TSHR Variant Screening and Phenotype Analysis in 367 Chinese Patients With Congenital Hypothyroidism.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype-phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions: We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Pivotal Role of GSTO2 in Ferroptotic Neuronal Injury After Intracerebral Hemorrhage.

Previous research has found that an adaptive response to ferroptosis involving glutathione peroxidase 4 (GPX4) is triggered after intracerebral hemorrhage. However, little is known about the mechanisms underlying adaptive responses to ferroptosis. To explore the mechanisms underlying adaptive responses to ferroptosis after intracerebral hemorrhage, we used hemin-treated HT22 cells to mimic brain injury after hemorrhagic stroke in vitro to evaluate the antioxidant enzymes and performed bioinformatics analysis based on the mRNA sequencing data. Further, we determined the expression of GSTO2 in hemin-treated hippocampal neurons and in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH) by using Western blot. After hemin treatment, the antioxidant enzymes GPX4, Nrf2, and glutathione (GSH) were upregulated, suggesting that an adaptive response to ferroptosis was triggered. Furthermore, we performed mRNA sequencing to explore the underlying mechanism, and the results showed that 2234 genes were differentially expressed. Among these, ten genes related to ferroptosis (Acsl1, Ftl1, Gclc, Gclm, Hmox1, Map1lc3b, Slc7a11, Slc40a1, Tfrc, and Slc39a14) were altered after hemin treatment. In addition, analysis of the data retrieved from the GO database for the ten targeted genes showed that 20 items on biological processes, 17 items on cellular components, and 19 items on molecular functions were significantly enriched. Based on the GO data, we performed GSEA and found that the glutathione metabolic process was significantly enriched in the hemin phenotype. Notably, the expression of glutathione S-transferase omega (GSTO2), which is involved in glutathione metabolism, was decreased after hemin treatment, and overexpression of Gsto2 decreased lipid reactive oxygen species level in hemin-exposed HT22 cells. In addition, the expression of GSTO2 was also decreased in a mouse model of hippocampus-intracerebral hemorrhage (h-ICH). The decreased expression of GSTO2 in the glutathione metabolic process may be involved in ferroptotic neuronal injury following hemorrhagic stroke.

[Diagnostic efficacy of prostate cancer using targeted biopsy with 6-core systematic biopsy for patients with PI-RADS 5].

OBJECTIVE: To investigate the diagnostic efficacy of targeted biopsy (TBx), systematic biopsy (SBx), TBx+6-core SBx in prostate cancer (PCa) / clinically significant prostate cancer (cs-PCa) for patients with prostate imaging reporting and data system (PI-RADS) score of 5, and thereby to explore an optimal sampling scheme. METHODS: The data of 585 patients who underwent multiparametric magnetic resonance imaging (mpMRI) with at least one lesion of PI-RADS score 5 at Peking University First Hospital from January 2019 to June 2022 were retrospectively analyzed. All patients underwent mpMRI / transrectal ultrasound (TRUS) cognitive guided biopsy (TBx+SBx). With the pathological results of combined biopsy as the gold standard, we compared the diagnostic efficacy of TBx only, SBx only, and TBx+6-core SBx for PCa/csPCa. The patients were grouped according to mpMRI T-stage (cT2, cT3, cT4) and the detection rates of different biopsy schemes for PCa/csPCa were compared using Cochran's Q and McNemar tests. RESULTS: Among 585 patients with a PI-RADS score of 5, 560 (95.7%) were positive and 25(4.3%) were negative via TBx+SBx. After stratified according to mpMRI T-stage, 233 patients (39.8%) were found in cT2 stage, 214 patients (36.6%) in cT3 stage, and 138 patients (23.6%) in cT4 stage. There was no statistically significant difference in the detection rate of PCa/csPCa between TBx+6-core SBx and TBx+SBx (all P>0.999). Also, there was no statistically significant difference in the detection rate of PCa/csPCa between TBx and TBx+SBx in the cT2, cT3, and cT4 subgroups (PCa: P=0.203, P=0.250, P>0.999; csPCa: P=0.700, P=0.250, P>0.999). The missed diagnosis rate of SBx for PCa and csPCa was 2.1% (12/560) and 1.8% (10/549), and that of TBx for PCa and csPCa was 1.8% (10/560) and 1.4% (8/549), respectively. However, the detection rate of TBx+6-core SBx for PCa and csPCa was 100%. Compared with TBx+SBx, TBx and TBx+6-core SBx had a fewer number of cores and a higher detection rate per core (P < 0.001). CONCLUSION: For patients with a PI-RADS score of 5, TBx and TBx+6-core SBx showed the same PCa/csPCa detection rates and a high detection rates per core as that of TBx+SBx, which can be considered as an optimal scheme for prostate biopsy.

[Application of dynamic contrast enhanced status in multiparametric magnetic resonance imaging for prostatic cancer with PI-RADS 4 lesion].

OBJECTIVE: To evaluate the diagnostic value of dynamic contrast enhanced (DCE) of multiparametric magnetic resonance imaging (mpMRI) for prostate imaging reporting and data system (PI-RADS) 4 lesion in prostate peripheral zone. METHODS: The clinical data of patients with PI-RADS 4 lesion in prostate peripheral zone who underwent prostate biopsy from January 2018 to September 2021 in Peking University First Hospital were retrospectively included. According to DCE status, the patients were divided into the conventional group (4 points for diffusion-weighted imaging) and the comprehensive group (3 points for diffusion-weighted imaging + 1 point for DCE positive). Pearson's chi-square test or Fisher's exact test for comparison was conducted between prostate cancer and non-cancer patients. Univariate and multivariate Logistic regression were performed to analyze the correlation of positive biopsy with age, total prostate specific antigen (PSA), free PSA/total PSA (f/tPSA), prostate volume (PV), PSA density (PSAD) and DCE status. RESULTS: Among the 267 prostate biopsy patients, 217 cases were diagnosed as prostatic cancer (81.27%) and 50 cases were non-cancer (18.73%). Statistical analysis between the prostatic cancer group and the non-cancer group showed that there were significant differences in age, tPSA, PV and PSAD (all P < 0.05), but no significant differences in f/tPSA between the two groups. About different PI-RADS 4 lesion groups, the conventional group and the comprehensive group showed significant difference in biopsy results (P=0.001), and the conventional group had a higher positive rate. The PV of comprehensive group was larger than that of the conventional group. Among the prostate cancer patients diagnosed by biopsy, statistical analysis between the conventional group and comprehensive group showed that there were not significant differences in International Society of Urological Pathology (ISUP) grade and distinguishing clinically significant prostate cancer (all P > 0.05). Logistic univariate analysis showed that the diagnosis of prostate cancer was related to age, tPSA, f/tPSA, PV and DCE group status (all P < 0.05). Multivariate analysis showed that age, tPSA, PV and DCE group status (all P < 0.05) were independent risk factors for the diagnosis of prostatic cancer. CONCLUSION: tPSA, f/tPSA, PV and PSAD are the indicators to improve the diagnosis of prostatic cancer with PI-RADS 4 lesion in peripheral zone lesions. DCE status is worth considering, so that we can select patients for biopsy more accurately, reduce the rate of missed diagnosis of prostate cancer as well as avoid unnecessary prostate puncture.

Multimodal recurrence scoring system for prediction of clear cell renal cell carcinoma outcome: a discovery and validation study.

BACKGROUND: Improved markers for predicting recurrence are needed to stratify patients with localised (stage I-III) renal cell carcinoma after surgery for selection of adjuvant therapy. We developed a novel assay integrating three modalities-clinical, genomic, and histopathological-to improve the predictive accuracy for localised renal cell carcinoma recurrence. METHODS: In this retrospective analysis and validation study, we developed a histopathological whole-slide image (WSI)-based score using deep learning allied to digital scanning of conventional haematoxylin and eosin-stained tumour tissue sections, to predict tumour recurrence in a development dataset of 651 patients with distinctly good or poor disease outcome. The six single nucleotide polymorphism-based score, which was detected in paraffin-embedded tumour tissue samples, and the Leibovich score, which was established using clinicopathological risk factors, were combined with the WSI-based score to construct a multimodal recurrence score in the training dataset of 1125 patients. The multimodal recurrence score was validated in 1625 patients from the independent validation dataset and 418 patients from The Cancer Genome Atlas set. The primary outcome measured was the recurrence-free interval (RFI). FINDINGS: The multimodal recurrence score had significantly higher predictive accuracy than the three single-modal scores and clinicopathological risk factors, and it precisely predicted the RFI of patients in the training and two validation datasets (areas under the curve at 5 years: 0·825-0·876 vs 0·608-0·793; p<0·05). The RFI of patients with low stage or grade is usually better than that of patients with high stage or grade; however, the RFI in the multimodal recurrence score-defined high-risk stage I and II group was shorter than in the low-risk stage III group (hazard ratio [HR] 4·57, 95% CI 2·49-8·40; p<0·0001), and the RFI of the high-risk grade 1 and 2 group was shorter than in the low-risk grade 3 and 4 group (HR 4·58, 3·19-6·59; p<0·0001). INTERPRETATION: Our multimodal recurrence score is a practical and reliable predictor that can add value to the current staging system for predicting localised renal cell carcinoma recurrence after surgery, and this combined approach more precisely informs treatment decisions about adjuvant therapy. FUNDING: National Natural Science Foundation of China, and National Key Research and Development Program of China.

Aryl-to-Vinyl 1,4-Nickel Migration/Reductive Cross-Coupling Reaction for the Stereoselective Synthesis of Multisubstituted Olefins.

The aryl-to-vinyl nickel 1,4-migration (1,4-Ni migration) reaction has been reported for the first time. The generated alkenyl Ni species undergo a reductive coupling reaction with unactivated brominated alkanes affording a series of trisubstituted olefins. This tandem reaction exhibits mild conditions, a broad substrate scope, high regioselectivity, and excellent Z/E stereoselectivity. A series of controlled experiments have shown that the critical 1,4-Ni migration process is reversible. In addition, the alkenyl nickel intermediates obtained after migration are highly Z/E stereoselective and do not undergo Z/E isomerization. The obtained trace isomerization products are caused by the instability of the product.

Long-term safety and efficacy of fecal microbiota transplantation in 74 children: A single-center retrospective study.

Background: Fecal microbiota transplantation (FMT) is an effective treatment for intestinal and extra-intestinal disorders. Nonetheless, long-term safety and efficacy remain major challenges for FMT applications. To date, few long-term follow-up studies have been published on FMT in children. Methods: Retrospective reviewed the medical charts of 74 patients who underwent 508 FMT courses between August 2014 and July 2019 at our medical center. All the FMT procedures followed uniform standards. Baseline characteristics pre-FMT and follow-up data were collected at 1, 3, 6, 12, 36, 60, and 84 months after FMT. All potential influencing factors for adverse events (AEs) were analyzed and assessed using regression analyses. Results: A total of 70 (13.7%) short-term AEs occurred in twenty-six patients (35.1%). Most AEs (88.5%) occurred within 2 days post-FMT. A total of 91.4% of the AEs were self-limiting. Ulcerative colitis (UC) and within four times of FMT were associated with a higher rate of AEs (p = 0.028 and p = 0.021, respectively). The primary clinical remission rate after FMT was as high as 72.9%. Twenty-five children were followed for more than 5 years after FMT. The clinical remission rates gradually decreased over time after FMT. During follow-up, none of the patients developed autoimmune, metabolic, or rheumatologic disorders or tumor-related diseases. However, nine children developed rhinitis, five developed rhinitis, were underweight, and six developed constipation. Conclusions: FMT is a safe and effective treatment for dysbiosis in children. The long-term efficacy of FMT for each disease decreased over time. Moreover, multiple FMTs are recommended 3 months post-FMT for recurrent diseases.

Laparoscopic Glissonian pedicle versus hilar dissection approach hemihepatectomy: A prospective, randomized controlled trial.

BACKGROUND/PURPOSE: This over 7-year case study is the first to compare the results of laparoscopic Glissonian pedicle approach hemihepatectomy (LGAH) and laparoscopic hilar dissection approach hemihepatectomy (LHAH) in a randomized controlled trial (RCT). METHODS: Patients who had undergone laparoscopic hemihepatectomy, either LGAH or LHAH, between March 2012 and December 2019 at our center were prospectively enrolled and assigned to the LGAH or LHAH group. Both groups were stratified and compared, and the preoperative and follow-up outcomes were analyzed. The primary endpoint was total operative time. RESULTS: The groups were equally matched for age, sex, HBsAg, Child-Pugh class, benign disease, malignancy, liver cirrhosis, tumor diameter and type of resection. Ninety-six patients had undergone LGAH and 94 had undergone LHAH. No preoperative death occurred in the two groups. LGAH did not enhance the postoperative overall complication rates (P = .465) or intraoperative blood loss (P = .535) compared with LHAH. However, the overall operative time (P = .014) and hilar dissection time (P = .000) were significantly shorter in the LGAH group than in the LHAH group. No significant differences were found between the groups regarding the 1-year (P = .384), 3-year (P = .332), and 5-year overall survival rates (P = .662) or 1-year (P = .856), 3-year (P = .348), and 5-year disease-free survival rates (P = .573). CONCLUSIONS: LGAH and LHAH are both effective procedures for treating the hilar structures in selected patients. LGAH has advantages over LHAH in reducing total operation time under the condition where both procedures can be used. LGAH for selected patients is worthy of promotion owing to its simplicity and convenience. REGISTRATION NUMBER: NCT01567631 (http://www. CLINICALTRIALS: gov).

Laparoscopic middle-hepatic-vein-guided anatomical hemihepatectomy in the treatment of hepatolithiasis: a 10-year case study.

BACKGROUND: This retrospective 10-year case study evaluated the perioperative results and long-term efficacy of laparoscopic middle-hepatic-vein-guided hemihepatectomy (L-MHV-H) and traditional anatomical hemihepatectomy (TAH) in the treatment of hepatolithiasis (HL). METHODS: From January 2010 to December 2019, 99 patients with regional HL underwent laparoscopic anatomical hemihepatectomy (LAH) at our centre, including 43 patients in the L-MHV-H group and 56 patients in the TAH group. RESULTS: All patients in both groups were Child-Pugh grade A before operation. No significant between-group differences in general information, stone distribution, comorbidities, history of previous abdominal surgery or co-occurrence of gallstones and common bile duct stones were observed. The L-MHV-H group exhibited a higher intraoperative stone clearance rate (95.3% vs. 75.0%, p = 0.014) and a lower postoperative complication rate (10.1% vs. 48.2%, p = 0.005) compared with the TAH group. In the median follow-up time of 60 months (range 6-125 months), the L-MHV-H group had lower stone recurrence (2.3% vs. 19.6%, p = 0.013) and cholangitis recurrence (2.3% vs. 17.9%, p = 0.034) rates. No significant between-group differences in the other results were observed. CONCLUSIONS: L-MHV-H is safe and feasible for HL with certain advantages over TAH in improving the intraoperative stone clearance rate, reducing postoperative complication incidence and reducing stone and cholangitis recurrence rates.

Laparoscopic anterior hepatic transection for resecting lesions originating in the paracaval portion of the caudate lobe (with videos).

BACKGROUND: The paracaval portion of the caudate lobe is located in the core of the liver. Lesions originating in the paracaval portion often cling to or even invade major hepatic vascular structures. The traditional open anterior hepatic transection approach has been adopted to treat paracaval-originating lesions. With the development of laparoscopic surgery, paracaval-originating lesions are no longer an absolute contraindication for laparoscopic liver resection. This study aimed to evaluate the safety and feasibility of laparoscopic anterior hepatic transection for resecting paracaval-originating lesions. METHODS: This study included 15 patients who underwent laparoscopic anterior hepatic transection for paracaval-originating lesion resection between August 2017 and April 2020. The perioperative indicators, follow-up results, operative techniques and surgical indications were retrospectively evaluated. RESULTS: All patients underwent laparoscopic anterior hepatic transection for paracaval-originating lesion resection. The median operation time was 305 min (220-740 min), the median intraoperative blood loss was 400 ml (250-3600 ml), and the median length of postoperative hospital stay was 9 days (5-20 days). No conversion to laparotomy or perioperative deaths occurred. Six patients had Clavien grade III-IV complications (III/IV, 5/1). Two patients developed tumor recurrence after 13 months and 8 months. CONCLUSION: Although technically challenging, laparoscopic anterior hepatic transection is still a safe and feasible procedure for resecting paracaval-originating lesions in select patients.

Guanosine-5'-triphosphate cyclohydrolase 1 regulated long noncoding RNAs are potential targets for microglial activation in neuropathic pain.

Several studies have confirmed that microglia are involved in neuropathic pain. Inhibition of guanosine-5'-triphosphate cyclohydrolase 1 (GTPCH1) can reduce the inflammation of microglia. However, the precise mechanism by which GTPCH1 regulates neuropathic pain remains unclear. In this study, BV2 microglia were transfected with adenovirus to knockdown GTPCH1 expression. High throughput sequencing analysis revealed that the mitogen-activated protein kinase (MAPK) related pathways and proteins were the most significantly down-regulated molecular function. Co-expression network analysis of Mapk14 mRNA and five long noncoding RNAs (lncRNAs) revealed their correlation. Quantitative reverse transcription-polymerase chain reaction revealed that among five lncRNAs, ENSMUST00000205634, ENSMUST00000218450 and ENSMUST00000156079 were related to the downregulation of Mapk14 mRNA expression. These provide some new potential targets for the involvement of GTPCH1 in neuropathic pain. This study is the first to note the differential expression of lncRNAs and mRNA in GTPCH1 knockdown BV2 microglia. Findings from this study reveal the mechanism by which GTPCH1 activates microglia and provide new potential targets for microglial activation in neuropathic pain.

Formaldehyde induces ferroptosis in hippocampal neuronal cells by upregulation of the Warburg effect.

The mechanisms underlying formaldehyde (FA)-induced neurotoxicity have not yet been fully clarified. Ferroptosis is a novel regulatory cell death and the Warburg effect is involved in regulating neural function. In this study, we investigated whether FA-induced neurotoxicity is implicated in neuronal ferroptosis and determined whether the Warburg effect mediates FA-induced neuronal ferroptosis. We found that FA (0.1, 0.5 and 1.0 mM, 6 h) induced cell death in HT22 cells (a cell line of mouse hippocampal neuron), as evidenced by a decrease in cell viability and an increase in cell mortality; enhanced oxidative stress, as evidenced by a decrease in glutathione (GSH) and increases in malondialdehyde (MDA), 4-Hydroxynonenal (4-HNE), as well as reactive oxygen species (ROS); increased the iron content; and upregulated the ferroptosis-associated genes, including Ptgs2 (prostaglandin-endoperoxide synthase 2), GLS2 (glutaminase 2), solute carrier family 1 member 5 (SLC1A5), and solute carrier family 38 member 1 (SLC38A1) in HT22 cells, indicating the inductive role of FA in the ferroptosis of HT22 cells. Meanwhile, we found that FA (0.1, 1, 10 µmol) decreased the cross-sectional of mitochondria, increased the level of lipid ROS and iron content in primary hippocampal cells. We showed that FA (0.1, 0.5 and 1.0 mM, 6 h) upregulated the Warburg effect in HT22 cells, as evidenced by up-regulations of pyruvate kinase M2 (PKM2), pyruvate dehydrogenase kinase 1(PDK-1), and lactate dehydrogenase (LDHA) proteins; down-regulation of pyruvate dehydrogenase (PDH); and an increase in lactate production. Also, we found that FA (0.1, 1, 10 µmol, 7 d) upregulated the Warburg effect in hippocampal tissue, as evidenced by up-regulations of PKM2, PDK-1, and LDHA proteins; down-regulation of PDH. Furthermore, the inhibition of the Warburg effect by dichloroacetate (DCA) protected HT22 cells against FA-induced ferroptosis and cell death. Collectively, these data indicated that FA induces ferroptosis in hippocampal neuronal cells by upregulation of the Warburg effect.

Serum Progesterone and Testosterone Levels in Schizophrenia Patients at Different Stages of Treatment.

It has been suggested that dysregulation of hormones is associated with schizophrenia (SCZ). This study aimed to measure the serum levels of progesterone and testosterone in 125 SCZ patients at different stages of treatment and 96 healthy control (HC) subjects. Our results showed that first-episode drug-free SCZ patients had significantly increased testosterone levels when compared with HC subjects, and chronic medication, but not short-term medication, further increased the serum testosterone levels in the patients. Further analysis suggested that the sex of the patients did not affect testosterone levels. In contrast, serum progesterone levels did not show significant differences between first-episode, drug-free SCZ patients and controls, and the antipsychotics increased progesterone levels in the male SCZ patients, but not female patients. Interestingly, our analyses demonstrated that the serum progesterone levels were negatively correlated with PANSS total score and PNASS positive score, suggesting a correlation between blood hormone levels and disease severity in SCZ patients. Taken together, our data showed differential changes in serum testosterone and progesterone levels in SCZ patients with or without antipsychotics, and our results suggest that increased sex hormone levels may be a defensive response to protect the human body under stress.

A Network Analysis of Epigenetic and Transcriptional Regulation in a Neurodevelopmental Rat Model of Schizophrenia With Implications for Translational Research.

Prenatal administration of mitotoxin methylazoxymethanol acetate (MAM) in rats produces behavioral, pharmacological, and anatomical abnormalities once offspring reach adulthood, thus establishing a widely used neurodevelopmental model of schizophrenia. However, the molecular aspects underlying this disease model are not well understood. Therefore, this study examines epigenetic and transcriptional dysregulation in the prefrontal cortex and hippocampus of MAM rats as these are brain regions closely associated with schizophrenia pathogenesis. Upon sequencing messenger and microRNA (mRNA and miRNA, respectively), differential expression was revealed in the prefrontal cortex and hippocampus between MAM- and saline-treated rats; sequencing data were validated by qualitative real-time polymerase chain reaction. Bioinformatic analyses demonstrated that the differentially expressed (DE) genes were strongly enriched in interactive pathways related to schizophrenia, including chemical synaptic transmission, cognition, and inflammatory responses; also, the potential target genes of the DE miRNAs were enriched in pathways related to synapses and inflammation. The blood of schizophrenia patients and healthy controls was further analyzed for several top DE mRNAs: DOPA decarboxylase, ret proto-oncogene, Fc receptor-like 2, interferon lambda receptor 1, and myxovirus (influenza virus) resistance 2. The results demonstrated that the expression of these genes was dysregulated in patients with schizophrenia; combining these mRNAs sufficiently differentiated schizophrenia patients from controls. Taken together, this study suggests that the MAM model has the potential to reproduce hippocampus and prefrontal cortex abnormalities, relevant to schizophrenia, at the epigenetic and transcriptional levels. These data also provide novel targets for schizophrenia diagnoses and treatments.

LncRNA SNHG16 induces the SREBP2 to promote lipogenesis and enhance the progression of pancreatic cancer.

Aim: Blocking lipogenesis could significantly inhibit the progression of pancreatic cancer. Exploring the regulatory mechanisms of lipogenesis by lncRNA SNHG16 might be of great significance to control the development of pancreatic cancer. Methods: The proliferation, migration, invasion and lipogenesis were determined with 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, wound healing, transwell and Oil Red O staining assays, respectively. The interactions among lncRNA SNHG16, miR-195 and SREBP2 were analyzed by dual luciferase reporter assays. Results: Both the knock down of lncRNA SNHG16 and SREBP2 and overexpression of miR-195 suppressed the proliferation, migration, invasion and lipogenesis in pancreatic cancer cells. LncRNA SNHG16 directly sponged miR-195 to modulate the lipogenesis via regulating the expression of SREBP2. Conclusion: LncRNA SNHG16 accelerated the development of pancreatic cancer and promoted lipogenesis via directly regulating miR-195/SREBP2 axis.

Uterus globulin associated protein 1 (UGRP1) is a potential marker of progression of Graves' disease into hypothyroidism.

Approximately 20% of Graves' disease (GD) patients may result eventually in hypothyroidism in their natural course. Uterus globulin-associated protein 1 (UGRP1) was associated with GD in our previous study. Here we investigated the role of UGRP1 in the development of autoimmune thyroid disease (AITD). The results showed that UGRP1 was expressed in the thyrocytes of most Hashimoto's thyroiditis (HT) patients and a proportion of GD patients (293 HT and 198 GD). The pathologic features of UGRP1-positive thyrocytes resembled "Hürthle cells", and were surrounded by infiltrated leukocytes. The positivity rate of TPOAb in UGRP1-positive GD patients was much higher than that in -negative GD patients. Moreover, UGRP1 was co-expressed with Fas and HLA-DR in the thyrocytes of AITD patients. We also found IL-1ß but not Th1 or Th2 cytokines was able to upregulate the expression of UGRP1. Our findings indicated that UGRP1 may be a novel marker in thyrocytes to predict GD patients who develop hypothyroidism.

DDD score for renal tumor: An intuitive and comprehensive anatomical scoring system to access the outcomes of retroperitoneal laparoscopic partial nephrectomy.

OBJECTIVE: To present a DDD scoring system in assessing the complexity and outcomes of retroperitoneoscopic nephron-sparing surgery for kidney tumor. METHODS: We retrospectively evaluated 232 patients who underwent retroperitoneoscopic nephron-sparing surgery between January 2013 and September 2017 for a renal tumor. Both the DDD score and RENAL score were used to classify the tumors. The DDD score consisted of the maximal tumor diameter inside the kidney, the maximal tumor depth into the medulla or collecting system and the minimal distance from the tumor to the main renal vessels. RESULTS: The DDD scoring systems were significantly associated with warm ischemia time (P = 0.007) and estimated blood loss (P = 0.017). There was an insignificant positive correlation between the DDD score and the operative time (P = 0.051). Meanwhile, the RENAL score had a significant correlation with the decreasing value of the estimated glomerular filtration rate. Patients with high or moderate DDD scores had a 13.6-fold or 8.4-fold risk of overall complications than those with low DDD scores, respectively (all P < 0.05). As for RENAL score, patients with moderate scores had a 2.9-fold risk of overall complications compared with patients in the low scores group (P = 0.004). In the receiver operating characteristic curve analysis, the DDD score had the greatest area under the curve for overall complications (area under the curve 0.625, P = 0.009), which was more than the RENAL score (area under the curve 0.620, P = 0.013). CONCLUSIONS: The DDD score is an intuitive renal tumor scoring system that is more effective than the RENAL score in complexity assessment, and marginally better in prediction of the risk of overall complications of retroperitoneal laparoscopic nephron-sparing surgery.

Segmental ureterectomy can be performed safely in patients with urothelial carcinoma of distal ureter.

INTRODUCTION: We aimed to compare oncological outcomes by surgery type (segmental ureterectomy [SU] vs. radical nephroureterectomy [RNU]) in a large cohort of patients with upper tract urothelial carcinoma (UTUC) of the distal ureter. METHODS: We performed a retrospective analysis of 219 patients with UTUC of the distal ureter among 931 patients with UTUC who underwent SU and RNU. Clinicopathological outcomes were evaluated. Cancer-specific survival (CSS), overall survival (OS), local recurrence-free survival (RFS), intravesical recurrence-free survival (IVRFS), contralateral recurrence-free survival, and distal metastasis-free survival were assessed by the Kaplan-Meier method and Cox regression, estimating hazard ratios (HR) and 95% confidence intervals (CIs). RESULTS: A total of 179 (81.7%) patients underwent RNU and 40 (18.3%) underwent SU: 85 males (47.5%) with RNU and 17 (42.5%) with SU (p=0.568). The median age with RNU and SU was 71 years (range 31-86) and 70 years (range 46-90), respectively (p=0.499). The T stage of the two groups did not differ (p=0.122), nor did mean tumour length (3.35±2.62 vs. 3.25±2.14; p=0.953), grade (p=0.075), tumour necrosis (p=0.634), or followup time (months) (58.1±8.1 vs. 63.7±3.4; p=0.462). The two groups did not differ in CSS (p=0.358) or OS (p=0.206), and surgery type did not predict CSS (HR 0.862; 95% CI 0.469-1.585; p=0.633) or OS (HR 0.764; 95% CI 0.419-1.392; p=0.379). Local RFS was higher with RNU than SU (96.2% vs. 86.0%; p=0.02), but the groups did not differ in IVRFS (p=0.661), contralateral RFS (p=0.183), or distant metastasis-free survival (p=0.078). On multivariate analysis, SU was associated with local RFS (HR 5.069; 95% CI 1.029-24.968; p=0.046) and distant metastasis-free survival (HR 6.497; 95% CI 1.196-35.283; p=0.03). Local RFS was lower with SU than RNU for patients with pT3-4 stage (p=0.006). CONCLUSIONS: Long-term oncological outcomes were equivalent with SU and RNU in patients with UTUC of the distal ureter. SU affected local recurrence survival, especially with advanced tumour stage, and distant metastasis survival.

Laparoscopic Radical Cystectomy With Extracorporeal Neobladder: Our Initial Experience.

OBJECTIVE: To illustrate our technique to construct the Institute of Urology Peking University (IUPU) orthotopic ileal bladder and present our initial experience. METHODS: From August 2017 to April 2018, 12 patients with bladder cancer underwent radical cystectomy (RC), pelvic lymph node dissection and extracorporeal construction of an IUPU neobladder (IUPUB) by an experienced surgeon. We present the demographic, clinicopathologic, perioperative, and follow-up data. We also describe our step-by-step surgical technique for the IUPUB in this article. RESULTS: Laparoscopic RC with an extracorporeal IUPUB was successfully accomplished in 11 patients, and 1 patient was converted to open RC with an IUPUB. The median total operative time and median time spent suturing the pouch were 248 minutes and 23 minutes, respectively. The median estimated blood loss was 150 mL. The median time to recovery of bowel function (tolerance of a liquid diet) was 3½ days. The urinary catheter was removed on post-operative day 21 in 10 patients. The ureteral stents and stoma catheter were removed on day 7 after cystography. At a median followup of 7½ months, 2 patients had early complications (<30 days), and no major complications (grade ≥ 3) occurred. The follow-up outcomes were satisfactory. The limitations included the small sample size and short-term outcomes. CONCLUSION: Our technique of constructing the IUPUB is feasible and safe. The operative time and early complication rates are acceptable.

The significance of the initial symptom in Chinese patients with upper tract urothelial carcinoma: Regular health examination is still underutilized.

This paper is to elucidate the correlation between different symptoms of UTUC and the clinicopathological characteristics and prognosis. The clinicopathological data of 700 consecutive patients with UTUC who were treated with radical nephroureterectomy were reviewed, and symptoms were categorized into three groups: S1-no direct symptoms, S2-local symptoms (including hematuria and flank pain) and S3-systemic symptoms. We found that the distributions of patients in the S1, S2 and S3 groups were 96 (13.7%), 601 (85.9%) and 3 (0.4%), respectively, and most patients in S1 were incidentally found to have abnormal findings on ultrasound during regular health examination. Altogether, 534 patients (76.3%) presented with gross hematuria, and 111 (15.9%) presented with flank pain. Patients in S1 had a higher rate of hydronephrosis (p < 0.001), ureteral tumors (p < 0.001), worse pre-operative renal function (p = 0.020) and lower tumor stage (p = 0.038). The presence of hematuria was significantly related with renal pelvic tumors (p < 0.001), higher pre-operative eGFR (p = 0.047), papillary tumor architecture (p = 0.005) and less hydronephrosis (p < 0.001); and the presentation of flank pain was correlated with older age (p = 0.008), ureteral location (p < 0.001), hydronephrosis (p < 0.001), sessile architecture (p < 0.001) and higher tumor grade (p = 0.003). The presence of hematuria or flank pain also failed to reach significance as an independent prognostic factor. In conclusion, asymptomatic UTUC patients are featured for more hydronephrosis and lower tumor stage, while patients who presented with flank pain had a higher risk of sessile architecture and higher tumor grade. Regular health examinations might play a useful role in the early detection of UTUC patients with no symptoms.