Objective To compare different treatment methods for patients with gastric calculi and provide data support for clinical treatment.Methods A total of 197 patients diagnosed with gastric calculi by gastroscopy at the General Hospital of Ningxia Medical University and Cardio-Cerebrovascular Disease Hospital of General Hospital of Ningxia Medical University from July 2013 to January 2024 were enrolled.The study collected general information and other data of the patients,and divided them into groups based on the selected treatment method using a real-world research approach.The subjects were divided into four groups:drug conservative treatment group,endoscopic homemade snare treatment group,disposable snare treatment group,and stone fragmentation treatment group.Statistical analysis was performed using one-way analysis of variance.Results Gastric calculi were more common in men,with an average age of(55.45±14.21).85.3%of the patients had a history of eating persimmon,86.3%had ulcers,and 65.9%were located in the gastric angle.The self-made snare group had the lowest treatment cost,while the stone fragmentation group had the highest.There was no significant difference in the remission time of clinical symptoms among the three endoscopic treatment methods.The self-made snare had the highest patient satisfaction,but the drug combined with carbonated beverage group had the longest remission time of clinical symptoms and the lowest patient satisfaction.The frequency and duration of endoscopic treatment of dark green gastric stones were significantly higher than those of mottled and golden yellow gastric stones.Conclusion When treating patients with gastric stones,it is important to consider the size and color of the stone,as well as the patient's preferences.Patients should be fully informed about their condition and the advantages of different treatments.For patients with larger stones(about 5 cm),endoscopic snare treatment is recommended as the first choice.

Objective To evaluate the application efficacy of low-dose test method combined with variable helical pitch(VHP)technology in computed tomography angiography(CTA)of lower extremity arteries.Methods Eighty patients with CTA imaging of bilateral lower extremity arteries were selected and divided into group A and group B on average.VHP technology was used in group A,and conventional fixed pitch scanning was used in group B.The objective and subjective image quality of the two groups were compared,and the radiation dose and contrast agent dosage of the two groups were recorded and compared.Results The subjective image quality evaluation of group A was significantly better than that of group B,and the difference was statistically significant(Kappa test,P<0.05).In the objective image quality evaluation,the CT value and signal-to-noise ratio(SNR)value of the common iliac artery,popliteal artery and anterior tibial artery in group A were higher than those in group B at the same level,and the differences were statistically significant(P<0.05);The effective dose(ED)value in group A was(6.74±1.20)mSv,and that in group B was(7.93±1.78)mSv(P<0.05).The dosage of contrast agent in group A was significantly lower than that in group B[(73.97±12.15)mL in group A,(82.50±2.61)mL in group B](P<0.05).Conclusion Low-dose test method combined with VHP technology not only can reduce the radiation dose and contrast agent dosage,but also can effectively improve the success rate and image quality of lower extremity arteries examination,which is worthy of clinical application.

Objective:To explore the clinical manifestations and genetic etiology of a Chinese pedigree affected with Familial focal epilepsy with variable foci (FFEVF).Methods:A FFEVF pedigree presented at the Department of Medical Genetics of Linyi Maternal and Child Health Care Hospital on March 14, 2023 was selected as the study subject. The proband was subjected to whole exome sequencing (WES). Candidate variants were verified by Sanger sequencing of the proband and other affected members and bioinformatic analysis. This study was approved by Medical Ethics Committee of the Linyi Maternal and Child Health Care Hospital (Ethics No. QTL-YXLL-2023048).Results:WES revealed that the proband has harbored a heterozygous c. 1642C>T (p.Arg548Cys) missense variant in exon 15 of the NPRL3 gene. Sanger sequencing confirmed that the variant was inherited from the proband′s father, and multiple members of the pedigree had also harbored the same variant. Based on guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as variant of unknown significance (PM2_supporting + PP3). Conclusion:The clinical phenotype of FFEVF patients caused by variants of NPRL3 gene is extensive, and the patients may present with neurological abnormality of autism spectrum disorder in addition to seizures.

ObjectiveTo investigate the protective effect of cytochrome P4502D6 （CYP2D6） and cytochrome P4503A4 （CYP3A4）， key enzymes of drug metabolism in liver， on acute liver injury in water extract of Glycyrrhizae Radix et Rhizoma （WEOGRR）. MethodHealthy male Kunming mice were divided into normal group， model group， WEOGRR low-， medium- and high-dose groups （5， 10， 15 g·kg^-1·d^-1） and positive drug group （diammonium glycyrrhizinate， 75 mg·kg^-1·d^-1）， with 10 in each group. One week after preventive administration， acute liver injury model was induced by single intragastric administration of 270 mg·kg^-1 Tripterygium Glycosides tablets， and samples were collected after 18 h. The pathological changes of liver were observed by hematoxylin-eosin （HE） staining. Serum liver function indexes including alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， γ-glutamyl transpeptadase （γ-GT）， alkaline phosphatase （ALP）， and total bilirubin （TBIL） as well as the levels of oxidative stress indexes including malondialdehyde （MDA） and superoxide dismutase （SOD） in hepatocytes were determined by biochemical method. Real-time polymerase chain reaction （Real-time PCR） and Western blot were performed to detect the mRNA and protein expression levels of CYP2D6 and CYP3A4， respectively. ResultCompared with normal group， model group had significant hepatocyte swelling and inflammatory cell infiltration （P<0.01）， increased AST， ALT， γ-GT， ALP and TBIL （P<0.05）， elevated MDA and decreased SOD （P<0.01） as well as down-regulated mRNA and protein expression levels of CYP2D6 and CYP3A4 （P<0.05）. Compared with the model group， the normal group had intact liver structure without obvious abnormality， and the WEOGRR groups and positive drug group presented alleviated hepatocyte swelling and inflammatory cell infiltration （P<0.01）， reduced AST， ALT， γ-GT， ALP and TBIL （P<0.01）， lowered MDA and increased SOD （P<0.01） as well as up-regulated expression levels of CYP2D6 and CYP3A4 （P<0.01）. ConclusionThe protective effect of WEOGRR on acute liver injury induced by Tripterygium glycosides tablets may be related to reducing the contents of AST， ALT， γ-GT， ALP and TBIL in serum， inhibiting MDA and increasing the activity of SOD in liver cells， and enhancing the activities of CYP2D6 and CYP3A4， thus accelerating the metabolism of toxic substances.

Objective:To compare the differences in the prevalence of mild micro-hepatic encephalopathy (MHE) among patients with cirrhosis by using the psychometric hepatic encephalopathy score (PHES) and the Stroop smartphone application (Encephal App) test.Methods:This prospective, multi-center, real-world study was initiated by the National Clinical Medical Research Center for Infectious Diseases and the Portal Hypertension Alliance and registered with International ClinicalTrials.gov (NCT05140837). 354 cases of cirrhosis were enrolled in 19 hospitals across the country. PHES (including digital connection tests A and B, digital symbol tests, trajectory drawing tests, and serial management tests) and the Stroop test were conducted in all of them. PHES was differentiated using standard diagnostic criteria established by the two studies in China and South Korea. The Stroop test was evaluated based on the criteria of the research and development team. The impact of different diagnostic standards or methods on the incidence of MHE in patients with cirrhosis was analyzed. Data between groups were differentiated using the t-test, Mann-Whitney U test, and χ2 test. A kappa test was used to compare the consistency between groups. Results:After PHES, the prevalence of MHE among 354 cases of cirrhosis was 78.53% and 15.25%, respectively, based on Chinese research standards and Korean research normal value standards. However, the prevalence of MHE was 56.78% based on the Stroop test, and the differences in pairwise comparisons among the three groups were statistically significant (kappa = -0.064, P < 0.001). Stratified analysis revealed that the MHE prevalence in three groups of patients with Child-Pugh classes A, B, and C was 74.14%, 83.33%, and 88.24%, respectively, according to the normal value standards of Chinese researchers, while the MHE prevalence rates in three groups of patients with Child-Pugh classes A, B, and C were 8.29%, 23.53%, and 38.24%, respectively, according to the normal value standards of Korean researchers. Furthermore, the prevalence rates of MHE in the three groups of patients with Child-Pugh grades A, B, and C were 52.68%, 58.82%, and 73.53%, respectively, according to the Stroop test standard. However, among the results of each diagnostic standard, the prevalence of MHE showed an increasing trend with an increasing Child-Pugh grade. Further comparison demonstrated that the scores obtained by the number connection test A and the number symbol test were consistent according to the normal value standards of the two studies in China and South Korea ( Z = -0.982, -1.702; P = 0.326, 0.089), while the other three sub-tests had significant differences ( P < 0.001). Conclusion:The prevalence rate of MHE in the cirrhotic population is high, but the prevalence of MHE obtained by using different diagnostic criteria or methods varies greatly. Therefore, in line with the current changes in demographics and disease spectrum, it is necessary to enroll a larger sample size of a healthy population as a control. Moreover, the establishment of more reliable diagnostic scoring criteria will serve as a basis for obtaining accurate MHE incidence and formulating diagnosis and treatment strategies in cirrhotic populations.

Objective:To develop the anti-CD30 monoclonal antibody 64Cu-1, 4, 7-trizacyclononane-1, 4, 7-triacetic acid (NOTA)-CD30 and visualize CD30 expression in lymphoma non-invasively. Methods:The CD30 expression levels of 5 cell lines (Karpas299, Raji, Daudi, Ramos, and U266) were assessed by Western blot. Cell lines with high and low CD30 expression were selected for flow cytometry to evaluate the specific binding affinity of anti-CD30 monoclonal antibody. Thirteen NSG mice were used to established CD30 positive and negative subcutaneous xenograft models. 64Cu-NOTA-CD30 was obtained and 64Cu-NOTA-immunoglobulin (Ig)G was used as the control. ImmunoPET imaging was performed 2, 24, and 48 h after the injection of 64Cu-NOTA-CD30 or 64Cu-NOTA-IgG. Finally, the biodistribution studies were conducted. Repeated-measures analysis of variance and Bonferroni test were conducted for comparison. Results:Karpas299 showed the highest CD30 expression, while Raji showed the lowest. Flow cytometry showed specific binding affinity of the anti-CD30 monoclonal antibody to the Karpas299 cell line. The radiochemical purities of the probes were both higher than 95%. In microPET, the 64Cu-NOTA-CD30 uptake of Karpas299 xenograft tumors increased over time, with (11.46±0.58), (17.60±1.16) and (19.46±0.99) percentage activity of injection dose per gram of tissue (%ID/g) at 2, 24 and 48 h respectively. The contrast to normal tissue was good at 48 h, with the tumor/heart (blood) ratio of 2.20±0.22. The uptake of 64Cu-NOTA-CD30 in Karpas299 tumor at 48 h after injection was significantly higher than that in Raji tumor ((6.10±1.03) %ID/g) and 64Cu-NOTA-IgG in Karpas299 tumor ((5.12±0.89) %ID/g; F=290.99, t values: 19.65 and 22.25, all P<0.001). The uptake of 64Cu-NOTA-CD30 and the control probe in the heart and liver decreased over time in all groups. Ex vivo biodistribution at 48 h was mainly consistent with the results of microPET in vivo. Conclusions:64Cu-NOTA-CD30 is able to visualize the expression level and distribution of CD30 non-invasively. It is promising to be applied for screening the beneficial groups and evaluating efficacy for CD30-targeted immunotherapy.

Objective:To investigate the diagnostic accuracy of serological indicators and evaluate the diagnostic value of a new established combined serological model on identifying the minimal hepatic encephalopathy (MHE) in patients with compensated cirrhosis.Methods:This prospective multicenter study enrolled 263 compensated cirrhotic patients from 23 hospitals in 15 provinces, autonomous regions and municipalities of China between October 2021 and August 2022. Clinical data and laboratory test results were collected, and the model for end-stage liver disease (MELD) score was calculated. Ammonia level was corrected to the upper limit of normal (AMM-ULN) by the baseline blood ammonia measurements/upper limit of the normal reference value. MHE was diagnosed by combined abnormal number connection test-A and abnormal digit symbol test as suggested by Guidelines on the management of hepatic encephalopathy in cirrhosis. The patients were randomly divided (7∶3) into training set ( n=185) and validation set ( n=78) based on caret package of R language. Logistic regression was used to establish a combined model of MHE diagnosis. The diagnostic performance was evaluated by the area under the curve (AUC) of receiver operating characteristic curve, Hosmer-Lemeshow test and calibration curve. The internal verification was carried out by the Bootstrap method ( n=200). AUC comparisons were achieved using the Delong test. Results:In the training set, prevalence of MHE was 37.8% (70/185). There were statistically significant differences in AMM-ULN, albumin, platelet, alkaline phosphatase, international normalized ratio, MELD score and education between non-MHE group and MHE group (all P<0.05). Multivariate Logistic regression analysis showed that AMM-ULN [odds ratio ( OR)=1.78, 95% confidence interval ( CI) 1.05-3.14, P=0.038] and MELD score ( OR=1.11, 95% CI 1.04-1.20, P=0.002) were independent risk factors for MHE, and the AUC for predicting MHE were 0.663, 0.625, respectively. Compared with the use of blood AMM-ULN and MELD score alone, the AUC of the combined model of AMM-ULN, MELD score and education exhibited better predictive performance in determining the presence of MHE was 0.755, the specificity and sensitivity was 85.2% and 55.7%, respectively. Hosmer-Lemeshow test and calibration curve showed that the model had good calibration ( P=0.733). The AUC for internal validation of the combined model for diagnosing MHE was 0.752. In the validation set, the AUC of the combined model for diagnosing MHE was 0.794, and Hosmer-Lemeshow test showed good calibration ( P=0.841). Conclusion:Use of the combined model including AMM-ULN, MELD score and education could improve the predictive efficiency of MHE among patients with compensated cirrhosis.

Triptolide is a key active component of the widely used traditional Chinese herb medicine Tripterygium wilfordii Hook.F.Although triptolide exerts multiple biological activities and shows promising efficacy in treating inflammatory-related diseases,its well-known safety issues,especially reproductive toxicity has aroused concerns.However,a comprehensive dissection of triptolide-associated testicular toxicity at single cell resolution is still lacking.Here,we observed testicular toxicity after 14 days of triptolide exposure,and then constructed a single-cell transcriptome map of 59,127 cells in mouse testes upon triptolide-treatment.We identified triptolide-associated shared and cell-type specific differentially expressed genes,enriched pathways,and ligand-receptor pairs in different cell types of mouse testes.In addition to the loss of germ cells,our results revealed increased macrophages and the inflammatory response in triptolide-treated mouse testes,suggesting a critical role of inflammation in triptolide-induced testicular injury.We also found increased reactive oxygen species(ROS)signaling and down-regulated pathways associated with spermatid development in somatic cells,especially Leydig and Sertoli cells,in triptolide-treated mice,indicating that dysregulation of these signaling pathways may contribute to triptolide-induced testicular toxicity.Overall,our high-resolution single-cell landscape offers comprehensive information regarding triptolide-associated gene expression profiles in major cell types of mouse testes at single cell resolution,providing an invaluable resource for understanding the underlying mechanism of triptolide-associated testicular injury and additional discoveries of therapeutic targets of triptolide-induced male reproductive toxicity.

【Objective】 To explore the effectiveness of creating the obstructive sleep apnea hypopnea syndrome (OSAHS) animal model of glossocoma using the botulinum toxin type A in white rabbits, and to explore the effectiveness and safety of magnetic traction hyoid suspension operation in the OSAHS animal model of glossocoma. 【Methods】 A total of 12 adult male experimental white rabbits were randomly divided into two groups. The animals in the experimental group were injected with 0.4 mL (10 U) of botulinum toxin type A in the genioglossus muscle to construct the OSAHS animal model of glossocoma. The animals in the control group were injected with 0.4 mL of normal saline. We designed and 3D printed a polyacrylate shell that could be loaded with inner and outer neodymium iron boron (NdFeB) magnets. After the modeling, a polyacrylate shell with the inner magnet device was fixed on the hyoid bone of the animals in the experimental group. All animals in the experimental group wore the polyacrylate orthotic neck brace containing the outer magnet 10 days after the operation. The arterial blood oxygen detector was used to record the oxygen saturation (SaO2) of the femoral artery, and multi-slice CT plain scan was used to measure the diameter of the narrowest part of the upper airway. 【Results】 The animals in the experimental group gradually showed decreased activity, labored breathing, blue lips and ear margins and other manifestations of hypoxemia 5 days after intramuscular injection of botulinum toxin type A in the genioglossus, and their body weight dropped from (3.72±0.21)kg to (3.40±0.20)kg, the average SaO2 of the femoral artery decreased from (93.84±5.14)% to (84.00±3.35)%, and the diameter of the narrowest part of the upper airway decreased from (4.83±0.47)mm to (3.52±0.83)mm (P<0.05). In the control group, the animals’ weight, the average SaO2 of the femoral artery, and the diameter of the narrowest part of the upper airway did not significantly change before and after injection of normal saline into the genioglossus muscle (P>0.05). The animals in the experimental group completed the magnetic traction hyoid suspension surgery. After wearing the orthotic neck brace containing an external magnet for hyoid magnetic traction, the food intake and activity of the animals in the experimental group increased, the color of the lips changed from purple to pink, the SaO2 of the femoral artery increased significantly to (90.44±5.95)%, and the diameter of the narrowest part of the upper airway increased significantly to (4.42±0.15)mm (P<0.05). 【Conclusion】 The genioglossus muscle injection of botulinum toxin type A in white rabbits could successfully establish the OSAHS animal model of glossocoma. Magnetic traction hyoid suspension surgery in the treatment of OSAHS animal model could effectively correct the upper airway stenosis related symptoms and hypoxemia caused by glossocoma.

Objective:To develop a neural network model for the evaluation of glomerular filtration rate (GFR) based on multilayer perceptual neural network, and to compare with the improved Chinese based creatinine GFR evaluation formula (C-GFR cr) and the evaluation formula (EPI-GFR cr) of the American Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) for the clinical applicability of multilayer perceptual neural network model in evaluating GFR. Methods:A total of 684 chronic kidney disease (CKD) patients used for developing a modified version of China′s based creatinine GFR evaluation formula were taken as the research object. The data of 454 patients were randomly selected as the development group and the data of the other 230 patients were as the verification group. The multilayer perceptual neural network GFR evaluation model (M-GFR cr) was established. With the double plasma GFR as the reference value (rGFR), the correlation, mean difference, mean absolute difference, precision and accuracy of C-GFR cr, EPI-GFR cr and M-GFR cr were compared. Results:Among the 684 CKD patients, there were 352 males and 332 females, with age of (49.9±15.8) years. The correlation between M-GFR cr and rGFR was the highest (Pearson correlation =0.93, P<0.001). The mean difference of M-GFR cr was lower than that of C-GFR cr ( Z=9.929, P<0.001) and EPI-GFR cr ( Z=10.573, P<0.001). The mean absolute difference of M-GFR cr was also lower than that of C-GFR cr ( Z=3.953, P<0.001) and EPI-GFR cr ( Z=4.210, P<0.001). The accuracy of ±15% of M-GFR cr was higher than that of C-GFR cr ( χ2=26.068, P<0.001) and EPI-GFR cr ( χ2=23.154, P<0.001). The accuracy of ±30% of M-GFR cr was also higher than that of C-GFR cr ( χ2=8.264, P=0.001) and EPI-GFR cr ( χ2=11.963, P=0.001). The results of different stages of CKD showed that in the early stage of CKD (CKD 1-2), the mean difference of M-GFR cr was lower than that of C-GFR cr ( Z=7.401, P<0.001) and EPI-GFR cr ( Z=8.096, P<0.001); the mean absolute difference of M-GFR cr was also lower than that of C-GFR cr ( Z=4.723, P<0.001) and EPI-GFR cr ( Z=4.946, P<0.001); the accuracy of ±15% of M-GFR cr was higher than that of C-GFR cr ( χ2=23.547, P<0.001) and EPI-GFR cr ( χ2=26.421, P<0.001); the accuracy of ±30% of M-GFR cr was also higher than that of C-GFR cr ( χ2=12.089, P=0.001) and EPI-GFR cr ( χ2=16.168, P<0.001). But there was no significant difference in the applicability among C-GFR cr, EPI-GFR cr and M-GFR cr in the advanced stages of CKD (CKD 3-5). Conclusion:Compared with the improved Chinese based creatinine GFR evaluation formula C-GFR cr and CKD-EPI evaluation formula EPI-GFR cr, the accuracy of multilayer perceptual neural network model to evaluate GFR in CKD patients has been significantly improved, especially in CKD 1-2 stage.