BACKGROUND: Human neutrophil lipocalin (HNL) has been used extensively to differentiate acute bacterial infection from febrile diseases as a biomarker to reflect the activation of the neutrophil. The serum HNL levels in the adult-onset Still's disease (AOSD) patients with and without infection, as well as the healthy controls (HCs), were analyzed statistically in this study to evaluate the value of HNL for the diagnosis of AOSD. METHODS: A total of 129 AOSD patients were enrolled, from whom blood samples were drawn and the AOSD diagnosis was confirmed through the review of the medical records, where the systemic score, demographic characteristics, clinical manifestations, and laboratory parameters were also collected for the patients; in addition, a total of 40 HCs were recruited among the blood donors from the healthcare center with the relevant information collected. The HNL test was done for the blood samples with the enzyme-linked immunosorbent assay and the analyses were done for the correlations of HNL with clinical manifestations and diagnostic effectiveness. RESULTS: The serum HNL increased significantly in the patients with only AOSD as compared with that in the HCs (139.76 ± 8.99 ng/mL vs . 55.92 ± 6.12 ng/mL; P  < 0.001). The serum HNL level was correlated with the white blood cell (WBC) count ( r  = 0.335, P  < 0.001), neutrophil count ( r  = 0.334, P  < 0.001), erythrocyte sedimentation rate ( r  = 0.241, P  = 0.022), C-reactive protein ( r  = 0.442, P  < 0.0001), and systemic score ( r  = 0.343, P  < 0.0001) in the AOSD patients significantly. Patients with fever, leukocytosis ≥15,000/mm 3 , and myalgia in the HNL-positive group were observed relatively more than those in the HNL-negative group ( P  = 0.009, P  = 0.023, and P  = 0.007, respectively). HNL was a more sensitive indicator than ferritin and C-reactive protein (CRP) to differentiate the AOSD patients with bacterial infection from AOSD-only patients, and the Youden index was 0.6 for HNL and 0.29 for CRP. CONCLUSION Serum HNL can be used as a biomarker for the diagnosis of the AOSD, and HNL is also observed to be associated with the disease activity.
Adult ; Humans ; Still's Disease, Adult-Onset/diagnosis* ; C-Reactive Protein/metabolism* ; Neutrophils/metabolism* ; Clinical Relevance ; Biomarkers ; Bacterial Infections

Objective:To study the expression of peripheral blood NKT-like cells in patients with systemic sclerosis (SSc), to explore the correlation between NKT-like cells and laboratory and clinical indicators of systemic sclerosis, and investigate the role of NKT-like cells in the occurrence and development of Systemic sclerosis.Methods:Forty-six SSc patients (SSc group) were enrolled from Department of Rheumatology and Immunology of Peking University People 's Hospital during December 2018 to December 2019. Thirty healthy subjects with matched age and sex were selected as healthy control group (HC group). The cell count and percentage of NKT-like cells and other lymphocyte subsets in peripheral blood were detected by flow cytometry. At the same time, other laboratory indexes were determined by different methods. Spearman's correlation analysis, Pearson's correlation analysis, Man-Whitney U test and Fisher's exact test were used to analyze the difference and correlation between NKT-like cells and other clinical and laboratory indicators. Results:Compared with HC group [165(72, 226)cells/μl], the cell count of NKT-like cells in peripheral blood of SSc group[30(19, 58)cells/μl] was significantly decreased ( Z=-5.69, P<0.001). Correlation analysis showed that the cell count of NKT-like cells was positively correlated with total T lymphocytes ( r=0.56, P<0.001), CD4 +T cells ( r=0.42, P=0.004), CD8 +T cells ( r=0.60, P<0.001), B cells ( r=0.50, P<0.001) and NK cells ( r=0.33, P=0.024), respectively. The percentage of NKT-like cells in lymphocytes was also positively correlated with the percentage of CD8 +T cells ( r=0.34, P=0.020), but not significantly correlated with other subset of lymphocytes. The ESR of the NKT-like cell decreased group was significantly higher than that of the NKT-like normal group[15(9, 28) mm/1 h vs 8 (4, 16) mm/1 h, Z=-2.04, P=0.042]. Moreover, the cell count of NKT-like cells was negatively correlated with ESR ( r=-0.34, P=0.019). Conclusion:The cell count and percentage of NKT-like cells in peripheral blood of SSc patients decreased significantly. NKT-like cells were not only positively correlated with a variety of lymphocyte subpopulations, but also negatively correlated with ESR. NKT-like cells may be used as an indicator to monitor the disease activity in patients with SSc.

In order to evaluate the efficacy of peroral endoscopic myotomy (POEM) for achalasia, data of 63 patients with achalasia who were treated with POEM in China-Japan Union Hospital of Jilin University from 2017 to 2021 were collected. Postoperative Eckardt score, high-resolution manometry and upper gastrointestinal radiography were compared with preoperative data. The mean age of the 63 patients was 49.0 years, and there were 31 famales. The preoperative Eckardt score was 9 (3), and the postoperative Eckardt score was 2 (2), with significant difference ( V=1 953, P<0.001). The lower esophageal sphincter pressure decreased significantly after operation compared with that before operation [9.90 (3.35) mmHg VS 26.80（13.85）mmHg， V=2 016, P<0.001]. Fifty-three patients (84.1%) had satisfactory curative effects. The incidence of adverse events was 3.2% (2/63). POEM is safe, effective and minimally invasive for the treatment of achalasia.

BACKGROUND: Excessive exposure to fluoride can reduce intelligence. Methylenetetrahydrofolate dehydrogenase, cyclohydrolase, and formyltetrahydrofolate synthetase 1 ( MTHFD1 ) polymorphisms have important roles in neurodevelopment. However, the association of MTHFD1 polymorphisms with children's intelligence changes in endemic fluorosis areas has been rarely explored. METHODS: A cross-sectional study was conducted in four randomly selected primary schools in Tongxu County, Henan Province, from April to May in 2017. A total of 694 children aged 8 to 12 years were included in the study with the recruitment by the cluster sampling method. Urinary fluoride (UF) and urinary creatinine were separately determined using the fluoride ion-selective electrode and creatinine assay kit. Children were classified as the high fluoride group and control group according to the median of urinary creatinine-adjusted urinary fluoride (UF Cr ) level. Four loci of MTHFD1 were genotyped, and the Combined Raven's Test was used to evaluate children's intelligence quotient (IQ). Generalized linear model and multinomial logistic regression model were performed to analyze the associations between children's UF Cr level, MTHFD1 polymorphisms, and intelligence. The general linear model was used to explore the effects of gene-environment and gene-gene interaction on intelligence. RESULTS: In the high fluoride group, children's IQ scores decreased by 2.502 when the UF Cr level increased by 1.0 mg/L (β = -2.502, 95% confidence interval [CI]:-4.411, -0.593), and the possibility for having "excellent" intelligence decreased by 46.3% (odds ratio = 0.537, 95% CI: 0.290, 0.994). Children with the GG genotype showed increased IQ scores than those with the AA genotype of rs11627387 locus in the high fluoride group ( P   <  0.05). Interactions between fluoride exposure and MTHFD1 polymorphisms on intelligence were observed (Pinteraction < 0.05). CONCLUSION Our findings suggest that excessive fluoride exposure may have adverse effects on children's intelligence, and changes in children's intelligence may be associated with the interaction between fluoride and MTHFD1 polymorphisms.
Child ; Creatinine ; Cross-Sectional Studies ; Fluorides/urine* ; Formate-Tetrahydrofolate Ligase ; Humans ; Intelligence/genetics* ; Methylenetetrahydrofolate Dehydrogenase (NADP) ; Methylenetetrahydrofolate Reductase (NADPH2)

Antiviral Agents/pharmacology* ; COVID-19 ; Coronavirus 3C Proteases ; Humans ; Lactams ; Leucine ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Nitriles ; Proline ; Protease Inhibitors/pharmacology* ; SARS-CoV-2

Lung cancer is one of the most common malignancies with the highest incidence rate and mortality rate worldwide, and non-small cell lung cancer (NSCLC) accounts for about 85%. Only 5% NSCLC patients are anaplastic lymphoma kinase (ALK) rearrangement positive NSCLC, but the prognosis of these patients is poor, and treatment is urgent. Ensartinib (X-396), a next-generation ALK tyrosine kinase inhibitor (ALK-TKI), has shown greater potency on inhibiting ALK activity and controlling brain metastases than crizotinib, which is indicated for the treatment of crizotinib-resistant, ALK-positive NSCLC patients. Several phase I to III clinical trials included both healthy volunteers and NSCLC patients have been conducted both in China and abroad. In this review, we briefly summarized the results of these trials, and preliminary efficacy, safety, pharmacology and pharmacokinetics/pharmacodynamics of ensartinib were discussed.

Objective:To investigate the 2 years’ efficacy of intravesical instillation of domestic BCG versus epirubicin in the prevention of recurrence of intermediate-risk or high-risk non-muscular invasive bladder cancer and predictive factors of BCG instillation.Methods:From July 2015 to June 2020, 18-75 years old patients with moderate to high-risk non muscle invasive bladder cancer (NMIBC) confirmed by pathological examination were involved. The ECOG score was 0-2. Exclusion criteria included ①immune deficiency or impairment (such as AIDS), using immunosuppressive drugs or radiotherapy, suspected allergic to BCG or epirubicin or excipients of the two drugs, fever or acute infectious diseases including active tuberculosis or receiving anti tuberculosis treatment, with severe chronic cardiovascular and cerebrovascular diseases or chronic kidney disease; ②combined with other urogenital system tumors or other organ tumors; ③combined with muscle invasive bladder urothelial carcinoma (≥T 2); ④undergoing chemotherapy, radiotherapy or immunotherapy within 4 weeks (immediate instillation after surgery not included); ⑤ pregnant or lactating women; ⑥ comfirmed or suspected bladder perforation; ⑦gross hematuria; ⑧cystitis with severe bladder irritation that may affect the evaluation; ⑨participat in other clinical trials within 3 months; ⑩alcohol or drug addiction; ?any risk factors that may increasing the risk of patients. Epirubicin 50 mg was irrigated immediately after the operation(TURBT or laser resection). The patients were randomly divided into BCG15 group, BCG19 group and epirubicin group by the ratio of 2∶2∶1, and the patients were maintained intravescical instillation for 1 year. The recurrence and adverse events of the three groups were compared. Univariate and multivariate analysis was performed to predict the risk factors of BCG irrigated therapy failure. Result:By June 15, 2020, the median follow-up duration was 22.1 months(12.1, 32.3), and there was no statistical difference between the groups ( P=0.9024). There were 274 patients enrolled in BCG19 group, 277 patients enrolled in BCG15 group and 130 patients enrolled in the epirubicin group. The drop-off rate was 16.6%(113 cases)and made no difference between groups( P=0.6222). There were no significant difference in age, gender, BMI, or ECOG score( P>0.05). During the follow-up, 116 cases was detected recurrence or progression. The recurrence rate of the three groups was 14.2% and 14.8% in BCG19 group and BCG15 group, and 27.7% in the epirubicin group. There was no difference in recurrence rate between BCG19 and BCG15 group( P=0.9464). The recurrence rate of BCG19 group was lower than that of the epirubicin group ( P=0.0017). The recurrence rate of BCG15 group was lower than that of the epirubicin group ( P=0.0020). There was no difference in the cumulative recurrence free survival rate between BCG19 and BCG15 group (95% CI0.57-1.46, P=0.7173). The cumulative recurrence free survival rate of BCG 19 group was better than that of the epirubicin group( HR=0.439, 95% CI0.26-0.74, P=0.0006), and the cumulative recurrence free survival rate of BCG15 group was better than that of the epirubicin group ( HR=0.448, 95% CI0.29-0.80, P=0.0021). The total incidence of adverse events in 19 BCG19, BCG15 and epirubicin group were 74.5%, 72.6% and 69.8% respectively. There was no difference in the incidence of adverse events between BCG19 and BCG15 group( P=0.6153). The incidence of adverse events in epirubicin group was lower than that of BCG19( P=0.0051) and BCG15( P=0.0167) groups.There was no significant difference in the incidence of serious adverse events (SAE) among the three groups ( P=0.5064). Log rank test univariate analysis and Cox risk regression model multivariate analysis showed that the history of bladder cancer recurrence( HR=6.397, 95% CI1.95-20.94, P=0.0001)was independent risk factor for BCG irrigation failure. Conclusions:The 2 years’ efficacy of intravesical instillation of domestic BCG is better than than of epirubicin with good tolerance and safety. There is no difference between BCG19 and BCG15 group. BCG doesn’t increase SAE compared with epirubicin. Recurrence status was an independent prognostic factor regarding recurrence-free survival.

Objective: The incidence of complications after skin soft tissue expansion is relatively high. Occurrence of infection often means the expander has to be taken out ahead of schedule. In this retrospective study, we wanted to identify independent risk factors of infection after skin soft tissue expansion, which could be helpful to guide clinical work. Methods: Demographic information of patients who underwent the skin soft tissue expansion at the department of plastic surgery of Xijing Hospital from January 2003 to December 2012 was collected. Univariate associations with infection were measured by logistic regression and represented as odds ratios. The p-value less than 0.1 was identified the potential risk factor. Multivariate logistic regression was used to calculate odds ratios for risk factors of infection. Independent risk factors were identified if the p-value was less than 0.05. Results: A total of 3382 implants were included in the study. The overall infection rate of tissue expansion was 5.2% in 177 implants. The result of multivariate logistic regression showed that preoperative white blood cell count, age, numbers of expander implanted and volume of expander were independent risk factors of infection. Conclusions Independent risk factors of infection were preoperative white blood cell count, age, numbers of expander implanted and volume of expander. The lower preoperative white blood cell count, age more than 18 years old, more numbers of expander implanted and the bigger volume of the expander, the higher possibility of complications occurred. The result was helpful to guide clinical work and reduce the incidence of infection.

Objective To solve the problem of castration resistant prostate cancer (castrationresistant prostate cancer,CRPC) the problem of drug resistance by studing the expression of the CUDC-101 inhibitor of castration resistant prostate cancer androgen receptor splice variant 7.Methods In this study,the expression of AR-V7 protein in prostate cancer cell lines PC-3,VCaP,22Rv1,LNCap was detected by imnmunoblotting between April 2015 and April 2016,and the highest expression level of cell lines was selected follow-up experiments.Through the cell proliferation and activity experiments,the epigenetic inhibitors:histone deacetylase inhibitor CUDC-101,histone methylation inhibitor DZNeP,DNA methylation inhibitor gemcitabine,histone acetyltransferase inhibitor MG149 to select an inhibitor that reduces the expression of AR-V7 protein in CRPC cells.22Rv1 cells were treated with 30 nmol and 300 nmol of CUDC101 and 1,10 and 20 μmol of Enzalutamide (MDV3100),respectively,and their inhibitory effects on the growth of 22Rv1 cells were examined.Results The results of immunoblotting showed that AR-V7 protein was only expressed in CRPC cell line 22Rv1 and negative in non-CRPC cell line.The expression of AR-V7 in 22Rv1 cells treated with CUDC-101 was significantly lower than that of negative control.While other inhibitors had no effect on the expression of AR-V7.In the cell proliferation and activity assay,the inhibitory rates of 30 nmol CUDC-101 and 1,10 and 20 μmol MDV3100 were 10％,35％ and 45％,respectively,higher than that of MDV3100 alone.28％ and 42％,the difference was statistically significant (P ＜ 0.05).The inhibitory rates of 300 nmol CUDC-101 and MDV3100 were 30％,60％ and 65％,respectively,which were significantly higher than those of MDV3100 alone (P ＜ 0.05).Conclusions CUDC-101 can inhibit the castration resistant prostate cancer androgen receptor splice variant 7 expression,and solved the resistance problem of CRPC.

Objective Decline in cognitive function caused by diabetes has become a research hotpots.The article aims to explore the relationship between serums regulated upon activation normal T cell expressed and secreted(RANTES) and cognitive dysfunction of newly diognosed T2DM patients, and provide a new way of prevention and treatment for newly diagnosed T2DM patients with cognitive dysfunction.Methods We retrospectively analyzed the general information and clinical biochemical indexes of the 123 patients who were first diagnosed of T2DM from March 2015 to September 2016 in Tangshan Worker''s Hospital.The levels of serum RANTES were measured by enzyme-linked immunosorbent assay (ELISA), and the cognitive function of all patients was assessed by Mini-mental State Examinatlon(MMSE)and Repeatable Battery for the Assessment of Neuropsyehologic Status(RBANS).Finally, newly diognosed T2DM patients were divided into T2DM non-cognitive disorder group and T2DM cognitive disorder group according to the MMSE score.We analyzed whether there are differences among general information,serum RANTES level and RBANS cognitive function score of two group patients.The correlations of RANTES with general information and cognitive scores were analyzed by single factor correlation and multiple stepwise regression analysis.Results ①The level of serum RANTESin T2DM cognitive disorder group[(2.62±0.37)mmol/L] was significantly higher compared to that in T2DM noncognitive disorder group[(2.29±0.36)mmol/L], and there was significant difference(P<0.001).②The instant memory,visual span,attention,delayed memory score and RBANS score of T2DM cognitive disorder group were(70.90±14.71)、(92.90±15.50)、(87.80±16.45)、(88.02±14.28)、(82.92±11.07), which were significant declined compared to those of T2DM non-cognitive disorder group [(85.28±13.97),(104.18±12.69),(101.51±12.94),(96.42±10.30),(95.84±9.94)], and there was significant difference (P≤0.05).There was no statistically significant difference between the two groups′ verbal function score [(96.08±7.87),(99.31±9.83)] (P=0.056).③The RANTES was negatively correlated with the total score of instant memory, visual span, verbal function, delayed memory score and RBANS score in T2DM patients(the valuue of r were-3.48、-2.35、-2.01、-3.02、-4.17).Conclusion There was a significant correlation between serum RANTES level and cognitive dysfunction, and elevated serum RANTES level could be used as an important indicator for monitoring newly diognosed T2DM patients with cognitive dysfunction.