Objective To identify the clinicopathologic factors influencing the prognosis of the patients with distal cholangiocarcinoma (dCCA) after radical pancreatoduodenectomy (PD). Methods Retrospectively analyze the clinical data of 231 dCCA post-PD cases in Peking University First Hospital from January 2005 to January 2015. The clinicopathologic parameters were analyzed using univariate and multivariate Cox regression models and Kaplan-Meier method. Results The 1-year, 3-year and 5-year survival rates of the 231 post-PD dCCA patients were 86.6%, 55.0% and 34.6% respectively. Univariate Cox regression analysis showed that the primary tumor invasion depth (T stage) (P=0.000), lymph node metastasis (N stage) (P=0.001), AJCC stage(P=0.000), total number of dissected lymph nodes (P=0.038), metastasis lymph node ratio (P=0.001), vascular tumor thrombus(P=0.001), nerve invasion (P=0.001) and pathological type (P=0.002) were related to the prognosis of patients with dCCA after PD. Multivariate Cox regression analysis showed that the higher degree of lymph node metastasis (P=0.001), total number of lymph nodes dissected ≤10 (P=0.029), positive vascular tumor thrombus (P=0.007), positive nerve invasion (P=0.001) and low differentiation of pathological type (P=0.029) were independent risk factors for poor prognosis of patients with dCCA after PD.Kaplan-Meier analysis showed that the degree of lymph node metastasis, total number of dissected lymph nodes, vascular tumor thrombus, nerve invasion, and pathological type could affect the overall survival (OS) of patients with dCCA after pD (P<0.005), but whether adjuvant chemotherapy or not had no significant effect on OS of positive lymph node metastasis patients with dCCA after PD (P>0.05). Conclusion The higher degree of lymph node metastasis, total number of lymph nodes dissected less than 10, vascular tumor thrombus, nerve invasion and low differentiation of pathological type are considered as the independent poor prognostic factors of post-PD dCCA patients.

Objective To study the expression and significance of extracellular signaling protein-regulated kinase 1/2(ERK1/2) signal protein and protein-degrading enzyme in cartilage and subchondral bone of osteoarthritis (OA) patients. Methods From December 2017 to December 2019, 50 knee tibial plateau samples of OA patients in the Joint Surgery Department and 10 healthy knee tibial plateau samples of patients with traumatic amputation (as control) in the Trauma Department were collected from the First Affiliated Hospital of Medical College of Shihezi University. The cartilage degeneration was observed by HE staining, and the degeneration of articular cartilage was detected by OARSI Modified Manking score. OA patients were divided into mild group and severe group according to the score. The expressions of ERK1/2, pERK1/2, MMP-3, MMP-9 and ADAMT5 protein in cartilage and subchondral bone were detected by immunohistochemical staining and Western blotting. The expressions of ERK1/2, MMP-3,MMP-9 and ADAMT5 mRNA in cartilage and subchondral bone were detected by real-time PCR (RT-qPCR), and the changes of subchondral bone microstructure were measured by micro-CT. Results HE staining showed that the cartilage became thinner, the chondrocytes arranged disorderly, and the thickness of subchondral bone increased in the mild group; the cartilage almost completely disappeared, the subchondral bone obviously exposed and deformed, and the calcified cartilage thickened in the severe group. The results of OARSI score showed that compared with control group, the OARSI scores were significantly higher[(8.14±0.56) points and (23.33±0.17) points vs. (3.53±0.11) points, P<0.05] in the mild group and severe group, and the score of the severe group was significantly higher than that of the mild group (P<0.05). Immunohistochemical staining and Western blotting results showed that compared with control group, the protein expression levels of pERK1/2, MMP-3, MMP-9 and ADAMT5 in cartilage and subchondral bone in the mild group and severe group increased (P<0.05), the mRNA expression levels of MMP-3, MMP-9 and ADAMT5 in cartilage and subchondral bone in mild group and severe group obviously increased (P<0.05), but there was no significant difference in the expression level of ERK1/2 mRNA and protein between the groups (P>0.05). Micro-CT scanning showed that the microstructure of subchondral bone in the mild and severe groups was seriously disordered with cell proliferation. Compared with control group, BV/TV, Tb.Th, Tb.N and BMD in cartilage and subchondral bone in mild group and severe group significantly increased, and Tb.Sp significantly decreased (P<0.05). Conclusions pERK1/2, MMP-3, MMP-9 and ADAMT5 are highly expressed in OA cartilage and subchondral bone, and the microstructure of subchondral bone is changed.The increased expression of pERK1/2 may be one of the reasons for the increased activity of cartilage-degrading enzymes and the changes of subchondral bone microstructure.

Objective To analyze the incidence and related factors of atelectasis in severe patients after hepatectomy. Methods A retrospective analysis was performed on 442 patients admitted to intensive care unit (ICU) after hepatectomy from 2014 to 2019 in Peking University People's Hospital. Patients were divided into atelectasis group (n=99) and non-atelectasis group(n=343) according to the occurrence of postoperative atelectasis. General information, complications, laboratory examination, operation, anesthesia, ICU admission and disease prognosis were compared between the two groups. Logistic regression model was used to analyze the risk factors of atelectasis after hepatectomy. Results Patients in the atelectasis group had higher mortality(5.1% vs. 0.5%, P=0.002), longer hospital stay [21(17, 29) d vs. 16(13, 21) d, P<0.001], longer endotracheal intubation time[8.0(4.0,16.0) h vs. 6.0(3.5,11.0) h, P=0.002], longer ICU stay [2(2, 5) d vs. 2(2, 2) d, P<0.001] and higher occurrence rate of hypoxemia(49.5% vs. 27.7%, P<0.001). Logistic regression analysis showed that longer operative time [odds ratio(OR)=1.005, P=0.001]and perioperative hypotension (OR=1.974, P=0.032) were independent risk factors for atelectasis in critically ill patients after hepatectomy. Conclusions The incidence of atelectasis is high after hepatectomy and patients with atelectasis after hepatectomy have higher rates of mortality, and longer hospital stays. Longer operative time and perioperative hypotension are independent risk factors for postoperative atelectasis.

Objective To analyze the clinical features of 9 patients with renin secreting tumor and review the related literature in order to improve the understanding, diagnosis and treatment of the disease. Methods The clinical data, diagnosis, treatment, pathological and immunohistochemical profiles of 9 patients with renin secreting tumor admitted in the First Medical Center of Chinese PLA General Hospital from January 2010 to February 2020 were retrospectively analyzed. The literature was searched by retrieving the related database from 2001 to 2020, combined with 142 similar cases collected by searching the database to analyze the clinical features of patients with renin secreting tumor. Results All the 9 patients with an average age of 22.6 years presented with hypertension, and 7 of the 9 with hypokalemia. The plasma renin levels in all the patients were significantly higher than normal range, and the plasma aldosterone levels were above the median normal reference interval. Postoperative pathological examination of all cases confirmed juxtaglomerular cell tumor. Immunohistochemical staining showed that all the tumor cell renin, vimentin and CD34 were positive, some neoplastic cells were positive for smooth muscle actin (SMA) and synaptophysin (Syn), and negative for S-100 protein (S-100) and chromogranin A (CgA). The blood pressure and serum potassium level returned to normal range in all patients after surgery. A total of 142 patients with renin secreting tumor have been reported in China from 2001 to 2020.Hypertension was the initial symptom of all the patients. Hypokalemia occurred in 87 of 142 patients. Plasma renin and aldosterone levels were above the normal range in 93 patients. No recurrence or metastasis occurred in all patients after surgery during follow-up. Conclusions Renin secreting tumor mostly is characterized as benign renal tumor with hypertension, hypokalemia, hyperreninemia and hyperaldosteronism. Surgery is preferred in treatment of this tumor for a good prognosis.

Objective To investigate the expression of FOXP3 in hormone receptor-positive breast cancer tissues and its effect on invasion and migration of MCF-7 cells. Methods Formalin-fixed, paraffin-embedded blocks from 66 hormone receptor-positive breast cancer patients who received surgery at Breast Center of the Fourth Hospital of Hebei Medical University from September 2010 to October 2011 were used in this study. The protein expression level of FOXP3 was detected by immunohistochemistry. The relationship between the FOXP3 expression levels and the clinicopathologic features was analyzed.Kaplan-Meier analysis was used to assess the overall survival rate, according to the presence or absence of FOXP3 expression. The expression levels of FOXP3 mRNA in breast cancer cell lines (MDA-MB-231, MDA-MB-453, MDA-MB-474, BR-3, and MCF-7)were detected by qRT-PCR. The MCF-7 cell line, with the highest expression level of FOXP3, was selected for the following gene silencing experiment. The si-FOXP3 transfection group (transfected with si-FOXP3), si-NC transfection group (transfected with si-NC), and blank control group (without treatment) were set. The expression of FOXP3 protein was detected by Western blotting, and the migration and invasion ability of cells was detected by scratch test and Transwell test. Results The FOXP3 exhibited a heterogeneous subcellular location in tumor cells. The positive expression ratio of FOXP3 in the nucleus was 40.90%(27/66), associated with negative lymph node metastasis, lower Ki-67 index, Luminal A typing, and TNM I stage (P<0.05); positive expression ratio of FOXP3 in the cytoplasm was 54.6%(36/66). Kaplan-Meier analysis indicated that nuclear FOXP3 expression correlated with better overall survival [96.30%(26/27) vs. 82.05%(32/39), P=0.042], but the cytoplasmic FOXP3 was not significantly associated with overall survival [88.89%(32/36) vs. 86.67%(26/30), P=0.715]. qRT-PCR results showed that the MCF-7 cell line has the highest expression level of FOXP3 mRNA in five breast cancer cell lines above (P<0.05). Thus, we performed the gene silencing experiment in the MCF-7 cell line. Compared with control group, knockdown of FOXP3 significantly enhanced the migration and invasion of MCF-7 cells (P<0.05). Conclusion In hormone receptor-positive breast cancer, the prognostic significance of FOXP3 expression is relevant to the different subcellular localization of FOXP3. Nuclear FOXP3 suggested an improved overall survival, whereas cytoplasmic FOXP3 was not significantly relevant to survival. FOXP3 may reduce the migration and invasion of MCF-7 cells, and it may be a prognostic marker for breast cancer.

Leptin, a fat factor synthesized in adipose tissue, is initially worked as a hormone substance regulating body fat balance. With in depth-study, researchers found that leptin has structural homology with such cytokines as interleukin-6 (IL-6), and its receptor, Ob-R, belongs to class Ⅰ cytokine receptor superfamily. Through binding to corresponding receptor, leptin can not only regulate the food intake and energy balance, but can also regulate the immune system. Rheumatoid arthritis (RA) is one of the common autoimmune diseases caused by many genetic and environmental factors. The fundamental pathological change of RA is chronic synovial inflammation and pannus formation, and leads to the destruction of cartilage, bone and surrounding tissue. Many immune cells and resident stromal cells are involved in RA pathological progress although the exact pathogenesis of RA remained unclear. It has been proved by in vivo experiment of RA animal model that leptin is related to the joint inflammation, and may participate in the pathogenesis and process of the disease. The immunomodulatory effects of leptin on the main effector cells of RA has been reviewed in present paper, aiming to expand ideas for related research.

Objective To investigate the changes of plasma peroxiredoxin 6 (PRDX6) level in patients with polycystic ovary syndrome (PCOS) and the relativity with glucose and lipid metabolism and sex hormone levels. Methods This is a retrospective case-control study. The clinical data were collected of 47 patients with PCOS (PCOS group) admitted to the Second Affiliated Hospital of Army Medical University from January to October 2020, and of 60 healthy people undergone medical examination in the same hospital during the same period (healthy control group). The two groups were further divided into two subgroups according to body mass index (BMI). Among them, 17 cases in PCOS group had BMI ≤24 kg/m², and 30 cases had BMI >24 kg/m²; and in healthy control group 36 cases had BMI ≤24 kg/m², and 24 cases had BMI >24 kg/m². The differences and correlations of plasma PRDX6 levels with glucose and lipid metabolism and sex hormone indexes between the two groups and subgroups were compared and analyzed. Receiver operating characteristic (ROC) curve was used to analyze the predictive value of PRDX6 on glucose and lipid metabolism and sex hormone indicators. Results The plasma PRDX6 level was significantly higher in PCOS group than in healthy control group (P<0.0001). Correlation analysis showed that the PRDX6 level was positively correlated with the glucose and lipid metabolism indexes triacylglycerol (TG), low density lipoprotein (LDL), fasting insulin (FINS), glycosylated hemoglobin(HbA_1c), insulin resistance index (HOMA-IR) and islets β cell function (HOMA-β), and negatively correlated with high-density lipoprotein (HDL) in all patients or when BMI >24 kg/m² (P<0.05); When BMI ≤24 kg/m², PRDX6 showed no relationship with glucose and lipid metabolism (P>0.05). PRDX6 was positively correlated with sex hormone indicators testosterone (T), luteinizing hormone (LH) and luteinizing hormone/follicle-stimulating hormone (LH/FSH), and negatively correlated with estradiol (E₂) and progesterone (P) in all patients or when BMI >24 kg/m² (P<0.05); When BMI ≤24 kg/m², PRDX6 was positively correlated with T and LH/FSH, and negatively correlated with E₂ and P. The area under the ROC curve (AUC) of PRDX6 for predicting HOMA-IR and sex hormone LH were 0.753 and 0.592, respectively (P<0.0001); the AUCs of PRDX6 for predicting HOMA-IR and sex hormone LH in PCOS patients were 0.917 and 0.544, respectively (P<0.0001, P=0.461). Conclusion The high level of PRDX6 expression might be a risk factor for abnormal glucose and lipid metabolism and hormone indexes in PCOS patients, so the PRDX6 factor may have a high predictive value for glucose and lipid metabolism in PCOS patients.

Objective To observe the effect and significance of TRIM33 gene on proliferation and migration of human gastric cancer cell SGC-7901. Methods The expression of TRIM33 in normal gastric mucosa and gastric cancer tissues and its relationship with clinicopathological features and prognosis were analyzed through TCGA and TIMER databases. Human gastric cancer cell line SGC-7901 was either untreated [negative control (NC) group] or transfected with a control vector (vector group) or transfected with vector carries si-TRIM33 (si-TRIM33 group). The downregulation of TRIM33 was validated using Western blotting.Further, the CCK-8 assay and plate clone formation assay were performed to detect cell proliferation ability. The scratch healing assay and Transwell assay were employed to test cell proliferation and migration ability. The expression of epithelial-mesenchymal transition (EMT) related proteins was tested by Western blotting. The correlation between TRIM33 expression and immune cell infiltration was analyzed through the TIMER database. Results The expression level of TRIM33 in gastric cancer was significantly higher than that in normal tissues, related to age, gender, tumor stage and lymph node metastasis (P<0.05). Cell experiment showed that SGC-7901 cells with low expression of TRIM33 showed enhanced migration, decreased EMT-related protein E-Cadherin, and significantly increased vimentin and N-Cadherin (P<0.05). TIMER database analysis showed that TRIM33 mRNA level positively correlated with the expression of CD4⁺ T cells, CD8⁺ T cells, B cells, centrioles, macrophages and natural killer cells (P<0.05), and positively correlated with M2 macrophages, CD8⁺ T cells, centrioles and gene markers of natural killer cells CD163, CXCL9, ITGAM, KIR3DL2 expression (P<0.05). Conclusion Downregulation of TRIM33 can promote the progression of gastric cancer, which is related to the poor prognosis of patients. The mechanism may be related to enhancing the migration characteristics of gastric cancer cells by regulating the infiltration of immune cells.

Tissue clearing is a fast-developing new histological technology. It treats large tissues, single organs, the whole body of rodents and large human specimens through a series of physicochemical principles and methods to rapidly achieve a high degree of optical transparency while maintaining their integrity, providing an important tool for obtaining three-dimensional structural information of biological tissues with high resolution. Combining the modern optical imaging and fluorescent labeling technology can significantly improve the imaging depth and image contrast, and help accelerate the process of acquiring fine structural and molecular function information such as neurons, synapses, and heterogeneous pathological components throughout the brain. It has become a promising alternative to classical histological techniques and is widely used in life science fields. The main methodological principles, advantages and disadvantages of brain tissue clearing are reviewed in present paper, and combs the application of tissue clearing in neurodegenerative diseases, observes the degenerative changes of fine structures such as neurons, axons and myelin at a holistic level, and the evolution of heterogeneous pathological components between cells at a whole brain scale, so for providing the possibility to eventually turn to the study of human neurodegenerative brain tissues.

Gastrointestinal dysfunction is one of the initiating factors for multiple organ failure. The European Society of Intensive Care Medicine (ESICM) proposed the definition of acute gastrointestinal injury (AGI) to describe dysfunction of the gastrointestinal tract in critically ill patients. AGI occurs frequently in the intensive care unit (ICU) and associates with clinical outcomes of ICU patients. The incidence of pain is high in the ICU, and analgesic drugs can significantly improve the prognosis of patients. But the administration of analgesic drugs is an important factor affecting gastrointestinal function. So, in order to prevent AGI in high-risk patients, both analgesic needs and low impact on gastrointestinal function need to be taken into account before choices of opioids are finalized. This review briefly summarizes the mechanisms of AGI in ICU patients and the studies related to the effects of analgesics on gastrointestinal motility and barrier in ICU patients with opioids as the core, providing a reference for clinical selection.