OBJECTIVE To investigate the ameliorative effect and mechanism of Euphorbia hirta L.-derived exosome-like nanovesicles（Eh-ENVs） on acetaminophen （APAP）-induced liver injury based on the nuclear factor erythroid 2 related factor 2 （Nrf2）/heme oxygenase-1 （HO-1）/NAD（P）H：quinone oxidoreductase 1 （NQO1） pathway. METHODS The safety of Eh-ENVs was evaluated by examining their effects on the viability of RAW264.7 and AML12 cells， as well as serum liver and kidney function indicators and histopathology of liver， lung， and other tissues in normal mice. A lipopolysaccharide （1 μg/mL）-induced RAW264.7 cell inflammation model was constructed to investigate the effects of 10 and 20 μg/mL Eh-ENVs on the mRNA expression of inflammatory factors and reactive oxygen species （ROS） level in model cells， and the uptake efficiency of Eh-ENVs by RAW264.7 cells was also examined. An APAP-induced liver injury mouse model was established to investigate the effects of 4 mg/kg Eh-ENVs on serum liver function indicators， liver histopathology， mRNA expression of inflammatory factors， malondialdehyde （MDA） level， superoxide dismutase （SOD） level， and mRNA and protein expressions related to the Nrf2/HO-1/NQO1 pathway in liver tissue of model mice. RESULTS In vitro results showed that Eh-ENVs had no inhibitory effect on the proliferation of RAW264.7 and AML12 cells；Eh-ENVs could be efficiently taken up by RAW264.7 cells and significantly reduced the mRNA expression of interleukin-1β （IL-1β）， tumor necrosis factor-α （TNF-α）， and ROS level in cells （ P ＜0.05）. In vivo results showed that 4 mg/kg Eh-ENVs had no obvious toxic side effects on normal mice，could significantly decrease the serum alanine transaminase （ALT） and aspartate transaminase （AST） levels in model mice （ P ＜0.05），upregulated/increased the mRNA expressions of IL-10， as well as the mRNA and protein expressions of Nrf2， HO-1， and NQO1， and SOD level in liver tissue （ P ＜0.05）， and down-regulated/decreased the mRNA expression of TNF-α， IL-1β and MDA level in liver tissue （ P ＜0.05）. CONCLUSIONS Eh-ENVs may activate the Nrf2/HO-1/NQO1 pathway to inhibit inflammatory response and alleviate oxidative stress， thereby improving APAP-induced liver injury.

Objective To systematically identify key risk biomolecules associated with the diagnosis of prostate cancer using multi-omics analysis methods, and to explore potential drug intervention targets. Methods Based on prostate cancer genome-wide association study data, GTEx v8 expression quantitative trait locus data, and The Cancer Genome Atlas database, this study screened for differentially expressed genes associated with prostate cancer pathogenesis through transcriptome imputation, summary data-based Mendelian randomization (SMR) analysis, colocalization analysis, and differential expression analysis.The identified differentially expressed genes were subjected to gene ontology analysis, single-cell RNA sequencing analysis, and correlation analysis with immune cell infiltration levels.Mendelian randomization (MR) was employed to investigate immune pathways and circulating metabolites associated with prostate cancer diagnosis.Potential drug targets for prostate cancer were screened using SMR analysis. Results Four differentially expressed genes associated with prostate cancer were identified, among which BHLHA15 (OR=1.08) was found to be associated with prostate cancer risk for the first time. MR analysis revealed that immune cell surface molecules and the inflammatory cytokine interleukin-17A (IL-17A) (OR=1.25) were risk factors for prostate cancer.MR analysis also indicated that higher levels of sebacate (OR=1.05) and cystine disulfide (OR=1.11) were associated with an increased risk of prostate cancer.Drug target analysis screened 14 potential target genes, among which high expression of OPRL1 was significantly correlated with poorer disease-free survival in prostate cancer patients (HR=2.00, P=0.024). Conclusion This study identified biomolecules associated with prostate cancer pathogenesis through multi-omics analysis, which may help deepen the clinical understanding of the pathogenic mechanisms underlying prostate cancer and reveal potential drug targets.

OBJECTIVE To explore the therapeutic efficacy and mechanism of oridonin （ORI） against obesity-related glomerulopathy （ORG） based on the liver X receptor α （LXRα） signaling pathway. METHODS Kidney tissues of LXRα wild-type homozygous （LXRα+/+） mice and LXRα homozygous knockout （LXRα－/－） mice were subjected to high-throughput renal transcriptome sequencing and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis to predict key pathways and targets regulated by LXRα， followed by verification via Western blot assay. An ORG mouse model was established by feeding a high-fat diet. The LXRα agonist GW3965 （30 mg/kg） was set as the positive control. After intragastric administration of 50 mg/kg and 100 mg/kg ORI once daily for 4 consecutive weeks， the body weight， renal weight， renal histopathological alterations， serum renal function indicators， blood lipid levels and inflammatory factor levels in renal tissue of mice were detected and observed to evaluate the efficacy of ORI in alleviating ORG. Meanwhile， the mRNA and protein expression levels of LXRα and its downstream targets in mouse renal tissues were detected to validate the mechanism by which ORI relieves ORG. RESULTS Compared with LXRα+/+ mice， the upregulated differentially expressed genes in renal tissues of LXRα－/－ mice were significantly enriched in the arachidonic acid（AA） metabolic pathway， and the expression level of Cyp4a12 was markedly elevated （adjusted P＜0.05）. Western blot results verified that cytochrome P450 family 4 subfamily A member 12（CYP4A12）protein expression was significantly increased in the kidneys of LXRα－/－ mice （P＜0.05）. Pharmacodynamic results showed that both 50 mg/kg and 100 mg/kg ORI notably improved renal pathological lesions in ORG mice； these two doses reduced body weight， renal weight， serum creatinine， blood urea nitrogen， blood lipid levels as well as renal interleukin-6 （IL-6） and IL-1β levels （P＜0.05）. In addition， ORI significantly upregulated the mRNA and protein expression of renal nuclear LXRα and ABCA1， and downregulated the mRNA and protein expression of CYP4A12（P＜0.05）. CONCLUSIONS ORI may exert an ameliorative effect on ORG by activating the LXRα signaling pathway， downregulating CYP4A12 expression， and inhibiting AA-induced inflammatory metabolism.

OBJECTIVE To study the effects of bergapten in the treatment of liver fibrosis and its mechanism based on serum metabolomics. METHODS Forty mice were divided into normal control group （0.5% carboxymethyl cellulose sodium solution）， model group （0.5% carboxymethyl cellulose sodium solution）， and BP low-dose and high-dose groups （50， 100 mg/kg）， with 10 mice in each group. Except for the normal control group， the other three groups were all treated with carbon tetrachloride to induce liver fibrosis model； they were given relevant medicine/solution intragastrically， once a day， for consecutive 8 weeks. After the last medication， the levels of alanine aminotransferase （ALT） and aspartate aminotransferase （AST） in serum were detected， and liver pathological changes were observed； the expressions of α-smooth muscle actin （α-SMA） and Collagen Ⅰ were detected in liver tissue； the serum of the mice was collected for metabolomics analysis. RESULTS Compared with the model group， serum levels of ALT and AST and protein expressions of α-SMA and Collagen Ⅰ in liver tissue were decreased significantly in BP high-dose and low-dose groups （P＜0.05）， while liver fibrosis was improved significantly. Meanwhile， metabolomics analyses showed that there were a total of 175 serum differential metabolites in the BP high-dose group and model group， of which 18 substances were upregulated and 157 substances were downregulated； the main metabolic pathways involved in bergapten intervention were pyrimidine metabolism， butanoate metabolism， fatty acid synthesis， tyrosine metabolism， β-alanine metabolism， nicotinic acid and nicotinamide metabolism， glutathione metabolism， etc. CONCLUSIONS BP is effective in the treatment of liver fibrosis by regulating pyrimidine metabolism， butanoate metabolism， glutathione metabolism and so on in rats with liver fibrosis.

Humans ; China/epidemiology* ; SARS-CoV-2 ; COVID-19

Based on the characteristics of medical imaging specialty, this paper introduces in detail several features of standardized residency training in the Department of Radiology in our hospital, from the aspects of teaching purpose, preliminary preparation and specific implementation, namely, the morning reading and analysis of difficult cases, the analysis of postoperative cases and missed diagnosis cases, and the teaching reading. At the same time, it also deeply analyzes the advantages, existing problems and solutions of this teaching practice. In order to provide reference for improving the teaching quality of the standardized residency training in the Department of Radiology.

Objective:To explore the clinical application of lateral thoracic artery perforator flap in repairing local defect after breast conserving surgery.Methods:The clinical data of 48 breast cancer patients planned to finish breast conserving surgery were retrospectively analyzed. The patients were divided into plastic breast-conserving group and routine breast conserving group. In the plastic breast-conserving group, 24 patients local defect repaired with the lateral thoracic artery perforator flap. In the routine breast conserving group, 24 patients local defect repaired with the fascial flap around the cutting edge. The operation related indexes and cosmetic effect from two groups were compared.Results:Both groups of patients successfully completed breast conserving surgery. The plastic breast-conserving group patients had significantly increased in operation time, operative blood loss, incision length and drainage tube indwelling time compared with the routine breast conserving group; the differences were statistically significant ( t=6.99, 9.37, 21.74, 8.80, P<0.05). The rate of secondary surgery enlarged was lower than fhat in the routine breast conserving group, and the difference was statistically significant (χ 2=4.76, P<0.05). There were 3 cases in the plastic breast conserving group and 1 case in the conventional breast conserving group. The skin at the edge of the flap was ischemic necrosis in the 4 cases, which healed after dressing change and drainage, and there was no significant difference ( P>0.05). The evaluation of postoperative cosmetic effect showed that the excellent and good rate of the observation group was 91.7%, compared with the routine breast conserving group (58.3%); the difference was statistically significant (χ 2=7.11, P<0.05). All patients were followed up for average 24 months, and local recurrence and distant metastasis were not observed. Conclusions:The lateral thoracic artery perforator flap for filling local defects in the lateral quadrant or central region of breast cancer is feasible, easy to operate, hides incision scar, better cosmetic effect and worthy of clinical promotion.

Objective:To explore the clinical effect of the simultaneous innervated "Bi-system bone flap" on preventing postoperative spontaneous resorption of the bone grafts and recovering lip sensation after reconstructing mandibular defects.Methods:Patients with segmental mandibular defects from the Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People’s Hospital were prospectively selected. Following the screening, they were randomly divided into an innervated group and a control group according to the random number table. When the free vascularized iliac bone flap was used to repair the mandibular defect, the ilioinguinal nerve was chosen to innervate a composite tissue flap containing one pedicle (deep circumflex iliac artery), double islands (an internal oblique muscle flap and an iliac bone flap) and one nerve (ilioinguinal nerve). We anastomosed the ilioinguinal nerve with the inferior alveolar nerve and the mental nerve in the innervated group. In the control group, no nerve was involved in the composite tissue flap which contained one pedicle (deep circumflex iliac artery) and double islands (internal oblique muscle flap and iliac bone flap). CT value(Hu) decrease rate, width and height of iliac bone flap 6 months after the operation were used to evaluate the postoperative resorption. The algesia examination, two-point discrimination test and current perception threshold (CPT) test of sensory nerves were used to evaluate the recovery of the lower lip sensation. P value less than 0.05 in independent-samples t test meant the statistically significant difference. Results:Eight patients between 17-38 years old were included with an averaged age of 29.5 years, and the range of mandibular defects was 5-9 cm. There were 4 cases in the innervated group and 4 cases in the control group. All the iliac bone flaps survived. The appearance was satisfactory, and no severe complications were found in the donor and recipient sites. In six-month follow-up, the CT value decrease rate of the bone grafts was (3.13±1.21)% in the innervated group, less than that (20.32±5.23)% in the control group, and the difference was statistically significant ( t=-6.401, P=0.006). Few changes of width and height of the bone grafts were found 6 months after surgery in both groups, and the difference was not statistically significant ( P>0.05). The sensation of the lower lip in the operation area was recovered in the innervated group to some extent, and no obvious pain was showed in the control group. In the two-point discrimination test, it was more than 20 mm in the affected side of the control group, while it was less than 20mm in the innervated group. In the healthy side of the two groups, it was less than 14 mm. The results of the quantitative sensory examination in affected lower lip by CPT test showed that two cases in the innervated group were mild sensory dysfunction, one slight sensory dysfunction and one moderate sensory dysfunction, while all cases in the innervated group were severe sensory dysfunction. The sensory dysfunction of the healthy side was milder than that of the affected side. Conclusions:The innervated "Bi-system" DCIA flap can prevent postoperative osteoporosis of the bone grafts and recover the sensation of the lower lip following mandibular reconstruction, improving the quality of mandibular defect reconstruction.

Objective:To explore the clinical effect of the simultaneous innervated "Bi-system bone flap" on preventing postoperative spontaneous resorption of the bone grafts and recovering lip sensation after reconstructing mandibular defects.Methods:Patients with segmental mandibular defects from the Department of Oral and Maxillofacial Head and Neck Oncology, Shanghai Ninth People’s Hospital were prospectively selected. Following the screening, they were randomly divided into an innervated group and a control group according to the random number table. When the free vascularized iliac bone flap was used to repair the mandibular defect, the ilioinguinal nerve was chosen to innervate a composite tissue flap containing one pedicle (deep circumflex iliac artery), double islands (an internal oblique muscle flap and an iliac bone flap) and one nerve (ilioinguinal nerve). We anastomosed the ilioinguinal nerve with the inferior alveolar nerve and the mental nerve in the innervated group. In the control group, no nerve was involved in the composite tissue flap which contained one pedicle (deep circumflex iliac artery) and double islands (internal oblique muscle flap and iliac bone flap). CT value(Hu) decrease rate, width and height of iliac bone flap 6 months after the operation were used to evaluate the postoperative resorption. The algesia examination, two-point discrimination test and current perception threshold (CPT) test of sensory nerves were used to evaluate the recovery of the lower lip sensation. P value less than 0.05 in independent-samples t test meant the statistically significant difference. Results:Eight patients between 17-38 years old were included with an averaged age of 29.5 years, and the range of mandibular defects was 5-9 cm. There were 4 cases in the innervated group and 4 cases in the control group. All the iliac bone flaps survived. The appearance was satisfactory, and no severe complications were found in the donor and recipient sites. In six-month follow-up, the CT value decrease rate of the bone grafts was (3.13±1.21)% in the innervated group, less than that (20.32±5.23)% in the control group, and the difference was statistically significant ( t=-6.401, P=0.006). Few changes of width and height of the bone grafts were found 6 months after surgery in both groups, and the difference was not statistically significant ( P>0.05). The sensation of the lower lip in the operation area was recovered in the innervated group to some extent, and no obvious pain was showed in the control group. In the two-point discrimination test, it was more than 20 mm in the affected side of the control group, while it was less than 20mm in the innervated group. In the healthy side of the two groups, it was less than 14 mm. The results of the quantitative sensory examination in affected lower lip by CPT test showed that two cases in the innervated group were mild sensory dysfunction, one slight sensory dysfunction and one moderate sensory dysfunction, while all cases in the innervated group were severe sensory dysfunction. The sensory dysfunction of the healthy side was milder than that of the affected side. Conclusions:The innervated "Bi-system" DCIA flap can prevent postoperative osteoporosis of the bone grafts and recover the sensation of the lower lip following mandibular reconstruction, improving the quality of mandibular defect reconstruction.

Objective:To explore the influencing factors of postoperative graft stenosis in patients undergoing left internal mammary artery-left anterior descending branch (LIMA-LAD) coronary artery bypass graft (CABG) surgery.Methods:A retrospective analysis of the clinical data of 86 patients who were admitted to the Second Affiliated Hospital of Hainan Medical College and received coronary angiography after CABG surgery from July 2019 to December 2020 due to recurrent chest tightness, chest pain and other symptoms. According to the degree of stenosis of the LIMA-LAD graft, the patients were divided into stenosis group ( n=25) and non-stenosis group ( n=61). The graft stenosis of patients in the stenosis group was ≥50%, and the graft stenosis of patients in the non-stenotic group was less than 50%. The general information, past medical history, CABG intraoperative data, current visit data and biochemical indicators of the two groups were compared. Measurement data were expressed as mean±standard deviation ( Mean± SD), comparison between groups was by t-test; count data comparison between groups was by Chi-square test. Logistic regression analysis was used to screen out the influencing factors of graft stenosis after CABG. Use the rms package in the R 4.0.2 software to build a nomogram prediction model. Using receiver operating characteristic (ROC) curve to evaluate the discriminative degree of the model. Use the calibration curve and deviation correction C-index to evaluate the nomogram prediction model. Use X-tile software to obtain the cutoff value of the nomogram model integral, use Kaplan-Meier method to draw the survival curve, and use Log-rank to test. Results:Logistic regression analysis showed that smoking, hypertension, pre-CABG left anterior descending branch (LAD) stenosis <75%, pre-CABG left internal mammary artery (LIMA) blood flow, and coronary angiography diffuse lesions are independent risk factors that affect LIMA-LAD graft stenosis after CABG ( P<0.05). The C-index value predicted by the nomogram model was 0.879 (95% CI: 0.818-0.955, P<0.001). The area under the ROC curve was 0.712 (95% CI: 0.594-0.801, P<0.001), with good discrimination. The calibration curve shows that the accuracy of the model prediction was good. Through the X-tile software screening to obtain the model score cutoff value, the patients were divided into low-risk group (≤54 points), medium-risk group (>54 points and ≤112 points), and high-risk group (>112 points). The results of survival analysis showed that the incidence of postoperative graft stenosis in the three groups was 20.9%, 50.0% and 80.0%, respectively. Conclusions:Smoking, hypertension, LAD stenosis before CABG <75%, LIMA blood flow before CABG, and coronary angiography diffuse lessions are independent risk factors that affect LIMA-LAD graft stenosis after CABG. The construction of a nomogram prediction model can provide a reference for evaluating the patency of the LIMA-LAD graft vessel before CABG operation, and reduce the probability of LIMA-LAD graft vessel stenosis after CABG operation.