Humans ; Alzheimer Disease ; Cross-Sectional Studies ; Creatine Kinase ; Brain/metabolism*

Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Objective:To investigate the incidence of postoperative complications in Chinese patients with gastric or colorectal cancer, and to evaluate the risk factors for postoperative complications.Methods:This was a national, multicenter, prospective, registry-based, cohort study of data obtained from the database of the Prevalence of Abdominal Complications After Gastro- enterological Surgery (PACAGE) study sponsored by the China Gastrointestinal Cancer Surgical Union. The PACAGE database prospectively collected general demographic characteristics, protocols for perioperative treatment, and variables associated with postoperative complications in patients treated for gastric or colorectal cancer in 20 medical centers from December 2018 to December 2020. The patients were grouped according to the presence or absence of postoperative complications. Postoperative complications were categorized and graded in accordance with the expert consensus on postoperative complications in gastrointestinal oncology surgery and Clavien-Dindo grading criteria. The incidence of postoperative complications of different grades are presented as bar charts. Independent risk factors for occurrence of postoperative complications were identified by multifactorial unconditional logistic regression.Results:The study cohort comprised 3926 patients with gastric or colorectal cancer, 657 (16.7%) of whom had a total of 876 postoperative complications. Serious complications (Grade III and above) occurred in 4.0% of patients (156/3926). The rate of Grade V complications was 0.2% (7/3926). The cohort included 2271 patients with gastric cancer with a postoperative complication rate of 18.1% (412/2271) and serious complication rate of 4.7% (106/2271); and 1655 with colorectal cancer, with a postoperative complication rate of 14.8% (245/1655) and serious complication rate of 3.0% (50/1655). The incidences of anastomotic leakage in patients with gastric and colorectal cancer were 3.3% (74/2271) and 3.4% (56/1655), respectively. Abdominal infection was the most frequently occurring complication, accounting for 28.7% (164/572) and 39.5% (120/304) of postoperative complications in patients with gastric and colorectal cancer, respectively. The most frequently occurring grade of postoperative complication was Grade II, accounting for 65.4% (374/572) and 56.6% (172/304) of complications in patients with gastric and colorectal cancers, respectively. Multifactorial analysis identified (1) the following independent risk factors for postoperative complications in patients in the gastric cancer group: preoperative comorbidities (OR=2.54, 95%CI: 1.51-4.28, P<0.001), neoadjuvant therapy (OR=1.42, 95%CI:1.06-1.89, P=0.020), high American Society of Anesthesiologists (ASA) scores (ASA score 2 points:OR=1.60, 95% CI: 1.23-2.07, P<0.001, ASA score ≥3 points:OR=0.43, 95% CI: 0.25-0.73, P=0.002), operative time >180 minutes (OR=1.81, 95% CI: 1.42-2.31, P<0.001), intraoperative bleeding >50 mL (OR=1.29,95%CI: 1.01-1.63, P=0.038), and distal gastrectomy compared with total gastrectomy (OR=0.65,95%CI: 0.51-0.83, P<0.001); and (2) the following independent risk factors for postoperative complications in patients in the colorectal cancer group: female (OR=0.60, 95%CI: 0.44-0.80, P<0.001), preoperative comorbidities (OR=2.73, 95%CI: 1.25-5.99, P=0.030), neoadjuvant therapy (OR=1.83, 95%CI:1.23-2.72, P=0.008), laparoscopic surgery (OR=0.47, 95%CI: 0.30-0.72, P=0.022), and abdominoperineal resection compared with low anterior resection (OR=2.74, 95%CI: 1.71-4.41, P<0.001). Conclusion:Postoperative complications associated with various types of infection were the most frequent complications in patients with gastric or colorectal cancer. Although the risk factors for postoperative complications differed between patients with gastric cancer and those with colorectal cancer, the presence of preoperative comorbidities, administration of neoadjuvant therapy, and extent of surgical resection, were the commonest factors associated with postoperative complications in patients of both categories.

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.

A 3-year-old male patient was diagnosed with neurofibromatosis type 1(NF1) for two years. The patient has multiple neurofibromas in retroperitoneum, lumbococcygeal paravertebral, lumbosacral spinal canal, and foramina. Due to retroperitoneal mass compression, the child suffered from urological complications such as hydronephrosis, ureterdilation, neurogenic bladder, etc., which seriously affected the urination function and resulted in multiple surgical treatments. Currently, the patient has been treated with mitogen activates extracelluar signal-regulated kinases(MEK) inhibitor selumetinib targeted therapy, and has voluntarily urinated, and his general state is better than before medication. The diagnosis and treatment of this case reflects the importance of multidisciplinary collaboration in the diagnosis and treatment of rare diseases.

【Objective】 To investigate the relationship between serum reproductive hormones and sperm parameters and outcomes of micro-testicular sperm extraction (Micro-TESE). 【Methods】 Clinical data of 1 091 patients treated in our hospital during Jan. and Dec.2021 were retrospectively analyzed. According to the sperm concentration,the patients were divided into non-obstructive azoospermia (NOA) group (group A,n=418),normal sperm concentration group (group B,n=615),mild to moderate oligospermia group (group C,n=18),severe oligospermia group (group D,n=18),and obstructive azoospermia group (group E,n=22). In group A,244 cases treated with Micro-TESE were grouped into the sperm-acquired group (Micro-TESE positive group,n=82) and non-sperm-acquired group (Micro-TESE negative group,n=162),and according to the pathological types of testicular tissue,the patients were divided into normal testicular tissue with hypospermatogenesis group (HYPO group,n=129),maturation arrest group (MA group,n=10),and support-only cell syndrome group (SCO group,n=122). Differences in semen parameters and reproductive hormone levels were compared,and relationship between reproductive hormones and sperm parameters and Micro-TESE outcomes was determined with Pearson correlation analysis. 【Results】 In the sperm concentration subgroup,the testicular volume of group A was lower than that of group B and group E (P<0.05); the levels of follicle stimulating hormone (FSH) and luteinizing hormone (LH) in group A were the highest (P<0.05),but the level of testosterone (T) was the lowest (P<0.05); the levels of anti-mullerian hormone (AMH) and serum inhibin B (INHB) in group A were lower than those in group B and group E (P<0.05),the normal sperm morphology rate in group B was higher than that in group A and group E (P<0.05); the percentage of forward moving sperm in group B was the highest (P<0.05). Pearson correlation analysis revealed that sperm concentration,normal sperm morphology rate,and percentage of forward moving sperm were negatively correlated with age,FSH,LH (P<0.05),and positively correlated with testicular volume,T,AMH,and INHB (P<0.05). NOA patients were grouped according to testicular histology and pathology. The INHB in the SCO group was the smallest of the three groups (P<0.05); the FSH and LH levels in the SCO group were higher than those in the MA group (P<0.05),while the 17β-estradiol (E2) levels in the HYPO group were higher than those in the SCO group (P<0.05). NOA patients were grouped according to the results of Micro-TESE surgical treatment. There was a statistically significant difference in AMH and INHB levels between the Micro-TESE positive and negative groups (P<0.05). The binary logistic regression analysis of factors affecting the Micro-TESE outcomes of NOA patients showed AMH was negatively correlated with the Micro-TESE outcome (OR=0.904,95%CI:0.91-1.08,P<0.05). 【Conclusion】 Age,FSH,LH,AMH,and INHB are correlated with sperm concentration,normal sperm morphology rate,and percentage of forward moving sperm. The INHB level was the lowest in the SCO group. The results of Micro-TESE in patients with NOA can be predicted by serum AMH level.

Objective:To explore whether a longitudinal integrated clerkship (LIC) model is more conducive to medical students' post competency and satisfaction with clerkships compared with the traditional block rotation clerkship.Methods:We selected 72 students who participated in graduating clerkships at The First Affiliated Hospital of Harbin Medical University from June 2018 to June 2019. They were equally divided into experimental group and control group to adopt LIC and traditional block rotation clerkship models, respectively. After completing the clerkships, the two groups were evaluated for post competency through objective testing of theoretical medical knowledge and basic clinical skills and rating of the other five competence items by the students themselves and their teachers. At the same time, a questionnaire was delivered to both groups for the degree of satisfaction with clerkships. The t-test and chi-squared test were performed using SPSS 23.0. Results:The objective tests and students' self-evaluation showed that the experimental group had significantly higher scores of theoretical medical knowledge [(8.02±1.11) vs. (7.50±0.97)], basic clinical skills [(7.63±0.90) vs. (6.93±0.73)], medical professional responsibility [(7.74±0.56) vs. (7.31±0.78)], clinical communication [(8.10±1.06) vs. (7.22±0.60)], team work [(7.84±0.62) vs. (7.11±0.69)], literature searching [(6.25±0.60) vs. (4.78±0.84)], and scientific research ability [(4.26±0.88) vs. (2.46±1.20)] compared with the control group (all P<0.05). The experimental group had significantly higher teacher-rated scores of medical professional responsibility [(8.03±0.74) vs. (6.59±0.70)], clinical communication [(7.95±0.73) vs. (6.87±0.67)], team work [(7.96±0.75) vs. (6.95±0.69)], literature searching [(4.84±0.84) vs. (3.30±0.69)], and scientific research ability [(4.53±1.03) vs. (2.70±1.05)] than the control group (all P<0.01). The scores of satisfaction were all higher in the experimental group than in the control group in terms of course arrangement satisfaction [(7.17±0.91) vs. 6.56±0.84)], teacher-student interaction satisfaction [(7.08±0.69) vs. (6.28±0.82)], self-improvement satisfaction [(7.28±0.45) vs. (6.36±0.49)], and clinical work smoothness [(7.72±0.82) vs. (6.81±0.71); all P<0.01]. Conclusion:Compared with the traditional block rotation model, the LIC model is more helpful for improving the post competency of medical students. LIC is a new clinical clerkship model that can potentially replace the traditional block rotation clerkship.

ObjectiveTo explore the effects of anxiety and depression on Internet gaming disorder in medical students， and to evaluate the moderating effect of gender， so as to provide references for the prevention and intervention of Internet gaming disorder in medical students. MethodsIn November 2021， a total of 11 771 medical students from a medical college in Sichuan province participated in an online survey through Wenjuanxing platform. Participants completed the Self-rating Anxiety Scale （SAS）， Self-rating Depression Scale （SDS） and the nine-item Internet Gaming Disorder Scale-Short Form （IGDS9-SF）. Then a hierarchical multiple regression analysis was conducted to discuss the moderating role of gender in the relationships between anxiety， depression and Internet gaming disorder in medical students. Results①Males scored lower on SDS （t=-8.302， P<0.01）， and higher on IGDS9-SF than females （t=33.384， P<0.01）. ②SAS score of medical students was positively correlated with SDS score （r=0.735， P<0.01）， SAS and SDS scores were positively correlated with IGDS9-SF score in medical students （r=0.288， 0.238， P<0.01）. ③Anxiety and depression could positively predict Internet gaming disorder （β=0.245， 0.058， t=18.864， 4.444， P<0.01）. ④Gender played a moderating effect between anxiety and Internet gaming disorder （β=-0.194， t=-4.518， P<0.01）. ConclusionAnxiety and depression have a positive predictive effect on Internet gaming disorder in medical students. Furthermore， the effects of anxiety on Internet gaming disorder are moderated by gender， and the anxiety of male students exhibits a markedly stronger impact on Internet gaming disorder than that of female students.

Catalase is widely used in the food, medical, and textile industries. It possesses exceptional properties including high catalytic efficiency, high specificity, and environmental friendliness. Free catalase cannot be recycled and reused in industry, resulting in a costly industrial biotransformation process if catalase is used as a core ingredient. Developing a simple, mild, cost-effective, and environmentally friendly approach to immobilize catalase is anticipated to improve its utilization efficiency and enzymatic performance. In this study, the catalase KatA derived from Bacillus subtilis 168 was expressed in Escherichia coli. Following separation and purification, the purified enzyme was prepared as an immobilized enzyme in the form of enzyme-inorganic hybrid nanoflowers, and the enzymatic properties were investigated. The results indicated that the purified KatA was obtained through a three-step procedure that included ethanol precipitation, DEAE anion exchange chromatography, and hydrophobic chromatography. Then, by optimizing the process parameters, a novel KatA/Ca₃(PO₄)₂ hybrid nanoflower was developed. The optimum reaction temperature of the free KatA was determined to be 35 ℃, the optimum reaction temperature of KatA/Ca₃(PO₄)₂ hybrid nanoflowers was 30-35 ℃, and the optimum reaction pH of both was 11.0. The free KatA and KatA/Ca₃(PO₄)₂ hybrid nanoflowers exhibited excellent stability at pH 4.0-11.0 and 25-50 ℃. The KatA/Ca₃(PO₄)₂ hybrid nanoflowers demonstrated increased storage stability than that of the free KatA, maintaining 82% of the original enzymatic activity after 14 d of storage at 4 ℃, whereas the free KatA has only 50% of the original enzymatic activity. In addition, after 5 catalytic reactions, the nanoflower still maintained 55% of its initial enzymatic activity, indicating that it has good operational stability. The K_m of the free KatA to the substrate hydrogen peroxide was (8.80±0.42) mmol/L, and the k_cat/K_m was (13 151.53± 299.19) L/(mmol·s). The K_m of the KatA/Ca₃(PO₄)₂ hybrid nanoflowers was (32.75±2.96) mmol/L, and the k_cat/K_m was (4 550.67±107.51) L/(mmol·s). Compared to the free KatA, the affinity of KatA/Ca₃(PO₄)₂ hybrid nanoflowers to the substrate hydrogen peroxide was decreased, and the catalytic efficiency was also decreased. In summary, this study developed KatA/Ca₃(PO₄)₂ hybrid nanoflowers using Ca²⁺ as a self-assembly inducer, which enhanced the enzymatic properties and will facilitate the environmentally friendly preparation and widespread application of immobilized catalase.
Catalase ; Nanostructures/chemistry* ; Hydrogen Peroxide/metabolism* ; Enzymes, Immobilized/chemistry* ; Catalysis