Objective To understand the prevalence and cause of eye diseases in the middle and old aged population in community was of important significance for the prevention and treatment of relevant diseases.The present study attempts to survey the prevalence of common eye diseases and conditions of blindness and low vision in 50 years and older population in community of Beijing.MethodsThis was an ophthalmologic epidemiology survey.The 2 833 target population was included and registered in Western Chang'an street community in door-to-door and questionnaire manner between October,2006-October,2007.Multiple factors,such as demography,general conditions,lifestyles,education degree,economical status,medical status and the awareness of relevant ophthalmic knowledge of participants were recorded and evaluated.Relevant eye examinations including uncorrected visual acuity,pinhole visual acuity,non-contact intraocular pressure test,slit-lamp,funduscopy and optometry examinations were performed in Beijing No.2 Hospital by trained ophthalmologists.Blindness and low vision were evaluated based on WHO criteria.The causes of leading-blindness and low vision were analyzed.Oral informed consent was obtained from all of the subjects.Results2 410 individuals of 2 833≥50-year-old participants received complete surveys according to the designed process in this study with an examined rate of 85.07%.The incidence of blindness and low vision in examinees was 0.79% and 5.64% respectively.The positive factors related to blindness and low vision appeared to be age,education and an awareness of relevant ophthalmic knowledge (χ~2=26.62,18.28,21.32,P＜0.001).The primary causes of blindness in examined population,in order,were cataract,glaucoma and retinopathy,and those of low vision were cataracts,refractive error and diabetic retinopathy.ConclusionIt is emphasized that early prevention and treatment for cataract,glaucoma,diabetic retinopathy and refractive errors can reduce the prevalence of blindness and low vision in people over 50 years in the Western Chang'an street community of Beijing.

Objective To investigate clinical efficacy and prognostic factors of hilar cholangiocarcinoma.Methods The retrospective case-control study was conducted.The clinicopathological data of 322 patients with hilar cholangiocarcinoma who were admitted to the Xiangya Hospital of Central South University between December 2005 and November 2015 were collected.Preoperative staging and classification of tumor and treatment planning were carried out according to the results of laboratory and imaging examinations.Observation indexes:(1) clinical features and results of assisted examinations;(2) treatments and results of pathological examination;(3) followup and survival;(4) prognostic factors analysis:gender,age,preoperative highest total bilirubin (TBil),preoperative carcinoembryonic antigen (CEA),preoperative CA19-9,preoperative CA242,preoperative CA125,treatment methods and TNM staging.The follow-up of outpatient examination and telephone interview was perfornmed to detect patients' survival up to November 2016.Survival curve was drawn using the Kaplan-Meier method.Survival and univariate analyses were done using the Log-rank test,and multivariate analysis was done using the Cox proportional hazard model.Results (1) Clinical features and results of assisted examinations:among the 322 patients,there were 301 patients with a chief complaint of jaundice.Of the 322 patients,the preoperative highest levels of TBil,DBil,ALT and AST in 322 patients were 3.9-785.2 μmol/L,1.6-410.2 μ mol/L,14.8-484.5 U/L and 21.4-539.8 U/L,respectively.Levels of ALP and GGT in 272 patients were 93.8-1 890.0 U/L and 2.0-1 832.8 U/L,respectively.Seventy-seven of 292 patients had an elevated CEA level,272 of 298 patients had an elevated CA19-9 level,153 of 260 patients had an elevated CA242 level and 86 of 260 patients had an elevated CA125 level.According to Bismuth-Corlette type,24 patients were detected in type Ⅰ,115 in type Ⅱ,55 in type Ⅲa,63 in type Ⅲb and 65 in type Ⅳ.(2) Treatments and results of pathological examination:Of the 322 patients,104 patients underwent radical resection,including 79 with hilar bile duct resection (9 combined with vascular resection and reconstruction) and 25 with extended hepatic lobectomy (16 combined with caudate lobectomy),and 218 patients underwent palliative treatments,including 134 with external biliary drainage and 84 with internal biliary drainage.Five patients were dead in the perioperative period,of which 2 died of acute liver failure,1 died of systemic infection and multiple organ failure,1 died of acute renal failure and 1 died of acute suppurative cholangitis,septic shock and disseminated intravascular coagulation.Of 263 patients receiving pathological examination,adenocarcinoma was detected in 253 patients (12 with high-differentiated adenocarcinoma,85 with moderate-differentiated adenocarcinoma,33 with low-differentiated adenocarcinoma and 123 with indefinite differentiation),mucinous adenocarcinoma in 5 patients,cholangiocarcinoma in 3 patients and neuroendocrine carcinoma in 2 patients.TNM staging of 322 patients:stage Ⅰ was detected in 8 patients,stage Ⅱ in 53 patients,stage Ⅲ in 132 patients,stage Ⅳ in 96 patients and indefinite stage in 33 patients.(3) Follow up and survival:among the 322 patients,296 were followed up for 12-132 months,with a median follow-up time of 65 months,including 94 with radical resection and 202 with palliative treatments.Among the 296 patients,the median survival time and 1-,3-,5-year survival rates were 10 months,47.1％,20.2％ and 9.5％,respectively.0f296 patients with follow-up,median survival time and 1-,3-,5-year survival rates were 31 months,84.0％,46.2％,25.0％ in 94 patients receiving radical resection and 7 months,29.9％,8.1％ and 2.3％ in 202 patients receiving palliative treatment,respectively,with a statistically significant difference between the 2 groups (x2=78.777,P＜ 0.05).Among the 94 patients receiving follow-up and radical resection,the median survival time and 1-,3-,5-year survival rates were 31 months,82.1％,45.1％,25.7％ in 73 patients undergoing hilar bile duct resection and 35 months,90.5％,49.8％,22.1％ in 21 patients undergoing hepatic lobectomy,respectively,with no statistically significant difference (x2=0.186,P＞0.05).Among the 73 patients undergoing hilar bile duct resection,median survival time and 1-,3-,5-year survival rates were 16 months,57.1％,0,0 in 7 patients combined with vascular resection and reconstruction and 34 months,84.6％,49.5％,27.5％ in 66 patients undergoing simplex hilar bile duct resection,respectively,showing a statistically significant difference (x2 =11.977,P＜ 0.05).(4) Prognostic factors analysis:results of univariate analysis showed that preoperative highest TBil,preoperative CEA,preoperative CA242,preoperative CA125,treatment methods and TNM staging were related factors affecting prognosis of patients with hilar cholangiocarcinoma (x2=25.009,18.671,9.359,33.628,94.729,77.136,P＜0.05).Multivariate analysis showed that preoperative highest TBil ≥ 342.0 μmol/L,preoperative CEA ≥ 5.00 μg/L,palliative treatments,TNM stage Ⅲ and Ⅳ were the independent risk factors affecting the poor prognosis of patients with hilar cholangiocarcinoma (HR =2.270,2.147,3.166,2.351,95％ confidence interval:1.587-3.247,1.446-3.188,2.117-4.734,1.489-3.712,P＜0.05).Conclusions Prognosis of hilar cholangiocarcinoma is still unsatisfactory.The R0 resection is the key in radical surgery.Preoperative highest TBil≥342.0 μmol/L,preoperative CEA ≥ 5.00 μg/L,palliative treatments,TNM stage Ⅲ-Ⅳ are independent risk factors affecting the poor prognosis of patients with hilar cholangiocarcinoma.

Sepsis is a life-threatening organ dysfunction caused by dysregulated host responses to infection. Despite significant advances in anti-infective, immunomodulatory, and organ function support technologies, the precise and targeted management of sepsis remains a challenge due to its high heterogeneity. Studies have identified disturbed tryptophan (TRP) metabolism as a common mechanism in multiple diseases, which is involved in both immune regulation and the development of multi-organ damages. The rise of research on intestinal microflora has further highlighted the critical role of microflora-regulated TRP metabolism in pathogen-host interactions and the "cross-talk" among multi-organs, making it a potential key target for precision medicine in sepsis. This article reviews TRP metabolism, the regulation of TRP metabolism by the intestinal microflora, and the characteristics of TRP metabolism in sepsis, providing clues for further clinical targeting of TRP metabolism for precision medicine in sepsis.
Humans ; Gastrointestinal Microbiome/physiology* ; Tryptophan/metabolism* ; Precision Medicine ; Sepsis

Objective To explore the diagnosis and treatment of atypical severe combined immunodeficiency disease (SCID). Methods The clinical data of atypical SCID in 7 children with IL2RG,JAK3,and RAG1 mutations were reviewed and analyzed from September 2012 to June 2017. Results In 7 cases (6 males and 1 female), there were 5 infants, 1 toddler and 1 school-age child. Cases 2, 4, and 6 were classic SCID clinical phenotypes. Cases 1, 3, 5, 7 were atypical SCID clinical phenotypes. Case 6 were diagnosed with Omenn syndrome. Cases 2, 5 were classic SCID immune phenotypes, cases 1, 3, 4, 6, 7 were atypical SCID immune phenotypes, and case 1 had maternal chimera. The next generation sequencing indicated that case 1 had a compound heterozygous JAK3 mutation with c.3097-1G>A/c.946-950GCGGA>ACinsGGT.Cases 2,3,and 4 had IL2RG mutations,with c.865C>T/p.R289X,c.664C>T/R222C,52delG,respectively.Case 5 had JAK3 mutations with c.2150A>G/p.E717G and c.1915-2A>G.Sanger sequencing indicated that case 6 had a RAG1 mutation of complex heterozygosity with c.994C>T/p.R332X and c.1439G>A/p.S480N. Case 7 had homozygous RAG1 mutation with c.2095C>T/p.R699W.Conclusion Under certain conditions,gene mutation can lead to atypical clinical and/or immune phenotypic SCID.

Objective:To compare the effects of two methods of marking surface landmarks on the patient’s positional stability when using a multifunctional body board in combination with thermoplastics to fix the abdominal and pelvic areas for radiotherapy patients.Methods:50 subjects who underwent positional fixation using a multifunctional body board in combination with thermoplastics from August 2022 to January 2023. The subjects were divided into two groups, A and B, with 25 cases each, according to the different methods of body surface marking. In group A, landmarks were marked on the body surface on the top edge of the thermoplastics. In group B, three sets of surface landmarks were marked on the patient’s body according to the laser line on the projection of the patient’s body surface when the thermoplastics were completed. Manual registration is performed using L3 to L5 as the main registration targets. The pre-treatment CBCT image is used to analyze the first-time positioning pass rate, setup errors in the x-, y-, and z-axis directions, and the distribution of positive and negative setup errors in both groups of patients. Results:The pass rates of the first-time positioning of patients in Groups A and B were 76.9% and 86.1%, respectively, which met the clinical requirements. Group B had a better first-time positioning pass rate than group A, and the difference between the two groups was statistically significant ( P < 0.05). The pendulum errors of group B were smaller than those of group A in both the x-axis and y-axis (all P < 0.05), and the difference between the two groups in terms of the pendulum errors in the z-axis direction was not statistically significant (all P > 0.05). The difference in the frequency distribution of the pendulum error in the positive and negative directions of the x- and z-axis between the two groups was not statistically significant (all P > 0.05). The difference in the frequency of distribution of the pendulum error in the positive and negative directions of the y-axis between the two groups was statistically significant ( P < 0.05). Conclusions:The proposed two methods of surface landmark marking are generally in line with the positioning requirements for conventional fractionation radiotherapy for abdominal and pelvic patients. Using a laser line on the projection of the patient’s body surface for three sets of surface landmark markings produces smaller setup errors and is better than using the top edge of the thermoplastics for surface landmark markings, improving the positional stability of abdominal and pelvic patients.

Objective To explore the effect of circadian rhythm genes on flavonoids biosynthesis in safflower and its molecular mechanism. Methods Based on the transcriptome and metabolomic database of safflower corolla, we screened the circadian rhythm genes that correlate with biosynthesis of flavonoids in safflower. qPCR was used to quantify the expressions of circadian rhythm genes in different flowering stages at different time points in a single day. LC-MS was performed to determine the accumulation of flavonoids. The correlation between them was analyzed as well. Yeast Two-Hybrid experiment was used to verify the interactive proteins of these genes. Results Seven circadian rhythm genes PRR1, PRR2, ELF3, FT, PHYB, GI and ZTL were obtained. PRR1 gene was positively correlated with flavonoids accumulation (r≥0.7). The full length of PRR1 is 3 201 bp, encoding 421 amino acids, which is highly homologous with rice OsPRR73 gene and named as CtPRR1 (GenBank accession number: MW492035). CtPRR1 was mainly expressed in flowers, and the expression level increased in the daytime and declined in the evening gradually. Correspondingly, the content of flavonoids showed an opposite variation. Both of them displayed a circadian rhythm with a negative correlation (r≥−0.7). In addition, 2 heat shock proteins along with 3 AP2 transcription factors interacting with CtPRR1 protein were obtained via Yeast Two-Hybrid experiment. Conclusion CtPRR1 negatively regulated the safflower flavonoids accumulation in a circadian rhythm way, which may be affected by these interacting proteins.

Collectively migrating tumor cells have been recently implicated in enhanced metastasis of epithelial malignancies. In oral squamous cell carcinoma (OSCC), v integrin is a crucial mediator of multicellular clustering and collective movement ; however, its contribution to metastatic spread remains to be addressed. According to the emerging therapeutic concept, dissociation of tumor clusters into single cells could significantly suppress metastasis-seeding ability of carcinomas. This study aimed to investigate the anti-OSCC potential of novel endostatin-derived polypeptide PEP06 as a cluster-dissociating therapeutic agent . Firstly, we found marked enrichment of v integrin in collectively invading multicellular clusters in human OSCCs. Our study revealed that metastatic progression of OSCC was associated with augmented immunostaining of v integrin in cancerous lesions. Following PEP06 treatment, cell clustering on fibronectin, migration, multicellular aggregation, anchorage-independent survival and colony formation of OSCC were significantly inhibited. Moreover, PEP06 suppressed v integrin/FAK/Src signaling in OSCC cells. PEP06-induced loss of active Src and E-cadherin from cell-cell contacts contributed to diminished collective migration of OSCC . Overall, these results suggest that PEP06 polypeptide 30 inhibiting v integrin/FAK/Src signaling and disrupting E-cadherin-based intercellular junctions possesses anti-metastatic potential in OSCC by acting as a cluster-dissociating therapeutic agent.

Immunotherapy has become a highly promising paradigm for cancer treatment. Herein, a chemo-immunotherapy was developed by encapsulating chemotherapeutic drug doxorubicin (DOX) and Toll-like receptor 7 agonist imiquimod (IMQ) in low molecular weight heparin (LMWH)-d--tocopheryl succinate (TOS) micelles (LT). In this process, LMWH and TOS were conjugated by ester bond and they were not only served as the hydrophilic and hydrophobic segments of the carrier, but also exhibited strong anti-metastasis effect. The direct killing of tumor cells mediated by DOX-loaded micelles (LT-DOX) generated tumor-associated antigens, initiating tumor-specific immune responses in combination with IMQ-loaded micelles (LT-IMQ). Furthermore, the blockade of immune checkpoint with programmed cell death ligand 1 (PD-L1) antibody further elevated the immune responses by up-regulating the maturation of DCs as well as the ratios of CD8 CTLs/T and CD4 T/T. Therefore, such a multifunctional strategy exhibited great potential for inhibiting the growth of orthotopic and metastatic breast cancer.