Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a complex disease that is often accompanied by mental health disorders. However, the potential mechanisms underlying the heterogeneous clinical presentation of CP/CPPS remain uncertain. This study analyzed widely targeted metabolomic data of expressed prostatic secretions (EPS) and plasma to reveal the underlying pathological mechanisms of CP/CPPS. A total of 24 CP/CPPS patients from The Second Nanning People's Hospital (Nanning, China), and 35 asymptomatic control individuals from First Affiliated Hospital of Guangxi Medical University (Nanning, China) were enrolled. The indicators related to CP/CPPS and psychiatric symptoms were recorded. Differential analysis, coexpression network analysis, and correlation analysis were performed to identify metabolites that were specifically altered in patients and associated with various phenotypes of CP/CPPS. The crucial links between EPS and plasma were further investigated. The metabolomic data of EPS from CP/CPPS patients were significantly different from those from control individuals. Pathway analysis revealed dysregulation of amino acid metabolism, lipid metabolism, and the citrate cycle in EPS. The tryptophan metabolic pathway was found to be the most significantly altered pathway associated with distinct CP/CPPS phenotypes. Moreover, the dysregulation of tryptophan and tyrosine metabolism and elevation of oxidative stress-related metabolites in plasma were found to effectively elucidate the development of depression in CP/CPPS. Overall, metabolomic alterations in the EPS and plasma of patients were primarily associated with oxidative damage, energy metabolism abnormalities, neurological impairment, and immune dysregulation. These alterations may be associated with chronic pain, voiding symptoms, reduced fertility, and depression in CP/CPPS. This study provides a local-global perspective for understanding the pathological mechanisms of CP/CPPS and offers potential diagnostic and therapeutic targets.
Humans ; Male ; Prostatitis/blood* ; Adult ; Pelvic Pain/blood* ; Metabolomics ; Prostate/metabolism* ; Middle Aged ; Chronic Pain/blood* ; Metabolome ; Case-Control Studies ; Tryptophan/blood* ; Depression/blood* ; Oxidative Stress/physiology* ; Chronic Disease ; Lipid Metabolism/physiology*

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

OBJECTIVE: This study is to obtain precise data on iron physiological requirements in Chinese children using single stable isotope tracer technique. METHODS: Thirty boys (10.6 ± 0.2 years) and 27 girls (10.4 ± 0.2 years) were received oral 6 mg ⁵⁷Fe each day for 5 consecutive days. Venous blood samples were subsequently drawn to examine the change of total iron concentration and ⁵⁷Fe abundance at day 0, 14, 28, 60, 90, 180, 360, 450, 540, 630, 720. The iron physiological requirement was calculated by iron loss combined with iron circulation rate once ⁵⁷Fe abundance stabilized in human body. RESULTS: The iron physiological requirement was significantly lower in boys than those values in girls (16.88 ± 7.12 vs. 18.40 ± 8.81 μg/kg per day, P < 0.05). Correspondingly, the values were calculated as 722.46 ± 8.43 μg/day for boys and 708.40 ± 7.55 μg/day for girls, respectively. Considering nearly 10% iron absorption rate, the estimated average iron physiological requirement was 6.0 mg/day in boys and 6.2 mg/day in girls. CONCLUSION This study indicate that iron physiological requirement could require more daily iron intake in girls as compare with the values in boys having the same body weight. These findings would be facilitate to the new revised dietary reference intakes.
Body Weight ; Child ; China ; Female ; Humans ; Iron ; Isotopes ; Male ; Nutritional Status

Objective: To compare the short-term and long-term outcomes between transanal total mesorectal excision (taTME) and laparoscopic total mesorectal excision (laTME) for mid-to-low rectal cancer and to evaluate the learning curve of taTME. Methods: This study was a retrospective cohort study. Firstly, consecutive patients undergoing total mesorectal excision who were registered in the prospective established database of Division of Colorectal Diseases, Department of General Surgery, Peking Union Medical College Hospital during July 2014 to June 2020 were recruited. The enrolled patients were divided into taTME and laTME group. The demographic data, clinical characteristics, neoadjuvant treatment, intraoperative and postoperative complications, pathological results and follow-up data were extracted from the database. The primary endpoint was the incidence of anastomotic leakage and the secondary endpoints included the 3-year disease-free survival (DFS) and the 3-year local recurrence rate. Independent t-test for comparison between groups of normally distributed measures; skewed measures were expressed as M (range). Categorical variables were expressed as examples (%) and the χ(2) or Fisher exact probability was used for comparison between groups. When comparing the incidence of anastomotic leakage, 5 variables including sex, BMI, clinical stage evaluated by MRI, distance from tumor to anal margin evaluated by MRI, and whether receiving neoadjuvant treatment were balanced by propensity score matching (PSM) to adjust confounders. Kaplan-Meier curve and Log-rank test were used to compare the DFS of two groups. Cox proportional hazard model was used to analyze and determine the independent risk factors affecting the DFS of patients with mid-low rectal cancer. Secondly, the data of consecutive patients undergoing taTME performed by the same surgical team (the trananal procedures were performed by the same main surgeon) from February 2017 to March 2021 were separately extracted and analyzed. The multidimensional cumulative sum (CUSUM) control chart was used to draw the learning curve of taTME. The outcomes of 'mature' taTME cases through learning curve were compared with laTME cases and the independent risk factors of DFS of 'mature' cases were also analyzed. Results: Two hundred and forty-three patients were eventually enrolled, including 182 undergoing laTME and 61 undergoing taTME. After PSM, both fifty-two patients were in laTME group and taTME group respectively, and patients of these two groups had comparable characteristics in sex, age, BMI, clinical tumor stage, distance from tumor to anal margin by MRI, mesorectal fasciae (MRF) and extramural vascular invasion (EMVI) by MRI and proportion of receiving neoadjuvant treatment. After PSM, as compared to laTME group, taTME group showed significantly longer operation time [(198.4±58.3) min vs. (147.9±47.3) min, t=-4.321, P<0.001], higher ratio of blood loss >100 ml during surgery [17.3% (9/52) vs. 0, P=0.003], higher incidence of anastomotic leakage [26.9% (14/52) vs. 3.8% (2/52), χ(2)=10.636, P=0.001] and higher morbidity of overall postoperative complications [55.8%(29/52) vs. 19.2% (10/52), χ(2)=14.810, P<0.001]. Total harvested lymph nodes and circumferential resection margin involvement were comparable between two groups (both P>0.05). The median follow-up for the whole group was 24 (1 to 72) months, with 4 cases lost, giving a follow-up rate of 98.4% (239/243). The laTME group had significantly better 3-year DFS than taTME group (83.9% vs. 73.0%, P=0.019), while the 3-year local recurrence rate was similar in two groups (1.7% vs. 3.6%, P=0.420). Multivariate analysis showed that and taTME surgery (HR=3.202, 95%CI: 1.592-6.441, P=0.001) the postoperative pathological staging of UICC stage II (HR=13.862, 95%CI:1.810-106.150, P=0.011), stage III (HR=8.705, 95%CI: 1.104-68.670, P=0.040) were independent risk factors for 3-year DFS. Analysis of taTME learning curve revealed that surgeons would cross over the learning stage after performing 28 cases. To compare the two groups excluding the cases within the learning stage, there was no significant difference between two groups after PSM no matter in the incidence of anastomotic leakage [taTME: 6.7%(1/15); laTME: 5.3% (2/38), P=1.000] or overall complications [taTME: 33.3%(5/15), laTME: 26.3%(10/38), P=0.737]. The taTME was still an independent risk factor of 3-year DFS only analyzing patients crossing over the learning stage (HR=5.351, 95%CI:1.666-17.192, P=0.005), and whether crossing over the learning stage was not the independent risk factor of 3-year DFS for mid-low rectal cancer patients undergoing taTME (HR=0.954, 95%CI:0.227-4.017, P=0.949). Conclusions: Compared with conventional laTME, taTME may increase the risk of anastomotic leakage and compromise the oncological outcomes. Performing taTME within the learning stage may significantly increase the risk of postoperative anastomotic leakage.
Anastomotic Leak/etiology* ; Humans ; Laparoscopy/methods* ; Postoperative Complications/epidemiology* ; Prognosis ; Prospective Studies ; Rectal Neoplasms/pathology* ; Rectum/surgery* ; Retrospective Studies ; Transanal Endoscopic Surgery/methods* ; Treatment Outcome

Objective: To explore the incidence and risk factors of postoperative surgical site infection (SSI) after colon cancer surgery. Methods: A retrospective case-control study was performed. Patients diagnosed with colon cancer who underwent radical surgery between January 2016 and May 2021 were included, and demographic characteristics, comorbidities, laboratory tests, surgical data and postoperative complications were extracted from the specialized prospective database at Department of General Surgery, Peking Union Medical College Hospital. Case exclusion criteria: (1) simultaneously multiple primary colon cancer; (2) segmental resection, subtotal colectomy, or total colectomy; (3) patients undergoing colostomy/ileostomy during the operation or in the state of colostomy/ileostomy before the operation; (4) patients receiving natural orifice specimen extraction surgery or transvaginal colon surgery; (5) patients with the history of colectomy; (6) emergency operation due to intestinal obstruction, perforation and acute bleeding; (7) intestinal diversion operation; (8) benign lesions confirmed by postoperative pathology; (9) patients not following the colorectal clinical pathway of our department for intestinal preparation and antibiotic application. Univariate analysis and multivariate analysis were used to determine the risk factors of SSI after colon cancer surgery. Results: A total of 1291 patients were enrolled in the study. 94.3% (1217/1291) of cases received laparoscopic surgery. The incidence of overall SSI was 5.3% (69/1291). According to tumor location, the incidence of SSI in the right colon, transverse colon, left colon and sigmoid colon was 8.6% (40/465), 5.2% (11/213), 7.1% (7/98) and 2.1% (11/515) respectively. According to resection range, the incidence of SSI after right hemicolectomy, transverse colectomy, left hemicolectomy and sigmoid colectomy was 8.2% (48/588), 4.5% (2/44), 4.8% (8 /167) and 2.2% (11/492) respectively. Univariate analysis showed that preoperative BUN≥7.14 mmol/L, tumor site, resection range, intestinal anastomotic approach, postoperative diarrhea, anastomotic leakage, postoperative pneumonia, and anastomotic technique were related to SSI (all P<0.05). Multivariate analysis revealed that anastomotic leakage (OR=22.074, 95%CI: 6.172-78.953, P<0.001), pneumonia (OR=4.100, 95%CI: 1.546-10.869, P=0.005), intracorporeal anastomosis (OR=5.288, 95%CI: 2.919-9.577,P<0.001) were independent risk factors of SSI. Subgroup analysis showed that in right hemicolectomy, the incidence of SSI in intracorporeal anastomosis was 19.8% (32/162), which was significantly higher than that in extracorporeal anastomosis (3.8%, 16/426, χ(2)=40.064, P<0.001). In transverse colectomy [5.0% (2/40) vs. 0, χ(2)=0.210, P=1.000], left hemicolectomy [5.4% (8/148) vs. 0, χ(2)=1.079, P=0.599] and sigmoid colectomy [2.1% (10/482) vs. 10.0% (1/10), χ(2)=2.815, P=0.204], no significant differences of SSI incidence were found between intracorporeal anastomosis and extracorporeal anastomosis (all P>0.05). Conclusions: The incidence of SSI increases with the resection range from sigmoid colectomy to right hemicolectomy. Intracorporeal anastomosis and postoperative anastomotic leakage are independent risk factors of SSI. Attentions should be paid to the possibility of postoperative pneumonia and actively effective treatment measures should be carried out.
Case-Control Studies ; Colonic Neoplasms/surgery* ; Humans ; Retrospective Studies ; Risk Factors ; Surgical Wound Infection/etiology*

OBJECTIVE: To analysis the relationship between different BMI (body mass index) and the clinical characteristics, laboratory examination indexes of newly diagnosed adult patients with acute myeloid leukemia (AML), so as to investigate the effects of BMI to the efficacy of first induction chemotherapy. METHODS: The clinical data of 145 newly diagnosed adult AML patients treated in the First Hospital of Lanzhou University from August 2015 to August 2019 were retrospective analyzed. According to the guidelines for prevention and control of overweight and obesity in Chinese adults, the BMI (kg/m RESULTS: Among the 145 newly diagnosed adult AML patients, there were 71 males and 74 females. The median age was 50 years old(range 18 to 82 years old). There were 21 patients in underweight group (14.5%), 79 patients in normal weight group (54.5%), and 45 patients in overweight and obese group (31.0%). The patients with higher BMI level showed the older in age（P=0.018）. There were significant differences in sex between the patients in each group(P=0.035). In overweight and obese patients, the number of male was significantly higher than female. There were no statistical differences in AML classification, comorbidities(Diabetes, hypertension, coronary heart disease), hospital days, whether secondary AML and FLT3 gene mutation among the patients in different BMI groups. There were significant differences in TG of the patients in the different groups, the overweight and obese patients were higher (P=0.007). There were no significant differences in WBC and Hb counts, ALB, TC, HDL, LDL, or LDH between the patients in each BMI group at newly diagnosed. The complete remission rate of the patients in the low body mass group or overweight and obese group were lower than that in the normal body weight group (P=0.035). The rate of documented infection during the first induction chemotherapy were significantly higher for the patients in low body mass group than those in normal weight group or overweight and obese group (P=0.038). There was no statistical difference in chemotherapy regimens, the number of chemotherapy until CR, febrile neutropenia, bleeding, and the time of neutropenia, liver and kidney toxicity among each BMI group. Multivariate analysis showed that overweight and obese (P=0.012) , FLT3 mutation (P=0.015) were the risk factors affecting the CR rate of the patients. And the patients with secondary AML, high-risk type, and newly diagnosed WBC ≥50×10 CONCLUSION In newly diagnosed adult patients with AML, low body mass, overweight and obesity, and FLT3 mutations were the factors reducing the early efficacy of AML patients. There were more adverse reactions induced by chemotherapy in the low body mass group. Therefore, inappropriate BMI level can be a risk factor for assessing the prognosis of adults with newly diagnosed AML.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Body Mass Index ; Cytarabine/therapeutic use* ; Female ; Humans ; Induction Chemotherapy ; Leukemia, Myeloid, Acute/drug therapy* ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Young Adult

Thrombomodulin (TM) is a single-chain transmembrane glycoprotein that mainly exists in vascular endothelial cells, hematopoietic progenitor cells, monocytes and macrophages. TM is mainly composed of five structural regions: the N-terminal lectin-like domain which plays a role in anti-inflammatory, and the six epidermal growth factor-like repeats which function as coagulation and fibrinolysis as well as serine-rich threonine regions and transmembrane domains and cytoplasmic domains. TM exhibits anti-inflammatory and anticoagulant effects by binding to thrombin to activate protein C, and TM-thrombin complex can also activate fibrinolytic inhibitors to suppress fibrinolysis. Previous reports showed that inhibiting epithelial mesenchymal transformation, mitogen-activated protein kinase or activating protein C and fibrinolytic inhibitor are the major mechanisms by which TM exerts anti-tumor properties. In atherosclerosis, TM can prevent atherosclerosis by blocking the activation of thrombin-mediated PAR-1 and inhibiting autophagy and apoptosis of endothelial cells. TM lectin-like domains can also bind to thrombin to inhibit its activity and further inhibit pulmonary thrombosis, fibrosis and inflammation. Moreover, TM protein is also involved in the pathogenesis of diabetic nephropathy, preeclampsia and ischemia-reperfu-sion injury. At present, TM is only clinically used for the treatment of sepsis and disseminated intravascular coagulation. Its role and therapeutic potential in cardiovascular and cerebrovascular diseases, cancers and other diseases deserve further exploration.

The concept of total mesorectal resection provides a quality control standard that can be followed for radical resection of rectal cancer, but some anatomical problems are still controversial. Compared with traditional open surgery, laparoscopic radical rectal surgery has better surgical vision, better neurological protection, better operating space. However, if the surgeon has insufficient understanding of the anatomy, collateral damage may occur, such as uncontrollable bleeding during the operation, postoperative urination and defecation dysfunction and so on. Based on the interpretation of the researches at home and abroad, combined with the clinical experience, we elucidate some associated issues, including anatomic variation of inferior mesenteric vessels, the controversy of inferior mesenteric artery ligation plane, the controversy of lymph node dissection in No. 253, the anatomical variation of middle rectal artery, and the anatomical controversy of lateral lymph node dissection in rectal cancer, in order to provide better cognitive process for the clinical front-line surgeons.
Humans ; Laparoscopy ; Lymph Node Excision ; Lymph Nodes ; Mesenteric Artery, Inferior ; Rectal Neoplasms/surgery* ; Rectum

Objective: Severe radiation-induced late rectal injury (sRLRI) directly affects the quality of life of patients with rectal cancer. Effective prediction of sRLRI before surgery may provide important information for the selection of surgical strategies and perioperative managements. The purpose of this study is to evaluate the feasibility of predicting sRLRI based on magnetic resonance imaging (MRI) features before and after radiotherapy for rectal cancer. Methods: This was a diagnostic study. Clinical and imaging data of 90 patients with rectal cancer receiving long-term radiotherapy from June 2013 to July 2018 in the Sixth Affiliated Hospital of Sun Yat-sen University were collected retrospectively. Case inclusion criteria: (1) rectal cancer was diagnosed by pathology and age of ≥ 18 years old; (2) patients received neoadjuvant chemoradiotherapy and anterior rectal resection; (3) follow up time ≥ 3 years; (4) patients had no history of other neoplasm. Exclusion criteria: (1) patients did not receive MRI examination in our hospital within 2 weeks before and/or 8 weeks after radiotherapy; (2) images were not good enough for evaluation; (3) medical records were incomplete; (4) patients had severe gastrointestinal diseases. According to the RTOG/EORTC classification criteria for radiation reactions, severe complications of grade 3-4 requiring surgical management were defined as sRLRI. T2WI and DWI images before and after radiotherapy were evaluated. The rectal wall thickness, bladder wall thickness, rectal sacral spacing and apparent diffusion coefficient (ADC) were measured. The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of the above indicators for sRLRI. Results: Among the 90 patients with rectal cancer, 34 (37.8%) developed sRLRI. Before radiotherapy, the median rectal wall thickness of sRLRI and non-sRLRI patients was 4.530 mm and 4.355 mm, respectively; the median bladder wall thickness was 3.962 mm and 3.868 mm, respectively; the median rectal sacral spacing was 15.557 mm and 12.433 mm, respectively; the median ADC value of rectal wall was 1.620 ×10(-3) mm(2)/s and 1.653 ×10(-3) mm(2)/s, respectively. There were no significant differences in above indicators between sRLRI and non-sRLRI patients (all P>0.05). After radiotherapy, compared with non-sRLRI patients, sRLRI patients had increased rectal wall thickness (median: 8.239 mm vs. 6.223 mm, Z=-3.512, P=0.001), rectal sacral spacing (median: 17.728 mm vs. 13.885 mm, Z=-2.247, P=0.025), and change of rectal wall thickness after radiotherapy (median: 98.106% vs. 49.584%, Z=-4.169, P<0.001). After radiotherapy, there were no significant differences in the bladder wall thickness and its change value, the ADC value of rectal wall and its change rate before and after radiotherapy between the two groups (all P>0.05). The area under the curve (AUC) of the change rates of rectal wall thickness after radiotherapy, rectal wall thickness and rectal sacral spacing after radiotherapy for predicting sRLRI was 0.763, 0.722 and 0.642, respectively, while the sensitivity was 85.3%, 70.6% and 76.5%, respectively, and the specificity was 64.3%, 71.4% and 57.1%, respectively. Conclusion: Based on MRI examinations, assessments of rectal wall thickness after radiotherapy, the change rate of rectal wall thickness after radiotherapy, and rectal sacral spacing after radiotherapy are helpful for evaluating the risk of sRLRI after radiotherapy for patients with rectal cancer.
Adolescent ; Chemoradiotherapy ; Diffusion Magnetic Resonance Imaging ; Humans ; Magnetic Resonance Imaging ; Neoadjuvant Therapy ; Quality of Life ; Rectal Neoplasms/radiotherapy* ; Retrospective Studies ; Treatment Outcome

【Objective】 To explore the maximum tolerated dose(MTD) of pegylated liposome doxorubicin(PLD) when combined with cisplatin as a modified regimen for osteosarcoma. 【Methods】 A total of 14 patients with pathologically confirmed metastatic or unresectable osteosarcoma received one cycle of PLD combined with cisplatin therapy. The study used a traditional 3+3 design, with three PLD dose levels(40, 50, and 60 mg/ m², day 1). It was designed to recruit three patients initially at each dose level. Cisplatin was given at a dose of 100 mg/m²(administered within four days) for each patients. Patients received prophylactic granulocyte stimulating factor therapy 48 h after chemotherapy. Toxicities were documented according to the the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0(NCI CTCAE v4.0) . 【Results】 Of the 14 patients, 9 were male and 5 female, with a median age of 20 years(range 14~43). Both of the patients at dose level of 60 mg/m² experienced dose-limiting toxicity(DLT) (grade 3 oral mucositis and grade 4 neutropenic fever). Only 1 of the 9 patients at dose level of 50 mg/m² experienced DLT(grade 4 thrombocytopenia lasting for more than 3 days) and thus the MTD was 50 mg/m². Most common grade 3~4 adverse events across all cohorts included neutropenia(12 cases, 12/14), thrombocytopenia(7 cases, 7/14), anemia(4 cases, 4/14) and oral mucositis(2 cases, 2/14). All the adverse events were relieved after symptomatic and supportive treatment. No treatment-related death was observed. 【Conclusions】 For advanced osteosarcoma, when combined with cisplatin, the MTD of PLD was 50 mg/m². The main DLT was oral mucositis and neutropenic fever. The adverse events can be relieved after symptomatic treatment.