Pharmacological perturbation studies based on protein-level signatures are fundamental for drug dis-covery.In the present study,we used a mass spectrometry(MS)-based proteomic platform to profile the whole proteome of the breast cancer MCF7 cell line under stress induced by 78 bioactive compounds.The integrated analysis of perturbed signal abundance revealed the connectivity between phenotypic behaviors and molecular features in cancer cells.Our data showed functional relevance in exploring the novel pharmacological activity of phenolic xanthohumol,as well as the noncanonical targets of clinically approved tamoxifen,lovastatin,and their derivatives.Furthermore,the rational design of synergistic inhibition using a combination of histone methyltransferase and topoisomerase was identified based on their complementary drug fingerprints.This study provides rich resources for the proteomic landscape of drug responses for precision therapeutic medicine.

Objective To construct a Type 1 diabetes model in miniature pigs and explore postoperative care strategies for effectively prolonging the survival time of the model pigs.Methods Seven Banna miniature pigs were selected for pancreatectomy.Glucose,vitamins,and antibiotics were administered for 3-5 days after surgery to aid recovery.Blood glucose and urine glucose levels were measured twice a day in the morning and evening to adjust insulin supplementation accordingly.The model pigs were observed daily and records were kept,including orexis,psychosis,weakness,skin ulcer,and feces and urine.Body weight was measured weekly until the death of the model animals.Based on the model pigs'condition,glucose injection and Ringer's lactate solution were administered to supplement nutrition and correct electrolyte imbalances.Results All seven Banna miniature pigs showed typical symptoms of diabetes:random blood glucose levels higher than 11.1 mmol/L after pancreatectomy,far exceeding the average blood glucose level of 6.0 mmol/L in normal pigs;positive urine glucose;and progressive weight loss.These features indicated the successful construction of Type 1 diabetes model.Additionally,Type 1 diabetic pigs that survived more than 8 weeks showed progressive hair loss and skin ulceration.Euthanasia was performed on model pigs when they were unable to stand or even eat independently,and pathological examination and HE staining were conducted on tissues collected from affected organs such as the liver,kidneys,and skin.Pathological sections revealed liver congestion,massive glycogen accumulation,ballooning degeneration of hepatocytes,and progressive liver fibrosis,along with glomerular congestion,vacuolar degeneration in renal tubular epithelial cells,proteinuria,dermal congestion,thinning of vascular walls,and varying degrees of parakeratosis and dyskeratosis in the liver,kidneys,and skin tissues due to prolonged hyperglycemia.The average survival time of the constructed Banna miniature pig diabetes model was 44 d,with a maximum survival time of 121 d.Conclusion Type 1 diabetes model can be constructed successfully in Banna miniature pigs through pancreatectomy.With meticulous postoperative care,a long-term Type 1 diabetes model with significant complications can be achieved,providing a stable large-animal model for Type 1 diabetes treatment strategies.

This study aimed to explore the value of magnetic resonance imaging (MRI) T 2 mapping in the assessment of dermatomyositis (DM) and polymyositis (PM). Thirty-three confirmed cases (myosin group) and eight healthy volunteers (healthy control group) at the Department of Rheumatology and Immunology, the First Affiliated Hospital of Kunming Medical University, from October 2016 to December 2017, were collected and analyzed. Multiple parameters of the myosin group were quantified, including creatine kinase (CK), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), complement C3, and complement C4. Disease status was evaluated using a panel of tools: myositis disease activity assessment tool-muscle (MDAAT-muscle), myositis disease activity assessment tool-whole (MDAAT-all), health assessment questionnaire (HAQ), medical outcomes study health survey short form-36 item (SF-36), hand muscle strength test (MMT-8) score, and MRI T 2 mapping of muscle (22 muscles in the pelvis and thighs) T 2 values. The results showed that in the myositis group, the measurements for CK, ESR, CRP, complement C3, and complement C4 were 457.2 (165.6, 1 229.2) IU/L, 20 (10, 42) mm/1h, 3.25 (2.38, 10.07) mg/L, 0.90 (0.83, 1.06) g/L, and 0.18 (0.14, 0.23) g/L, respectively. The scores for MMT-8, MDAAT-muscle, MDAAT-all, HAQ, and SF-36 were 57.12±16.23, 5.34 (4.00, 6.00), 34.63±12.62, 1.55 (0.66, 2.59), and 44.66±7.98, respectively. T 2 values were significantly higher in all 22 muscles of the pelvis and thighs of patients with DM or PM compared with the healthy controls [(54.99±11.60)ms vs. (36.62±1.66)ms, P<0.001], with the most severe lesions in the satrorius, iliopsoas, piriformis, gluteus minimus, and gluteus medius muscles. The total muscle T 2 value in the myositis group was positively correlated with CK, MDAAT-muscle, MDAAT-all, and HAQ ( r=0.461, 0.506, 0.347, and 0.510, respectively, all P<0.05). There was a negative correlation between complement C4, SF-36, and MMT-8 scores ( r=-0.424, -0.549, and -0.686, respectively, all P<0.05). Collectively, the findings from this study suggest that MRI T 2 mapping can objectively reflect the disease status of DM and PM.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

Objective:To compare the patient-reported outcomes and short-term clinical outcomes between robotic-assisted and laparoscopic-assisted radical gastrectomy for locally advanced gastric cancer.Methods:This single-center prospective randomized controlled trial was conducted in the Department of Gastrointestinal Surgery, Affiliated Hospital of Qingdao University from October 2020 to August 2022. Patients with locally advanced gastric cancer who were to undergo radical gastrectomy were selected and randomly divided into two groups according to 1∶1, and received robotic surgery and laparoscopic surgery, respectively. Patient-reported outcomes and short-term clinical outcomes (including postoperative complications, surgical quality and postoperative short-term recovery) were compared between the two groups by independent sample t test, Mann-Whitney U test, repeated ANOVA, generalized estimating equation, χ2 test and Fisher′s exact test. Results:A total of 237 patients were enrolled for modified intention-to-treat analysis (120 patients in the robotic group, 117 patients in the laparoscopic group). There were 180 males and 59 females, aged (63.0±10.2) years (range: 30 to 85 years). The incidence of postoperative complications was similar between the robotic group and laparoscopic group (16.7% (20/120) vs. 15.4% (18/117), χ2=0.072, P=0.788). The robotic group had higher patient-reported outcomes scores in general health status, emotional, and social domains compared to the laparoscopic group, differences in time effect, intervention effect, and interaction effect were statistically significant (general health status: χ2 value were 275.68, 3.91, 6.38, P value were <0.01, 0.048, 0.041; emotional: χ2 value were 77.79, 6.04, 6.15, P value were <0.01, 0.014, 0.046; social: χ2 value were 148.00, 7.57, 5.98, P value were <0.01, 0.006, 0.048). However, the financial burden of the robotic group was higher, the differences in time effect, intervention effect and interaction effect were statistically significant ( χ2 value were 156.24, 4.08, 36.56, P value were <0.01, 0.043,<0.01). Conclusion:Compared to the laparoscopic group, the robotic group could more effectively relieve postoperative negative emotions and improve recovery of social function in patients.

Objective:The aim of this study was to evaluate the safety and efficacy of prostatistic urethral lift (PUL) in treating benign prostate hyperplasia(BPH) through systematic review and Meta-analysis.Methods:A systematic literature search on CNKI, Wanfang, VIP, PubMed, Web of Science, Cochrane Library and Chinese Clinical Trial Registry to identify the relevant studies and data before September 2021. Information was extracted from each eligible article. All statistical analyses of this Meta-analyses were performed with Review Manager 5.3 and Stata 15.0 software to conduct a Meta-analysis of the symptom improvement of BPH patients before and 3 months and 12 months after PUL. The main evaluation indicators included: International Prostate Symptom Score (IPSS), maximum urinary flow rate (Q max), post-void residual (PVR), and Quality of Life Scale (QOL), Sexual Health Inventory for Men (SHIM). The complication rate of PUL was systematically evaluated. Results:A total of 12 clinical studies were included, and 850 patients accepted the PUL. The results showed that IPSS decreased significantly at both 3 and 24 months after PUL surgery ( MD = -11.77, 95% CI -12.47—-11.07, P<0.05; MD = -9.71, 95% CI-10.76—-8.66, P<0.05), Q max (ml/s) increased to a certain degree ( MD = 3.87, 95% CI 3.37—4.37, P<0.05; MD = 3.68, 95% CI 2.97—4.40, P<0.05), QOL decreased significantly ( MD=-2.57, 95% CI -2.76—-2.38, P<0.05; MD = -2.14, 95% CI -2.38—-2.91, P<0.05), SHIM score was unaffected ( P>0.05), compared with preoperative baseline data. PUL could be performed under local anesthesia, the main perioperative complications reported in the included studies were dysuria (17%±6%), hematuria (14%±5%) and pelvic pain (8%±6%), all of which were transient. Conclusions:PUL in the treatment of BPH has significant short-term and long-term efficacy with low surgical risk and complication rate, and can preserve normal ejaculation function. It is a safe and effective minimally invasive surgery, which can be used for BPH patients with intolerance to general anesthesia surgery or normal sexual function demand.

Objective:To investigate the personality traits of patients with anxious depression and the relationship between personality traits and clinical symptoms.Methods:From December 2011 to October 2014, 177 first-episode untreated patients with depression from the psychiatric department of the First Affiliated Hospital of Kunming Medical University and 185 healthy controls(HC group) recruited by the community were included.All patients were divided into anxious depression group ( n=92) and non-anxious depression group ( n=85) according to whether the anxiety/somatization factor score ≥7.The simplified version of Neuroticism Extraversion Openness Five-Factor Inventory (NEO-FFI) and the Hamilton depression scale-17 (HAMD-17) were used to assess all the subjects.Statistical analyses were conducted in SPSS 21.0.Analysis of covariance was used to compare the differences of the scores on personality dimensions among the three groups.The relationship between personality dimensions and anxious depression was confirmed by Logistic regression, linear regression analysis and generalized linear models. Results:The differences of the scores on the four dimensions of neuroticism ( F=108.863, P<0.01), extraversion ( F=86.357, P<0.01), agreeableness ( F=50.615, P<0.01), and conscientiousness ( F=24.730, P<0.01) among the three groups were statistically significant.Further pairwise comparision showed, the score of neuroticisms was higher in the anxious depression group(43.05±8.92) and non-anxious depression group(39.85±7.21) than that in the HC group (30.16±6.25)( P<0.01, Bonferroni corrected). The scores of extroversion (31.22±6.33, 32.61±6.83), agreeableness (38.66±5.80, 39.46±6.19) and conscientiousness (39.75±6.89, 38.85±7.26) were lower in the anxious depression group and non-anxious depression group than those in the HC group (40.29±5.37, 44.79±4.68, 44.09±5.66, all P<0.01, Bonferroni corrected). The score of neuroticisms in anxious depression group was higher than that in non-anxious depression group, and the difference was statistically significant ( P<0.01, Bonferroni corrected). Logistic regression analysis with age, gender and years of education controlled showed that the score of neuroticism ( B=0.082, OR=1.085, 95% CI=1.020-1.154, P=0.009) and conscientiousness ( B=0.060, OR=1.062, 95% CI=1.006-1.120, P=0.028) were risk factors for anxiety symptoms in patients with depression.Linear regression analysis showed that the scores on neuroticism had positive predictive effects on the anxiety/somatization factor score ( B=0.055, 95% CI=0.021-0.089, P=0.002) and cognitive impairment factor score ( B=0.074, 95% CI=0.023-0.125, P=0.005) in the anxious depression group. Conclusion:Compared to non-anxious depression, patients with anxious depression show higher level of neuroticism, and the level of neuroticism can positively predict the symptoms of anxiety and cognitive impairment.The high level of neuroticism and conscientiousness may be risk factors for the occurrence of anxiety symptoms in patients with depressed.

Objective:To investigate the role and mechanism of chemokine receptor type 4 (CXCR4) in renal injury and fibrosis caused by calcium oxalate crystals in mice.Methods:In June 2021, Fifteen male C57/BL6 mice were divided into control group (5 mice), model group (5 mice), and AMD3100 intervention group (5 mice) by random number table method. In model group and AMD3100 intervention group, glyoxylate (100 mg/kg) was injected intraperitoneal for 7 consecutive days for modeling. Meanwhile, the AMD3100 intervention group was also given intraperitoneal injection of AMD3100 (1 mg/kg) for 7 days. The control group was continuously injected with equal volume saline intraperitoneally. After 7 days, peripheral blood was collected from each group to determine the levels of serum urea nitrogen (BUN) and creatinine (Scr) to assess the renal function; HE, Von-Kossa, Picrosirius Red staining was also taken from the left kidney to observe the pathological changes of renal tissue. CXCR4, transforming growth factor β1 (TGF-β1) were detected by immunohistochemistry and western blot. The expression levels of PI3K/AKT pathway-related proteins were detected by western blot.Results:The results of biochemical indexes showed that the serum Scr [(108.03±13.56) μmol/L vs. (39.50±4.48)μmol/L, P<0.01)] and BUN[(5.66±0.48)mmol/L vs. (0.77±0.10)mmol/L, P<0.01) levels were significantly increased in model group compared with the control group. The AMD3100 intervention group was significantly lower than the model group in terms of Scr [(65.77±3.27)μmol/L vs. (108.03±13.56)μmol/L, P<0.05) and BUN [(2.97±0.44)mmol/L vs. (5.66±0.48)mmol/L, P<0.05) levels. The results of kidney pathology in mice showed that renal tubules were significantly dilated with inflammatory cell infiltration in the model group compared with the control group, and a large number of calcium oxalate crystals and collagen fibers were deposited. The extent of kidney damage, calcium oxalate crystals and collagen fibers deposition were significantly reduced in the AMD3100 intervention group compared with the model group. The results of western blotting showed that the relative expression of CXCR4(0.639±0.019 vs. 0.158±0.012, P<0.01) and TGF-β1(0.698+ 0.018 vs. 0.314+ 0.015, P<0.05) was significantly increased in the model group compared with the control group. The relative expression of CXCR4(0.322±0.231) in the AMD3100 intervention group compared with the model group (0.322±0.231 vs. 0.639±0.019, P<0.05) and TGF-β1(0.445+ 0.017 vs. 0.698+ 0.018, P<0.05) were significantly decreased. The results of immunohistochemical staining showed the trend of CXCR4 and TGF-β1 expression in each group consistent with the results of protein blotting assay. Western blotting results showed that the expression of p-PI3K (0.613±0.016 vs. 0.213±0.011, P<0.01) and p-AKT(0.149±0.013 vs. 0.047±0.014, P<0.01) was significantly increased in the model group compared with the control group. The expression of p-PI3K in the AMD3100 intervention group compared with the model group (0.292±0.020 vs. 0.613±0.016, P<0.05) and p-AKT (0.098±0.021 vs. 0.149±0.013, P<0.05)was significantly decreased. Conclusion:CXCR4 inhibits calcium oxalate crystal-induced kidney injury and interstitial fibrosis in mice by targeting the PI3K/AKT pathway.

Objective:To investigate the typing and clinical value of posterior group renal calyces.Methods:From April 2020 to June 2021, 640 patients (320 men and 320 women) who underwent CTU examination in our hospital with kidneys on both sides and normal or only mild hydronephrosis in the collecting system were analyzed. A total of 1 280 renal CTU three-dimensional reconstructed images were counted.The patients aged 52.4±11.9 years. The patients' CTU images were reconstructed in three dimensions using the spine as a marker to rotate the collecting system images in stereoscopic space to simulate a prone position. A two-person review was taken to observe the imaging morphology of the renal calyces in the prone position, and the 640 renal calyces in the posterior group of the left and right sides were counted for staging. Based on the morphology of the renal calyces and the influence on the establishment of surgical access, the posterior group of renal calyces was divided into 3 major types. Pot-belly type: the renal pelvis is shaped like a pot-belly, and the renal pelvis is directly connected to the cup-shaped minor calyces without a distinct major renal calyces. Classically branched: 2 or more major renal calyces are branched and converge to form the renal pelvis. Elongated branched: the major calyces are branched, with at least one major calyces having an axis length ≥0.9cm and a neck width ≤0.3cm.The classic branching type is divided into three types, a, b, and c, including seven subtypes, based on the relationship of the posterior group of the minor calyces to the major calyces. Type a is derived from group 1 major calyces only, type b is derived from group 2 major calyces at the same time, and type c is derived from the upper, middle and lower groups of major calyces at the same time. Type a contains 3 subtypes.Type a1 is derived from the upper group of major calyces only, type a2 is derived from the middle group of major calyces only, and type a3 is derived from the lower group of major calyces only. Type b is also divided into 3 subtypes. Type b1 is derived from the upper and middle groups of major calyces at the same time, type b2 is derived from the middle and lower groups of major calyces at the same time, and type b3 for the upper and lower renal major calyces. Type c had no corresponding subtype.Results:Statistical findings revealed that all kidneys had posterior group calyces. The morphological typing of the posterior group of calyces was 8.83% (113/1 280) for the pot-bellied type, which had the highest occurrence of 2 minor calyces (5.63%, 72/1 280). 71.25% (912/1 280) had the classically branched type, which had the highest occurrence of 3 minor calyces (31.17%, 399/1 280). 19.92% (255/1 280) had the elongated branched type, with the highest percentage of 3 occurring in the calyces (9.92%, 127/1 280). The anatomical typing of the classical branching type occurred in 20.50% (187/912) for type a, 66.45% (606/912) for type b, and 13.05% (119 /912) for type c. The percentage of occurrence of type a1/a2/a3 was 4.06% (37/ 912), 6.14% (56/ 912), and 10.31% (94/912). b1/b2/b3 types occurred in 2.03% (21/912), 7.46% (68/912), and 56.69% (517/912), respectively.Conclusions:The posterior group of calyces is structurally complex and extremely variable. In this study, the posterior group calyces were found to be present in all patients, and the posterior group calyces were morphologically divided into 3 types, with the highest percentage of occurrence of the classical branching type and the highest percentage of 3 posterior group minor calyces. The classical branching anatomical typing was highest in type b with the highest percentage of type b3, which combined with stone distribution, made it easy to choose the puncture location. The typing of the posterior group of calyces can provide an anatomical basis for PCNL puncture from the posterior group.

Objective    To investigate the prognostic survival status and influence factors for surgical treatment of esophageal squamous cell carcinoma (ESCC) in pathological stage T1b (pT1b). Methods    The patients with ESCC in pT1b undergoing Ivor-Lewis or McKeown esophagectomy in Lanzhou University Second Hospital from 2012 to 2015 were collected, including 78 males (78.3%) and 17 females (21.7%) with an average age of 61.4±7.4 years. Results    The most common postoperative complications were pneumonia (15.8%), anastomotic leakage (12.6%) and arrhythmia (8.4%). Ninety-three (97.9%) patients underwent R0 resection, with an average number of lymph node dissections of 14.4±5.6. The rate of lymph node metastasis was 22.1%, and the incidence of lymph vessel invasion was 13.7%. The median follow-up time was 60.4 months, during which 25 patients died and 27 patients relapsed. The overall survival rate at 3 years was 86.3%, and at 5 years was 72.7%. Multivariate Cox regression analysis showed that lymph node metastasis (P=0.012, HR=2.60, 95%CI 1.23-5.50) and lympovascular invasion (P=0.014, HR=2.73, 95%CI 1.22-6.09) were independent risk factors for overall survival of pT1b ESCC. Conclusion    Esophagectomy via right chest approach combined with two-fields lymphadenectomy is safe and feasible for patients with pT1b ESCC. The progress of pT1b ESCC with lymph node metastasis or lymphovascular invasion is relatively poor.