Current application and future perspective of CRISPR/cas9 gene editing system mediated immune checkpoint for liver cancer treatment.

Liver cancer, which is well-known to us as one of human most prevalent malignancies across the globe, poses a significant risk to live condition and life safety of individuals in every region of the planet. It has been shown that immune checkpoint treatment may enhance survival benefits and make a significant contribution to patient prognosis, which makes it a promising and popular therapeutic option for treating liver cancer at the current time. However, there are only a very few numbers of patients who can benefit from the treatment and there also exist adverse events such as toxic effects and so on, which is still required further research and discussion. Fortunately, the clustered regularly interspaced short palindromic repeat/CRISPR-associated nuclease 9 (CRISPR/Cas9) provides a potential strategy for immunotherapy and immune checkpoint therapy of liver cancer. In this review, we focus on elucidating the fundamentals of the recently developed CRISPR/Cas9 technology as well as the present-day landscape of immune checkpoint treatment which pertains to liver cancer. What's more, we aim to explore the molecular mechanism of immune checkpoint treatment in liver cancer based on CRISPR/Cas9 technology. At last, its encouraging and powerful potential in the future application of the clinic is discussed, along with the issues that already exist and the difficulties that must be overcome. To sum it all up, our ultimate goal is to create a fresh knowledge that we can utilize this new CRISPR/Cas9 technology for the current popular immune checkpoint therapy to overcome the treatment issues of liver cancer. .

The fate of flavonoids after oral administration: a comprehensive overview of its bioavailability.

Despite advancements in synthetic chemistry, nature remains the primary source of drug discovery, and this never-ending task of finding novel and active drug molecules will continue. Flavonoids have been shown to possess highly significant therapeutic activities such as anti-inflammatory, anti-oxidant, anti-viral, anti-diabetic, anti-cancer, anti-aging, neuroprotective, and cardioprotective, etc., However, it has been found that orally administered flavonoids have a critical absorption disorder and, therefore, have low bioavailability and show fluctuating pharmacokinetic and pharmacodynamic responses. A detailed investigation is required to assess and analyze the variation in the bioavailability of flavonoids due to interactions with the intestinal barrier. This review will emphasize on the bioavailability and the pharmacological applications of flavonoids, key factors affecting their bioavailability, and strategies for enhancing bioavailability, which may lead to deeper understanding of the extent of flavonoids as a treatment and/or prevention for different diseases in clinics.

Pseudomembranous necrotizing laryngotracheobronchitis due to Mycoplasma pneumoniae: a case report and literature review.

BACKGROUND: Pseudomembranous necrotizing laryngotracheobronchitis refers to an acute diffuse necrotizing inflammation in the mucosa of the larynx, trachea, and bronchus. It often occurs in infants and children having viral infections secondary to bacterial infections. Mycoplasma pneumoniae (M. pneumoniae) is a common pathogen that causes pneumonia in children. In recent years, serious complications due to M. pneumoniae infection, including necrotizing pneumonia, pulmonary embolism, and pleural effusion, have been increasingly reported. CASE PRESENTATION: An 11-year-old girl was admitted to our unit with cough, fever, and hoarseness persistent for a week. The results of the M. pneumoniae serological test, PCR examination with bronchial aspirate and bronchoalveolar lavage fluid (BALF), next-generation sequencing (mNGS) for BALF, all suggested the presence of M. pneumoniae infection. High-resolution CT scanning of the chest showed inflammation of the middle and lower lobes of the right lung. By bronchoscopy, the necrosis of the vocal cords, trachea, and bronchial mucosa was observed; each bronchial lumen contained a large amount of white viscous sputum. Pathological findings for bronchial mucosa suggested inflammatory necrosis. After administration of azithromycin and glucocorticoids, the symptoms of the patients were ameliorated. After 2 weeks post-discharge, the X-ray scan of her chest indicated the pneumonia resolution in the right lung. CONCLUSIONS: In patients with pneumonia due to M. pneumoniae infection, which causes obvious hoarseness, bronchoscopy is necessary even if the lung lesions are not massively consolidated. When necrotizing lesions of the larynx, trachea, and bronchi are detected by bronchoscopy, the necrotic tissues in the corresponding parts should be conducted tissue biopsy for pathological examination. Apart from macrolide antibiotics, the administration of small doses of glucocorticoids is necessary.

Family functioning, coping strategy, and suicidal ideation among adolescents.

Background and aim: Adolescent suicide has become a central issue around the world, including in Malaysia, which needs attention. The current study investigated the mediating effect of coping strategy in the association between family functioning and suicidal ideation among adolescents in Kuala Lumpur, Malaysia. Method: A total of 852 school-attending adolescents aged 13-17 years were recruited by multistage cluster sampling. The relationships between all the study variables were analysed using Pearson's correlation. Moreover, the mediation model was tested using SPSS PROCESS macro, while sex differences in suicidal ideation were examined using independent samples t-test. Results: Results showed that family cohesion, family flexibility, and problem-focused coping negatively correlated with adolescents' suicidal ideation. Problem-focused coping also mediated the association between family flexibility and suicidal ideation. There was a significant difference in suicidal ideation for males and females. Conclusion: Family functioning and coping strategy are related to adolescents' suicidal ideation, while problem-focused coping plays a crucial role in the relationship between family flexibility and suicidal ideation.

Mir-135a enhances cellular proliferation through post-transcriptionally regulating PHLPP2 and FOXO1 in human bladder cancer.

BACKGROUND: Bladder cancer is the most common malignancy in urinary system and the ninth most common malignancy in the world. MicroRNAs (miRNAs) are small, non-coding RNAs that regulate gene expression by targeted repression of transcription and translation and play essential roles during cancer development. We investigated the expression of miR-135a in bladder cancer and explored its bio-function during bladder cancer progression. METHODS: The expression of miR-135a in bladder cancer cells and tissues are performed by using Real-time PCR assay. Cell viability assay (MTT assay), colony formation assay, anchorage-independent growth ability assay and Bromodeoxyuridine labeling and immunofluorescence (BrdUrd) assay are used to examine cell proliferative capacity and tumorigenicity. Flow cytometry analysis is used to determine cell cycle progression. The expressions of p21, p27, CyclinD1, Ki67, PHLPP2 and FOXO1 are measured by Western blotting assay. Luciferase assay is used to confirm whether FOXO1 is the direct target of miR-135a. RESULTS: miR-135a is upregulated in bladder cancer cells and tissues. Enforced expression of miR-135a promotes bladder cancer cells proliferation, whereas inhibition of miR-135a reverses the function. Furthermore, for the first time we demonstrated PHLPP2 and FOXO1 are direct targets of miR-135a and transcriptionally down-regulated by miR-135a. Suppression of PHLPP2 or FOXO1 by miR-135a, consisted with dysregulation of p21, p27, Cyclin D1 and Ki67, play important roles in bladder cancer progression. CONCLUSION: Our study demonstrates that miR-135a promotes cell proliferation in bladder cancer by targeting PHLPP2 and FOXO1, and is performed as an onco-miR.

Reciprocal effects between microRNA-140-5p and ADAM10 suppress migration and invasion of human tongue cancer cells.

ADAM10, overexpressed in tongue squamous cell carcinoma (TSCC), has been well documented for its role in tumor progression and metastasis. In the present study, we evaluated the inhibition effect of microRNAs (miRNAs) on the TSCC and identified that miR-140-5p could directly targets ADAM10 and inhibits the invasion and migration of TSCC cells. LAMC1, HDAC7 and PAX6, clustered into migration-related genes, were validated to be direct targets of miR-140-5p, while IGF1R and PSEN1 were not responsible to the regulation. Most intriguingly, ERBB4 was upregulated by miR-140-5p even though the interaction between ERBB4 3'UTR and miR-140-5p existed simultaneously. Meanwhile, ADAM10 is involved in the "positive" regulation of ERBB4 and negative regulation of PAX6 by miR-140-5p. Taken together, our results suggest that miR-140-5p play a role in TSCC cell migration and invasion, and two brand new relationships between miRNA and its targets emerged: (1) ADAM10 is not just a direct target of miR-140-5p, the repressed ADAM10 also helps to enhance the effect of miR-140-5p to other target genes: ERBB4 and PAX6; (2) ERBB4 is "positively" regulated by miR-140-5p.

Heavy metal ions affecting the removal of polycyclic aromatic hydrocarbons by fungi with heavy-metal resistance.

The co-occurrence of polycyclic aromatic hydrocarbons (PAHs) and heavy metals (HMs) is very common in contaminated environments. It is of paramount importance and great challenge to exploit a bioremediation to remove PAHs in these environments with combined pollution. We approached this question by probing the influence of HMs coexisting with PAHs on the removal of PAHs by Acremonium sp. P0997 possessing metal resistance. A removal capability for naphthalene, fluorene, phenanthrene, anthracene, and fluoranthenepresentalone (98.6, 99.3, 89.9, 60.4, and 70 %, respectively) and in a mixture (96.9, 71.8, 67.0, 85.0, and 87.9 %, respectively) was achieved in mineral culture inoculated with Acremonium sp. P0997, and this strain also displayed high resistance to the individual HMs (Mn(2+), Fe(2+), Zn(2+), Cu(2+), Al(3+), and Pb(2+)). The removal of individual PAHs existing in a mixture was differently affected by the separately tested HMs. Cu(2+)enhanced the partition process of anthracene to dead or alive mycelia and the contribution of the biosorption by this strain but imposed a little negative influence on the contribution of biodegradation to the total removal of anthracene individually in a culture. However, Mn(2+) had an inhibitory effect on the partition process of anthracene to dead or alive mycelia and decreased the contributions of both biosorption and biodegradation to the total anthracene removal. This work showcased the value of fungi in bioremediation for the environments with combined pollution, and the findings have major implications for the bioremediation of organic pollutants in metal-organic mixed contaminated sites.

Design, Optimization, and Modeling of a Hydraulic Soft Robot for Chronic Total Occlusions.

Chronic total occlusion (CTO) is one of the most severe and sophisticated vascular stenosis because of complete blockage, greater operation difficulty, and lower procedural success rate. This study proposes a hydraulic-driven soft robot imitating the earthworm's locomotion to assist doctors or operators in actively opening thrombi in coronary or peripheral artery vessels. Firstly, a three-actuator bionic soft robot is developed based on earthworms' physiological structure. The soft robot's locomotion gait inspired by the earthworm's mechanism is designed. Secondly, the influence of structure parameters on actuator deformation, stress, and strain is explored, which can help us determine the soft actuators' optimal structure parameters. Thirdly, the relationship between hydraulic pressure and actuator deformation is investigated by performing finite element analysis using the bidirectional fluid-structure interaction (FSI) method. The kinematic models of the soft actuators are established to provide a valuable reference for the soft actuators' motion control.

Functional analysis of a lily SHORT VEGETATIVE PHASE ortholog in flowering transition and floral development.

Lilium is a commercially important genus of bulbous flowers, investigating the flowering molecular mechanisms is important for flowering regulation of lily. MADS-box SHORT VEGETATIVE PHASE (SVP) orthologs are involved in the flowering transition and floral organ differentiation in many plants. In this study, we identified an SVP ortholog from L. × formolongi (LfSVP), which was closely related to Arabidopsis SVP according to phylogenetic analysis. Tissue-specific expression patterns indicated that LfSVP expression levels peaked in the leaves and showed low expression levels in flowering tepals. Stage-dependent expression patterns of LfSVP showed high transcription level in the flowering induction stage under different photoperiods and exhibited transcription peak in the floral budding development stage under long days. Overexpressed LfSVP led to delayed flowering and floral organ defects in Arabidopsis independent of photoperiod. Tobacco rattle virus -induced gene silencing of LfSVP caused a strongly earlier flowering time and floral organ defects of L. × formolongi. Moreover, LfSVP can interact with L. × formolongi APETALA1 (AP1) in both yeast and tobacco cells, and the two may interact to regulate floral organ differentiation. In conclusion, LfSVP is a flowering repressor and may be involved in the regulation of floral organ differentiation. This study will be helpful for the molecular breeding of short-life-period and rich floral patterns lily varieties.

Synergistic anti-tumor effect of dual drug co-assembled nanoparticles based on ursolic acid and sorafenib.

Both ursolic acid (UA) and sorafenib (Sora) have been generally utilized in cancer treatment, and the combination of the two has also shown a good anti-tumor effect. However, single-agent therapy for Hepatocellular carcinoma (HCC) has the disadvantages of multi-drug resistance, poor water solubility and low bioavailability, and the application of traditional nanocarrier materials is limited due to their low drug loading and low carrier-related toxicity. Therefore, we prepared US NPs with different proportions of UA and Sora by solvent exchange method for achieving synergistic HCC therapy. US NPs had suitable particle size, good dispersibility and storage stability, which synergistically inhibited the proliferation of HepG2 cells, SMMC7721 cells and H22 cells. In addition, we also proved that US NPs were able to suppress the migration of HepG2 cells and SMMC7721 cells and reduce the adhesion ability and colony formation ability of these cells. According to the results, US NPs could degrade the membrane potential of mitochondrial, participate in cell apoptosis, and synergistically induce autophagy. Collectively, the carrier-free US NPs provide new strategies for HCC treatment and new ideas for the development of novel nano-drug delivery systems containing UA and Sora.

Multifunctional metal-coordinated Co-assembled carrier-free nanoplatform based on dual-drugs for ferroptosis-mediated cocktail therapy of hepatocellular carcinoma growth and metastasis.

The heterogeneity of hepatocellular carcinoma (HCC) and the complexity of the tumor microenvironment (TME) pose challenges to efficient drug delivery and the antitumor efficacy of combined or synergistic therapies. Herein, a metal-coordinated carrier-free nanodrug (named as USFe3+ LA NPs) was developed for ferroptosis-mediated multimodal synergistic anti-HCC. Natural product ursolic acid (UA) was incorporated to enhance the sensitivity of tumor cells to sorafenib (SRF). Surface decoration of cell penetration peptide and epithelial cell adhesion molecule aptamer facilitated the uptake of USFe3+ LA NPs by HepG2 cells. Meanwhile, Fe3+ ions could react with intracellular hydrogen peroxide, generating toxic hydroxyl radical (·OH) for chemodynamical therapy (CDT) and amplified ferroptosis by cystine/glutamate antiporter system (System Xc-), which promoted the consumption of glutathione (GSH) and inhibited the expression of glutathione peroxidase 4 (GPX4). Notably, these all-in-one nanodrugs could inhibit tumor metastasis and induced immunogenic cell death (ICD). Last but not least, the nanodrugs demonstrated favorable biocompatibility, augmenting the immune response against the programmed death-ligand 1 (PD-L1) by increasing cytotoxic T cell infiltration. In vivo studies revealed significant suppression of tumor growth and distant metastasis. Overall, our work introduced a novel strategy for applications of metal-coordinated co-assembled carrier-free nano-delivery system in HCC combination therapy, especially in the realms of cancer metastasis prevention and immunotherapy.

Dual-drug controllable co-assembly nanosystem for targeted and synergistic treatment of hepatocellular carcinoma.

The effectiveness of chemotherapeutic agents for hepatocellular carcinoma (HCC) is unsatisfactory because of tumor heterogeneity, multidrug resistance, and poor target accumulation. Therefore, multimodality-treatment with accurate drug delivery has become increasingly popular. Herein, a cell penetrating peptide-aptamer dual modified-nanocomposite (USILA NPs) was successfully constructed by coating a cell penetrating peptide and aptamer onto the surface of sorafenib (Sora), ursolic acid (UA) and indocyanine green (ICG) condensed nanodrug (USI NPs) via one-pot assembly for targeted and synergistic HCC treatment. USILA NPs showed higher cellular uptake and cytotoxicity in HepG2 and H22 cells, with a high expression of epithelial cell adhesion molecule (EpCAM). Furthermore, these NPs caused more significant mitochondrial membrane potential reduction and cell apoptosis. These NPs could selectively accumulate at the tumor site of H22 tumor-bearing mice and were detected with the help of ICG fluorescence; moreover, they retarded tumor growth better than monotherapy. Thus, USILA NPs can realize the targeted delivery of dual drugs and the integration of diagnosis and treatment. Moreover, the effects were more significant after co-administration of iRGD peptide, a tumor-penetrating peptide with better penetration promoting ability or programmed cell death ligand 1 (PD-L1) antibody for the reversal of the immunosuppressive state in the tumor microenvironment. The tumor inhibition rates of USILA NPs + iRGD peptide or USILA NPs + PD-L1 antibody with good therapeutic safety were 72.38 % and 67.91 % compared with control, respectively. Overall, this composite nanosystem could act as a promising targeted tool and provide an effective intervention strategy for enhanced HCC synergistic treatment.

New antifungal scaffold derived from a natural pharmacophore: synthesis of α-methylene-γ-butyrolactone derivatives and their antifungal activity against Colletotrichum lagenarium.

Thirty new and thirty-four known analogues were designed and synthesized to improve the potential use of the α-methylene-γ-butyrolactone ring, a natural pharmacophore. All structures were confirmed by (1)H and (13)C NMR, MS, and single-crystal X-ray diffraction analyses. The results of antifungal and cytotoxic activity indicated that the synthesized analogues showed significant inhibitory activity and limited selectivity. Compound 45 exhibited the highest antifungal activity with IC50=22.8 µM but moderate cytotoxic activity with IC50=28.5 µM (against BGC823 cell line) and 7.7 µM (against HeLa cell line). Analysis of structure-activity relationships revealed that the incorporation of an aromatic ring into the ß, γ positions of the lactone ring improved antifungal activity, and that the introduction of electron-withdrawing groups into the aromatic rings increased the activity compared with electron-donating groups. The above results identified 4-phenyl-3-phenyl-2-methylenebutyrolactone (33) as a lead scaffold for discovering and developing novel and improved crop-protection agents.

Bladder preservation in complicated invasive urothelial carcinoma following treatment with cisplatin/gemcitabine plus tislelizumab: A case report.

BACKGROUND: Invasive urothelial carcinoma (UC) with squamous and glandular differentiation is a highly malignant and complicated pathological subtype, and the standard care is radical cystectomy (RC). However, urinary diversion after RC significantly reduces patient quality of life, thus bladder-sparing therapy has become a research hotspot in this field. Recently, five immune checkpoint inhibitors have been approved for systemic therapy of locally advanced or metastatic bladder cancer by the Food and Drug Administration, but the efficacy of immunotherapy combined with chemotherapy for invasive UC is still unknown, especially for pathological subtypes with squamous and glandular differentiation. CASE SUMMARY: We report the case of a 60-year-old male who complained of repetitive painless gross hematuria and was diagnosed with muscle-invasive bladder cancer with squamous and glandular differentiation, defined as cT3N1M0 according to the American Joint Committee on Cancer, who had a strong desire to preserve the bladder. Immunohistochemical staining revealed that programmed cell death-ligand 1 (PD-L1) expression in the tumor was positive. Thus, a transurethral resection to maximize removal of the bladder tumor was performed under cystoscopy, and the patient subsequently received a combination of chemotherapy (cisplatin/gemcitabine) and immunotherapy (tislelizumab) treatment. No tumor recurrence in the bladder was observed following pathological and imaging examination after 2 cycles and 4 cycles of treatment, respectively. The patient achieved bladder preservation and has been tumor-free for more than two years. CONCLUSION: This case shows that the combination of chemotherapy and immunotherapy might be an effective and safe treatment strategy for PD-L1 expression positive UC with divergent histologic differentiation.

CRISPR/Cas9-based application for cancer therapy: Challenges and solutions for non-viral delivery.

CRISPR/Cas9 genome editing is a promising therapeutic technique, which makes precise and rapid gene editing technology possible on account of its high sensitivity and efficiency. CRISPR/Cas9 system has been proved to able to effectively disrupt and modify genes, which shows great potential for cancer treatment. Current researches proves that virus vectors are capable of effectively delivering the CRISPR/Cas9 system, but immunogenicity and carcinogenicity caused by virus transmission still trigger serious consequences. Therefore, the greatest challenge of CRISPR/Cas9 for cancer therapy lies on how to deliver it to the target tumor site safely and effectively. Non-viral delivery systems with specific targeting, high loading capacity, and low immune toxicity are more suitable than viral vectors, which limited by uncontrollable side effects. Their medical advances and applications have been widely concerned. Herein, we present the molecule mechanism and different construction strategies of CRISPR/Cas9 system for editing genes at the beginning of this research. Subsequently, several common CRISPR/Cas9 non-viral deliveries for cancer treatment are introduced. Lastly, based on the main factors limiting the delivery efficiency of non-viral vectors proposed in the existing researches and literature, we summarize and discuss the main methods to solve these limitations in the existing tumor treatment system, aiming to introduce further optimization and innovation of the CRISPR/Cas9 non-viral delivery system suitable for cancer treatment.

[Clinical characteristics and surgical treatment for localized Castleman's disease].

OBJECTIVE: To investigate the clinical characteristics and treatment of localized Castleman's disease (CD), and review the literatures to improve the diagnosis and management of this disease. METHODS: The clinical symptoms, histopathology, CT, MRI findings and results of surgery in 20 patients with localized CD were evaluated retrospectively. RESULTS: The average age of the patients was 37.7 years. The lesions were located in the retroperitoneal space (9 cases), mediastinum (7 cases), pelvic cavity (1 case), neck (1 case), upper arm (1 case), and axillary (1 case). All patients underwent surgical resection, including 9 cases for retroperitoneal resection (6 cases had open operation and 3 cases laparoscopic resection) and 7 cases for mediastinal resection (open operation in 5 cases and thoracoscopic resection in 2 cases). The Castleman's disease was confirmed by histopathology. There were hyaline vascular type of CD in 17 cases, plasma cell type of CD in 1 case, and mixed cellularity type of CD in 2 cases. The duration of follow-up ranged from 12 to 165 months for 16 cases. Among them 15 patients were alive without recurrence, and 1 case had recurrence in the primary site at 47 months after the operation. CONCLUSIONS: Patients with Castleman's disease have no typical clinical symptoms and have normal laboratory results. The majority of patients are of hyaline vascular type of the disease. Imaging examination is helpful to diagnosis, and the final diagnosis depends on pathologic examination. Complete surgical resection of the tumor is the best treatment for localized Castleman's disease.

[Factors associated with increased blood loss in patients undergoing radical cystectomy in a contemporary series].

OBJECTIVE: To evaluate factors predictive of blood loss in radical cystectomy in a contemporary series. METHODS: From December 1996 to December 2008, clinical data of 233 patients who underwent radical cystectomy were reviewed retrospectively. Various preoperative and operative factors were assessed for their association with blood loss using univariate, multivariate regression and correlation analysis. RESULTS: One hundred eighty-one patients underwent open radical cystectomy and 52 cases were treated by laparoscopic radical cystectomy. Overall mean operative time was (339 ± 84) minutes, and mean blood loss was (818 ± 756) ml. On univariate analysis, body mass index (F = 9.039), history of pelvic operation (t = -4.365), anesthetic techniques (t = 3.125), surgical type (t = 6.643), use of Ligasure (t = 6.923), and urethra resection (t = -1.984) correlated with blood loss. However, multiple linear regression showed that body mass index (R(2) = 0.256, P < 0.001), history of pelvic operation (R(2) = 0.222, P < 0.001), use of Ligasure (R(2) = 0.172, P < 0.001), and surgical type (R(2) = 0.271, P = 0.027) were significant predictors of blood loss. The transfusion was required in 176 of 233 patients (75.5%) with a median requirement of (649 ± 569) ml. Likewise logistical regression analysis revealed that older age (OR = 3.2, P = 0.010), female gender (OR = 33.7, P = 0.013), anemia (OR = 6.6, P = 0.039), increased blood loss (OR = 14.3, P < 0.001), open radical cystectomy (OR = 6.4, P = 0.036) and nonuse of Ligasure (OR = 10.1, P < 0.001) were predictors of transfusion need. CONCLUSIONS: Increased body mass index, history of pelvic operation, open radical cystectomy, and non-use of Ligasure were independent predictors of increased blood loss during radical cystectomy. Such a prediction formula has an important role in identifying high risk patient for increased blood loss and transfusion need before radical cystectomy.

[The analysis of perioperative complications during radical cystectomy using a standardized reporting system].

OBJECTIVES: To analyze the perioperative complications of radical cystectomy using a standardized reporting methodology. METHODS: The clinical data of 233 cases of radical cystectomy from January 1996 to December 2008 were reviewed. Two hundred male patients and 33 female patients were included. The mean age was 58.9 years old. All complications within 30 days of surgery were recorded and classified using a 5-grade modification of the Clavien system. RESULTS: Overall mean operative time was 339 (170 - 610) minutes, and mean blood loss was 818 (range 100 to 3500) ml. Of the 233 subjects at least 1 postoperative complication developed in 84 (36.1%), including five cases of intraoperative complications. According to the modified Clavien system, 27 patients (11.6%) had grade 1, 38(16.3%) had grade 2, 16(6.9%) had grade 3, and 3(1.7%) had grade 4 complications. The most frequent complication was gastrointestinal complications (15.9%), then the incision-related complications (15.0%) and lung infections (4.7%). An association between hypoproteinemia and any complication was found after adjusting for confounding variables (OR = 2.963, 95%CI: 1.451 - 6.050, P = 0.003), and American society of anesthesia score (ASA score) was significantly associated with any major complication (OR = 2.520, 95%CI: 1.003 - 6.332, P = 0.049). CONCLUSIONS: Radical cystectomy is associated with a high perioperative complications, using the modification of the Clavien system has allowed us to stratify complications during radical cystectomy. Hypoproteinemia is independently associated with any complication in these patients and ASA score was significantly associated with any major complication.

Successful robot-assisted partial nephrectomy for giant renal hilum angiomyolipoma through the retroperitoneal approach: A case report.

BACKGROUND: Giant renal angiomyolipomas (AMLs) may lead to complications including flank pain, hematuria, hypertension, retroperitoneal hemorrhage and even death. Giant AMLs which grow around renal hilar vessels and the ureter are rare. Most previous reports on the treatment of giant renal AMLs have focused on open surgery or a transperitoneal approach, with few studies on the retroperitoneal approach for large AMLs. We here report a case of giant renal hilum AML successfully treated with robot-assisted laparoscopic nephron sparing surgery the retroperitoneal approach, with a one-year follow-up. CASE SUMMARY: A 34-year-old female patient was diagnosed with renal AML 11 years ago and showed no discomfort. The tumor gradually increased in size to a giant AML over the years, which measured 63 mm × 47 mm ×90 mm and was wrapped around the right hilum. Therefore, a robotic laparoscopic partial nephrectomy (LPN) via the retroperitoneal approach was performed. The patient had no serious postoperative complications and was discharged soon after the operation. At the one-year follow-up, the patient's right kidney had recovered well. CONCLUSION: Despite insufficient operating space via the retroperitoneal approach, LPN for giant central renal AMLs can be completed using a well-designed procedure with the assistance of a robotic system.

Four Systemic Lupus Erythematosus Subgroups, Defined by Autoantibodies Status, Differ Regarding HLA-DRB1 Genotype Associations and Immunological and Clinical Manifestations.

OBJECTIVE: The heterogeneity of systemic lupus erythematosus (SLE) constitutes clinical and therapeutical challenges. We therefore studied whether unrecognized disease subgroups can be identified by using autoantibody profiling together with HLA-DRB1 alleles and immunological and clinical data. METHODS: An unsupervised cluster analysis was performed based on detection of 13 SLE-associated autoantibodies (double-stranded DNA, nucleosomes, ribosomal P, ribonucleoprotein [RNP] 68, RNPA, Smith [Sm], Sm/RNP, Sjögren's syndrome antigen A [SSA]/Ro52, SSA/Ro60, Sjögren's syndrome antigen B [SSB]/La, cardiolipin [CL]-Immunoglobulin G [IgG], CL-Immunoglobulin M [IgM], and ß2 glycoprotein I [ß2 GPI]-IgG) in 911 patients with SLE from two cohorts. We evaluated whether each SLE subgroup is associated with HLA-DRB1 alleles, clinical manifestations (n = 743), and cytokine levels in circulation (n = 446). RESULTS: Our analysis identified four subgroups among the patients with SLE. Subgroup 1 (29.3%) was dominated by anti-SSA/Ro60/Ro52/SSB autoantibodies and was strongly associated with HLA-DRB1*03 (odds ratio [OR] = 4.73; 95% confidence interval [CI] = 4.52-4.94). Discoid lesions were more common for this disease subgroup (OR = 1.71, 95% CI = 1.18-2.47). Subgroup 2 (28.7%) was dominated by anti-nucleosome/SmRNP/DNA/RNPA autoantibodies and associated with HLA-DRB1*15 (OR = 1.62, 95% CI = 1.41-1.84). Nephritis was most common in this subgroup (OR = 1.61, 95% CI = 1.14-2.26). Subgroup 3 (23.8%) was characterized by anti-ß2 GPI-IgG/anti-CL-IgG/IgM autoantibodies and a higher frequency of HLA-DRB1*04 compared with the other patients with SLE. Vascular events were more common in Subgroup 3 (OR = 1.74, 95% CI = 1.2-2.5). Subgroup 4 (18.2%) was negative for the investigated autoantibodies, and this subgroup was not associated with HLA-DRB1. Additionally, the levels of eight cytokines significantly differed among the disease subgroups. CONCLUSION: Our findings suggest that four fairly distinct subgroups can be identified on the basis of the autoantibody profile in SLE. These four SLE subgroups differ regarding associations with HLA-DRB1 alleles and immunological and clinical features, suggesting dissimilar disease pathways.