all rats was recorded. Muscles and kidneys were evaluated morphologically. Results The compressed hind limbs of all rats swelled significantly after three hours of reperfusion (P ＜ 0. 05). All serum K + , CK, CR and BUN were increased significantly with the increase and prolongation of the compression area, time and weight (P ＜ 0.05). Signs of direct cellular damage and ischemia-reperfusion injury were found in histology specimens of local compressed muscle.Hyperemia of glomeruli and renal tubule was found in the kidneys. Renal tubular necrosis and renal tubular cast were observed in group with compression weight ≥3 kg and compression duration ≥6 hours.Conclusions Increase and prolongation of the compression area, time and weight can aggravate the severity of crush injury. Compression area is more risky factor of severe crush injury. Both hind limbs ascompression area, compression weight ≥ 3 kg and compression duration ≥ 6 hours can be the effective experimental conditions for establishment of crush syndrome model in rats.

Objective To determine the content of gentiopicroside and to evaluate the quality of Radix Gentianae Macrophyllae in Gansu province.Methods The HPLC method was performed on Waters C18 column.Methanol-water(3 ∶7) were used as the mobile phase,the flow rate was at 1.0 mL?min-1 with the detection wavelength being 254 nm.Results For gentiopicroside,the linear range was 1.7352～17.3520 ?g and the average recovery was 97.06 %with RSD=2.5 %.Conclusion The content of gentiopicroside in all of the samples produced in Gansu province is higher than or approach to the standard for Radix Gentianae Macrophyllae in Chinese Pharmacopoeia.

Objective To investigate the feasibility of chemical exchange saturation transfer (CEST) imaging in the measurement of myocardial creatine (Cr) metabolites in phantom model using 3.0 T MR. Methods Five phantoms were made according to the volume percentage of Cr ranging from 10 to 50 mmol/L with an interval of 10 mmol/L. 3.0 T MR examinations with base protocol sequence,sequence with and without ECG were performed. Signal to noise,CrEST effect and Z spectra were analyzed. Comparison of signal noise ratio (SNR) among the three methods was performed using an analysis of variance. Bivariate correlations were obtained through Pearson analysis. Results Phantom studies demonstrated that different concentrations of Cr exhibited significant CEST effect with the three sequences. The SNR obtained by sequences with and without ECG were both higher than that of base sequence (both P<0.05). Moreover,no significance of SNR was found between sequences with and without ECG (P>0.05). There were positive correlation of MTR between sequences with ECG,sequences without ECG and base protocol sequence (r2= 0.974 and 0.997, both P<0.05). Conclusion Compared with base protocol sequence, the optimized sequence with ECG can acquire higher SNR CrEST images,indicating that myocardial CrEST imaging could be performed in clinical practice.

OBJECTIVE: To carry out carrier screening for Spinal muscular atrophy (SMA) in reproductive-aged individuals from Dongguan region and determine the carrier frequency of SMN1 gene mutations. METHODS: Reproductive-aged individuals who underwent SMN1 genetic screening at the Dongguan Maternal and Child Health Care Hospital from March 2020 to August 2022 were selected as the study subjects. Deletions of exon 7 and 8 (E7/E8) of the SMN1 gene were detected by real-time fluorescence quantitative PCR (qPCR), and prenatal diagnosis was provided for carrier couples by multiple ligation-dependent probe amplification (MLPA). RESULTS: Among the 35 145 subjects, 635 were found to be carriers of SMN1 E7 deletion (586 with heterozygous E7/E8 deletion, 2 with heterozygous E7 deletion and homozygous E8 deletion, and 47 with sole heterozygous E7 deletion). The carrier frequency was 1.81% (635/35 145), with 1.59% (29/1 821) in males and 1.82% (606/33 324) in females. There was no significant difference between the two genders (χ² = 0.497, P = 0.481). A 29-year-old woman was found to harbor homozygous deletion of SMN1 E7/E8, and was verified to have a SMN1∶SMN2 ratio of [0∶4], none of her three family members with a [0∶4] genotype had clinical symptoms. Eleven carrier couples had accepted prenatal diagnosis, and one fetus was found to have a [0∶4] genotype, and the pregnancy was terminated. CONCLUSION This study has determined the SMA carrier frequency in Dongguan region for the first time and provided prenatal diagnosis for carrier couples. The data can provide a reference for genetic counseling and prenatal diagnosis, which has important clinical implications for the prevention and control of birth defects associated with SMA.
Humans ; Child ; Pregnancy ; Male ; Female ; Adult ; Homozygote ; Sequence Deletion ; Prenatal Diagnosis ; Genetic Testing ; Muscular Atrophy, Spinal/genetics* ; Survival of Motor Neuron 1 Protein/genetics* ; Genetic Carrier Screening

Objective:To evaluate the efficacy of first-line tyrosine kinase inhibitors (TKI) plus immune checkpoint inhibitors (ICI) in metastatic fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC).Methods:The data of 87 metastatic FH-deficient RCC patients from West China Hospital ( n=44), Renji Hospital ( n=27) and Sun Yat-sen University Cancer Center (n=16) from Mar 2019 to Aug 2022 were retrospectively analyzed. The median age was 37(30, 47) years, the male to female ratio was 1.9∶1. The median size of tumor was 7.5(5.0, 10.0) cm. Sixty-one patients (70.1%) had germline FH mutations, and 26 patients (29.9%) had somatic FH mutations. Forty-nine patients (56.3%) metastasis disease at initial diagnosis, and 38 patients (43.7%) had metachronous metastasis. The most common site of metastasis was lymph node (41/87, 47.1%), followed by bone (33/87, 37.9%), liver (22/87, 25.3%), and lung (14/87, 16.1%). Fifteen patients (17.2%) had weak expression of FH protein and 59 patients (67.8%) had positive PD-L1 expression. The most common treatments were sintilimab plus axitinib (52/87, 59.8%), followed by pembrolizumab plus cabozantinib (7/87, 8.0%), tirelizumab plus axitinib (6/87, 6.9%), pembrolizumab plus axitinib (5/87, 5.7%), and toripalimab plus axitinib (4/87, 4.6%). Thirteen patients (13/87, 14.9%) received other ICI plus TKI combination treatments. Statistical analysis was conducted using R 4.2.3 software. Kaplan Meier survival curve was used to evaluate survival data, and log-rank test was used to compare differences between treatment groups. Results:The overall objective response rate (ORR) and disease control rate (DCR) of first-line TKI + ICI were 39.1% and 89.7%, respectively. The median progression-free survival (PFS) and overall survival (OS) were 16.5 months and 71.0 months, respectively. For first-line sintilimab plus axitinib, the ORR and DCR were 44.2% and 92.3%, respectively. The median PFS was 17.3 months and the median OS was not reached for this combination treatment. The efficacy of first-line tirelizumab plus axitinib was inferior to other treatment strategies (median PFS: 4.0 vs. 16.6 months, P<0.001; median OS: 22.0 vs. 71.0 months, P=0.043). Subgroup analyses further showed that the efficacy of ICI+ TKI combination therapy was consistent in patients with different clinicopathologic and genomic features. However, patients with liver metastasis had shorter OS than those without liver metastasis (median OS: 26.3 vs. 71.0 months, P=0.021). Conclusion:First-line TKI + ICI is effective for metastatic FH-deficient RCC and can significantly prolong the survival of the patients.

Objective:Central nervous system leukemia(CNSL)is one of the main causes of recurrence and death in patients with acute leukemia.This study aims to dynamically monitor minimal residual disease(MRD)in cerebrospinal fluid and bone marrow of patients with different types of acute leukemia by flow cytometry(FCM),and to compare the timeliness and consistency of MRD detection between the 2 methods to further explore the application value of monitoring MRD in cerebrospinal fluid. Methods:A total of 199 patients with acute leukemia admitted to the Guangdong Provincial people's Hospital between October 2018 and January 2022 were retrospectively analyzed,and multiparametric FCM method was adopted to summarize and analyze MRD in cerebrospinal fluid of patients with different types of leukemia and MRD in cerebrospinal fluid and bone marrow specimens of the same patients,and its role in assessing the prognostic value of patients was discussed. Results:Among the 199 acute leukemia cases,a total of 31 cases(15.58%)were positive MRD in the cerebrospinal fluid,of which 18 cases(58%)were detected earlier than the corresponding bone marrow specimens.Among the 19 patients with acute T lymphoblastic leukemia,134 patients with acute B lymphoblastic leukemia,and 46 patients with acute myeloid leukemia counted,there were 4,18,and 9 patients with positive MRD in the cerebrospinal fluid.The Kappa value of the concordance test between the results of cerebrospinal fluid MRD and bone marrow MRD in different types of acute leukemia was only 0.156,demonstrating a low concordance between them. Conclusion:Dynamic monitoring of cerebrospinal fluid MRD by FCM can be used as a monitoring index for central nervous system leukemia,and monitoring cerebrospinal fluid can detect MRD earlier compared with bone marrow,which complements each other as a sensitive index for evaluating prognosis with significant guidance in clinic.