Objective To explore the role of mitophagy in pancreatic cancer cachexia-induced muscle atrophy and its underlying mechanism.Methods Six male C57BL/6J mice(8 weeks old,weighing 20～30 g)were equally and randomly divided into a control group(intrapancreatic injection of normal saline)and a cachexia group(orthotopic pancreatic injection of KPC1199 cells).After successful model establishment,gastrocnemius muscles were harvested for transmission electron microscopy(TEM)to assess mitochondrial ultrastructure.Western blotting was performed to quantify mitochondrial respiratory chain complexes(Ⅰ～Ⅳ)and autophagy-related proteins,while immunofluorescence staining was conducted to evaluate mitochondrial-lysosomal colocalization.In in vitro experiments,C2C12 myoblasts were differentiated into myotubes,and then divided into a control group(standard culture)and a cachexia group(co-cultured with KPC1199 cells for 48 h using transwell chambers).Mitochondrial-lysosomal colocalization and autophagy-related protein expression were analyzed with immunofluorescence assay and Western blotting.The mitochondrial division inhibitor Mdivi-1(20 μmol/L)was added to the co-culture system to assess its myotube diameter.Results Compared to the control mice,the cachectic mice exhibited mitochondrial swelling,reduced cristae density,and significantly increased mitochondrial-lysosomal colocalization in gastrocnemius muscle(P<0.05).Western blotting revealed the expression levels of mitochondrial respiratory chain proteins complexⅠ(1.00±0.04 vs 0.51±0.04,P<0.05),complexⅡ(1.00±0.13 vs 0.73±0.15,P<0.05),complexⅢ(1.00±0.20 vs 0.64±0.01,P<0.05),complexⅣ(1.00±0.06 vs 0.65±0.02,P<0.05)and PGC1α(1.00±0.03 vs 0.62±0.06,P<0.05)were decreased,and the levels of mitophagy markers,LC3-Ⅰ/Ⅱ(1.00±0.14 vs 1.65±0.25,P<0.05),PINK1(1.00±0.11 vs 1.51±0.05,P<0.05),and BNIP3(1.00±0.22 vs 2.02±0.10,P<0.05)were elevated when compared to the control.In the C2C12 myotube model,tumor cell co-culture increased mitochondrial-lysosomal colocalization and upregulated mitophagy-related protein expression(P<0.05),consistent with the in vivo findings.Mdivi-1 treatment increased myotube diameter from 220.6±35.5 μm to 315.0±39.1 μm(R2=0.666 5,P<0.05).Conclusion Mitophagy is activated in pancreatic cancer cachexia-induced muscle atrophy.Inhibiting mitophagy can effectively alleviate muscle atrophy induced by pancreatic cancer cachexia.

Objective To analyze the relationship of silent information regulator 2(SIRT2)with the occurrence and severity of cognitive impairment in patients with acute cerebral infarction(ACI).Methods Clinical data of 150 ACI patients(study group)complicated with cognitive im-pairment admitted in our hospital from May 2022 to May 2024 were collected and analyzed retro-spectively.According to the severity of cognitive impairment,they were divided into mild(45 cases),moderate(66 cases)and severe subgroups(39 cases).Another 125 ACI patients without cognitive dysfunction admitted in our hospital during the same period were recruited and served as the control group.Spearman correlation analysis was adopted to analyze the correlation between serum SIRT2 level and cognitive impairment and disease severity.ROC curve analysis was applied to assess the value of serum SIRT2 level for cognitive impairment and its severity,and its area under the curve(AUC)was calculated.Results The serum SIRT2 level was significantly higher in the study group than the control group(20.38±5.19 mg/L vs 14.66±4.49 mg/L,P＜0.05),so was in the severe subgroup than the moderate and mild subgroups,and in the moderate subgroup than the mild subgroup(P＜0.05).Spearman analysis showed that serum SIRT2 level was posi-tively correlated with the occurrence and severity of cognitive impairment(r=0.510,r=0.527,P＜0.01).ROC curve analysis indicated that the AUC value of serum SIRT2 level in evaluating the occurrence of cognitive impairment was 0.796(95％CI:0.743-0.842),with a cutoff value,sensitivity and specificity of 19.0 mg/L,63.33％and 84.00％,respectively,and the AUC value was 0.747(95％CI:0.655-0.824)in assessing the severity of cognitive impairment,with a cutoff value,sensitivity and specificity of 17.2 mg/L,75.76％and 71.11％,respectively(P＜0.05).Conclusion Serum SIRT2 level is closely associated with the occurrence and severity of cognitive impairment in ACI patients.

Objective To analyze the relationship of silent information regulator 2(SIRT2)with the occurrence and severity of cognitive impairment in patients with acute cerebral infarction(ACI).Methods Clinical data of 150 ACI patients(study group)complicated with cognitive im-pairment admitted in our hospital from May 2022 to May 2024 were collected and analyzed retro-spectively.According to the severity of cognitive impairment,they were divided into mild(45 cases),moderate(66 cases)and severe subgroups(39 cases).Another 125 ACI patients without cognitive dysfunction admitted in our hospital during the same period were recruited and served as the control group.Spearman correlation analysis was adopted to analyze the correlation between serum SIRT2 level and cognitive impairment and disease severity.ROC curve analysis was applied to assess the value of serum SIRT2 level for cognitive impairment and its severity,and its area under the curve(AUC)was calculated.Results The serum SIRT2 level was significantly higher in the study group than the control group(20.38±5.19 mg/L vs 14.66±4.49 mg/L,P＜0.05),so was in the severe subgroup than the moderate and mild subgroups,and in the moderate subgroup than the mild subgroup(P＜0.05).Spearman analysis showed that serum SIRT2 level was posi-tively correlated with the occurrence and severity of cognitive impairment(r=0.510,r=0.527,P＜0.01).ROC curve analysis indicated that the AUC value of serum SIRT2 level in evaluating the occurrence of cognitive impairment was 0.796(95％CI:0.743-0.842),with a cutoff value,sensitivity and specificity of 19.0 mg/L,63.33％and 84.00％,respectively,and the AUC value was 0.747(95％CI:0.655-0.824)in assessing the severity of cognitive impairment,with a cutoff value,sensitivity and specificity of 17.2 mg/L,75.76％and 71.11％,respectively(P＜0.05).Conclusion Serum SIRT2 level is closely associated with the occurrence and severity of cognitive impairment in ACI patients.

BACKGROUND:Bone grafting is one of the important steps in the treatment of thoracolumbar burst fractures.Because the fracture involves the spinal canal or is accompanied by spinal cord nerve damage,severe fracture bleeding and other factors,minimally invasive bone grafting for thoracolumbar burst fractures is restricted.At present,the minimally invasive treatment of thoracolumbar burst fractures is limited to percutaneous screw fixation under the tunnel.Minimally invasive percutaneous bone grafting of injured vertebrae is rarely reported,and percutaneous precise bone grafting under the endplate has not yet been reported. OBJECTIVE:To investigate the clinical effect of subcutaneous endplate bone graft support reduction combined with percutaneous pedicle screw short-segment fixation in the treatment of A3+B2 thoracolumbar burst fractures. METHODS:From June 2017 to December 2021,90 patients with A3+B2 type asymptomatic thoracolumbar burst fracture were randomly divided into 3 groups according to admission time.In group A,33 patients received the bone graft funnel accurately placed through the pedicle channel by percutaneous puncture under C-arm fluoroscopy,bone graft support reduction under the fracture endplate,percutaneous pedicle screw fixation.In group B,30 patients received multifissure intermuscular approach through pedicle bone graft support reduction combined with pedicle screw fixation.In group C,27 patients received percutaneous pedicle screw short-segment fixation under postural reduction.All patients were followed up for at least 18 months after surgery.The clinical data of the three groups,including preoperative,postoperative and last follow-up Cobb angle,anterior edge height ratio and visual analog scale pain score,were compared and analyzed. RESULTS AND CONCLUSION:(1)There were no significant differences in age,sex,injury segment and causative factors among the three groups(P>0.05).(2)All patients at follow-up had no neurological impairment,no obvious lumbar posterior deformity or intractable low back pain.(3)The operation time of group C was less than that of group A and group B(P<0.05).Intraoperative blood loss was less in group A and group C than in group B(P<0.05).(4)There were no significant differences in the anterior edge height ratio and Cobb angle among the three groups(P>0.05).Postoperative data in groups A and B were better than that in group C.At last follow-up,group A and group B outperformed group C(P<0.05).The height and Cobb angle of the vertebral body lost in the three groups were smaller in groups A and B than those in group C(P<0.05).(5)Visual analog scale pain score was better in groups A and C than that in group B after surgery(P<0.05).There was no significant difference in visual analog scale pain score among the three groups at last follow-up(P>0.05).(6)In group C,there was one case of loose internal fixation and displacement in 1 month after surgery,and the vertebral height was lost again with back pain,and after strict bed rest for 6 weeks,the vertebral height loss was not aggravated,the pain was relieved,and the internal fixation was removed after 1 year,and the height loss at the last follow-up was not aggravated.There were no cases of failure of internal fixation in groups A and B.(7)It is indicated that subcutaneous endplate bone graft support reduction combined with percutaneous pedicle screw short-segment fixation in the treatment of A3+B2 thoracolumbar burst fracture has the advantages of less trauma,less bleeding and light postoperative pain symptoms,and the effect of injury vertebral reduction and height maintenance is the same as the reduction through pedicle bone grafting support and short segment fixation with pedicle screws through the multifidus space approach.

Objective:To explore the clinical characteristics of superior mesenteric artery ischemic diseases.Methods:The clinical and followup data of 141 hospitalized patients with ischemic disease of superior mesenteric artery in the Affiliated Hospital of Southwest Medical University from 1999 to 2021 were reviewed.Results:There were 99 males (70.2%) and 42 females (29.8%). The average age of the patients was (63.75±13.16) years; 127 patients (90.1%) complained abdominal pain.The number of all-cause deaths in the perioperative period was 27 (19.1%). ROC curve analysis showed that the optimal cutoff value of the age with predictive value was 64.5 years. The results of multivariate COX regression analysis showed that age ≥65 years old ( HR=3.855, 95% CI: 1.739-8.545), neutrophil count ( HR=1.072, 95% CI: 1.018-1.130), heart failure ( HR=2.863, 95% CI: 1.332-6.154), creatinine ( HR=1.009, 95% CI: 1.003-1.015), D-Dimer ( HR=1.112, 95% CI: 1.025-1.205) was an independent risk factor for all-cause death from superior mesenteric artery ischemic disease. Long-term survival rate of SMAD group was significantly higher than that of other SMAID; By comparing the clinical characteristics of different SMAID, neutrophil count, neutrophil ratio, D-dimer of SMAE group and SMAT group were significantly higher than that of SMAD group and ASSMA group. Conclusions:SMAID usually occurs in elderly men over 65 years old, with abdominal pain as the main symptom and often accompanied by hypertension. Risk factors included age, increased WBC count and D-dimer; The neutrophil count, neutrophil ratio, D-dimer in SMAE and SMAT group were significantly higher than that of SMAD and ASSMA group.

Objective:To compare the clinical outcomes of endovascular therapy in acute stroke patients with anterior circulation tandem occlusions caused by atherosclerosis or dissection.Methods:A retrospective cohort study. A total of 98 patients with anterior circulation tandem lesions undergoing endovascular therapy in the Wuhan NO.1 Hospital (March 2016 to March 2022) were analyzed. Median age was 64(55,71) years old, and 82.7% (81/98 cases) were males. According to the lesion etiology, the patients were divided into atherosclerosis and dissection groups. The differences in clinical outcomes between the two groups were investigated, including favorable 90-day functional outcome (modified Rankin Scale score of 0-2), successful reperfusion (modified Thrombolysis in Cerebrovascular Infarction score of 2b-3), symptomatic intracranial hemorrhage, stroke-associated pneumonia, 90-day all-cause mortality, and average hospitalization days. Logistic regression analysis was used to adjust for potential confounders affecting functional outcomes in both groups, and to determine odds ratios and 95% confidence intervals.Results:Seventy-one patients were grouped into the atherosclerotic cause and 27 into the dissection cause cohorts. The rate of favorable 90-day functional outcome was 43.7% (31/71 cases) in the atherosclerosis group versus 55.6% (15/27 cases) in the dissection group (adjusted odds ratio=1.339; 95% confidence interval, 0.374-4.798; P=0.654). No significant differences were found in other clinical outcomes between the two groups (all P>0.05). Conclusion:The clinical prognosis of patients with tandem lesions caused by atherosclerotic stenosis or artery dissection was similar after endovascular therapy. Future studies are still needed to verify our results.

Gut bacterial nitroreductases play an important role in reduction of various nitroaromatic compounds to the corresponding N-nitroso compounds, hydroxylamines or aromatic amines, most of which are carcinogenic and mutagenic agents. Inhibition of gut nitroreductases has been recognized as an attractive approach for reducing mutagen metabolites in the colon, so as to prevent colon diseases. In this study, the inhibitory effects of 55 herbal medicines against Escherichia coli(E. coli) nitroreductase (EcNfsA) were examined. Compared with other herbal extracts, Syzygium aromaticum extract showed superior inhibitory potency toward EcNfsA mediated nitrofurazone reduction. Then, the inhibitory effects of 22 major constituents in Syzygium aromaticum against EcNfsA were evaluted. Compared with other tested natural compounds, ellagic acid, corilagin, betulinic acid, oleanic acid, ursolic acid, urolithin M5 and isorhamnetin were found with strong to moderate inhibitory effect against EcNfsA, with IC₅₀ values ranging from 0.67 to 28.98 mol·L^-1. Furthermore, the inhibition kinetic analysis and docking simulation demonstrated that ellagic acid and betulinic acid potently inhibited EcNfsA (K_i < 2 μmol·L ^-1) in a competitively inhibitory manner, which created strong interactions with the catalytic triad of EcNfsA. In summary, our findings provide new scientific basis for explaining the anti-mutagenic activity of Syzygium aromaticum, where some newly identified EcNfsA inhibitors can be used for developing novel agents to reduce the toxicity induced by bacterial nitroreductase.
Ellagic Acid/pharmacology* ; Escherichia coli ; Kinetics ; Nitroreductases/pharmacology* ; Plant Extracts/pharmacology* ; Syzygium

Objective: To analyzed perioperative safety of cytoreductive surgery (CRS) for patients with colorectal cancer peritoneal metastasis (CRPM) and to construct a predictive model for serious advese events (SAE). Methods: A descriptive case-series study was conducted to retrospectively collect the clinicopathological data and treatment status (operation time, number of organ resection, number of peritoneal resection, and blood loss, etc.) of 100 patients with peritoneal metastases from colorectal cancer or appendix mucinous adenocarcinoma who underwent CRS at the Sixth Affiliated Hospital of Sun Yat-sen University from January 2019 to August 2021. There were 53 males and 47 females. The median age was 52.0 (39.0-61.8) years old. Fifty-two patients had synchronous peritoneal metastasis and 48 had metachronous peritoneal metastasis. Fifty-two patients received preoperative neoadjuvant therapy. Primary tumor was located in the left colon, the right colon and the rectum in 43, 28 and 14 cases, respectively. Fifteen patients had appendix mucinous adenocarcinoma. Measures of skewed distribution are expressed as M (range). Perioperative safety was analyzed, perioperative grade III or higher was defined as SAE. Risk factors associated with the occurrence of SAEs were analyzed using multivariate logistic regression. A nomogram was plotted by R software to predict SAE, the efficacy of which was evaluated using the area under the ROC curve (AUC) and correction curves. Results: The median peritoneal cancer index (PCI) score was 16 (1-39). Sixty-eight (68.0%) patients achieved complete tumor reduction (tumor reduction score: 0-1). Sixty-two patients were treated with intraperitoneal hyperthermic perfusion chemotherapy (HIPEC). Twenty-one (21.0%) patients developed 37 SAEs of grade III-IV, including 2 cases of ureteral injury, 6 cases of perioperative massive hemorrhage or anemia, 7 cases of digestive system, 15 cases of respiratory system, 4 cases of cardiovascular system, 1 case of skin incision dehiscence, and 2 cases of abdominal infection. No grade V SAE was found. Multivariate logistic regression analysis showed that CEA (OR: 8.980, 95%CI: 1.428-56.457, P=0.019), PCI score (OR: 7.924, 95%CI: 1.486-42.259, P=0.015), intraoperative albumin infusion (OR: 48.959, 95%CI: 2.115-1133.289, P=0.015) and total volume of infusion (OR: 24.729, 95%CI: 3.956-154.562, P=0.001) were independent risk factors for perioperative SAE in CRS (all P<0.05). Based on the result of multivariate regression models, a predictive nomogram was constructed. Internal verification showed that the AUC of the nomogram was 0.926 (95%CI: 0.872-0.980), indicating good prediction accuracy and consistency. Conclusions: CRS is a safe and effective method to treat CRPM. Strict screening of patients and perioperative fluid management are important guarantees for reducing the morbidity of SAE.
Adenocarcinoma, Mucinous/therapy* ; Adult ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Appendiceal Neoplasms/surgery* ; Colorectal Neoplasms/pathology* ; Combined Modality Therapy ; Cytoreduction Surgical Procedures/methods* ; Female ; Humans ; Hyperthermia, Induced/methods* ; Male ; Middle Aged ; Peritoneal Neoplasms/secondary* ; Retrospective Studies ; Survival Rate

Pancreatic lipase (PL), a crucial enzyme in the digestive system of mammals, has been proven as a therapeutic target to prevent and treat obesity. The purpose of this study is to evaluate and characterize the PL inhibition activities of the major constituents from Fructus Psoraleae (FP), one of the most frequently used Chinese herbs with lipid-lowering activity. To this end, a total of eleven major constituents isolated from Fructus Psoraleae have been obtained and their inhibition potentials against PL have been assayed by a fluorescence-based assay. Among all tested compounds, isobavachalcone, bavachalcone and corylifol A displayed strong inhibition on PL (IC < 10 μmol·L). Inhibition kinetic analyses demonstrated that isobavachalcone, bavachalcone and corylifol A acted as mixed inhibitors against PL-mediated 4-methylumbelliferyl oleate (4-MUO) hydrolysis, with the K values of 1.61, 3.77 and 10.16 μmol·L, respectively. Furthermore, docking simulations indicated that two chalcones (isobavachalcone and bavachalcone) could interact with the key residues located in the catalytic cavity of PL via hydrogen binding and hydrophobic interactions. Collectively, these finding provided solid evidence to support that Fructus Psoraleae contained bioactive compounds with lipid-lowering effects via targeting PL, and also suggested that the chalcones in Fructus Psoraleae could be used as ideal leading compounds to develop novel PL inhibitors.

Standardized rotary residency training is an important part of clinical medical education. Traditional clinical teaching can't meet the rapid development of oncology medicine. In the rotary residency training in oncology department, we put forward the problems encountered in clinical practice, stimulate the interest and initiative of residence, the PBL teaching model is combined with the evidence-based medicine in the teaching process through the relevant training, literature review and discussion. By standardizing the treatment concept the residence's understanding of the basic theory and frontier knowledge of oncology was improved, the thinking innovation and clinical practice ability of the residency doctors were enhanced.