Clinical analysis of prophylactic para-aortic intensity-modulated radiation in cervical cancer.

AIM: This study aimed to compare the survival and toxicity of patients with International Federation of Gynecology and Obstetrics (FIGO) 2009 stage IB1-IIIC cervical cancer without common iliac node metastasis treated with extended-field intensity-modulated radiotherapy (EF-IMRT) or pelvic IMRT (P-IMRT). MATERIALS AND METHODS: Thirty-one patients treated with EF-IMRT and 37 patients who underwent P-IMRT were analysed retrospectively. Both groups were treated with high-dose-rate 192Ir two-dimensional brachytherapy and concurrent chemotherapy. The chi-square test and Kaplan-Meier method were used to compare toxicity and survival between the two groups. RESULTS: The median follow-up time of EF-IMRT group and P-IMRT group was 22 and 30 months, respectively. The 3-year overall survival (OS), progression-free survival (PFS), and para-aortic lymph node metastasis-free survival (PAMFS) in the EF-IMRT group and P-IMRT group were 87% versus 74.6%, 83.6% versus 61.7%, and 96% versus 80.5%, respectively. Treatment regimens, tumour size, and radiation time were independent prognostic factors of OS and PFS. Treatment regimens, tumour size, and total equivalent dose in 2 Gy/f (EQD2) of point A were independent prognostic factors of PAMFS. Five patients in the EF-IMRT group and 14 patients in P-IMET group experienced treatment failure. The cumulative incidence of grade 3 and 4 acute leukopenia in the EF-IMRT group was 51.6%, in comparison with 27.03% in the pelvic group. No difference was found in thrombocytopenia between two groups. CONCLUSIONS: Patients with FIGO 2009 stage IB1-IIIC cervical cancer without common iliac node metastases may be benefit from EF-IMRT. Notably, EF-IMRT exhibits increased toxicity incidence; however, this remains within an acceptable range.

First-Line Therapy for Type 2 Diabetes With Sodium-Glucose Cotransporter-2 Inhibitors and Glucagon-Like Peptide-1 Receptor Agonists : A Cost-Effectiveness Study.

BACKGROUND: Guidelines recommend sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP1) receptor agonists as second-line therapy for patients with type 2 diabetes. Expanding their use as first-line therapy has been proposed but the clinical benefits may not outweigh their costs. OBJECTIVE: To evaluate the lifetime cost-effectiveness of a strategy of first-line SGLT2 inhibitors or GLP1 receptor agonists. DESIGN: Individual-level Monte Carlo-based Markov model. DATA SOURCES: Randomized trials, Centers for Disease Control and Prevention databases, RED BOOK, and the National Health and Nutrition Examination Survey. TARGET POPULATION: Drug-naive U.S. patients with type 2 diabetes. TIME HORIZON: Lifetime. PERSPECTIVE: Health care sector. INTERVENTION: First-line SGLT2 inhibitors or GLP1 receptor agonists. OUTCOME MEASURES: Life expectancy, lifetime costs, incremental cost-effectiveness ratios (ICERs). RESULTS OF BASE-CASE ANALYSIS: First-line SGLT2 inhibitors and GLP1 receptor agonists had lower lifetime rates of congestive heart failure, ischemic heart disease, myocardial infarction, and stroke compared with metformin. First-line SGLT2 inhibitors cost $43 000 more and added 1.8 quality-adjusted months versus first-line metformin ($478 000 per quality-adjusted life-year [QALY]). First-line injectable GLP1 receptor agonists cost more and reduced QALYs compared with metformin. RESULTS OF SENSITIVITY ANALYSIS: By removing injection disutility, first-line GLP1 receptor agonists were no longer dominated (ICER, $327 000 per QALY). Oral GLP1 receptor agonists were not cost-effective (ICER, $823 000 per QALY). To be cost-effective at under $150 000 per QALY, costs for SGLT2 inhibitors would need to be under $5 per day and under $6 per day for oral GLP1 receptor agonists. LIMITATION: U.S. population and costs not generalizable internationally. CONCLUSION: As first-line agents, SGLT2 inhibitors and GLP1 receptor agonists would improve type 2 diabetes outcomes, but their costs would need to fall by at least 70% to be cost-effective. PRIMARY FUNDING SOURCE: American Diabetes Association.

[Diagnosis and treatment of blunt high-grade pancreatic trauma].

The clinical data of 20 patients with blunt high-grade pancreatic trauma who were admitted to the Department of Hepatobiliary and Pancreatic Surgery of Changhai Hospital Affiliated to Naval Military Medical University from December 2003 to February 2022 were retrospectively analyzed. There were 15 males and 5 females with a median age of 39 years (range: 14-54 years). The degree of pancreatic injury was graded according to the American Association for the Surgery of Trauma (AAST) scale, including 10 cases of grade Ⅲ (50%), 8 cases of grade Ⅳ (40%), and 2 cases of grade Ⅴ (10%). Then, the strategy of diagnosis and treatment for blunt high-grade pancreatic trauma was summarized. The diagnostic rate of CT was 78.9%. Finally, 17 cases (85%) were cured and 3 cases (15%) died. Among the 10 patients with grade Ⅲ pancreatic injury, 7 cases received distal pancreatectomy and splenectomy, 1 case received distal pancreatectomy with spleen preserved, 1 case received pancreatic duct stent placement under endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous catheter drainage (PCD), and 1 case received only PCD. Among 8 cases of grade Ⅳ, 3 cases underwent Roux-en-Y pancreaticojejunostomy, 1 case received distal pancreatectomy and splenectomy, 1 case underwent distal pancreatectomy with spleen preserved, 2 cases received necrotic tissue removal+external drainage of pancreatic duct+abdominal drainage, and 1 case received exploratory laparotomy and gauze packing hemostasis. For 2 cases of grade Ⅴ, 1 underwent pylorus preserving pancreaticoduodenectomy, and the other case underwent pancreaticoduodenectomy combined with right hemicolectomy and splenectomy. Therefore, the treatment of blunt high-grade pancreatic trauma should follow the individualized treatment strategy, pay attention to the control of bleeding, extensive external drainage, appropriate debridement and resection and rational application of damage control surgery, select appropriate patients for conservative treatment, and ultimately benefit the patient.

[Establishment of the quality assessment system for pancreatic cancer surgery: from "single complication assessment" to "textbook outcome"].

With the development of neoadjuvant therapy and a multidisciplinary team, the treatment of pancreatic cancer has gradually expanded from "resection" to "cure"."Curative resection" as the core part of the integrated treatment model for patients, its quality directly determines the short-term outcome and affects the long-term prognosis. Previously, the "single complication assessment" model was used to measure the quality of pancreatic cancer surgery. However, the incidence of any specific complication cannot cover the entire surgical procedure, making it difficult to quantify and standardize the interpretation of the outcomes. Recently, the concept of textbook outcome, a comprehensive indicator, has gained popularity in surgical research. Textbook outcome includes multiple complication parameters and reflects optimal surgical outcomes in an "all or none" approach. Implementing a quality improvement program that focuses on textbook outcome will increase the overall standard of complex surgery, ultimately advancing the surgical care of pancreatic cancer in the future. In this article, the latest advances in relevant research are analyzed to provide a brief overview of the textbook outcome of pancreatic cancer.

[Quality assessment indictors and benchmarks for pancreatic surgery].

Pancreatic surgery is the most complex type of abdominal surgery,with high technical requirements and long learning curve,and the quality of surgery is directly related to the prognosis of the patients. In recent years,more and more indicators have been used to evaluate the quality of pancreatic surgery,such as operation time,intraoperative blood loss,morbidity,mortality, prognosis and so on,and different evaluation systems have been established,including benchmarking,auditing,outcome evaluation based on risk factor adjustment and textbook outcomes. Among them,the benchmark is the most widely used to evaluate surgical quality and is expected to become the standard for comparison among peers. This article reviews existing quality evaluation indicators and benchmarks for pancreatic surgery and anticipates its future application prospects.

Shisa6 mediates cell-type specific regulation of depression in the nucleus accumbens.

Depression is the leading cause of disability and produces enormous health and economic burdens. Current treatment approaches for depression are largely ineffective and leave more than 50% of patients symptomatic, mainly because of non-selective and broad action of antidepressants. Thus, there is an urgent need to design and develop novel therapeutics to treat depression. Given the heterogeneity and complexity of the brain, identification of molecular mechanisms within specific cell-types responsible for producing depression-like behaviors will advance development of therapies. In the reward circuitry, the nucleus accumbens (NAc) is a key brain region of depression pathophysiology, possibly based on differential activity of D1- or D2- medium spiny neurons (MSNs). Here we report a circuit- and cell-type specific molecular target for depression, Shisa6, recently defined as an AMPAR component, which is increased only in D1-MSNs in the NAc of susceptible mice. Using the Ribotag approach, we dissected the transcriptional profile of D1- and D2-MSNs by RNA sequencing following a mouse model of depression, chronic social defeat stress (CSDS). Bioinformatic analyses identified cell-type specific genes that may contribute to the pathogenesis of depression, including Shisa6. We found selective optogenetic activation of the ventral tegmental area (VTA) to NAc circuit increases Shisa6 expression in D1-MSNs. Shisa6 is specifically located in excitatory synapses of D1-MSNs and increases excitability of neurons, which promotes anxiety- and depression-like behaviors in mice. Cell-type and circuit-specific action of Shisa6, which directly modulates excitatory synapses that convey aversive information, identifies the protein as a potential rapid-antidepressant target for aberrant circuit function in depression.

Helicobacter pylori Immunoproteomic Profiles in Gastric Cancer.

Chronic Helicobacter pylori infection is the major risk factor for gastric cancer (GC). However, only some infected individuals develop this neoplasia. Previous H. pylori serology studies have been limited by investigating small numbers of candidate antigens. Therefore, we evaluated humoral responses to a nearly complete H. pylori immunoproteome (1527 proteins) among 50 GC cases and 50 controls using Nucleic Acid Programmable Protein Array (NAPPA). Seropositivity was defined as median normalized intensity ≥2 on NAPPA, and 53 anti-H. pylori antibodies had >10% seroprevalence. Anti-GroEL exhibited the greatest seroprevalence (77% overall), which agreed well with ELISA using whole-cell lysates of H. pylori cells. After an initial screen by H. pylori-NAPPA, we discovered and verified that 12 antibodies by ELISA in controls had ≥15% of samples with an optical reading value exceeding the 95th percentile of the GC group. ELISA-verified antibodies were validated blindly in an independent set of 100 case-control pairs. As expected, anti-CagA seropositivity was positively associated with GC (odds ratio, OR = 5.5; p < 0.05). After validation, six anti-H. pylori antibodies showed lower seropositivity in GC, with ORs ranging from 0.44 to 0.12 (p < 0.05): anti-HP1118/Ggt, anti-HP0516/HsIU, anti-HP0243/NapA, anti-HP1293/RpoA, anti-HP0371/FabE, and anti-HP0875/KatA. Among all combinations, a model with anti-Ggt, anti-HslU, anti-NapA, and anti-CagA had an area under the curve of 0.73 for discriminating GC vs. controls. This study represents the first comprehensive assessment of anti-H. pylori humoral profiles in GC. Decreased responses to multiple proteins in GC may reflect mucosal damage and decreased bacterial burden. The higher prevalence of specific anti-H. pylori antibodies in controls may suggest immune protection against GC development.

Uncovering metabolic reservoir cycles in MYC-transformed lymphoma B cells using stable isotope resolved metabolomics.

The use of metabolomic technologies and stable isotope labeling recently enabled us to discover an unexpected role of N-acetyl-aspartyl-glutamate (NAAG): NAAG is a glutamate reservoir for cancer cells. In the current study, we first found that glucose carbon contributes to the formation of NAAG and its precursors via glycolysis, demonstrating the existence of a glucose-NAAG-glutamate cycle in cancer cells. Second, we found that glucose carbon and, unexpectedly, glutamine carbon contribute to the formation of lactate via glutaminolysis. Importantly, lactate carbon can be incorporated into glucose via gluconeogenesis, demonstrating the existence of a glutamine-lactate-glucose cycle. While a glucose-lactate-glucose cycle was expected, the finding of a glutamine-lactate-glucose cycle was unforeseen. And third, we discovered that glutamine carbon is incorporated into γ-aminobutyric acid (GABA), revealing a glutamate-GABA-succinate cycle. Thus, NAAG, lactate, and GABA can play important roles as storage molecules for glutamate, glucose, and succinate carbon in oncogenic MYC-transformed P493 lymphoma B cells (MYC-ON cells) but not in non-oncogenic MYC-OFF cells. Altogether, examining the isotopic labeling patterns of metabolites derived from labeled 13C6-glucose or 13C515N2-glutamine helped reveal the presence of what we have named "metabolic reservoir cycles" in oncogenic cells.

Effect of Interleukin-17 gene on glomerular ultrastructure and podocyte injury in adriamycin nephropathy rat models.

The aim of this study was to investigate the mechanism of interleukin-17 (IL-17) gene in renal tissues of rats suffering from adriamycin (ADM) nephropathy and its effect on the expression level of characteristic proteins, such as Podocalyxin and Nephrin, in podocytes. Sprague-Dawley (SD) rats were randomly divided into a control group (treated with normal saline) and an ADM group (treated with adriamycin). ADM model rats were transfected with lentivirus and divided into a transfection group (transfected with recombinant plasmid IL-17-shRNA) and a negative control group (transfected with plasmid shNC). Coomassie brilliant blue G-250 (CBB) method was adopted to detect the levels of albumin in urine to validate the model. The ultrastructure of rat glomeruli was observed, and the ratio of T helper 17 cells/regulatory T cells (Th17/Treg) was measured by flow cytometry (FCM). The expression levels of IL-17, forkhead box P3 (Foxp3), Nephrin, and Podocalyxin were detected by real-time quantitative PCR (RT-qPCR) and western blot analysis. Results of the study showed that the proteinuria content of the ADM group was significantly higher than that of the control group (P<0.05). In the ADM group, the glomerular basement membrane had uneven thickness and incomplete structure, which showed foot process fusion and electron dense accumulation. However, the glomerular basal membrane in the transfected rats was thin and intact, and a small amount of epithelial foot process fusion and electron density accumulation were observed. The percentages of Th17 cells and IL-17 levels in the ADM group were significantly higher than those in the control group, while the percentages of Treg cells, Foxp3, Nephrin, and Podocalyxin levels were significantly lower than those in the control group (P<0.05). The percentages of Th17 cells, IL-17, Nephrin, and Podocalyxin in the transfection group were significantly higher than those in the ADM group and the negative control group, while the percentages of Treg cells and Foxp3 were significantly lower than those in the ADM group and the negative control group (P<0.05). The results of this study showed that abnormal activation of Th17/IL-17 cells caused podocyte injury and promoted the occurrence and progression of ADM nephropathy. In addition, inhibition of IL-17 gene expression could improve the imbalance of number of Th17 and Treg cells, which may be potentially applied in treatment of patients with primary nephrotic syndrome (PNS).

Identification of hub genes and pathways in the development of gastric cancer by gene co­expression network analysis.

There are many risk factors for gastric cancer (GC), including chronic atrophic gastritis, which involves multiple genes and signaling pathways. Weighted gene co-expression network analysis (WGCNA) was performed on GSE111762 to construct free-scale gene co-expression networks and identified four significant modules that consisted of blue, dark orange, dark red and dark violet. In each module, genes with the most connectivity were selected as hub genes, including G antigen 12J (GAGE12J) in blue, proline, histidine and glycine rich 1 (PHGR1) in dark orange, DNA polymerase gamma 2, accessory subunit (POLG2) in dark red and collagen type XXI alpha 1 chain (COL21A1) in dark violet. The transcription level of COL21A1 and GAGE12J was up-regulated in atrophic gastritis vs normal gastric mucosa, but down-regulated in GC vs atrophic gastritis. PHGR1 was consistently down-regulated from normal gastric mucosa to GC, while POLG2 was up-regulated. Gene set enrichment analysis (GSEA) was then conducted to study the biological functions of hub genes in the development of GC. It showed that multiple tumorigenesis-related pathways were enriched, including peroxisome, DNA repair and KRAS signaling pathway in COL21A1, IL6-JAK-STAT3, epithelial mesenchymal transition (EMT) and TNFα-NF-κB signaling pathway in PHGR1, MYC targets, E2F targets and angiogenesis in POLG2 and peroxisome, Notch signaling pathway and androgen response in GAGE12J. The identified four genes, especially for COL21A1, PHGR1 and POLG2, were important in GC tumorigenesis and affected many cancer-related pathways.

Metabolism of Immune Cells in the Tumor Microenvironment.

The tumor microenvironment (TME) is a complex biological structure surrounding tumor cells and includes blood vessels, immune cells, fibroblasts, adipocytes, and extracellular matrix (ECM) [1, 2]. These heterogeneous surrounding structures provide nutrients, metabolites, and signaling molecules to provide a cancer-friendly environment. The metabolic interplay between immune cells and cancer cells in the TME is a key feature not only for understanding tumor biology but also for discovering cancer cells' vulnerability. As cancer immunotherapy to treat cancer patients and the use of metabolomics technologies become more and more common [3], the importance of the interplay between cancer cells and immune cells in the TME is emerging with respect to not only cell-to-cell interactions but also metabolic pathways. This interaction between immune cells and cancer cells is a complex and dynamic process in which immune cells act as a determinant factor of cancer cells' fate and vice versa. In this chapter, we provide an overview of the metabolic interplay between immune cells and cancer cells and discuss the therapeutic opportunities as a result of this interplay in order to define targets for cancer treatment. It is important to understand and identify therapeutic targets that interrupt this cancerpromoting relationship between cancer cells and the surrounding immune cells, allowing for maximum efficacy of immune checkpoint inhibitors as well as other genetic and cellular therapies.

Targeting Metabolic Cross Talk Between Cancer Cells and Cancer-Associated Fibroblasts.

Although cancer has classically been regarded as a genetic disease of uncontrolled cell growth, the importance of the tumor microenvironment (TME) [1, 2] is continuously emphasized by the accumulating evidence that cancer growth is not simply dependent on the cancer cells themselves [3, 4] but also dependent on angiogenesis [5-8], inflammation [9, 10], and the supporting roles of cancer-associated fibroblasts (CAFs) [11-13]. After the discovery that CAFs are able to remodel the tumor matrix within the TME and provide the nutrients and chemicals to promote cancer cell growth [14], many studies have aimed to uncover the cross talk between cancer cells and CAFs. Moreover, a new paradigm in cancer metabolism shows how cancer cells act like "metabolic parasites" to take up the high-energy metabolites, such as lactate, ketone bodies, free fatty acids, and glutamine from supporting cells, including CAFs and cancer-associated adipocytes (CAAs) [15, 16]. This chapter provides an overview of the metabolic coupling between CAFs and cancer cells to further define the therapeutic options to disrupt the CAF-cancer cell interactions.

[Diagnostic efficacy for predicting intraductal papillary mucinous neoplasms of the pancreas with high grade dysplasia or invasive carcinoma based on the surgery indications in different guidelines].

Objective: To evaluate the performance of the European Evidence-based Guidelines on Pancreatic Cystic Neoplasms (EEGPCN)(2018) and International Association of Pancreatology(IAP) Guideline(Version 2017) in predicting high grade dysplasia/invasive carcinoma-intraductal papillary mucinous neoplasm(HGD/INV-IPMN). Methods: A retrospective analysis of 363 patients,who underwent surgical resection in Changhai Hospital affiliated to Navy Medical University from January 2012 to December 2018 and were pathologically identified as (intraductal papillary mucinous neoplasm, IPMN),was performed. The patients,including 230 males and 133 females,aging (61.7±10.1) years(range:19 to 83 years). The proportion of HGD/INV-IPMN who met with the absolute indication(AI) of EEGPCN and high risk stigma(HRS) of IAP were compared. The binary Logistic regression analysis was used to find the independent risk factors of HGD/INV-IPMN.Eight combinations of risk factors derived from relative indication/worrisome feature or risk factors in this study,were made to evaluate the diagnostic efficacy. The area under curve(AUC) of receiver operating characteristics was used to evaluate the the cutoff value of risk factors(①CA19-9≥37 U/ml,②diameter of main pancreatic duct 5.0-9.9 mm,③enhancing mural nodule<5 mm,④(acute) pancreatiti,⑤acyst diameter ≥40 mm,⑤bcyst diameter ≥30 mm, ⑥thickened or enhancing cyst walls,⑦neutrophile granulocyte to lymphocyte ratio(NLR)≥2, ⑧cyst located in head, uncinate or neck,⑨carcinoembryonic antigen(CEA) ≥5 µg/L) number for predicting HGD/INV-IPMN.The accuracy,sensitivity,specificity,positive predictive value,negative predictive value,true positive,true negative,false positive,false negative,positive likelihood ratio,negative likelihood ratio,Youden index and F1 score were calculated. Results: Ninety-two patients(49.5%) of 186 ones who met AI and 85 patients(48.3%) of 176 ones who met HRS were respectively confirmed as HGD/INV-IPMN. In those patients who were not met AI,tumor location,thickened/enhancing cyst wall,CA19-9 elevated,NLR≥2 and CEA elevated were significantly (P<0.05) correlated with HGD/INV-IPMN. And tumor location(head/uncinate/neck vs. body/tail,OR=3.284,95%CI:1.268-8.503,P=0.014),thickened/enhancement cyst wall (with vs.without,OR=2.713,95%CI:1.177-6.252,P=0.019),CA19-9(≥37 U/L vs.<37 U/L, OR=5.086,95%CI:2.05-12.62,P<0.01) and NLR(≥2 vs.<2,OR=2.380,95%CI:1.043-5.434,P=0.039) were the independent risk factors of HGD/INV-IPMN. Patients with ≥4 risk factors of 9 in combination Ⅷ(①②③④⑤b⑥⑦⑧⑨) were diagnosed as HGD/INV-IPMN with the moderate accuracy(71.0%),moderate sensitivity (62.0%) and moderate specificity (73.0%). Patients with ≥4 risk factors of 9 in Combination Ⅶ(①②③④⑤a⑥⑦⑧⑨) were diagnosed as HGD/INV-IPMN with the highest specificity(83.0%) and patients with ≥3 risk factors of 8 in combination Ⅵ(①②③④⑤b⑥⑧⑨) were diagnosed as HGD/INV-IPMN with the highest sensitivity(74.0%). The AUC for diagnosis of HGD/INV-IPMN in combination Ⅵ,Ⅶ and Ⅷ were 0.72,0.75 and 0.75,respectively. Older patients and younger patients could respectively refer to combination Ⅶ and combination Ⅵ to improve the management of IPMN. Conclusions: Patients who meet AI of EEGPCN should undertake resection, otherwise the method we explored is recommended. The method of improvement for diagnosis of HGD/INV-IPMN is relatively applicable and efficient for decision-making of surgery, especially for younger patients with decreasing of missed diagnosis and elder patients with decreasing of misdiagnosis.

Genuine tripartite Einstein-Podolsky-Rosen steering in the cascaded nonlinear processes of third-harmonic generation.

Recently, Einstein-Podolski-Rosen (EPR) steering has important application in quantum information processing, and it has been received considerable attention because of its uniqueness. The properties of quantum steering among three output fields generated by cascaded nonlinear processes of quasi-phase-matching third-harmonic generation in an optical cavity are investigated. Based on the criteria for multipartite EPR steering which proposed by He and Reid [PRL, 111, 250403 (2013)], the genuine tripartite EPR steering among pump, second-harmonic, and third-harmonic is demonstrated. The parameters which affect the quantum property are also discussed.

Defining the gonadotrophin requirement for the selection of a single dominant follicle in cattle.

The aim was to define the pattern and physiological concentrations of FSH and LH required for the selection of a single dominant follicle in mono-ovulatory species. A series of five experiments was carried out using gonadotrophin-releasing hormone agonist-induced hypogonadal heifers. Animals were infused with different patterns of either FSH and/or LH followed by an ovulatory dose of human chorionic gonadotrophin. Follicular response was monitored by ultrasound scanning and blood samples were collected to measure concentrations of FSH, LH, oestradiol and progesterone. The main findings were: (1) physiological concentrations of FSH given as a continuous infusion and for an adequate duration, in the presence of basal LH, with or without LH pulses, are capable of inducing a superovulatory response, (2) initial exposure to FSH followed by LH pulses alone stimulate the development of multiple preovulatory follicles, confirming that ovarian follicles are capable of transferring dependence on gonadotrophins from FSH to LH, (3) while LH pulses appear not to have a major effect on the pattern of preovulatory follicle development, adequate LH pulsatile support is required for full oestradiol synthesis and (4) the duration of initial exposure to FSH and the ability to transfer the dependence from FSH to LH are critical for the selection of a single dominant follicle. In conclusion, this experimental series confirms that the duration of initial exposure to FSH and the ability of the selected follicle to transfer its gonadotrophic dependence from FSH to LH are critical for the selection of a single dominant follicle in cattle.

LncRNA TUG1 promotes tumor growth and metastasis of esophageal squamous cell carcinoma by regulating XBP1 via competitively binding to miR-498.

Esophageal squamous cell carcinoma (ESCC) is a major subtype of esophageal cancer with high mortality. Previous reports suggested that lncRNA taurine upregulated gene 1 (TUG1) functioned as an oncogene in numerous cancers. The purpose of this study was to explore the potential mechanism of TUG1 carcinogenesis in ESCC. The expression of TUG1 and miR-498 was measured by a quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation and apoptosis were assessed by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry. Cell migration and invasion were identified through the transwell assay. The interaction between miR-498 and TUG1 or X-box binding protein 1 (XBP1) was predicted by bioinformatics software starBase and verified by luciferase reporter assay. The expression of XBP1 was quantified by qRT-PCR and western blot analysis. Xenograft tumor mouse model was established to determine the function of TUG1 in vivo. TUG1 was upregulated in ESCC tissues and cells, and its high expression was associated with tumor lymph node metastasis and low cumulative survival. TUG1 knockdown inhibited proliferation, migration, and invasion but promoted apoptosis in ESCC cells. It was confirmed that miR-498 was a target of TUG1, and XBP1 was a target of miR-498. The expression of miR-498 was reduced in ESCC tissues while XBP1 expression was notably enhanced. Mechanism analysis manifested that TUG1 regulated proliferation, apoptosis, migration, and invasion by upregulating XBP1 via targeting miR-498 in vitro. Furthermore, knockdown of TUG1 attenuated tumor growth in vivo. TUG1 accelerated tumorigenesis and metastasis by inducing XBP1 expression through directly targeting miR-498 in ESCC.

Estimated prevalence and impact of the experience of becoming a victim of exhibitionism and frotteurism in Korea: A general population based study.

Exhibitionism and frotteurism are often considered just nuisance crimes but may cause serious distress to the victims. Previous studies of victim experience have focused on specific groups, such as healthcare professionals or university students. To estimate the prevalence of victimisation by exhibitionism and frotteurism among young general population adults in Korea and to describe the impact of such experiences, trained researchers randomly recruited young adults for face to face interviews at transport hubs and on university campuses. In addition, we posted the questionnaire as a Google survey to a limited number of local websites. Data were analysed descriptively. Of 900 people directly approached, 747 (83%) agreed participation, as did 423 online. These two samples were similar demographically, so combined for analyses. Two hundred and thirty-five (20%) reported experiencing exhibitionism and 130 (11%) frotteurism. Exposure victims were older (means 23.2:21.1 years) and more likely to be women than frotteur victims. All but two exposure and nine frotteur perpetrators were said to be men. Reporting to police was rare (17 exposure, 2 frotteur); most exposure victims (73%) but under half of frotteur victims told family or friends. All but 15% of each group had bad feelings about the experience, varying by experience type. Ten percent of exposure and 20% of frotteur victims described distress lasting months; more reported enduring behaviour changes, like avoiding subways. Although our sample is unlikely to be wholly representative of the general population, our research examines a broader range of people than previous studies. Most victims of these "nuisance crimes" were distressed by them, and, hitherto less well recognised, at least a fifth of such victims may have long-term distress. Further research could establish the extent to which support outside the family or friends' group or treatment would be indicated.

[Five million wear simulation and particle analysis of carbon-based nano-multilayer coatings titanium alloy femoral head].

Objective: To analyze the wear debris characteristics ofcarbon-based nano- multilayer coatings on Ti(6)Al(4)V alloys and compared with the cobalt chromium molybdenum alloy (CoCrMo) femoral head to evaluate the friction and wear performance of the new coated femoral head. Methods: Three groups were set up in the wear simulation experiment according to the type of femoral head. Group A: imported Cobalt-Chromium-Molybdenum alloy femoral head (CoCrMo); group B: Titanium alloy femoral head (Ti(6)Al(4)V) with carbon-based nano-multilayer coatings; group C: domestic Cobalt-Chromium-Molybdenum alloy femoral head (CoCrMo). All heads were jointed with an ultra-high molecular weight polyethylene (UHMWPE) acetabular cup. Serum samples were collected and stored in the hip joint simulator. After the sample has been digested and diluted, it was filtered through 5 µm, 1.2 µm and 0.4 µm filters, and the filter paper was collected for testing. Scanning electron microscope (SEM) was used to randomly select regions on the filter to obtain images of wear debris. Energy dispersive X-ray spectroscopy (EDS) was used to determine the elemental type of the particle and to eliminate possible contamination. The composition and structure of the abrasive chips were measured using Fourier transform infrared spectrometer (FTIR). The parameters related to the wear debris includingparticle size, shape, number and volume were calculated. The differences in correlation parameters between the groups were compared to evaluate the friction and wear properties of the new coated joints. Results: The main component of the wear debris produced was UHMWPE, and the particle size was mostly below 1 µm. The submicron particle ratio of group B was 49.4%, which was significantly lower than that of the group A and C (75% and 60%, respectively; χ(2)=66.032, 31.754, both P<0.017). The shape was mainly round, and there was no statistical difference between the groups (χ(2)=0.590, P=0.744). The number of particles in group B was significantly less than that of group C on all filters (t=9.960, 8.019, 5.790, all P<0.01), and less than group A on the 0.4 µm filter (t=7.810, P=0.000). Conclusion: The frictional wear performance of the new carbon-based nano-multilayer coatings femoral head is significantly better than that of the domestic femoral head, and even partially exceeds the imported femoral head level, which helps to reduce the production of particles and prevent osteolysis and aseptic loosening induced by UHMWPE particles.

[Thoughts on the reform of preventive medicine education in the context of new medicine].

Talent training is the core and foundation of public health system construction. Shortage of talents in the field of disease prevention and public health exposed by COVID-19 pandemic highlights the importance of developing preventive medical education. This article analyzes the challenges of medical education in the dilemma of "separation of medical treatment and prevention", and the new requirements for preventive medical education in the construction of New Medicine under the Healthy China strategy. Four aspects including stepping up the resource allocation and investment, educating responsible public health professionals, the education of all medical students who implement the core competence of public health, and the establishment of a continuing education system for preventive medicine have been considered. A series of specific suggestions are put forward including the establishment of a full-chain closed-loop research system to support the cultivation of top-notch innovative public health talents, strengthening the assessment of core public health capabilities for clinical medical professional admission, formulating a "medical and preventive integration" training program for primary health personnel, and implementing "combination of peace and war" public health personnel reserve system, with the purpose of providing reference for the reform and development of preventive medical education in China.

[Overview of tumor stroma ratio in pancreatic ductal adenocarcinoma].

The current studies show that tumor microenvironment of malignant tumor plays critical roles in the tumor progression. The stroma is the main component of tumor microenvironment and the tumor-stroma ratio (TSR) may reflect the relationship of tumor and tumor microenvironment, which has drawn increasing attention from the field of clinical research of cancer.With poor survival,pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease characterized by an intense fibrotic stromal response and the clinical researches related with TSR in PDAC are more significant for patients management compared with that in other tumors.The evaluation methods for TSR are not inconsistent in different studies. But the evaluation result of TSR in pathological method based on whole-mount slide image agrees with that in radiological method, so as the prognosis prediction, that TSR>1 indicated poor prognosis.So TSR can be a stratification marker for patients with PDAC to optimize the tumor stage system used currently. The radiological evaluation before surgery widen the clinical application of TSR in the precise and individual management of patients with PDAC.The comparison for evaluation methods of TSR and the relationship of TSR and prognosis are still needed thorough investigation in ongoing studies with a larger number of patients in multiple centers.