Pancreatic cancer remains one of the deadliest cancer types with few effective treatment options. While the overexpression of ubiquitin-specific protease 14 (USP14) has been observed in many tumor cells, including pancreatic cancer cells, its precise role in pancreatic cancer is not well defined. Here, we investigated the biological function of USP14 in pancreatic cancer and its molecular mechanisms. Our analysis of the Cancer Genome Atlas database revealed that USP14 was highly expressed in pancreatic cancer tissues,and further investigation revealed that its expression level was negatively correlated with the prognosis of patients. In SW1990 and MIAPaCa2 pancreatic cancer cells,we established stable USP14-knockdown cell lines using the shRNA-USP14 lentivirus and found that USP14 knockdown inhibited the proliferation and migration ability of pancreatic cancer cells by CCK8, colony formation assay, wound-healing and Transwell assays. Western blotting analysis showed that downregulation of USP14 expression resulted in a decrease in CyclinD3 protein levels, while overexpression of USP14 increased the protein levels in SW1990 and MIAPaCa2 pancreatic cancer cells. Furthermore, co-immunoprecipitation demonstrated that USP14 interacts with CyclinD3 and ubiquitination assays show that overexpression of USP14 reduces the ubiquitination level of CyclinD3. Moreover, CRISPR / Cas9-mediated USP14 knockout in SW1990 pancreatic cancer cells resulted in decreased CyclinD3 protein levels. These findings suggest that USP14 promotes the proliferation and migration ability of pancreatic cancer cells by interacting with CyclinD3, highlighting USP14 as a potential therapeutic target for pancreatic cancer.

OBJECTIVE: The study aimed to analyze the applicability of the World Health Organization's exclusionary guidelines for Urinary creatinine (Ucr) in the general Chinese population, and to identify Ucr related factors. METHODS: We conduct a cross-sectional study using baseline data from 21,167 participants in the China National Human Biomonitoring Program. Mixed linear models and restricted cubic splines (RCS) were used to analyze the associations between explanatory variables and Ucr concentration. RESULTS: The geometric mean and median concentrations of Ucr in the general Chinese population were 0.90 g/L and 1.01 g/L, respectively. And 9.36% samples were outside 0.3-3.0 g/L, including 7.83% below the lower limit and 1.53% above the upper limit. Middle age, male, obesity, smoking, higher frequency of red meat consumption and chronic kidney disease were associated significantly with higher concentrations of Ucr. Results of the RCS showed Ucr was positively and linearly associated with body mass index, inversely and linearly associated with systolic blood pressure, diastolic blood pressure, triglycerides level, and glomerular filtration rate, and were non-linearly associated with triiodothyronine. CONCLUSION The age- and gender-specific cut-off values of Ucr that determine the validity of urine samples in the general Chinese population were recommended. To avoid introducing bias into epidemiologic associations, the potential predictors of Ucr observed in the current study should be considered when using Ucr to adjust for variations in urine dilution.
Middle Aged ; Male ; Humans ; Creatinine ; Cross-Sectional Studies ; Asian People ; Glomerular Filtration Rate ; China

OBJECTIVES: This study aimed to compare the salivary biochemical indices between caries-free individuals and those with early childhood caries (ECC), and construct a saliva-based caries diagnostic model by analyzing the correlation between salivary biochemical indices and caries severity. METHODS: A total of 120 children aged 4-6 years were selected and divided into two groups: individuals with ECC (C group, RESULTS: The NO CONCLUSIONS Salivary biochemical indices can contribute to the diagnosis and risk assessment of ECC.
Child ; Child, Preschool ; Dental Caries/diagnosis* ; Dental Caries Susceptibility ; Humans ; Saliva

Objective: To systematically evaluate the efficacy and safety of PD-1/PD-L1 inhibitor combined with chemotherapy as comparing with chemotherapy alone for the first-line treatment of advanced NSCLC (non-small lung cancer). Methods: RCTs (randomized controlled trials) on PD-1/PD-L1 inhibitor combined with chemotherapy compared with chemotherapy alone for the first-line treatment of advanced NSCLC were searched in the PubMed, Cochrane Library, EMbase, EBSCO, Chinese Biomedical Literature Database (CBM), Chinese Journal Full-text Database (CNKI), and Chinese Scientific Journal Full-text Database (VIP). RevMan 5.2 software was used for the Meta-analysis. Results: Six RCTs with 3 238 advanced NSCLC patients were included in this study. Meta-analysis showed that the combination therapy group was more effective than the chemotherapy alone group in OS (HR=0.86, 95%CI=0.79~ 0.94, P=0.0006) and PFS (HR=0.81, 95%CI=0.78~0.84, P<0.00001). The incidence of adverse reactions, such as thrombocytopenia of grade 1-5, vomiting, diarrhea, hypothyroidism, hyperthyroidism, rash, pneumonitis, colitis, hepatitis, dysgeusia, hepatitis of grade 3-5 and colitis, in combined treatment group were all higher than those in chemotherapy alone group, the differences were statistically significant (P<0.01 or P<0.05). Conclusions: Compared with chemotherapy alone, PD-1/PD-L1 inhibitor combined with chemotherapy can significantly improve the OS and PFS of patients with advanced NSCLC in the first-line treatment, while the overall incidence of adverse reactions is higher than chemotherapy.

【Objective】Due to the tough nature of skin tissue and a high presence of RNases，the isolation of skin RNA by the classical Trizol method presents a challenge. Therefore，we adapted and tested different sample treatment protocols to improve the Trizol method for high- quality extraction of skin RNA.【Methods】In this study，normal skin of mice processed by different treatments（Tri：submersion Trizol；Pro：RNA sample protector；Cry：cryopreservation in liquid nitrogen frozen and then - 80 ℃ refrigerator；LNG：liquid nitrogen grinding；Cut：scissor cutting）were used as the experimental groups. Spinal cord tissue（Sp）was used as the reference group，and skin tissue of mouse psoriasis model induced by imiquimod（IMQ）was used as the validation group. We compared skin RNA concentration，purity and integrity， as well as IL- 1β mRNA expression extracted by conventional Trizol methods（1-Tri，Nor）and modified Trizol methods（2-Tri，LNG-Tri，Tri-Cut，Pro），which were determined by UV spectrophotometry，agar gel electrophoresis and quantitative reverse transcription PCR（qRT- PCR）.【Results】① Compared with spinal cord（Sp），the total RNA of normal skin tissue extracted with the same classical Trizol method（1-Tri）was with lower yields，more obvious DNA contamination and 5S RNA bands，and higher IL-1β mRNA relative expression，suggesting that skin tissue was relatively special and the classical Trizol methods of skin RNA extraction should be improved. ② Among the different treatment methods of skin tissue，2-Tri and LNG-Tri methods resulted in higher RNA concentrations，lower RNA degradation and lower DNA contamination，and the expression of IL-1β mRNA was closer to normal levels. More importantly，the skin RNA samples extracted by the 2-Tri method can reflect more realistically the variation of IL-1β mRNA expression between normal and psoriasiform groups.【Conclusion】Improved 2-Tri or LNG-Tri method has the advantage of high quality of total RNA，and 2-Tri can more reliably reflect the mRNA expression pattern under physiological and pathological conditions.

Objective: To explore the effect of PDCA nursing model combined with token reward on the compliance and negative emotions of children with hypospadias. Methods: A total of 120 children with hypospadias who were admitted to Children′s hospital affiliated to Zhengzhou University from February 2017 to December 2017 were selected as study subjects. According to the time of admission, they were divided into observation group and control group, with 60 cases in each group. The control group was given routine nursing care, the observation group was given PDCA nursing mode combined with token rewards intervention on the basis of routine care. The self-made children's behavioral compliance assessment table was used to compare the compliance of the two groups of children. Achenbach Child Behavior Check List (CBCL) scores were performed before and after the intervention. The hospitalization time and the incidence of complications were calculated. Results: There was no significant difference in CBCL scores between the two groups at admission (t=0.965, P=0.102). The scores of compliance and CBCL scores of the observation group were (43.12±3.99) points and (17.62±7.30) points respectively, the scores of control group were (30.67±4.53), (24.23±6.67), the difference was statistically significant (t=15.977, 5.184, P<0.01). The hospitalization time and complication rate of the observation group were (18.73±0.84)d, 15.00% (9/60), which were significantly lower than (20.92±1.90) d, 31.67% (19/60) of the control group, and the difference was statistically significant (t=8.166, χ²=4.658, P<0.01 or 0.05). Conclusions The PDCA nursing model combined with token reward can improve the compliance of children with hypospadias and improve their negative emotions.

Objective: To explore the recovery time and risk factors of coagulopathy caused by rodenticide poisoning through analyzing and following up the confirmed cases, and to provide more useful guidance information for the clinic practice. Methods: A total of 96 cases with coagulation dysfunction caused by anticoagulant rodenticide poiso-ning in Children′s Hospital, Chongqing Medical University from January 2014 to December 2016, were analyzed retrospectively.The recovery time of coagulation function and the relationship between recovery time and drug involved way, dysfunction organs and poison concentration were studied respectively. Results: (1) A total of 96 patients were hospitalized because of severe coagulopathy caused by the poisoning of second generation anticoagulant rodenticide.Brodifacoum was detected from 33 blood samples and the median concentration was 364 μg/L (55-4 654 μg/L). Bromadiolone was detected from 7 blood samples and the median concentration was 130 μg/L (18-652 μg/L). Brodifacoum and Bromadiolone were both detected from 8 cases and the median concentration was 741 μg/L (63-6 000 μg/L) and 11 μg/L (3-3 694 μg/L), respectively.(2) A total of 57 cases of the patients were successfully followed up.A total of 18 cases were confirmed with oral poisoning, 16 cases with dermal poisoning, while 23 cases denied any involved ways of poisoning, and 7 cases had organs dysfunction.The follow-up time was 12-54 months.All the hospitalized patients were given specific antidote Vitamin K treatment and recovered successfully without any sequelae.(3) The median recovery time of coagulopathy caused by rodenticide poisoning was 2.5 months.(4) The recovery time of coagulation function was positively correlated with the plasma concentration of Brodifacoum(r=0.619, P<0.01). (5) There was no significant correlation between recovery time and organ dysfunction or drug involved ways of poisoning involvement (all P>0.05). Conclusions The recovery time of coagulation dysfunction caused by anticoagulant rodenticide in children is much longer.The higher the concentration of Brodifacoum poison is, the longer the recovery time.Enough supplementation course of Vitamin K should be given according to the follow-up of coagulation function.

Objective: To observe the changes in nutrition indicators and the effect on chemotherapy complications as well as the safety of enteral nutrition by way of providing enteral nutrition support for children with acute lymphoblastic leukemia (ALL) at the stage of induction chemotherapy. Methods: From November 2016 to September 2017, 60 children with newly diagnosed ALL at the Hematology Oncology Center of Beijing Children′s Hospital were enrolled in this study.They were randomly divided into an experimental group and a control group, 30 cases for each group.The experimental group was given a high-calorie diet, high-quality protein, and high-medium-chain trigly-ceride enteral nutrition on the basis of a conventional low-fat diet, and the duration lasted the whole induction treatment of ALL children; while the control group was given a low-fat diet routinely.By analyzing relevant indicators before induction chemotherapy (D0), chemotherapy day 15 (D15), and after chemotherapy (D33), the changes in nutritional status and the effect on chemotherapy complications in 2 groups were investigated. Results: There was no significant difference in the body mass index (BMI) and the thickness of triceps skinfold between 2 groups before and after chemotherapy (all P>0.05). The upper arm circumference increased after chemotherapy in the experimental group[before treatment: (15.80±2.63) cm, after treatment: (16.27±2.57) cm], while that of the control group decreased slightly[before chemotherapy: (17.19±3.71) cm, after chemotherapy: (17.15±3.64) cm], and the difference between 2 groups was statistically significant (P<0.05). After chemotherapy, the total protein levels in two groups decreased[the experimental group: (64.52±4.85) g/L, the control group: (61.97±4.65) g/L] which was significantly different from that before chemotherapy [the experimental group: (68.17±6.37) g/L, the control group: (68.08±5.14) g/L] (P<0.01). The total protein level of the experimental group after chemotherapy was significant higher than that in the control group (P<0.05). Both albumin levels in 2 groups increased after chemotherapy [(42.45±4.32) g/L in the experimental group and (41.15±3.73) g/L in the control group], and there was a significant difference between 2 groups before chemotherapy [(39.54±3.26) g/L in the experimental group and (40.01±4.37) g/L in the control group] (P<0.05). The level of prealbumin increased after chemotherapy in both groups [(324.57±64.328) mg/L in the experimental group and (293.07±69.09) mg/L in the control group] compared with that before chemotherapy [(121.10±35.13) mg/L in the experimental group and(131.20±52.77) mg/L in the control group]. The change was statistically significant (P<0.01). The albumin level in the experimental group before chemotherapy was lower than that in the control group after chemotherapy, but it was higher than that in the control group after chemotherapy.Protein differences were statistically significant (P<0.05). The reduction rate of elemental iron in the experimental group after chemotherapy was lower than that in the control group, but it was not statistically significant (P>0.05). Elemental zinc was not significantly different compared with the control group.The incidence of neutropenia after chemotherapy in ALL children was higher (37/60 cases, 61.67%). The recovery of neutropenia after chemotherapy in the experimental group was better than that in the control group.After chemotherapy, the severity of anemia in the experimental group was lighter than that in the control group.The amount of blood transfusion required and amount of transfusion per capita were less than those in the control group (54 person-times vs.74 person-times, 2.45 times vs.3.08 times). The total number of transfused blood products was less than that of the control group (78 person-times vs.101 person-times), but none of the findings above were statistically significant (all P>0.05). The degree of hepatic damage in the experimental group decreased after chemotherapy, but there was no significant change in the control group.The initial activated partial thromboplastin time(APTT) prolongation in the trial group was more than that in the control group (5 cases vs.3 cases), and less than the control group (0 case vs.1 case) after chemotherapy.The frequency of fever in the experimental group during chemotherapy was less than that in the control group (6 cases vs.8 cases), and the average time of fever was shorter than that in the control group (2.8 d vs.4.1 d). None of the above findings were statistically significant (all P>0.05). During the course of chemotherapy, 0 pancreatitis occurred in the experimental group, and 1 pancreatitis occurred in the control group.There was no difference in remission rates between 2 groups of chemotherapy for 15 days and chemotherapy for 33 days. Conclusions The nutritional status of children with ALL was reduced after initial induction chemotherapy.Enteral nutrition support was helpful to maintain the nutritional status for children at the initial stage of chemotherapy, high-calorie diet, high-quality protein, and high-medium-chain triglyceride enteral nutrition support improves blood system tolerance to chemotherapy and reduces chemotherapy complications.

Objective: To investigate the clinical and pathologic features, diagnosis and differential diagnosis of hypertrophic port-wine stain (PWS). Methods: Cases of hypertrophic PWS, collected from Henan Provincial People′s Hospital between 2012 and 2018, were retrospectively analyzed for their clinical and pathologic features, immunophenotype and histochemical data, and the relevant literature was reviewed. Results: Twenty-four cases of PWS were included in this cohort, located in the head and neck region (20 cases), limbs (2 cases), and trunk (2 cases). The clinical presentations were mainly red or purple-red plaques or slow growing, painless nodules, or thickened and raised above the skin surface. Microscopically, deformed blood vessels showed honeycomb-like, plexiform or cluster-like growth pattern, and diffusely involved the dermis, skin appendages, subcutaneous fat tissue, and deep skeletal muscles; The vascular lumen of the deformed vessels was dilated (≥100 μm in diameter), and in 18 cases the lumen was greater than 400 μm. The superficial dermis mainly contained few deformed capillaries. The deep wall showed thickening of blood vessel wall and fibrous tissue hyperplasia. Elastic fiber and Masson staining indicated abnormal venous vessel, which in some cases contained small amount of abnormal arterioid vessel,without vascular endothelial cell proliferation in all cases. In 24 cases, 19 cases had epidermal atrophy, 6 with vascular chronic inflammation or epidermal ulcer, 4 with capillary hemangioma, 4 with sebaceous gland hyperplasia, 2 with epidermal papillary hyperplasia and 2 with vascular keratomas. Conclusions PWS is a common congenital capillary malformation. The number of histologically deformed capillaries is reduced and they usually locate in the superficial part. The deep vascular wall is increased with thick venous malformation, diffusely involving the dermis and deep skeletal muscle. Furthermore, PWS needs to be differentiated from infantile hemangioma, cavernous hemangioma and vascular keratomas.