Objective:To analyze clinical efficacy of intensity-modulated chemoradiotherapy for patients with anal squamous cell carcinoma and identify prognostic factors.Methods:Clinical data of patients with anal squamous cell carcinoma who received intensity-modulated chemoradiotherapy in the Cancer Hospital of Chinese Academy of Medical Sciences from January 1, 2010 to January 1, 2022 were retrospectively analyzed. Regular follow-up was carried out. The main indexes included disease-free survival (DFS), locoregional failure-free survival (LRFFS) and overall survival (OS), and adverse reactions were recorded. The survival curve was delineated by Kaplan-Meier method and the influencing factors of survival were analyzed by Cox regression models.Results:A total of 65 patients were enrolled with 19 (29%) males and 46 (71%) females. According to the American Joint Committee on Cancer (AJCC) 7 th edition staging, there were 7 (11%), 28 (43%), 10 (15%), and 20 (31%) patients with stage I, II, IIIa, and IIIb, respectively. Before the chemoradiotherapy, 2 (3%) patients received chemotherapy and 12 (18%) patients received local resection. The median dose of radiotherapy was 54 Gy (range: 45-64 Gy) and the main concurrent chemotherapy regimen was capecitabine combined with cisplatin ( n=34, 52%). The completion rate of radiotherapy during concurrent chemoradiotherapy was 100%, and the chemotherapy completion rate was 88%. During the therapy, 5 patients (8%) were interrupted but completed concurrent chemoradiotherapy in full dose, and 8 patients (12%) reduced the dose of concurrent chemotherapy due to the toxicities. During the chemoradiotherapy, 15 cases (23%) experienced grade 3-4 leukopenia, and 17 cases (26%) experienced grade 3-4 radiation dermatitis. No treatment-related death occurred during the treatment. The median follow-up time was 50.4 months (range: 4.4-142.2 months), local recurrence occurred in 7 cases (11%), distant metastasis occurred in 3 cases (5%), and the 5-year DFS, LRFFS and OS rates were 78.8%, 86.5% and 85.1%, respectively. Cox univariate analysis indicated that T stage was significantly associated with DFS ( P=0.006), and tended to be associated with OS ( P=0.054). Conclusions:Intensity-modulated radiotherapy combined with concurrent chemotherapy is an effective treatment for anal squamous cell carcinoma, with tolerable acute toxicities. T stage is an influencing factor of DFS in anal squamous cell carcinoma patients.

With the development of modern sequencing techniques and bioinformatics, genomes that were once thought to be noncoding have been found to encode abundant functional micropeptides (miPs), a kind of small polypeptides. Although miPs are difficult to analyze and identify, a number of studies have begun to focus on them. More and more miPs have been revealed as essential for energy metabolism homeostasis, immune regulation, and tumor growth and development. Many reports have shown that miPs are especially essential for regulating glucose and lipid metabolism and regulating mitochondrial function. MiPs are also involved in the progression of related diseases. This paper reviews the sources and identification of miPs, as well as the functional significance of miPs for metabolism-related diseases, with the aim of revealing their potential clinical applications.
Humans ; Open Reading Frames ; Peptides ; Glucose ; Genome ; Metabolic Diseases

Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.

NDFIP1 has been previously reported as a tumor suppressor in multiple solid tumors, but the function of NDFIP1 in NSCLC and the underlying mechanism are still unknown. Besides, the WW domain containing proteins can be recognized by NDFIP1, resulted in the loading of the target proteins into exosomes. However, whether WW domain-containing transcription regulator 1 (WWTR1, also known as TAZ) can be packaged into exosomes by NDFIP1 and if so, whether the release of this oncogenic protein via exosomes has an effect on tumor development has not been investigated to any extent. Here, we first found that NDFIP1 was low expressed in NSCLC samples and cell lines, which is associated with shorter OS. Then, we confirmed the interaction between TAZ and NDFIP1, and the existence of TAZ in exosomes, which requires NDFIP1. Critically, knockout of NDFIP1 led to TAZ accumulation with no change in its mRNA level and degradation rate. And the cellular TAZ level could be altered by exosome secretion. Furthermore, NDFIP1 inhibited proliferation in vitro and in vivo, and silencing TAZ eliminated the increase of proliferation caused by NDFIP1 knockout. Moreover, TAZ was negatively correlated with NDFIP1 in subcutaneous xenograft model and clinical samples, and the serum exosomal TAZ level was lower in NSCLC patients. In summary, our data uncover a new tumor suppressor, NDFIP1 in NSCLC, and a new exosome-related regulatory mechanism of TAZ.
Humans ; Carcinoma, Non-Small-Cell Lung/metabolism* ; Carrier Proteins/metabolism* ; Cell Line ; Cell Proliferation ; Exosomes/metabolism* ; Lung Neoplasms/genetics* ; Membrane Proteins/metabolism* ; Transcriptional Coactivator with PDZ-Binding Motif Proteins/metabolism*

Objective To investigate the safety of young recipients undergoing living donor renal transplantation from elderly relative donors through long-term follow-up of the pathological changes. Methods According to the age of donors, 28 young recipients were divided into the observation group (n=14, elderly donors) and control group (n=14, young and middle-aged donors). The 7-year survival after renal transplantation, the serum creatinine (Scr) levels at various postoperative time points were compared between two groups. The chronic pathological injury scores of renal allograft biopsy at time-zero, postoperative 6-month and 7-year were compared between two groups. The expression levels of renal interstitial fibrosis indicators connective tissue growth factor (CTGF), transforming growth factor (TGF)-β, laminin (LN), fibronectin (FN), cell senescence indicators intercellular connexin (Cx)-43 and mammalian target of rapamycin (mTOR) at postoperative 6-month and 7-year were compared between two groups. Results The 7-year survival rates in the observation and control groups were 78.5% and 92.8% with no statistical significance (P > 0.05). In the observation and control groups, the levels of Scr were 190 and 160 μmol/L at the postoperative 7 d, and 170 and 125 μmol/L at postoperative 1 month. At each postoperative time point, the levels of Scr in the observation group were significantly higher than those in the control group (all P > 0.05). The total chronic pathological injury scores of renal transplant biopsy at time-zero in the observation group was significantly higher than that in the control group (P > 0.05), whereas the total chronic pathological injury scores at postoperative 7-year did not significantly differ between two groups (P > 0.05). Within either group, the total chronic pathological injury scores at postoperative 7-year was remarkably higher than those at time-zero and postoperative 6-month (both P < 0.05). The expression levels of CTGF, TGF-β, LN, FN, mTOR, Cx43 of renal transplant tissue at postoperative 7-year did not significantly differ between two groups (all P > 0.05). Conclusions The long-term follow-up outcomes demonstrate that the pathological changes of young recipients undergoing renal transplantation from elderly donors are similar to those from young and middle-aged donors. It is safe and feasible for young recipients to undergo renal transplantation from elderly donors in the pathological perspective.

Objective: To investigate the dosimetric characteristics of conventional two-dimensional radiotherapy of the chest wall, supra-and infra-clavicular regions, and the incidental irradiation dosage of the internal mammary region after modified mastectomy in breast cancer patients. Methods: Clinical data of 20 breast cancer patients including 10 left and 10 right cases who received radiotherapy after modified mastectomy between 2015 and 2016 were retrospectively analyzed. All patients received irradiation to the chest wall, supra-and infraclavicular regions at a prescription dose of 43.5 Gy in 15 fractions with conventional technique. One anterior-posterior (AP) photon field irradiation was delivered for the supra-and infra-clavicular regions, and one electron field for the chest wall. The supra-and infraclavicular regions were re-planned by using two AP/PA fields and the doses of organ at risk were evaluated. Results: With conventional radiotherapy, the D₉₀ of the supra-and infra-clavicular regions were more than 39.15 Gy (EQD₂≥45 Gy) in 17 patients (85%), and the median D₉₀ of the chest wall was 35.38 Gy. The median dose of incidental internal mammary region was 13.65 Gy. Patients with lower body mass index (BMI) received higher D₉₀ in both supra-and infra-clavicular and chest wall irradiation (P=0.039, 0.347). Conclusions Irradiation at D₉₀ of 39.15 Gy to the supra-and infra-clavicular regions with AP/PA fields can meet the prescription dose requirement of ≥90% in most cases and does not increase the irradiation dose to normal tissues. The dose distribution of one electron field of the chest wall is poor. Incidental internal mammary region can be irradiated at a limited dosage. BMI is an influencing factor for dose distribution.

Objective To investigate that butyrate-producing probiotic clostridium butyricum improves the intestinal epithelial barrier function in food allergic mice by regulating TWIK-related potassium channel-1 (Trek1) expression in intestinal epithelial cells.Methods An intestinal allergy mouse model was created,then the model construction effect was verified by detecting the related indicators by ELISA,flow cytometer.The change of small intestinal tissue permeability was detected by the Ussing chambers.The Trek1 expressions in mouse jejunum tissue in control group and allergy group were detected by Western blot and immunofluorescent method;in the Transwell system,T84 cells were used to establish epithelial cellular monolayer for exposing to the allergic mediators,the Trek1 mRNA and protein expression were detected by qRT-PCR and Western blot.Then the allergic mice were grouped and treated by different methods including normal saline,SIT,SIT/SB,SB,SIT/CB,CB,SIT/CB/Spadin,the expression of mice intestinal Trek1,intestinal barrier function and allergic reaction indicators were detected.Results Compared with the control group,the small intestinal Trek1 protein and tissue expression level in the food allergic mice were significantly decreased,the intestinal mucosal permeability was significantly increased,the differences were statistically significant(P＜0.05);after T84 cells exposing to the allergic mediators,Trek1 mRNA and protein expression were significantly decreased(P＜0.05),but adding p38 inhibitor in advance could antagonize this change;the single use of SIT,clostridium butyricum and sodium butyrate could increase the intestinal Trek1 expression in food allergic mice,and alleviated the allergic reaction(P＜0.05),whereas the combined use of SIT and clostridium butyricum or sodium butyrate had more significant effect(compared with the SIT group,P＜0.05),moreover could significantly decrease small intestinal mucosal permeability and improved the intestinal barrier function(P＜0.05).Conclusion Sodium butyrate or butyrate-producing probiotic clostridium butyricum can restore the intestinal barrier function,alleviates the allergic reaction and strengthens the SIT curative effect in allergic mice by increasing Trek1 expression.

Objective To investigate the effectiveness of Lactobacillus paracasei N1115 combined with fructooligosaccharides (FOS) in the treatment of nonalcoholic fatty liver disease(NAFLD) in a mouse model and to analyze the possible mechanism.Methods Fifty male C57BL/6 mice were randomly divided into five groups and respectively given normal diet (ND group), high-fat diet (HFD group), HFD containing Lactobacillus paracasei N1115 (HFD+L) (2.2×109 CFU/ml), HFD containing FOS (HFD+FOS) (4 g/kg per day) and HFD containing Lactobacillus paracasei N1115 and FOS for 16 consecutive weeks.Levels of triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), lipopolysaccharide (LPS) and diamine oxidase (DAO) in serum samples from each group were measured.Expression of tight-junction proteins (Claudin-1 and Occludin), p38 and phosphorylated p38 (p-p38) in intestinal tissues were analyzed.Results Compared with the HFD group, the HFD+FOS+L group showed decreased levels of TC, TG, LDL, LPS and DAO in serum samples, but increased serum HDL level (P<0.05).Moreover, combined treatment with Lactobacillus paracasei N1115 and FOS alleviated liver lipid deposition, significantly increased the expression of Claudin-1 and Occludin in intestine and inhibited the phosphorylation of p38 (P<0.05).Conclusion Lactobacillus paracasei N1115 combined with FOS may increase the expression of Claudin-1 and Occludin through inhibiting the phosphorylation of intestinal p38, which is conducive to maintaining the intestinal mucosal barrier integrity and alleviating NAFLD.

Objective: To investigate the effects of Lactobacillus paracasei N1115 combined with fructooligosaccharides (FOS) on non-alcoholic fatty liver disease (NAFLD) in mice and its possible mechanism. Methods: A total of 50 male C57 mice were randomly and equally divided into five experimental groups. Group 1 received a normal diet (ND). Other four groups received a high-fat diet (HFD) to establish NAFLD models. In addition to HFD, group 3 received Lactobacillus paracasei N1115 (2.2×10⁹ CFU/mL), group 4 received FOS (4 g/kg per day), and group 5 received Lactobacillus paracasei N1115 (2.2×10⁹ CFU/mL) and FOS (4 g/kg per day). All groups received continuous intervention for 16 weeks. The following indices were measured for all groups after intervention: general condition, the levels of fasting blood glucose, insulin, and lipopolysaccharide (LPS), and the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and interferon (IFN)-γ in the serum and liver. The mRNA levels of Toll-like receptor (TLR)4, nuclear factor (NF)-κb, insulin receptor (InsR), and insulin receptor substrate (IRS)-1 were measured by real-time RT-PCR. The data were subjected to one-way analysis of variance and comparison between groups was made by Bonferroni method. Results: Compared with group 2, groups 3, 4, and 5 had significantly lower body weight, Lee's index, liver index, and the levels of blood glucose and insulin resistance (P < 0.05). The serum level of LPS in group 2 was significantly higher than that in the other experimental groups (group 1: 8.80 ± 0.85 U/L, group 3: 12.31 ± 1.01 U/L, group 4: 12.27 ± 0.98 U/L, and group 5: 10.17 ± 0.79 U/L vs group 2: 15.45 ± 1.14 U/L, F = 55.117, P < 0.001). The levels of TNF-α, IL-1β, IL-6, and IFN-γ in the serum and liver in group 2 were also significantly higher than those in the other groups (P < 0.05). Group 2 had significantly higher mRNA levels of TLR4 and NF-κb in the liver than the other groups (F = 82.933, P < 0.001; F = 149.033, P < 0.001); however, it had significantly lower mRNA levels of InsR and IRS-1 in the liver than the other groups (F = 33.347, P < 0.001; F = 70.225, P < 0.001). Conclusion Lactobacillus paracasei N1115 combined with FOS can reduce the level of LPS in the blood circulation, inhibit activation of the LPS/TLR4 signaling pathway, and reduce the release of inflammatory factor and the body's insulin resistance, so it can relieve NAFLD.

Objective To investigate the effects of two cholesterol-lowering probiotics, DM9054 (Lac-tobacillus Rhamnosus GG, LGG) in combination with 86066 (Lactobacillus plantarum WCFS1, LP), on the metabolism of bile acid via a rat model of non-alcoholic fatty liver disease (NAFLD) and the possible mecha-nism. Methods Twenty-one SD male rats were randomly divided into three groups including control group, NAFLD model group and probiotics intervention group. Rats in the control group received normal diet. The rat model of NAFLD was established by feeding rats with chronic high fat diet (45% of calories derived from fat di-et) for 20 weeks. Rats in the probiotics intervention group were given high fat diet together with cholesterol-low-ering probiotics through oral gavage. General indexes of each group including body weight and the levels of tri-glyceride, cholesterol and CK18-M30 in serums samples were detected. The expression of cholesterol 7-alpha hydroxy-lase (CYP7A1), fibroblast growth factor receptor 4 (FGFR4), farnesoid X receptor (FXR), fibroblast grwoth factor 15 (FGF15) and apical sodium-dependent bile acid transparter(ASBT) at mRNA level were de-tected by using real-time polymerase chain reaction (real-time PCR). Western blot assay was used to detect the protein expression of CYP7A1, FXR in liver tissues and ASBT in ileum tissues. The expression of FXR in liver and ileum tissues were analyzed by immunohistochemistry. Results Rats with NAFLD showed loss of body weight and decreased levels of the serological markers after treating with the probiotics (P<0. 05). Compared with the rats in model group, enhanced expression of CYP7A1 and inhibited expression of FXR in liver tissues, activated FXR-FGF15 pathway in ileum tissues as well as down-regulated expression of ASBT in ileum tissues were detected in rats receiving probiotics intervention (P<0. 05). No significant difference in the expression of FGFR4 at mRNA level was observed between NAFLD rats with or without probiotics intervention (P>0. 05). Conclusion Probiotics intervention might up-regulate the expression of CYP7A1 by suppressing the FXR path-way in liver tissues and inhibiting the expression of ASBT in ileum tissues. Treating NAFLD rats with cholester-ol-lowering probiotics could activate the FXR-FGF15 pathway in ileum tissues and enhance the metabolism of bile acid, which contributed to the alleviation of NAFLD.