ObjectiveTo investigate the mechanism of danshenol A （DA） pretreatment in alleviating myocardial ischemia-reperfusion injury （MIRI） by regulating cardiomyocyte ferroptosis by in vivo and in vitro experiments. MethodsA MIRI model was established in SD rats， and an in vitro oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed with H9C2 cells. Both models were treated with DA. H9C2 cells were allocated into blank， model （OGD/R）， DA， ferroptosis inducer （erastin）， and ferroptosis inhibitor （Fer-1） groups. Cell viability was assessed by the methyl thiazolyl tetrazolium （MTT） assay. Biochemical assays were performed to measure the superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）， and ferrous ion （Fe²⁺） levels. Dihydroethidium （DHE） fluorescence assay was adopted to quantify the reactive oxygen species （ROS） level. Real-time PCR and Western blot were employed to quantify the mRNA and protein levels， respectively， of prostaglandin-endoperoxide synthase 2 （PTGS2）， glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， and acyl-coA synthetase long-chain family 4 （ACSL4）. Sixty SPF-grade healthy male SD rats were randomly assigned to control， model （MIRI）， DA， erastin， and Fer-1 groups. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the serum levels of cardiac troponin I （cTnI）， lactate dehydrogenase （LDH）， and creatine kinase （CK）. Histopathological changes in the myocardial tissue were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling （TUNEL）. The effect of DA on cardiomyocyte ferroptosis were observed and analyzed by in vivo and in vitro experiments. ResultsIn vitro experiment： compared with the blank group， the OGD/R model group showed reduced cell viability， elevated levels of ROS， MDA， and Fe²⁺， up-regulated mRNA and protein levels of ACSL4， lowered levels of SOD and GSH， and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05，P<0.01）. The DA and Fer-1 groups exhibited consistent trends： cell viability， SOD and GSH levels， and the mRNA and protein levels of PTGS2， GPX4， and FTH1 were significantly restored， while the ROS， MDA， and Fe²⁺ levels， and the mRNA and protein levels of ACSL4 were reduced （P<0.05，P<0.01）. In vivo experiment： Compared with the control group， the MIRI model group showed elevated serum levels of cTnI， LDH， and CK， increased cardiomyocyte apoptosis rate， risen levels of ROS， MDA， and Fe²⁺， and up-regulated mRNA and protein levels of ACSL4. However， both DA and Fer-1 groups exhibited reductions in the indicators above （P<0.05）. Compared with the control group， the MIRI model group demonstrated reduced levels of SOD and GSH and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05）. In contrast， both DA and Fer-1 upregulated these indicators （P<0.05）， effectively reversing the trends in the model group. In addition， the MIRI model group showed swelling of cardiomyocytes， disarrangement of cardiac muscle fibers， and massive inflammatory cell infiltration， which were alleviated in the DA and Fer-1 groups. ConclusionDA alleviates MIRI by inhibiting ferroptosis and inflammation， demonstrating therapeutic potential in acute myocardial infarction.

ObjectiveTo investigate the mechanism of danshenol A （DA） pretreatment in alleviating myocardial ischemia-reperfusion injury （MIRI） by regulating cardiomyocyte ferroptosis by in vivo and in vitro experiments. MethodsA MIRI model was established in SD rats， and an in vitro oxygen-glucose deprivation/reoxygenation （OGD/R） model was constructed with H9C2 cells. Both models were treated with DA. H9C2 cells were allocated into blank， model （OGD/R）， DA， ferroptosis inducer （erastin）， and ferroptosis inhibitor （Fer-1） groups. Cell viability was assessed by the methyl thiazolyl tetrazolium （MTT） assay. Biochemical assays were performed to measure the superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione （GSH）， and ferrous ion （Fe²⁺） levels. Dihydroethidium （DHE） fluorescence assay was adopted to quantify the reactive oxygen species （ROS） level. Real-time PCR and Western blot were employed to quantify the mRNA and protein levels， respectively， of prostaglandin-endoperoxide synthase 2 （PTGS2）， glutathione peroxidase 4 （GPX4）， ferritin heavy chain 1 （FTH1）， and acyl-coA synthetase long-chain family 4 （ACSL4）. Sixty SPF-grade healthy male SD rats were randomly assigned to control， model （MIRI）， DA， erastin， and Fer-1 groups. Enzyme-linked immunosorbent assay （ELISA） was adopted to measure the serum levels of cardiac troponin I （cTnI）， lactate dehydrogenase （LDH）， and creatine kinase （CK）. Histopathological changes in the myocardial tissue were observed by hematoxylin-eosin （HE） staining. Cardiomyocyte apoptosis was detected by terminal deoxynucleotidyl transferase-mediated nick end labeling （TUNEL）. The effect of DA on cardiomyocyte ferroptosis were observed and analyzed by in vivo and in vitro experiments. ResultsIn vitro experiment： compared with the blank group， the OGD/R model group showed reduced cell viability， elevated levels of ROS， MDA， and Fe²⁺， up-regulated mRNA and protein levels of ACSL4， lowered levels of SOD and GSH， and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05，P<0.01）. The DA and Fer-1 groups exhibited consistent trends： cell viability， SOD and GSH levels， and the mRNA and protein levels of PTGS2， GPX4， and FTH1 were significantly restored， while the ROS， MDA， and Fe²⁺ levels， and the mRNA and protein levels of ACSL4 were reduced （P<0.05，P<0.01）. In vivo experiment： Compared with the control group， the MIRI model group showed elevated serum levels of cTnI， LDH， and CK， increased cardiomyocyte apoptosis rate， risen levels of ROS， MDA， and Fe²⁺， and up-regulated mRNA and protein levels of ACSL4. However， both DA and Fer-1 groups exhibited reductions in the indicators above （P<0.05）. Compared with the control group， the MIRI model group demonstrated reduced levels of SOD and GSH and down-regulated mRNA and protein levels of PTGS2， GPX4， and FTH1 （P<0.05）. In contrast， both DA and Fer-1 upregulated these indicators （P<0.05）， effectively reversing the trends in the model group. In addition， the MIRI model group showed swelling of cardiomyocytes， disarrangement of cardiac muscle fibers， and massive inflammatory cell infiltration， which were alleviated in the DA and Fer-1 groups. ConclusionDA alleviates MIRI by inhibiting ferroptosis and inflammation， demonstrating therapeutic potential in acute myocardial infarction.

[Objective] To investigate the clinical manifestations and explore the experience of diagnosis and treatment of spontaneous perirenal urine extravasation after urinary tract obstruction so as to improve the understanding of the disease. [Methods] The clinical data of 23 patients with spontaneous perirenal urine extravasation after obstruction treated at our hospital during 2018 and 2020 were retrospectively analyzed, including the primary diseases, clinical manifestations, imaging examination, treatment and prognosis. The key points of diagnosis and treatment were summarized. [Results] Of the 23 patients, there were 15 males and 8 females, with an average age of 43.4 years. These cases were diagnosed by imaging tests such as ultrasound, computed tomography urography (CTU) and CT. Ureteroscopic lithotripsy was performed in 3 patients with ureteral calculi, retrograde ureteral catheterization in 4 patients and percutaneous nephrostomy in 13 patients. Afterwards, a second phase surgery was performed based on the patients' condition. Of the 3 patients with tumor metastasis who underwent retrograde ureteral catheterization, 2 operation were successful, and 1 operation failed and then converted to nephrostomy and drainage under B-ultrasound localization. [Conclusion] CTU should be performed as soon as possible to make a definite diagnosis. Treatment can be achieved with ureteral retrograde catheterization or percutaneous nephrostomy to achieve local decompression, followed by secondary surgery to treat the primary cause of obstruction.

Preterm birth is the most common maternal complication in twin pregnancies. In recent years, cervical cerclage has been of long-standing interest in the prevention of preterm birth in twin pregnancies. However, its clinical application in the treatment of cervical insufficiency of twin pregnancies remains a controversial subject. In addition, infection or inflammation conditions are considered to be closely related to the perinatal outcomes of twin pregnancies after cervical cerclage. This paper reviews the research progress on cervical cerclage in twin pregnancies, recommending cervical cerclage for twin pregnancies with cervical length≤15 mm or cervical dilatation, while it is not suggested for those with cervical length of 15-25 mm or history-indicated cervical cerclage. The clinical significance of preoperative evaluation of intraamniotic infection or inflammation of twin pregnancies needs to be further explored, but it is necessary to avoid the effect of antibiotic use on the evaluation of surgical effects.

Objective:To clarify the clinicopathological features, prognosis, and recurrence pattern of early-onset gastric cancer (EOGC).Methods:Using data from the gastric cancer database of Zhongshan Hospital, Fudan University, we performed a retrospective, large-scale, real-world study of 5046 patients with gastric cancer who had undergone redical or palliative gastrectomy from January 2013 to December 2018, including 425 patients with EOGC (age ≤45 years) and 4621 controls. All those patients were pathologically confirmed adenocarcinoma with complete follow-up of five years. Residue gastric cancer and patients without complete clinical or follow-up data were excluded. We used a combination of outpatient and telephone follow-up, ending in October 2022 (median duration of follow-up 60 months), and compared the clinicopathological features and prognosis of the two groups.Results:The clinicopathological features of EOGC included female predominance (61.1% [262/425 vs. 26.3% [1217/4621], χ 2=234.215, P<0.001), fewer comorbidities (31.3% [133/425] vs. 58.5% [2703/4621], χ 2=34.378, P<0.001), poorer differentiation (90.6% [385/425] vs. 78.2% [3614/4621], χ 2=30.642, P<0.001), higher proportion of diffuse type (53.9% [229/425] vs. 18.3% [846/4621], χ 2=274.474, P<0.001), higher proportion of T4 stage (44.7% [190/425] vs. 37.5% [1733/4621], χ 2=17.535, P=0.001), more lymph node metastases (60.5% [257/425] vs. 53.9% [2491/4621], χ 2=6.764, P=0.009), and higher proportion of pathological stage III/IV (47.5% [202/425] vs. 42.4% [1959/4621], χ 2=4.093, P=0.043). The 5-year overall survival rates of the EOGC and control groups were 55.1% and 49.1%, respectively. Overall survival was significantly better in the EOGC than in the control group ( P<0.001). According to subgroup analysis, the prognosis of pathological stage I/II/III EOGC was better than that of the control group. Recurrence rates were similar in the two groups, whereas patients with EOGC had a higher proportion of peritoneal recurrence (7.8% [33/425] vs. 3.2% [146/4621], χ 2=23.741, P<0.001) and a lower proportion of distant metastasis (4.9% [21/425] vs. 8.3% [385/4621], χ 2=6.247, P=0.012). Conclusion:EOGC has unique clinicopathological features and recurrence patterns and resectable EOGC has a better prognosis, suggesting that patients with EOGC should be actively treated with the focus on preventing peritoneal recurrence.

Objective To investigate the relationship between the expression level of miRNA Let-7 and the deletion of DNA mismatch repair(dMMR)proteins in endometrial carcinoma(EC).Methods A total of 74 patients with EC who underwent radical surgery at Lianyungang Maternal and Child Health Hospital in Jiangsu Province from May 2016 to December 2022 were selected.Immunohistochemistry was used to detect the expression of dMMR proteins(including MLH1,PMS2,MSH2,and MSH6),while real-time fluorescence quantitative polymerase chain reaction(qRT-PCR)was performed to measure the relative expression levelof miRNA Let-7.According to the expression of dMMR proteins,EC patients were divided into the complete expression group(n=43)and the absent expression group(n=31).Logistic multivariate regression analysis was conducted to identify risk factors associated with dMMR protein deficiency,and receiver operating characteristic(ROC)curve was plotted to evaluate the predictive value of relevant factors.Results In 74 cases of EC,the expression level of miRNA Let-7 was higher in the myographic infiltration＜1/2 group than in the myographic infiltration ≥ 1/2 group,and the difference was significant(t=1.79,P=0.04).The deletion rate of dMMR protein expression was 41.89％,the deletion rate in patients aged＜55 years and miRNA Let-7 low expression group(＜0.715)were higher than those in ≥ 55 years and miRNA Let-7 high expression group(≥ 0.715),with significant differences(x2=3.92,4.50,all P＜0.05).Logistic regression analysis revealed that miRNA Let-7 expression level was an independent risk factor for dMMR expression deletion(P=0.012).Spearman correlation analysis demonstrated a negative correlation between miRNA Let-7 expression level and dMMR protein deletion(r=-0.247,P=0.034).ROC curve analysis indicated that the expression level of miRNA Let-7 had a certain predictive value for dMMR protein deletion in EC patients,with an AUC of 0.737,an optimal critical value of 0.77,a sensitivity and a specificity of 0.651 and 0.806,respectively.Conclusion The expression level of miRNA Let-7 was correlated with the deletion of dMMR proteins in patients diagnosed with EC.Moreover,it served as a potential risk factor for dMMR protein deficiency.It may offer valuable insights into predicting dMMR expression deletion.

Objective:To clarify the clinicopathological features, prognosis, and recurrence pattern of early-onset gastric cancer (EOGC).Methods:Using data from the gastric cancer database of Zhongshan Hospital, Fudan University, we performed a retrospective, large-scale, real-world study of 5046 patients with gastric cancer who had undergone redical or palliative gastrectomy from January 2013 to December 2018, including 425 patients with EOGC (age ≤45 years) and 4621 controls. All those patients were pathologically confirmed adenocarcinoma with complete follow-up of five years. Residue gastric cancer and patients without complete clinical or follow-up data were excluded. We used a combination of outpatient and telephone follow-up, ending in October 2022 (median duration of follow-up 60 months), and compared the clinicopathological features and prognosis of the two groups.Results:The clinicopathological features of EOGC included female predominance (61.1% [262/425 vs. 26.3% [1217/4621], χ 2=234.215, P<0.001), fewer comorbidities (31.3% [133/425] vs. 58.5% [2703/4621], χ 2=34.378, P<0.001), poorer differentiation (90.6% [385/425] vs. 78.2% [3614/4621], χ 2=30.642, P<0.001), higher proportion of diffuse type (53.9% [229/425] vs. 18.3% [846/4621], χ 2=274.474, P<0.001), higher proportion of T4 stage (44.7% [190/425] vs. 37.5% [1733/4621], χ 2=17.535, P=0.001), more lymph node metastases (60.5% [257/425] vs. 53.9% [2491/4621], χ 2=6.764, P=0.009), and higher proportion of pathological stage III/IV (47.5% [202/425] vs. 42.4% [1959/4621], χ 2=4.093, P=0.043). The 5-year overall survival rates of the EOGC and control groups were 55.1% and 49.1%, respectively. Overall survival was significantly better in the EOGC than in the control group ( P<0.001). According to subgroup analysis, the prognosis of pathological stage I/II/III EOGC was better than that of the control group. Recurrence rates were similar in the two groups, whereas patients with EOGC had a higher proportion of peritoneal recurrence (7.8% [33/425] vs. 3.2% [146/4621], χ 2=23.741, P<0.001) and a lower proportion of distant metastasis (4.9% [21/425] vs. 8.3% [385/4621], χ 2=6.247, P=0.012). Conclusion:EOGC has unique clinicopathological features and recurrence patterns and resectable EOGC has a better prognosis, suggesting that patients with EOGC should be actively treated with the focus on preventing peritoneal recurrence.

In recent years,with the development of gene testing and new drug research,the diagnosis and treatment of inherited diseases have made rapid progress,corresponding to higher requirements for genetics education.As a teacher of medical genetics,the author joined the course remodeling during last 10 years from a web-based study of genetic disorders to a"case-based learning"supported by flipped classroom in order to optimize teaching effects and learning outcomes.The result of this remodeling project proposes a new strategy to guide perspectives course de-sign in future.

Dopamine D₃ receptor (D₃R) is implicated in multiple psychotic symptoms. Increasing the D₃R selectivity over dopamine D₂ receptor (D₂R) would facilitate the antipsychotic treatments. Herein, novel carbazole and tetrahydro-carboline derivatives were reported as D₃R selective ligands. Through a structure-based virtual screen, ZLG-25 (D₃R K_i = 685 nmol/L; D₂R K_i > 10,000 nmol/L) was identified as a novel D₃R selective bitopic ligand with a carbazole scaffold. Scaffolds hopping led to the discovery of novel D₃R-selective analogs with tetrahydro-β-carboline or tetrahydro-γ-carboline core. Further functional studies showed that most derivatives acted as hD₃R-selective antagonists. Several lead compounds could dose-dependently inhibit the MK-801-induced hyperactivity. Additional investigation revealed that 23j and 36b could decrease the apomorphine-induced climbing without cataleptic reaction. Furthermore, 36b demonstrated unusual antidepressant-like activity in the forced swimming tests and the tail suspension tests, and alleviated the MK-801-induced disruption of novel object recognition in mice. Additionally, preliminary studies confirmed the favorable PK/PD profiles, no weight gain and limited serum prolactin levels in mice. These results revealed that 36b provided potential opportunities to new antipsychotic drugs with the multiple antipsychotic-like properties.

ObjectiveTo establish a rat model of hyperuricemia （HUA）， to study the effect of Liqing granules on lowering serum uric acid， and to evaluate its safety . MethodsMale SD rats were randomly divided into solvent control group and model group according to their body weight. For the model group， serum uric acid （SUA） was determined after 7 days of intra-gastric administration of potassium oxyazinate. The model group were randomly divided into model control group， positive control group， and low， medium， high dose group based on SUA level. Each group from the model group continued to receive potassium oxyazinate in the morning. The animals in the model groups received 0.5% CMC-Na， 10 mg·kg^-1 benzbromarone （Doses by body weight） and Liqing granules 0.6， 1.2， 2.4 g·kg^-1 （Doses by body weight）， respectively in the afternoon. 0.5% CMC-Na suspension with the same volume was given both in the morning and afternoon for the solvent control group. Levels of SUA， creatinine （CREA）， alanine aminotransferase （ALT） and aspartate transaminase （AST） were determined after 32 and 45 days administration of the test substance. ResultsSUA of the model group was （218±23） μmol·L^-1 after 7 days of modeling， which was significantly higher than that of the solvent control group （P<0.001）. After 32 days administration of the test substance， SUA didn’t significantly decrease in each dose group （P>0.05）. CREA in the medium and high dose groups significantly decreased （P<0.05）. After 45 days administration of the test substance， SUA in each dose group was significantly decreased （P<0.001）， but CREA， ALT， and AST were not significantly different in each dose group in comparison with the model control group （P>0.05）. ConclusionLiqing granules can assist in lowering blood serum uric acid in the rat HUA model， and no damage to liver and kidney function is found.