Objective To investigate whether the activation of secretory prophospholipase A2 (sPLA2) plays the role in the pathophysiological mechanism of acute aristolochic acid nephropathy (AAN) in rats. Methods Wistar rats were randomly divided into two groups. Model group received decocted Aristolochia Manshuriensis Kom 30 g·kg-1d-1 by gavage for 7 days following tap water in same way for additional 7 days. Control group received only tap water by garage at parallel time. The renal pathological changes were observed at the 4th, 8th and 14th day. The injury of renal tubules and interstitium was observed under light microscope following a semi-quantity grade. The level of Scr was measured to evaluate glomerular function. Urinary N-acetyl-beta-glucosaminidase (NAG) was tested as renal tubular injury marker. The activity of sPLA2 in serum was detected by manifesting the color of thiols in the substrate. The protein expression of renal cortex and medulla COX-2 was analyzed by Western blot. The metabolic products of pretaglandins (PC, s) including 6-kcto-PGF1α and TXB2 in the plasma and urine were assayed by radioimmunoassay. The ratio of 6-keto-PGF1α/TXB2 was calculated. Results After Aristolochia administration, the tubulointerstitial injury and Scr increased in AA rats and reached the peak at the 8th day, the tubulointerstitial injury index(8.14±2.55 vs 1.50±0.71, P<0.05) and Scr[(0.24±0.10) vs (0.19±0.02) μmol/g, P<0.05] increased significantly in AA rats compared with control group. The activity of sPLA2 (μmol ·min-1·mg-1) in AA group elevated by 1.3-fold compared to control group at 8th day (133.15±17.05 vs 101.3±16.07, P<0.05), while theexpression of COX-2 in renal cortex increased (1.16±0.36 vs 0.69±0.28, P<0.05) with no change in renal medulla. Even though the levels of serum 6-keto-PGF1α and TXB2 did not change obviously in both AA and control group, but urinary levels of 6-keto-PGF1α and TXB2 increased by 2-fold and 3-fold in AA group compared to control group, respectively (all P<0.05), while the ratio of 6-keto-PGF1α/TXB2 decreased significantly (207.53±17.52 vs 296.64±51.31, P<0.05). All of above changes recovered to the control level at the 14th day except the tubulointerstitial injury index. Conclusion Serum sPLA2 is activated in the rots with acute kidney injury induced by aristolochic acid, which accompanied by up-regulated expression of COX-2 in renal cotex and increased the metabolic products of vasoconstrictive PG s in urine. These changes may participate the mechanism of renal peritubular ischemia in AAN.

OBJECTIVE:To establish a method for the determination of related substances in lorcaserin hydrochloride.METHODS:HPLC method was adopted.The determination was performed on Welch ultimate XB-ODS column with mobile phase consisted of Sodium dihydrogen phosphate (pH =6.5)-acetonitrile (gradient elution) at the flow rate of 1.0 mL/min.The detection wavelength was set at 220 nm,and column temperature was 35 ℃.The sample size was 20 μL.RESULTS:The linear ranges of impurity 1,2,3 were 0.075 60-7.560 μg/mL(r=0.999 9),0.081 40-8.140 μg/mL(r=0.999 9),0.099 24-9.924 μg/mL(r=0.999 9),respectively.The limits of quantification were 0.075 60,0.081 40,0.099 25 μg/mL.The limits of detection were 0.022 68,0.024 42,0.029 77 μg/mL.RSD of precision test was lower than 2.0％.Impurity 1 was found in stability test and reproducibility test,RSD＜2.0％.The recoveries were 98.53％-102.45％ (RSD=1.06％,n=9),98.26％-101.64％ (RSD=1.03 ％,n=9),100.08％-102.10％ (RSD=0.70％,n=9),respectively.CONCLUSIONS:The method is sensitive,rapid,accurate and reliable,which can be used to determine the related substances of lorcaserin hydrochloride.

Objective: To explore the association between processed food consumption and anxiety symptoms among college students in Yunnan Province, so as to provide a reference for the prevention and treatment of anxiety symptoms in this population. Methods: A cluster random sample of 2 515 first year students from two universities in Yunnan Province was selected to carry out a longitudinal investigation which included a baseline survey (November 2021, T1) and three follow up visits (June 2022, T2; November 2022, T3; June 2023, T4). The food frequency questionnaire was administered to assess processed food consumption, and the Depression Anxiety Stress Scale-21 (DASS-21, Chinese version) was used to evaluate anxiety symptoms. A generalized estimation equation model was used to analyze the relationship between processed food consumption and anxiety symptoms. Results: The detection rates of T1-T4 anxiety symptoms among college students in Yunnan Province were 29.70%, 36.70%, 37.69% and 38.73 %, respectively, and the corresponding anxiety symptom scores were 4(0,8), 4(0,10), 4(0,12), 2(0,14). After controlling for demographic variables and confounding factors in the generalized estimation equation model, a statistically significant association was found between consumption of carbonated beverages ( β=0.06, 95%CI =0.03-0.08), and other processed snacks ( β= 0.04 , 95%CI =0.01-0.07) ( P <0.05). The stratified analysis by gender showed that the consumption of carbonated beverages ( β=0.08, 95%CI =0.05-0.12) and fast food ( β=0.03, 95%CI =0.00-0.06) was significantly associated with anxiety symptoms in female college students ( P <0.05). There was no significant association between processed food consumption and anxiety symptoms in male college students ( P >0.05). Conclusions Processed food consumption by college students in Yunnan Province may increase the risk of anxiety symptoms, particularly among female students. There is a need to strengthen guidance in respect to processed food consumption, so as to prevent and treat anxiety symptoms.

OBJECTIVETo determine the feasibility and efficacy of endoscopic submucosal dissection(ESD) in treating early gastric cancer(EGC) and precancerous lesions in the remnant stomach of patients after gastrectomy.

METHODSClinical data of 36 patients with EGC and precancerous lesions in remnant stomach undergoing ESD in Endoscopy Center of Zhongshan Hospital from January 2008 to December 2013 were retrospectively analyzed. Operative, postoperative conditions and long-term follow-up of these patients were evaluated.

RESULTSBoth the success rate and the complete resection rate were 100%. The average maximum diameter of the tumor was 1.5(range 0.6-4.5) cm. During the ESD process, two bleeding cases were treated successfully by endoscopic hemostasis. The average operation time was 40(10-80) min. The delayed hemorrhage developed in 2 cases within 1-3 days after operation, and were also treated successfully by endoscopic hemostasis. There was no perforation or delayed perforation. No emergency surgery was required for the complication. Twelve cases were diagnosed as mild-moderate dysplasia, 7 cases as high grade intraepithelial neoplasia, 16 cases as hyperplastic polyps, and 1 case as signet ring cell carcinoma with T1 stage, who underwent operation for resecting gastric stump and lymph node dissection 7 days after ESD without subsequent follow-up. The curative resection rate was 92.7%(35/36). The median follow-up of the remaining 35 patients was 36(6-78) months without discomfort and recurrence under gastroscopy.

CONCLUSIONESD is safe and effective for EGC and precancerous lesions in the remnant stomach.

Adenocarcinoma ; Dissection ; Gastrectomy ; Gastric Mucosa ; Gastric Stump ; Gastroscopy ; Hemostasis, Endoscopic ; Humans ; Lymph Node Excision ; Neoplasm Recurrence, Local ; Operative Time ; Retrospective Studies ; Stomach Neoplasms

Objective To determine the feasibility and efficacy of endoscopic submucosal dissection(ESD) in treating early gastric cancer(EGC) and precancerous lesions in the remnant stomach of patients after gastrectomy. Methods Clinical data of 36 patients with EGC and precancerous lesions in remnant stomach undergoing ESD in Endoscopy Center of Zhongshan Hospital from January 2008 to December 2013 were retrospectively analyzed. Operative, postoperative conditions and long-term follow-up of these patients were evaluated. Results Both the success rate and the complete resection rate were 100%. The average maximum diameter of the tumor was 1.5 (range 0.6-4.5) cm. During the ESD process, two bleeding cases were treated successfully by endoscopic hemostasis. The average operation time was 40 (10-80) min. The delayed hemorrhage developed in 2 cases within 1-3 days after operation , and were also treated successfully by endoscopic hemostasis. There was no perforation or delayed perforation. No emergency surgery was required for the complication. Twelve cases were diagnosed as mild-moderate dysplasia, 7 cases as high grade intraepithelial neoplasia, 16 cases as hyperplastic polyps, and 1 case as signet ring cell carcinoma with T1 stage, who underwent operation for resecting gastric stump and lymph node dissection 7 days after ESD without subsequent follow-up. The curative resection rate was 92.7%(35/36). The median follow-up of the remaining 35 patients was 36 (6-78) months without discomfort and recurrence under gastroscopy. Conclusion ESD is safe and effective for EGC and precancerous lesions in the remnant stomach.

Objective To determine the feasibility and efficacy of endoscopic submucosal dissection(ESD) in treating early gastric cancer(EGC) and precancerous lesions in the remnant stomach of patients after gastrectomy. Methods Clinical data of 36 patients with EGC and precancerous lesions in remnant stomach undergoing ESD in Endoscopy Center of Zhongshan Hospital from January 2008 to December 2013 were retrospectively analyzed. Operative, postoperative conditions and long-term follow-up of these patients were evaluated. Results Both the success rate and the complete resection rate were 100%. The average maximum diameter of the tumor was 1.5 (range 0.6-4.5) cm. During the ESD process, two bleeding cases were treated successfully by endoscopic hemostasis. The average operation time was 40 (10-80) min. The delayed hemorrhage developed in 2 cases within 1-3 days after operation , and were also treated successfully by endoscopic hemostasis. There was no perforation or delayed perforation. No emergency surgery was required for the complication. Twelve cases were diagnosed as mild-moderate dysplasia, 7 cases as high grade intraepithelial neoplasia, 16 cases as hyperplastic polyps, and 1 case as signet ring cell carcinoma with T1 stage, who underwent operation for resecting gastric stump and lymph node dissection 7 days after ESD without subsequent follow-up. The curative resection rate was 92.7%(35/36). The median follow-up of the remaining 35 patients was 36 (6-78) months without discomfort and recurrence under gastroscopy. Conclusion ESD is safe and effective for EGC and precancerous lesions in the remnant stomach.

Objective:To explore the surgical technique and results of three-dimensional aortic valve anatomic repair for bicuspid aortic valve (BAV) with aortic regurgitation (AR).Methods:This is a retrospective case series study. From August 2021 to December 2023, 130 consecutive patients with BAV-AR underwent aortic valve anatomic repair at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University,and the data were retrospectively analyzed. There were 115 males and 15 females, aged (38.6±11.7) years (range: 15 to 67 years). All patients received modified aortic root reconstruction, to do three-dimensional root remodeling, including the basal ring, sinus of Valsalva and sino-tubular junction simultaneously. Perioperative and follow-up data were collected and analyzed. Comparisons between groups were performed using independent samples t-test, Wilcoxon paired signed-rank test, or χ2 test. Results:No patient transferred to valve replacement during the operation. The cardiopulmonary bypass time ( M(IQR)) was 109(34) minutes (range:67 to 247 minutes), and the aortic cross-clamp time was 76(26) minutes (range: 32 to 158 minutes). Preoperative transesophageal echocardiography showed 123 patients (94.6%) presented with moderate or severe regurgitation. Immediately postoperative transesophageal echocardiography showed no regurgitation in 22 patients (16.9%), trace regurgitation in 81 patients (62.3%) and mild regurgitation in 27 patients (20.8%). Follow up was completed in all patients, with a follow-up of 5.5(9.4) months (range: 0.1 to 27.6 months). No mortality was observed during follow-up. Echocardiography was obtained in 112 patients at the latest follow-up, including no regurgitation in 4 patients (3.6%), trace regurgitation in 58 patients (51.8%), mild regurgitation in 45 patients (40.2%), moderate regurgitation in 4 patients (3.6%), and severe regurgitation in 1 patient (0.9%). Conclusion:For patients with BAV-AR who have good valve quality and no severe aortic sinus dilation, the recent outcomes of three-dimensional anatomical repair technique, focusing on overall remodeling of the aortic root, are satisfactory.

Objective:To explore the surgical technique and results of three-dimensional aortic valve anatomic repair for bicuspid aortic valve (BAV) with aortic regurgitation (AR).Methods:This is a retrospective case series study. From August 2021 to December 2023, 130 consecutive patients with BAV-AR underwent aortic valve anatomic repair at the Department of Cardiothoracic Surgery, Zhongshan Hospital, Fudan University,and the data were retrospectively analyzed. There were 115 males and 15 females, aged (38.6±11.7) years (range: 15 to 67 years). All patients received modified aortic root reconstruction, to do three-dimensional root remodeling, including the basal ring, sinus of Valsalva and sino-tubular junction simultaneously. Perioperative and follow-up data were collected and analyzed. Comparisons between groups were performed using independent samples t-test, Wilcoxon paired signed-rank test, or χ2 test. Results:No patient transferred to valve replacement during the operation. The cardiopulmonary bypass time ( M(IQR)) was 109(34) minutes (range:67 to 247 minutes), and the aortic cross-clamp time was 76(26) minutes (range: 32 to 158 minutes). Preoperative transesophageal echocardiography showed 123 patients (94.6%) presented with moderate or severe regurgitation. Immediately postoperative transesophageal echocardiography showed no regurgitation in 22 patients (16.9%), trace regurgitation in 81 patients (62.3%) and mild regurgitation in 27 patients (20.8%). Follow up was completed in all patients, with a follow-up of 5.5(9.4) months (range: 0.1 to 27.6 months). No mortality was observed during follow-up. Echocardiography was obtained in 112 patients at the latest follow-up, including no regurgitation in 4 patients (3.6%), trace regurgitation in 58 patients (51.8%), mild regurgitation in 45 patients (40.2%), moderate regurgitation in 4 patients (3.6%), and severe regurgitation in 1 patient (0.9%). Conclusion:For patients with BAV-AR who have good valve quality and no severe aortic sinus dilation, the recent outcomes of three-dimensional anatomical repair technique, focusing on overall remodeling of the aortic root, are satisfactory.

Mosaic variants resulting from postzygotic mutations are prevalent in the human genome and play important roles in human diseases. However, except for cancer-related variants, there is no collection of postzygotic mosaic variants in noncancer disease-related and healthy individuals. Here, we present MosaicBase, a comprehensive database that includes 6698 mosaic variants related to 266 noncancer diseases and 27,991 mosaic variants identified in 422 healthy individuals. Genomic and phenotypic information of each variant was manually extracted and curated from 383 publications. MosaicBase supports the query of variants with Online Mendelian Inheritance in Man (OMIM) entries, genomic coordinates, gene symbols, or Entrez IDs. We also provide an integrated genome browser for users to easily access mosaic variants and their related annotations for any genomic region. By analyzing the variants collected in MosaicBase, we find that mosaic variants that directlycontribute to disease phenotype show features distinct from those of variants in individuals with mild or no phenotypes, in terms of their genomic distribution, mutation signatures, and fraction of mutant cells. MosaicBase will not only assist clinicians in genetic counseling and diagnosis but also provide a useful resource to understand the genomic baseline of postzygotic mutations in the general human population. MosaicBase is publicly available at http://mosaicbase.com/ or http://49.4.21.8:8000.

Objective:To explore the expression pattern of aryl hydrocarbon receptor (AhR) in mice peritoneal macrophages (PMs) after major trauma and analyze the effects of enhanced AhR expression on the inflammatory cytokine level and bactericidal ability after trauma.Methods:The experimental study method was used. Forty 6-8-week-old male C57BL/6J mice (the same mouse age, sex, and strain below) were divided into control group, post trauma hour (PTH) 2 group, PTH 6 group, and PTH 12 group according to the random number table (the same grouping method below), with 10 mice in each group. Mice in the latter 3 groups were constructed as severe trauma model with fracture+blood loss, while mice in control group were left untreated. The primary PMs (the same cells below) were extracted from the mice in control group, PTH 2 group, PTH 6 group, and PTH 12 group when uninjured or at PTH 2, 6, and 12, respectively. Then the protein and mRNA expressions of AhR were detected by Western blotting and real-time fluorescence quantitative reverse transcription polymerase chain reaction, respectively, and the gene expressions of AhR signaling pathway related molecules were analyzed by transcriptome sequencing. Twenty mice were divided into control group and PTH 6 group, with 10 mice in each group, and the PMs were extracted. The level of ubiquitin of AhR was detected by immunoprecipitation. Twelve mice were divided into dimethyl sulfoxide (DMSO) alone group, PTH 6+DMSO group, MG-132 alone group, and PTH 6+MG-132 group, with 3 mice in each group. After the corresponding treatment, PMs were extracted, and the protein expression of AhR was detected by Western blotting. Twenty mice were constructed as PTH 6 model. Then, the PMs were extracted and divided into empty negative control adenovirus (Ad-NC) group and AhR overexpression adenovirus (Ad-AhR) group. The protein expression of AhR was detected by Western blotting at 36 h after some PMs were transfected with the corresponding adenovirus. The rest cells in Ad-NC group were divided into Ad-NC alone group and Ad-NC+endotoxin/lipopolysaccharide (LPS) group, and the rest cells in Ad-AhR group were divided into Ad-AhR alone group and Ad-AhR+LPS group. The expressions of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in the cell supernatant were detected by enzyme-linked immunosorbent assay at 12 h after the corresponding treatment ( n=6). Twenty mice were obtained to extract PMs. The cells were divided into control+Ad-NC group, PTH 6+Ad-NC group, control+Ad-AhR group, and PTH 6+Ad-AhR group, and the intracellular bacterial load was detected by plate spread method after the corresponding treatment ( n=6). Data were statistically analyzed with one-way analysis of variance, least significant difference test, analysis of variance for factorial design, and independent sample t test. Results:Compared with 1.16±0.28 of control group, the protein expressions of AhR in PMs in PTH 2 group (0.59±0.14), PTH 6 group (0.72±0.16), and PTH 12 group (0.71±0.17) were all significantly decreased ( P<0.05). The overall comparison of the difference of AhR mRNA expression in PMs among control group, PTH 2 group, PTH 6 group, and PTH 12 group showed no statistical significance ( P>0.05). The AhR signaling pathway related molecules included AhR, AhR inhibitor, cytochrome P450 family member 1b1, cytochrome P450 family member 11a1, heat shock protein 90, aryl hydrocarbon receptor-interaction protein, and heat shock protein 70 interaction protein. The heat shock protein 90 expression of PMs in PTH 2 group was higher than that in control group, while the expressions of other molecules did not change significantly after trauma. Compared with that in control group, the level of ubiquitin of AhR in PMs in PTH 6 group was increased. Compared with that in DMSO alone group, the protein expression of AhR in PMs in PTH 6+DMSO group was decreased, while that in PMs in MG-132 alone group had no significant change. Compared with that in PTH 6+DMSO group, the protein expression of AhR in PMs in PTH 6+MG-132 group was up-regulated. At transfection hour 36, compared with that in Ad-NC group, the protein expression of AhR in PMs in Ad-AhR group was increased. At treatment hour 12, compared with those in Ad-NC+LPS group, the expressions of IL-6 and TNF-α in PM supernatant of Ad-AhR+LPS group were significantly decreased (with t values of 4.80 and 3.82, respectively, P<0.05). The number of intracellular bacteria of 1×10 6 PMs in control+Ad-NC group, PTH 6+Ad-NC group, control+Ad-AhR group, and PTH 6+Ad-AhR group was (3.0±1.8), (41.8±10.2), (1.8±1.2), and (24.2±6.3) colony forming unit, respectively. Compared with that in PTH 6+Ad-NC group, the number of intracellular bacteria of PMs in PTH 6+Ad-AhR group was significantly decreased ( t=3.61, P<0.05). Conclusions:Ubiquitin degradation of AhR in PMs of mice after major trauma results in decreased protein expression of AhR. Increasing the expression of AhR in post-traumatic macrophages can reduce the expressions of LPS-induced inflammatory cytokines IL-6 and TNF-α, and improve the bactericidal ability of macrophages after trauma.