Identification of novel immune ferroptosis-specific genes associated with prognostic features in hepatocellular carcinoma

Background:As the most common iron metabolism and storage organ,the specific regulatory mechanism and prognostic relevance of hepatocellular carcinoma(HCc)need further study.Objective:We aimed to perform a multi-omics integration and a ferroptosis-associated signature of HCC.Methods:Gene Expression Omnibus was searched for available data with ferroptosis inducers,and three independent datasets(GSE104462,GSE112384,and GSE142591)were collected.Multi-omic data with available clinical information of TCGA-LIHC and CHCC were retrieved from the Cancer Genome Atlas(TCGA,http://cancergenome.nih.gov/)and iProX database(www.iprox.org,IPx0000937000).Integrated multi-omics analyses revealed the difference among biological functions,the activation status of key signaling pathways,tumor microenvironment,and sorafenib resistance in HCC.Single-sample gene set enrichment analysis(ssGSEA)identified a novel panel associated with clinical and molecular attributes,including survival,immune microenvironment,sorafenib resistance,genetic profile,liver-specific proteome,and phosphoproteome.Results:We performed a multi-omics integrationfor ferroptosis-associated characterization of HCC using paired tumor and adjacent liver tissues from 370 samples of TCGA.We proposed a novel panel including twelve genes that could reflect the prognosis and capacity of ferroptosis(ATAD2,DTL,DUT,E2F2,GINS2,FOXK1,MCM4,MCM5,MTHFD1,PHF19,POLA1,THOC6).Samples with high ferroptosis prognostic scores suggested significantly inferior survival(P=0.0028),a lower degree of ferroptosis(P<0.001),and greater ferroptosis induction capacity(P<0.001).Conclusion:The score in our study revealed the inherent state and further potential of ferroptosis in tumor cells,which also distinct features in tumor metabolism,microenvironment,clinical phenotype,and potential therapeutics.

Correlations among core species corresponding to the clinical staging of periodontitis

The correlation between microbiota plays a vital role in the progression of periodontal disease.This study investigated the in situ interaction networks between periodontal pathogens in periodontal and peri-implant disease.We used quantitative real-time polymerase chain reaction and Pearson’s correlation coefficients to quantify the copy numbers and correlations of four oral core species—Fusobacterium nucleatum,Porphyromonas gingivalis,Prevotella intermedia,and Streptococcus gordonii—from 80 subgingival sites(healthy and with periodontitis or gingivitis)in patients with periodontitis,and 68 subgingival sites(healthy and with periodontitis,gingivitis,peri-implantitis,or peri-implant mucositis)in patients with implants.The highest bacterial counts were observed for Porphyromonas gingivalis and Prevotella intermedia at all the sites.Within the same cohorts,the bacterial loads were greater at diseased sites than at healthy sites.Bacterial counts did not differ among clinical sites in the same group(P>0.05)but differed between periodontitis and peri-implant mucositis sites in the two groups.Porphyromonas gingivalis,F.nucleatum,and Prevotella intermedia had strong correlations at gingivitis and healthy sites and moderate correlations at periodontitis sites in patients with periodontitis.In patients with implants,Prevotella intermedia,F.nucleatum,and S.gordonii had strong correlations only at peri-implantitis sites.Also,based on metagenomic analysis,F.nucleatum and Prevotella intermedia were significantly correlated at the subgingival plaque in peri-implantitis and periodontitis samples.Our results suggest that variations in microbe-microbe interactions in subgingival plaque reflect changes in the progression of periodontal disease,providing a new perspective for understanding the mechanisms of periodontitis and peri-implantitis.

Treatment and surveillance for non-muscle-invasive bladder cancer:a clinical practice guideline(2021 edition)

Non-muscle invasive bladder cancer(NMIBC)is a major type of bladder cancer with a high incidence worldwide,resulting in a great disease burden.Treatment and surveillance are the most important part of NIMBC management.In 2018,we issued“Treatment and surveillance for non-muscle-invasive bladder cancer in China:an evidencebased clinical practice guideline”.Since then,various studies on the treatment and surveillance of NMIBC have been published.There is a need to incorporate these materials and also to take into account the relatively limited medical resources in primary medical institutions in China.Developing a version of guideline which takes these two issues into account to promote the management of NMIBC is therefore indicated.We formed a working group of clinical experts and methodologists.Through questionnaire investigation of clinicians including primary medical institutions,24 clinically concerned issues,involving transurethral resection of bladder tumor(TURBT),intravesical chemotherapy and intravesical immunotherapy of NMIBC,and follow-up and surveillance of the NMIBC patients,were determined for this guideline.Researches and recommendations on the management of NMIBC in databases,guideline development professional societies and monographs were referred to,and the European Association of Urology was used to assess the certainty of generated recommendations.Finally,we issued 29 statements,among which 22 were strong recommendations,and 7 were weak recommendations.These recommendations cover the topics of TURBT,postoperative chemotherapy after TURBT,Bacillus Calmette–Guérin(BCG)immunotherapy after TURBT,combination treatment of BCG and chemotherapy after TURBT,treatment of carcinoma in situ,radical cystectomy,treatment of NMIBC recurrence,and follow-up and surveillance.We hope these recommendations can help promote the treatment and surveillance of NMIBC in China,especially for the primary medical institutions.

Non-invasive assessment of liver fibrosis in chronic hepatitis B

The goal of this review is to provide a comprehensive picture of the role,clinical applications and future perspectives of the most widely used non-invasive techniques for the evaluation of hepatitis B virus(HBV)infection.During the past decade many non-invasive methods have been developed to reduce the need for liver biopsy in staging fibrosis and to overcome whenever possible its limitations,mainly:invasiveness,costs,low reproducibility,poor acceptance by patients.Elastographic techniques conceived to assess liver stiffness,in particular transient elastography,and the most commonly used biological markers will be assessed against their respective role and limitations in staging hepatic fibrosis.Recent evidence highlights that both liver stiffness and some bio-chemical markers correlatewith survival and major clinical end-points such as liver decompensation,development of hepatocellular carcinoma and portal hypertension.Thus the non-invasive techniques here discussed can play a major role in the management of patients with chronic HBV-related hepatitis.Given their prognostic value,transient elastography and some bio-chemical markers can be used to better categorize patients with advanced fibrosis and cirrhosis and assign them to different classes of risk for clinically relevant outcomes.Very recent data indicates that the combined measurements of liver and spleen stiffness enable the reliable prediction of portal hypertension and esophageal varices development.

Carcinosarcoma of the liver with mesenchymal differentiation

We report an extremely rare case where a mesenchymal differentiation, especially embryonal sarcoma, was demonstrated in cholangiocarcinoma. At autopsy, a yellowish-white tumor (15 cm x 12 cm) was found in the right hepatic lobe, and there were several daughter nodules in both hepatic lobes. Histologically, most of the main tumor and all of the daughter nodules examined showed sarcomatous changes (spindle cells, pleomorphic cells and hyalization). Histologic examination of a part of the main tumor disclosed a focus of adenocarcinoma within the tumor. The frequent transitions between the adenocarcinomatous areas and the sarcomatous areas suggested that sarcomatous transformation occurred in the cholangiocarcinoma and then spread rapidly. Immunohistochemically, the adenocarcinomatous elements were positive for cytokeratin, carcinoembryonic antigen (CEA) and epithelial membrane antigen, and negative in the sarcomatous cells. Vimentin was positive only in the sarcomatous elements. The findings of the present case support the view that carcinosarcomas represent carcinomas that develop sarcomatous elements via metaplasia of the epithelial element.

Endoscopic submucosal dissection for small submucosal tumors of the rectum compared with endoscopic submucosal resection with a ligation device

AIM To evaluate the efficacy and safety of endoscopic submucosal dissection(ESD) for small rectal submucosal tumors(SMTs).METHODS Between August 2008 and March 2016, 39 patients were treated with endoscopic submucosal resection with a ligation device(ESMR-L)(n = 21) or ESD(n = 18) for small rectal SMTs in this study. Twenty-five lesions were confirmed by histological evaluation of endoscopic biopsy prior to the procedure, and 14 lesions were not evaluated by endoscopic biopsy. The results for the ESMR-L group and the ESD group were retrospectively compared, including baseline characteristics and therapeutic outcomes.RESULTS The rate of en bloc resection was 100% in both groups. Although the rate of complete endoscopic resectionwas higher in the ESD group than in the ESMR-L group(100% vs 95.2%), there were no significant differences between the two groups(P = 0.462). In one patient in the ESMR-L group with a previously biopsied tumor, histological complete resection with a vertical margin involvement of carcinoid tumor could not be achieved, whereas there was no incomplete resection in the ESD group. The mean length of the procedure was significantly greater in the ESD group than in the ESMR-L group(14.7 ± 6.4 min vs 5.4 ± 1.7 min, P < 0.05). The mean period of the hospitalization was also significantly longer in the ESD group than in the ESMR-L group(3.7 ± 0.9 d vs 2.8 ± 1.5 d, P < 0.05). Postoperative bleeding was occurred in one patient in the ESMR-L group.CONCLUSION Both ESMR-L and ESD were effective for treatment of small rectal SMTs. ESMR-L was simpler to perform than ESD and took less time.

Unusual gastric and pancreatic metastatic renal cell carcinoma presentation 10 years after surgery and immunotherapy: A case report and a review of literature

肾的房间癌(RCC ) 是最普通的肾的肿瘤，为所有恶意的 2%-3% 的财务。尽管 RCC 被知道造血地传播，到胃的孤立的 RCC 转移是一个稀罕事件。在这篇文章，我们描述 RCC 的胃的复发 10 年以前与切除术和 interleukin-2 (IL-2 ) 对待的以后开发了 RCC 和 1 年的胰腺的复发的一个病人的临床的功课。积累的证据显示胰和胃的那变形参与应该与 RCC 的历史在任何病人被怀疑在 RCC 切除术和免疫疗法以后与胃肠的症状介绍甚至 10 年。

^(89)锶联合云克治疗晚期乳腺癌骨转移80例疗效观察(英文)

Objective: The aim of our study was to evaluate the efficacy of 89 Sr combined with Technetium [99Tc] Methylenediphosphonate Injection(99Tc-MDP) in the treatment of cancer pain in the advanced breast cancers with bone metastases. Methods: A total of 80 patients with various degrees of bone pain due to multiple metastases of breast cancer were treated with 89 Sr combined with 99Tc-MDP. 89 Sr was given intravenously at 4m Ci on day 1 during the 3-month schedule. After 7 days, 99Tc-MDP was given at 22 mg/day on days 1–10 during the 1-month schedule, for 3 to 6 months. Results: The effective rate of relieving pain was 83.75%. The effective rate of curing bone metastases was 81.25%. So there was a significant improvement in the quality of life of the patients. Conclusion: 89 Sr combined with 99Tc-MDP are effective in the treatment of cancer pain in the breast cancers with bone metastasis, and can obviously repair the bone destruction caused by metastases, thereby improving the quality of life in advanced breast cancer patients with bone metastases.

Differential expression of hepatic apurinic/apyrimidinic endonuclease 1,a DNA repair enzyme,in chronic hepatitis

AIM:To determine hepatic expression of apurinic/apyrimidinic endonuclease 1(APE-1)and 8-hydroxydeoxyguanosine(8-OHdG)in patients with chronic hepatitis B and C.METHODS:Liver biopsies were obtained from 27 patients with chronic hepatitis B virus(HBV),30 with chronic hepatitis C virus(HCV),6 with autoimmune hepatitis(AIH),and 6 with primary biliary cirrhosis(PBC).Normal liver tissue was obtained from surgical resection specimens of four patients.Hepatic APE-1 protein and mRNA expression were assayed by Western blot and by real-time polymerase chain reaction,respectively.Hepatocellular APE-1 and 8-OHdG expression were determined by immunohistochemistry.RESULTS:The staining intensity of hepatocellular nuclear APE-1 was lower in the HBV group than in the other groups(P < 0.05).Hepatic APE-1 protein levels were reduced in the HBV group relative to the other groups.Hepatic APE-1 mRNA levels were also lower in the HBV group.The proportion of hepatocytes with 8-OHdG-positive nuclei was increased in the HCV,AIH and PBC groups(P < 0.05),but not in the HBV group.Hepatocellular nuclear APE-1 levels were positively correlated with hepatocellular 8-OHdG levels in both the HBV and HCV groups(HBV,r = 0.34,P < 0.05;HCV,r = 0.54,P < 0.01).CONCLUSION:An imbalance between oxidative DNA damage and APE-1 expression may contribute to hepatocarcinogenesis in chronic viral hepatitis.

Microstructure, mechanical, and corrosion properties of extruded low-alloyed Mg–xZn–0.2Ca alloys

The microstructure, mechanical, and corrosion properties of extruded low-alloyed Mg xZn 0.2Ca (x=0, 1.0, 2.0, 3.0) alloys were investigated in this study. Findings from scanning electron microscope, X-ray diffraction and transmission electron microscopy results indicate that the amount of ternary Ca2Mg6Zn3 phase, as the only secondary phase in 1.0Zn, 2.0Zn, and 3.0Zn alloys, gradually increases with the addition of Zn, while the Mg2Ca phase was observed in the Mg 0.2Ca alloy only. Zn has a strong effect on the orientation and intensity of textures, which also influence mechanical behaviors, as revealed by electron back-scatter diffraction. Among all the alloys, the Mg 2.0Zn 0.2Ca alloy obtains the maximum tensile strength (278 MPa) and yield strength (230 MPa). Moreover, Zn addition has an evident influence on the corrosion properties of Mg xZn 0.2Ca alloy, and Mg 1.0Zn 0.2Ca alloy exhibits the minimum corrosion rate. This paper provides a novel low-alloyed magnesium alloy as a potential biodegradable material.

Visualization of sphingolipids and phospholipids in the fundic gland mucosa of human stomach using imaging mass spectrometry

AIM:To analyze the lipid distribution in gastric mucosae.METHODS:Imaging mass spectrometry(MS)is a useful tool to survey the distribution of biomolecules in surgical specimens.Here we used the imaging MS apparatus named i MScope to identify the dominant molecules present in the human gastric mucosa near the fundic glands.Five gastric specimens were subjected to iM Scope analysis.These specimens were also analyzed by immunohistochemistry using MUC5 AC,H(+)-K(+)-ATPaseβ Claudin18 antibodies.RESULTS:Three major molecules with m/z 725.5,780.5,and 782.5 detected in the gastric mucosa were identified as sphingomyelin(SM)(d18:1/16:0),phosphatidylcholine(PC)(16:0/18:2),and PC(16:0/18:1),respectively,through MS/MS analyses.Using immunohistological staining,SM(d18:1/16:0)signals were mainly colocalized with the foveolar epithelium marker MUC5 AC.In contrast,PC(16:0/18:2)signals were observed in the region testing positive for the fundic gland marker H(+)-K(+)-ATPaseβ.PC(16:0/18:1)signals were uniformly distributed throughout the mucosa.CONCLUSION:Our basic data will contribute to the studies of lipid species in physical and pathological conditions of the human stomach.

Time and department distribution of hypoglycemia occurrences in hospitalized diabetic patients

Hypoglycemia occurred on hospitalized patients would result in severe complications.So we monitored the blood glucose of hospitalized patients with diabetes in 14 clinical departments from January to December 2013.Totally 105728 cases of blood glucose were monitored and 1374 cases of hypoglycemia were detected.The incidence of hypoglycemia was 1.29%.Among which,317 cases of severe hypoglycemia were detected and the incidence of severe hypoglycemia was 0.29%.The peak periods of hypoglycemia were 0:00~2:00,22:00~24:00,2:00~4:00,8:00~10:00 and 10:00~12:00.The symptomatic hypoglycemia accounted for 47.01%,The asymptomatic hypoglycemia accounted for 52.98%.The incidence of hypoglycemia was 1.49%in medical departments and 0.87%in surgical departments.It is suggested to be vigilant of high risk periods of hypoglycemia,detect and treat asymptomatic hypoglycemia timely and rationally administer antidiabetics to prevent hypoglycemia.

有无循环性血管活性因子的慢性荨麻疹患者血清P物质水平未见升高

The neuropeptide substance P is a possible candidate as histamine-releasing factor in some patients with chronic ordinary urticaria (COU), particularly in those with evidence of a nonautoantibody circulating histamine-releasing factor. In this study, serum substance P levels were measured by enzyme immunoassay in 117 COU patients, 40 atopic subjects and 24 normal subjects. In vivo and in vitro assays for histamine-releasing factors, autologous serum skin test (ASST) and basophil histamine release (BHR) assay, respectively, were performed in all COU patients. Mean serum substance P concentration was not significantly different in COU patients and in normal subjects; however, significantly higher levels were detected in atopic subjects than in COU patients (P < .0.003). ASST and BHR assays allowed us to distinguish different subsets of COU patients. Mean serum substance P concentration did not vary significantly in the different subsets of patients. Nevertheless, interestingly three patients with positive ASST and negative BHR assay showed very high substance P levels. These results suggest that substance P does not play an important role as histamine- releasing factor in COU in general but only in occasional patients in whom it might act as a trigger of urticarial symptoms.

Preliminary Report on Species and Occurrence Regularity of Diseases,Pests and Weeds of Corn in Angola

[ Objective] The paper was to understand species of diseases, pests and weeds and their occurrence periods and dynamic changes of quantity during corn growing period in rainy and dry seasons in Angola. [ Method] Using systematic investigation method, the species and occurrence regularity of diseases, pests and weeds of corn in Pedras Negras farm （ Malanje）, Sanza Pombo farm （Uige） and Catete farm （Luanda） in the Mrican continent, the Republic of Angola, were studied in two dry seasons and a rainy season from 2011 to 2012. [ Result] The occurrence status of pests and diseases of corn during dry and rainy seasons were basically similar, and only individual diseases and pests had different incidence degrees. The corn varieties from the United States and Brazil had prominent advan- tages in resistance to diseases and barren. Due to different climate environments in dry and rainy seasons, the unearthed rate of weeds in fields was also different. Soil moisture had great impact on weed population and density. Soil layer depth greatly influenced unearthed speed and unearthed rate of weeds. [ Conclusion ] The study cleared species, occurrence period and harmful levels of pests, diseases and weeds of corn in three provinces of Angola.

Abdominal and gastrointestinal manifestations in COVID-19 patients: Is imaging useful?

Coronavirus disease 2019(COVID-19)can be considered a systemic disease with a specific tropism for the vascular system,in which the alterations of the microcirculation have an important pathogenetic role.The lungs are the main organ involved in COVID-19,and severe progressive respiratory failure is the leading cause of death in the affected patients;however,many other organs can be involved with variable clinical manifestations.Concerning abdominal manifestations,the gastrointestinal tract and the hepatobiliary system are mainly affected,although the pancreas,urinary tract and spleen may also be involved.The most common gastrointestinal symptoms are loss of appetite,followed by nausea and vomiting,diarrhea and abdominal pain.Gastrointestinal imaging findings include bowel wall thickening,sometimes associated with hyperemia and mesenteric thickening,fluid-filled segments of the large bowel and rarely intestinal pneumatosis and ischemia.Hepatic involvement manifests as an increase in the enzymatic levels of alanine aminotransferase,aspartate aminotransferase,serum bilirubin andγ-glutamyl transferase with clinical manifestations in most cases mild and transient.The most frequent radiological features are hepatic steatosis,biliary sludge and gallstones.Edematous acute pancreatitis,kidney infarct and acute kidney injury from acute tubular necrosis have been described more rarely in COVID-19.Lastly,splenic involvement is characterized by splenomegaly and by the development of solitary or multifocal splenic infarcts with classic wedge shaped or even rounded morphology,with irregular or smooth profiles.In summary,the abdominal radiological findings of COVID-19 are nonspecific and with poor pathological correlation reported in the literature.Ultrasound and particularly computed tomography with multiphasic acquisition are the diagnostic methods mainly utilized in COVID-19 patients with abdominal clinical symptoms and signs.Although radiological signs are not specific of abdominal and gastrointestinal involvement,the diagnostic imaging modalities and in particular computed tomography are helpful for the clinician in the management,evaluation of the severity and evolution of the COVID-19 patients.

Severe Ectopic Cushing’s Syndrome Due to ACTH-Secreting Pheochromocytoma

We report a new case of ectopic Cushing’s syndrome caused by an ACTH-producing pheochromocytoma. A 55-year-old woman presented with a history of severe proximal muscle weakness, polyuria, progressive virilization, anxiety, dyspnea on exercise, difficult to treat hypertension, and type 2 diabetes mellitus since 4 months. The laboratory data demonstrated ACTH-dependent hypercortisolism. The abdominal computed tomography scan showed a 30 mm well-defined mass in the left adrenal gland suggestive for pheochromocytoma. The adrenal veins were sampled, with intraprocedural cortisol measurement, to dosing selective ACTH and cathecolamines. The results established clearly the left adrenal gland as the source of ACTH overproduction. A left sided adrenalectomy was performed with subsequent resolution of Cushing’s syndrome. The patient was discharged in good clinical condition.

Long non-coding RNAMIR22HG inhibits the adipogenesis of human bone marrow mesenchymal stem cells with the involvement of Wnt/β-catenin pathway

Osteoporosis is a frequently occurring bone remodeling disorder worldwide with one characteristic being decreasing bone mineral density and a predisposition to bone fracture,which diminishes patients’quality of life.Several studies showed that imbalance between the osteogenesis and adipogenesis of bone marrow mesenchymal stem cells(BMSCs)took part in the development of osteoporosis.In previous study,we found MIR22HG regulated the osteogenesis of human BMSCs positively.In this study,we found that MIR22HG was decreased during the adipogenesis of human BMSCs and exerted negative effects on adipogenesis with the involvement of Wnt/β-catenin signaling pathway both in vitro and in vivo.Nitazoxanide could inhibit Wnt signaling and relieve MIR22HG’s suppression on adipogenesis.These findings indicated that MIR22HG had great potential in clinical application for osteoporosis treatment and prevention.

Characteristics of staphylococcal cassette chromosome mec and lugdunin operon genes in the complete genome of Staphylococcus lugdunensis

Staphylococcus lugdunensis(S.lugdunensis)is a coagulase-negative Staphylococcus comprising the normal skin microbiota,primarily colonizing the lower abdomen and extremities.[1]S.lugdunensis has attracted substantial attention in recent years since the discovery of lugdunin by Zipperer et al[2]in 2016.Lugdunin is a secondary metabolite synthesized by non-ribosomal peptide synthetase(NRPS)that inhibits the growth of various grampositive bacteria,including methicillin-resistant S.aureus(MRSA),[2]suggesting its potential as an antibiotic.

PRELIMINARY STUDY ON THE STABILITY OF MONOCENTRIC RING CHRO-MOSOME ABERRATION

Most of ring chromosome aberrations are monocentric rings (r). So far, in the study of chromosome aberrations induced by physical and chemical clastogens, r has been regarded as an unstable one and classified as dicentric (dic).Using FPG technique in cytogenetic investigation of human blood irradiated with γ-rays in various doses in vitro, the authors of this paper previously observed a higher r incidence in cells at the second division.Recently, Scheid has discovered this phenomenon too and pre-