Objective To explore the role of TMAO from gut microbiota in non-alcoholic fatty liver disease(NAFLD),we detected the serum level of TMAO and its precursor metabolites in NAFLD,as well as the expression level of Eubacterium rectum,Bacteroidetes multiforme,Lactobacillus and bifidobacterium in the intestinal flora.Methods We collected 118 subjects and divided into NAFLD group(86 cases)and healthy control group(32 cases)randomly.We also detected the serum level of TMAO and its precursor metabolites in subjects by high performance liquid chromatography tandem mass spectrometry detection(LC-MS),and the expression of target bacterial DNA was detected by qRT-PCR.Results Serum TMAO,TMA and choline levels were significantly increased in NAFLD(P<0.05),and liver fat content was positively correlated with TMAO(P<0.05).The expression level of Lactobacillus and Eubacterium rectum in NAFLD group were increased(P<0.05);the expression level of Bifidobacterium and Bacteroides multiform were decreased(P<0.05).The serum TMAO level was positively correlated with Eubacterium rectum(r=0.280,P<0.05),and negatively correlated with Bifidobacterium(r=-0.332,P<0.05).Conclusion The level of TMAO in serum shows a positive correlation with NAFLD.The structure of intestinal flora in individuals with NAFLD is altered and linked to TMAO.This suggests that the intestinal flora may have a significant impact on the development of NAFLD through TMAO.

Objective: To learn the status and influencing factors of development among infants at ages of 0 to 36 months in Xiaoshan District, Hangzhou City, so as to provide the reference for promoting healthy development of infants. Methods: Infants at ages of 0-36 months who underwent physical examination in Child Health Clinic of Xiaoshan District Community Health Service Center were selected in 2022. General data of infants and their mothers were collected through questionnaires, and the development status of infants was screened by Age and Stages Questionnaire (third edition). Factors affecting the development status were identified using a multivariable logistic regression model. Results: A total of 2 519 infants were investigated, including 1 339 males (53.16%) and 1 180 females (46.84%). There were 608 infants with abnormal development of at least one functional area of communication (CM), gross motor (GM), fine motor (FM), problems solving (CG) and personal-social (PS). The abnormal rate was 24.14%, and the abnormal rates of the above functional areas were 9.77%, 6.59%, 7.98%, 6.39% and 9.33%, respectively. Multivariable logistic regression analysis showed that gender (male, OR=1.563, 95%CI: 1.191-2.052), mother's childbearing age (≥35 years, OR=1.411, 95%CI: 1.001-1.988), mother's educational level (lower than junior college, OR=1.460, 95%CI: 1.116-1.912) were factors affecting abnormal development of CM; preterm birth (OR=2.323, 95%CI: 1.315-4.103) was factors affecting abnormal development of GM; gender (male, OR=1.654, 95%CI: 1.225-2.232) was factors affecting abnormal development of FM; gender (male, OR=1.511, 95%CI: 1.086-2.102) and mode of delivery (cesarean section, OR=1.460, 95%CI: 1.060-2.010) were factors affecting abnormal development of CG; gender (male, OR=1.340, 95%CI: 1.019-1.763) and birth weight (low birth weight, OR=1.985, 95%CI: 1.149-3.432) were factors affecting abnormal development of PS. Conclusions The rate of abnormal development among infants at ages of 0 to 36 months in Xiaoshan District is 24.14%. Gender, preterm birth, mode of delivery, birth weight, mother's childbearing age and mother's educational level could affect the development status of infants.

To investigate the prevalence and epidemiological characteristics of diabetic retinopathy (DR) in Yunnan Province, explore its risk factors, and provide a basis for the prevention and treatment of chronic complications of diabetes mellitus (DM). This is a large cross-sectional study, in all, 1 524 DM patients in 16 communities and villages of Yunnan Province who were registered in health service centers were included in this study from August to November 2019. All patients completed a uniform questionnaire, anthropometric measurements, biochemical measurements, and auxiliary examinations. Logistic regression analysis was used to screen the risk factors of DR. The prevalence rates of DR, mild non-proliferative DR (mild-NPDR), and referable DR (RDR) were 16.0% (244/1 524), 4.5% (69/1 524), and 11.5% (175/1 524), respectively. Glycated hemoglobin A 1c (HbA 1c)≥7.0% was the risk factor of mild-NPDR ( OR=1.872, 95% CI 1.055-3.323) and RDR ( OR=4.821, 95% CI 2.917-7.969). Blood pressure≥130/80 mmHg (1 mmHg=0.133 kPa) was the risk factor of mild-NPDR ( OR=1.933, 95% CI 1.112-3.358) and RDR ( OR=1.505, 95% CI 1.063-2.130). In Yunnan Province, 16.0% DM patients had accompanying DR, wherein about 71.7% of them required an ophthalmology referral, and the high incidence of RDR in DM patients was associated with poor control of blood glucose and blood pressure.

Protein corona (PC) has been identified to impede the transportation of intravenously injected nanoparticles (NPs) from blood circulation to their targeted sites. However, how intestinal PC (IPC) affects the delivery of orally administered NPs are still needed to be elucidated. Here, we found that IPC exerted "positive effect" or "negative effect" depending on different pathological conditions in the gastrointestinal tract. We prepared polystyrene nanoparticles (PS) adsorbed with different IPC derived from the intestinal tract of healthy, diabetic, and colitis rats (H-IPC@PS, D-IPC@PS, C-IPC@PS). Proteomics analysis revealed that, compared with healthy IPC, the two disease-specific IPC consisted of a higher proportion of proteins that were closely correlated with transepithelial transport across the intestine. Consequently, both D-IPC@PS and C-IPC@PS mainly exploited the recycling endosome and ER-Golgi mediated secretory routes for intracellular trafficking, which increased the transcytosis from the epithelium. Together, disease-specific IPC endowed NPs with higher intestinal absorption. D-IPC@PS posed "positive effect" on intestinal absorption into blood circulation for diabetic therapy. Conversely, C-IPC@PS had "negative effect" on colitis treatment because of unfavorable absorption in the intestine before arriving colon. These results imply that different or even opposite strategies to modulate the disease-specific IPC need to be adopted for oral nanomedicine in the treatment of variable diseases.

Objective : The study provided evidence for clinical prevention of colorectal cancer by analyzing the characteristics of recurrence after colorectal polypectom． Methods : According to the number of polyps during the second colonoscopy，patients were divided into multiple recurrence group ( ≥3) and non-multiple recurrence group (＜3) ．The characteristics and risk factors of polyp recurrence were analyzed. Results : The clinical data of 370 patients who underwent two colorectal polypectomy were retrospectively analyzed．In univariate statistical analysis， polyp size (P = 0. 033) ，polyp site (P = 0. 002) ，and polyp color (P = 0. 032) were the risk factors for multiple polyp recurrence．In multivariate regression analysis，the number of polyps detected at the first colonoscopy (P = 0. 001) and the polyp site (P = 0. 001) were independent risk factors for multiple recurrence． Conclusion Multi- ple polyps on the first colonoscopy and polyps in the distal colon indicate an increased risk of multiple recurrence.

Targeted programmed death-ligand 1 (PD-L1) and CXC chemokine receptor type 4 (CXCR4), gene sequences encoding anti-PD-L1 nanobody and anti-CXCR4 nanobody were cloned into the pET-22b (+) vector to construct recombinant expression plasmid of anti-PD-L1&CXCR4 bispecific nanobody, which was connected with 6 × His tag and transformed into E.coli BL21 (DE3). The expressed proteins were then found to exist as a soluble form in the supernatant of bacterial lysate after induction of IPTG.Three purification methods were used to obtain the target protein in order to improve the yield and purity of the bispecific nanobody.The bacterial supernatant was separated and purified by His Trap FF affinity chromatographic column.The target protein output could exceed 1 mg/L, and the product purity could reach up to 97%.Besides, the anti-PD-L1&CXCR4 bispecific nanobody shows a specific binding ability to two antigens on the cell surface, enhancing the cytotoxicity of IL-2 activated human peripheral blood mononuclear cells (PBMC) to tumor cell line AsPC-1, which lays the foundation for further evaluation of its drug efficacy in vivo.

Objective To explore the relationship between iodine and fluoride content in drinking water and the incidence of adult thyroid nodules in Cangzhou,Hebei.Methods According to the previous reports on iodine and fluoride levels in drinking water in Cangzhou,from November 2016 to January 2017,Cangzhou was divided into high iodine,low iodine,normal iodine and fluorine,low iodine and high fluorine,high iodine and high fluorine areas,and according to the different contents of iodine and fluorine in drinking water,high iodine and high fluorine area was further divided into high iodine and high fluorine 1 (iodine:743.30 μg/L,fluorine:4.27 mg/L),2 (iodine:119.31μg/L,fluorine:4.67 mg/L) and 3 (iodine:105.30 μg/L,fluorine:1.64 mg/L) subareas.Subjects who lived for 20 or more years and aged 30 or older,without serious disease and not taken iodized salt were selected.Palpation was used to examine the size,texture,mass,tenderness and mobility of the thyroid gland.The boundary,internal echo,blood flow and quantity of nodules were observed and recorded by color Doppler.Results The prevalence difference of thyroid nodules [36.8％ (629/1 710),32.8％ (636/1 938),25.1％ (427/1 700)] in high iodine,low iodine and normal iodine and fluorine areas was statistically significant (x2 =55.597,P ＜ 0.05).The prevalences of thyroid nodules in both high iodine and low iodine areas were higher than that of normal iodine and fluorine area (P＜ 0.016 7).The prevalence difference of thyroid nodules [43.3％ (749/1 730),39.8％ (712/1 790),34.9％ (623/1 785)] in high iodine and high fluorine 1,2 and 3 subareas was statistically significant(x2 =26.220,P ＜ 0.05).Compared with low iodine area,the prevalence of thyroid nodules [41.2％ (735/1 785)] in low iodine and high fluorine area was increased (x2 =6.288,P ＜ 0.05).Conclusions Both high iodine and low iodine can induce thyroid nodules.In water source areas with high iodine content,both high iodine and high fluorine are the factors inducing thyroid nodules.The prevalence of thyroid nodules in low iodine and high fluorine area is significantly higher than that of low iodine area.

Objective Through the analysis of misdiagnosis left renal vein entrapment syndrome,to improve the understanding and reduce the misdiagnosis of this disease.Methods 82 cases of left renal vein compression syn-drome were diagnosed with ultrasound,65 cases were misdiagnosed.Clinical data of these 65 patients were analyzed.Results In 82 cases,only 11 doctors from renal department of internal medicine,pediatrics,department of urology wrote application for it.Among the 65 misdiagnosed cases,30 cases of male,female 35 cases.The age ranged from 6 to 37 years old,the average age was 16.1 years.The misdiagnosis duration ranged from 2 months to 42 months,the median time was 7 months.43 cases of low back pain or backache,urinary tract irritation in 5 cases,60 cases of abnor-mal urinalysis:a simple urinary protein in 15 cases,21 cases of simple hematuria,proteinuria,hematuria 24 cases. 31 cases were misdiagnosed as chronic glomerulonephritis,occult nephritis(asymptomatic proteinuria and hematuria syndrome)in 11 cases,acute nephritis comprehensive sign in 9 cases,7 cases of lumbar muscle strain,urinary tract infection in 4 cases,1 case of urinary tract stones,pelvic inflammatory disease in 2 cases.In the 16 cases complicated with glomerular nephritis,were treated as the glomerular nephritis before (11 cases of chronic nephritis,5 cases of asymptomatic proteinuria and hematuria syndrome).12 cases of abnormal urine fluctuation,after a delay of 3 -16 months referral doctor was diagnosed with left renal vein entrapment syndrome.Conclusion The disease has no char-acteristic clinical manifestations,and most clinicians were short in understanding of the disease,so the misdiagnosis rate is high.The clinicians should improve the understanding of the disease,in order to reduce the misdiagnosis rate.

A microscopic fluorescence spectrometric analysis ( MFSA) system was set in the laboratory. A novel method for in situ determination of Anthracene ( Ant) adsorbed onto root surface micro-zone of two kinks of mangrove plant, named Kandelia obovata ( K. obovata) and Avicennia marina ( A. marina) by MFSA was established. Fluorescence spectra of Ant adsorbed on root surface micro-zone were obtained by synchronous scanning mode. The signal to noise (S/N) of Ant (5. 3 pg/μm2) adsorbed on K. obovata and A. marina root surface micro-zone increased up to 5. 5 and 6. 8 while wavelength offset (△λ) both were at 60 nm, respectively. The linear dynamic ranges of established method were 5. 3-63. 2 pg/μm2 for K. obovata and 10. 5-52. 6 pg/μm2 for A. marina, with the detection limits of 1. 1 pg/μm2 and 5. 5 pg/μm2 , respectively. The relative standard deviations were both less than 12 . 5% ( n=9 ) , and the recoveries were 98 . 1% -117. 0% and 81. 2%-110. 9%, respectively. The result showed that the MFSA system had ability to obtain quantitative information of fluorescence spectra and fluorescence image of Ant adsorbed onto plant roots surface micro-zone.

Objective To explore the effect of lymphovascular invasion (LVI) on prognosis in the high-grade stage pT1 bladder cancer after first transurethral resection of bladder tumor (TURBT). Methods Thirty-five high-grade stage pT1 bladder cancer patients who underwent first TURBT and showed LVI positive according to the postoperative pathological (observation group) and 70 high-grade stage pT1 bladder cancer patients who underwent first TURBT and showed LVI negative according to the postoperative pathological (control group) were enrolled into the study. The tumor recurrence rate, tumor progression rate, recurrence-free survival (RFS) and overall survival (OS) were compared between 2 groups. Results The follow-up time in observation group was 15 - 71 (42.1 ± 18.1) months, and in control group was 20-72 (50.9 ± 12.2) months. The tumor recurrence rate and tumor progression rate in observation group were significantly higher than those in control group:88.6%(31/35) vs. 34.3%(24/70) and 54.3%(19/35) vs. 22.9%(16/70), and there were statistical differences (P<0.01). The RFS and OS in observation group were significantly shorter than those in control group: (19.7 ± 4.5) months vs. (46.8 ± 9.2) months and (43.4 ± 12.6) months vs. (63.4 ± 7.1) months, and there were statistical differences (P<0.05). Conclusions There is a significant correlation between LVI and tumor recurrence and progression in the high-grade pT1 bladder cancer after first TURBT, and the LVI can predict disease progression and poor prognosis.