Identification of in vivo metabolites of Citri Sarcodactylis Fructus by UHPLC-Q/Orbitrap HRMS.

INTRODUCTION: Citri Sarcodactylis Fructus has the effects of relieving cough, removing phlegm, and reducing asthma, but little is known about the metabolic and distribution of its chemical constituents in vivo. Therefore, it is necessary to study the metabolism of Citri Sarcodactylis Fructus in vivo. OBJECTIVE: We aimed to (1) analyze the distribution of prototype compounds and metabolites of the chemical constituents of Citri Sarcodactylis Fructus in rat and (2) infer the metabolites and metabolic pathways of the chemical constituents. MATERIALS AND METHODS: A C18 column (3 × 100 mm, 2.6 µm) was used. The mobile phase was water containing 0.1% formic acid (eluent A) and acetonitrile containing 0.1% formic acid (eluent B) at a discharge rate of 0.3 mL/min. Mass spectra of biological samples were collected in electrospray ionization (ESI) positive ion mode in the m/z 100-1500 scan range. The obtained biological samples were then subjected to chemical analysis, including plasma, urine, feces, and heart, liver, spleen, lungs, kidneys, stomach, and small intestine tissues. Prototype compounds and metabolites were identified. RESULTS: In all, 40 prototype compounds and 78 metabolites, including 26 phase I metabolites and 52 phase II metabolites, were identified using UHPLC-Q/Orbitrap HRMS. Eight possible metabolic pathways (reduction, hydrolysis, dehydration, methylation, hydroxylation, sulfation, glucuronidation, and demethylation) were proposed. The prototype compounds were predominantly distributed in lung tissues. The metabolites were mainly distributed in plasma and kidney tissues. CONCLUSION: We systematically investigated the metabolites of Citri Sarcodactylis Fructus in vivo. We suggest metabolic pathways that might be relevant for further metabolic studies and screening of active ingredients of Citrus Sarcodactylis Fructus in vivo.

Panscleritis After Blunt Ocular Trauma in A Child with Epididymitis.

We reported an 8-year-old boy with panscleritis in left eye and right epididymitis after falling on the ground. Etiologic diagnosis played a key role in this case. Systemic examinations ruled out systemic autoimmune diseases, tumors, and infections as the cause of scleritis and suggested that the disease was caused by a local delayed-type hypersensitivity (DTH) induced by ocular trauma and was non-infectious. Still, the right epididymitis was infectious. Both conditions were treated successfully using steroids and antibiotics, respectively. Thus, early etiologic diagnosis and reasonable treatment are crucial to prevent visual loss.

Increases prognostic value of clinical-pathological nomogram in patients with esophageal squamous cell carcinoma.

Background: This study was intended to construct a brand new prognostic nomogram after combine clinical and pathological characteristics to increases prognostic value in patients with esophageal squamous cell carcinoma. Methods: A total of 1,634 patients were included. Subsequently, the tumor tissues of all patients were prepared into tissue microarrays. AIPATHWELL software was employed to explore tissue microarrays and calculate the tumor-stroma ratio. X-tile was adopted to find the optimal cut-off value. Univariate and multivariate Cox analyses were used to screen out remarkable characteristics for constructing the nomogram in the total populations. A novel prognostic nomogram with clinical and pathological characteristics was constructed on the basis of the training cohort (n=1,144). What's more performance was validated in the validation cohort (n=490). Clinical-pathological nomogram were assessed by concordance index, time-dependent receiver operating characteristic, calibration curve and decision curve analysis. Results: The patients can divide into two groups with cut-off value of 69.78 for the tumor-stroma ratio. It is noteworthy that the survival difference was noticeable (P<0.001). A clinical-pathological nomogram was constructed by combining clinical and pathological characteristics to predict the overall survival. In comparison with TNM stage, the concordance index and time-dependent receiver operating characteristic of the clinical-pathological nomogram showed better predictive value (P<0.001). High quality of calibration plots in overall survival was noticed. As demonstrated by the decision curve analysis, the nomogram has better value than the TNM stage. Conclusions: As evidently revealed by the research findings, tumor-stroma ratio is an independent prognostic factor in patients with esophageal squamous cell carcinoma. The clinical-pathological nomogram has an incremental value compared TNM stage in predicting overall survival.

Survival influence of gender on 42,345 patients with gastric cardia adenocarcinoma.

PURPOSE: Some studies indicated that gender is associated with prognostic of cancer, However, currently the prognostic value of gender for gastric cardia adenocarcinoma (GCA) survival is unclear. The aim of our study is to reveal the influence of gender on the prognosis of patients with GCA. PATIENTS AND METHODS: A total of 42,345 cases Chinese GCA patients were enrolled from our previously established GCA and esophageal cancer databases. The clinicopathological characteristics were retrieved from medical records in hospital. The follow-up was performed through letter, telephone or home interview. Among GCA patients, there were 32,544 (76.9%) male patients with the median age 62 years (range 17-97) and 9,801 (23.1%) female patients with the median age 61 years (range 17-95 years). The Chi-square test and Kaplan-Meier method were used to compare the continuous variables and survival. Cox proportional hazards model was used for competing risk analyses, hazard ratios (HRs) and 95% confidence intervals (CIs) were evaluated. RESULTS: Men had shorter GCA-specific survival than women by multivariate analysis (HR 1.114; 95% CI 1.061 to 1.169; P < 0.001). Whether premenopausal, perimenopausal or postmenopausal, the survival of women was better than that of men (premenopausal vs. male, P < 0.001; perimenopausal vs. male, P < 0.001; postmenopausal vs. male, P = 0.035). It was worth noting that in patients with stages I, II, III, and IV, female patients survive longer than male patients (P = 0.049; P = 0.011; P < 0.001; P = 0.044, respectively). CONCLUSION: Gender is an independent prognostic factor for patients with GCA. In comparison with men, women have a significantly better outcome. Smoking and drinking may be protective factors for male GCA patients.

An updated patent review of IDO1 inhibitors for cancer (2018-2022).

INTRODUCTION: Indoleamine 2,3-dioxygenase 1 (IDO1) is highly related to the immune evasion of a wide range of malignancies due to its role in the immune suppression caused by the depletion of tryptophan (Trp) and the accumulation of kynurenine (Kyn). The combination of IDO1 inhibitors with other treatments represents a promising strategy in immunotherapy, although considerable challenges lie ahead. AREAS COVERED: This review focuses on patent publications searched from Espacenet and Google Scholar, and related to IDO1 inhibitors with potential anti-cancer utilization during the period 2018-2022. EXPERT OPINION: Despite the clinical trial failure of the first-in-class IDO1 inhibitor epacadostat in combination with pembrolizumab, numerous studies have been carried on to pursue more efficient IDO1-based immune-modulating therapeutic solutions. A large number of IDO1 inhibitors with new structures and design concepts have been produced with the impetus of crystallographic studies, and have shown great research potential. The elaboration on the combination of IDO1 inhibitors with other targeting agents, the more precise selection of patients, the identification of more reliable biomarkers for evaluating the IDO1 treatment, and the investigation of possible toxicity, are critical factors to promote IDO1-based immunotherapies from bench to bedside.

Transthoracic, thoracoabdominal, and transabdominal surgical approaches for gastric cardia adenocarcinomas: a survival evaluation based on a cohort of 7103 patients.

BACKGROUND: This study compared the survival outcomes of different surgical approaches to determine the optimal approach for gastric cardia adenocarcinoma (GCA) and aimed to standardize the surgical treatment guidelines for GCA. METHODS: A total of 7103 patients with GCA were enrolled from our previously established gastric cardia and esophageal carcinoma databases. In our database, when the epicenter of the tumor was at or within 2 cm distally from the esophagogastric junction, the adenocarcinoma was considered to originate from the cardia and was considered a Siewert type 2 cancer. The main criteria for the enrolled patients included treatment with radical surgery, no radio- or chemotherapy before the operation, and detailed clinicopathological information. Follow-up was mainly performed by telephone or through home interviews. According to the medical records, the surgical approaches included transthoracic, thoracoabdominal, and transabdominal approaches. Kaplan-Meier and Cox proportional hazards regression models were applied to correlate the surgical approach with survival in patients with GCA. RESULTS: There were marked differences in age and tumor stage among the patients who underwent the three surgical approaches (P < 0.001). Univariate analysis showed that survival was related to sex, age, tumor stage, and N stage (P < 0.001 for all). Cox regression model analysis revealed that thoracoabdominal approach (P < 0.001) and transabdominal approach (P < 0.001) were significant risk factors for poor survival. GCA patients treated with the transthoracic approach had the best survival (5-year survival rate of 53.7%), and survival varied among the different surgical approaches for different tumor stages. CONCLUSION: Thoracoabdominal approach and transabdominal approach were shown to be poor prognostic factors. Patients with (locally advanced) GCA may benefit from the transthoracic approach. Further prospective randomized clinical trials are necessary.

Serum Metabolomic Profiling Reveals Biomarkers for Early Detection and Prognosis of Esophageal Squamous Cell Carcinoma.

Esophageal squamous cell carcinoma (ESCC) is one of the most common aggressive malignancies worldwide, particularly in northern China. The absence of specific early symptoms and biomarkers leads to late-stage diagnosis, while early diagnosis and risk stratification are crucial for improving overall prognosis. We performed UPLC-MS/MS on 450 ESCC patients and 588 controls consisting of a discovery group and two validation groups to identify biomarkers for early detection and prognosis. Bioinformatics and clinical statistical methods were used for profiling metabolites and evaluating potential biomarkers. A total of 105 differential metabolites were identified as reliable biomarker candidates for ESCC with the same tendency in three cohorts, mainly including amino acids and fatty acyls. A predictive model of 15 metabolites [all-trans-13,14-dihydroretinol, (±)-myristylcarnitine, (2S,3S)-3-methylphenylalanine, 3-(pyrazol-1-yl)-L-alanine, carnitine C10:1, carnitine C10:1 isomer1, carnitine C14-OH, carnitine C16:2-OH, carnitine C9:1, formononetin, hyodeoxycholic acid, indole-3-carboxylic acid, PysoPE 20:3, PysoPE 20:3(2n isomer1), and resolvin E1] was developed by logistic regression after LASSO and random forest analysis. This model held high predictive accuracies on distinguishing ESCC from controls in the discovery and validation groups (accuracies > 89%). In addition, the levels of four downregulated metabolites [hyodeoxycholic acid, (2S,3S)-3-methylphenylalanine, carnitine C9:1, and indole-3-carboxylic acid] were significantly higher in early cancer than advanced cancer. Furthermore, three independent prognostic markers were identified by multivariate Cox regression analyses with and without clinical indicators: a high level of MG(20:4)isomer and low levels of 9,12-octadecadienoic acid and L-isoleucine correlated with an unfavorable prognosis; the risk score based on these three metabolites was able to stratify patients into low or high risk. Moreover, pathway analysis indicated that retinol metabolism and linoleic acid metabolism were prominent perturbed pathways in ESCC. In conclusion, metabolic profiling revealed that perturbed amino acids and lipid metabolism were crucial metabolic signatures of ESCC. Both panels of diagnostic and prognostic markers showed excellent predictive performances. Targeting retinol and linoleic acid metabolism pathways may be new promising mechanism-based therapeutic approaches. Thus, this study would provide novel insights for the early detection and risk stratification for the clinical management of ESCC and potentially improve the outcomes of ESCC.

Long-term effect of hospital volume on the postoperative prognosis of 158,618 patients with esophageal squamous cell carcinoma in China.

Background: The impact of hospital volume on the long-term survival of esophageal squamous cell carcinoma (ESCC) has not been well assessed in China, especially for stage I-III stage ESCC. We performed a large sample size study to assess the relationships between hospital volume and the effectiveness of ESCC treatment and the hospital volume value at the lowest risk of all-cause mortality after esophagectomy in China. Aim: To investigate the prognostic value of hospital volume for assessing postoperative long-term survival of ESCC patients in China. Methods: The date of 158,618 patients with ESCC were collected from a database (1973-2020) established by the State Key Laboratory for Esophageal Cancer Prevention and Treatment, the database includes 500,000 patients with detailed clinical information of pathological diagnosis and staging, treatment approaches and survival follow-up for esophageal and gastric cardia cancers. Intergroup comparisons of patient and treatment characteristics were conducted with the X2 test and analysis of variance. The Kaplan-Meier method with the log-rank test was used to draw the survival curves for the variables tested. A Multivariate Cox proportional hazards regression model was used to analyze the independent prognostic factors for overall survival. The relationship between hospital volume and all-cause mortality was assessed using restricted cubic splines from Cox proportional hazards models. The primary outcome was all-cause mortality. Results: In both 1973-1996 and 1997-2020, patients with stage I-III stage ESCC who underwent surgery in high volume hospitals had better survival than those who underwent surgery in low volume hospitals (both P<0.05). And high volume hospital was an independent factor for better prognosis in ESCC patients. The relationship between hospital volume and the risk of all-cause mortality was half-U-shaped, but overall, hospital volume was a protective factor for esophageal cancer patients after surgery (HR<1). The concentration of hospital volume associated with the lowest risk of all-cause mortality was 1027 cases/year in the overall enrolled patients. Conclusion: Hospital volume can be used as an indicator to predict the postoperative survival of ESCC patients. Our results suggest that the centralized management of esophageal cancer surgery is meaningful to improve the survival of ESCC patients in China, but the hospital volume should preferably not be higher than 1027 cases/year. Core tip: Hospital volume is considered to be a prognostic factor for many complex diseases. However, the impact of hospital volume on long-term survival after esophagectomy has not been well evaluated in China. Based on a large sample size of 158,618 ESCC patients in China spanning 47 years (1973-2020), We found that hospital volume can be used as a predictor of postoperative survival in patients with ESCC, and identified hospital volume thresholds with the lowest risk of death from all causes. This may provide an important basis for patients to choose hospitals and have a significant impact on the centralized management of hospital surgery.

The prognostic value of keratin pearls in patients with esophageal squamous cell carcinoma.

Keratin pearls (KP) is an important indicator of the degree of tumor cell differentiation of esophageal squamous cell carcinomas (ESCC). However, the independent prognostic value of KP in ESCC patients remains unclear. The hematoxylin-eosin (H&E) stained tissue microarrays (TMAs) or whole slides of the patients were prepared to identify the existence of KP. Kaplan-Meier (KM) survival analysis as well as univariate and multivariate Cox regression analyses were used to evaluate the prognostic value of KP. A nomogram based on KP and other clinicopathologic characteristics was constructed. The C-index, calibration curve, Receiver Operating Characteristic (ROC) curve, and Decision Curve Analysis (DCA) were used to evaluate the nomogram. The results indicated KP is a protective factor against lymph node metastasis and is closely associated with the differentiation degree in ESCC patients. KM survival analysis showed that the overall survival (OS) of patients with KP was significantly better than for patients without KP. In addition, multivariate Cox regression analysis revealed that KP was an independent predictor of OS. Furthermore, ROC curve demonstrated that KP combined with differentiation degree could more accurately predict the 5-year survival rate than differentiation degree alone. Importantly, the nomogram showed good discrimination and calibration abilities in both training and validation groups, which could more accurately predict the 3-, 5-, and 10-year survival rates of ESCC patients and adds to the predictive value of TNM stage alone. In conclusion, KP is an independent predictor of prognosis in patients with ESCC and provides incremental prognostic value to degree of differentiation.

Personalized Immunotherapy in Colorectal Cancers: Where Do We Stand?

Colorectal cancer (CRC) is the second leading cause of cancer death in the world. Immunotherapy using monoclonal antibodies, immune-checkpoint inhibitors, adoptive cell therapy, and cancer vaccines has raised great hopes for treating poor prognosis metastatic CRCs that are resistant to the conventional therapies. However, high inter-tumor and intra-tumor heterogeneity hinder the success of immunotherapy in CRC. Patients with a similar tumor phenotype respond differently to the same immunotherapy regimen. Mutation-based classification, molecular subtyping, and immunoscoring of CRCs facilitated the multi-aspect grouping of CRC patients and improved immunotherapy. Personalized immunotherapy using tumor-specific neoantigens provides the opportunity to consider each patient as an independent group deserving of individualized immunotherapy. In the recent decade, the development of sequencing and multi-omics techniques has helped us classify patients more precisely. The expansion of such advanced techniques along with the neoantigen-based immunotherapy could herald a new era in treating heterogeneous tumors such as CRC. In this review article, we provided the latest findings in immunotherapy of CRC. We elaborated on the heterogeneity of CRC patients as a bottleneck of CRC immunotherapy and reviewed the latest advances in personalized immunotherapy to overcome CRC heterogeneity.

A Systematic Review of the Potential Chemoprotective Effects of Resveratrol on Doxorubicin-Induced Cardiotoxicity: Focus on the Antioxidant, Antiapoptotic, and Anti-Inflammatory Activities.

PURPOSE: Although doxorubicin chemotherapeutic drug is commonly used to treat various solid and hematological tumors, its clinical use is restricted because of its adverse effects on the normal cells/tissues, especially cardiotoxicity. The use of resveratrol may mitigate the doxorubicin-induced cardiotoxic effects. For this aim, we systematically reviewed the potential chemoprotective effects of resveratrol against the doxorubicin-induced cardiotoxicity. METHODS: In the current study, a systematic search was performed based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline for the identification of all relevant studies on "the role of resveratrol on doxorubicin-induced cardiotoxicity" in the electronic databases of Web of Science, PubMed, and Scopus up to March 2021 using search terms in their titles and abstracts. Two hundred and eighteen articles were screened in accordance with a predefined set of inclusion and exclusion criteria. Finally, 33 eligible articles were included in this systematic review. RESULTS: The in vitro and in vivo findings demonstrated a decreased cell survival, increased mortality, decreased heart weight, and increased ascites in the doxorubicin-treated groups compared to the control groups. The combined treatment of resveratrol and doxorubicin showed an opposite pattern than the doxorubicin-treated groups alone. Furthermore, this chemotherapeutic agent induced the biochemical and histopathological changes on the cardiac cells/tissue; however, the results (for most of the cases) revealed that these alterations induced by doxorubicin were reversed near to normal levels (control groups) by resveratrol coadministration. CONCLUSION: The results of this systematic review stated that coadministration of resveratrol alleviates the doxorubicin-induced cardiotoxicity. Resveratrol exerts these chemoprotective effects through several main mechanisms of antioxidant, antiapoptosis, and anti-inflammatory.

GWAS follow-up study of esophageal squamous cell carcinoma identifies potential genetic loci associated with family history of upper gastrointestinal cancer.

Based on our initial genome-wide association study (GWAS) on esophageal squamous cell carcinoma (ESCC) in Han Chinese, we conducted a follow-up study to examine the single nucleotide polymorphisms (SNPs) associated with family history (FH) of upper gastrointestinal cancer (UGI) cancer in cases with ESCC. We evaluated the association between SNPs and FH of UGI cancer among ESCC cases in a stage-1 case-only analysis of the National Cancer Institute (NCI, 541 cases with FH and 1399 without FH) and Henan GWAS (493 cases with FH and 869 without FH) data (discovery phase). The top SNPs (or their surrogates) from discovery were advanced to a stage-2 evaluation in additional Henan subjects (2801 cases with FH and 3136 without FH, replication phase). A total of 19 SNPs were associated with FH of UGI cancer in ESCC cases with P < 10-5 in the stage-1 meta-analysis of NCI and Henan GWAS data. In stage-2, the association for rs79747906 (located at 18p11.31, P = 5.79 × 10-6 in discovery) was replicated (P = 0.006), with a pooled-OR of 1.59 (95%CI: 1.11-2.28). We identified potential genetic variants associated with FH of UGI cancer. Our findings may provide important insights into new low-penetrance susceptibility regions involved in the susceptibility of families with multiple UGI cancer cases.

Effects of Senegenin against hypoxia/reoxygenation-induced injury in PC12 cells.

OBJECTIVE: To investigate the effect and the potential mechanism of Senegenin (Sen) against injury induced by hypoxia/reoxygenation (H/R) in highly differentiated PC12 cells. METHODS: The cultured PC12 cells were treated with H/R in the presence or absence of Sen (60 µmol/L). Four groups were included in the experiment: control group, H/R group, H/R+Sen group and Sen group. Cell viability of each group and the level of lactate dehydrogenase (LDH) in culture medium were detected for the pharmacological effect of Sen. Hoechst 33258 staining and annexin V/propidium iodide double staining were used to analyze the apoptosis rate. Moreover, mitochondrial membrane potential (△Ψm), reactive oxygen species (ROS) and intracellular free calcium ([Ca(2+)]i) were measured by fluorescent staining and flow cytometry. Cleaved caspase-3 and activity of NADPH oxidase (NOX) were determined by colorimetric protease assay and enzyme linked immunosorbent assay, respectively. RESULTS: Sen significantly elevated cell viability (P<0.05), decreased the leakage of LDH (P<0.05) and apoptosis rate (P<0.05) in H/R-injured PC12 cells. Sen maintained the value of △Ψm (P<0.05) and suppressed the activity of caspase-3 (P<0.05). Moreover, Sen reduced ROS accumulation P<0.05) and [Ca(2+)]i increment (P<0.05) by inhibiting the activity of NOX (P<0.05). CONCLUSION: Sen may exert cytoprotection against H/R injury by decreasing the levels of intracellular ROS and [Ca(2+)]i, thereby suppressing the mitochondrial pathway of cellular apoptosis.

Association between glutathione S-transferases M1 and T1 gene polymorphisms and esophageal cancer prognosi.

OBJECTIVE: To investigate the independent factors affecting the prognosis of patients after resection of esophageal cancer, and to inquire into the relationship between GSTM1, GSTT1 gene polymorphisms and esophageal cancer prognosis. METHODS: The clinical data of 273 patients with esophageal cancer were retrospectively analyzed. The patients were followed-up after their surgery, and the gene polymorphisms of GSTM1 and GSTT1 in each individual were detected by polymerase chain reaction (PCR). The clinical features along with the gene polymorphisms of GSTM1 and GSTT1 associated with the prognosis of patients were analyzed by using the method of univariate analysis and Cox proportional hazard model. The cumulative survival rate was estimated by Kaplan-Meier methods, and the survival curves were compared by using the log-rank test. RESULTS: The overall cumulative survival rate of first year, third year and fifth year is 94.6%, 58.5% and 17.8%, respectively. The median survival time (MST) is 38.7 months. The results of univariate analysis showed that: infiltration depth, length of tumor, the number of lymph node metastasis, the region of lymph node metastasis and the genetic polymorphism of GSTM1 and GSTT1 gene loci were associated with the survival of postoperative patients. Cox multivariate analysis further indicated that the length of tumor, the number of lymph node metastasis and the combined genotype (1) [GSTM1 (+/+) or (+/-) & GSTT1 (-/-)] were the independent prognostic factors. The length of tumor, the number of lymph node metastasis were the risk factors for the prognosis, and the combined genotype (1) had protective effect on survival when compared with reference [GSTM1 (+/+) or (+/-) & GSTT1 (+/+) or (+/-)]. CONCLUSION: The length of tumor, the number of lymph node metastasis were confirmed as the independent prognostic factors of esophageal carcinoma, and the null genotypes for GSTT1 (-/-) might be a protective factor for survival and GSTM1 (-/-) might be a potential negative prognostic factor in patients with esophageal cancer.

Potent and Nontoxic Chemosensitizer of P-Glycoprotein-Mediated Multidrug Resistance in Cancer: Synthesis and Evaluation of Methylated Epigallocatechin, Gallocatechin, and Dihydromyricetin Derivatives.

We are interested in developing novel natural product-derived P-gp inhibitors to reverse cancer drug resistance. Here, we have synthesized 55 novel derivatives of methylated epigallocatechin (EGC), gallocatechin (GC), and dihydromyricetin (DHM). Three EGC derivatives (23, 35, and 36) and three GC derivatives (50, 51, and 53) are significantly better than epigallocatechin gallate (EGCG) with a relative fold (RF) ranging from 31.4 to 53.6. The effective concentration (EC50) of 23 and 51 ranges from 102 to 195 nM. Compounds 23 and 51 are noncytotoxic to fibroblasts with IC50 > 100 µM. Compound 23 is specific for P-gp without modulating activity toward MRP1 or BCRP. Compounds 23 and 51 are non-P-gp substrates. Important pharmacophores for P-gp modulation were identified. In summary, methylated EGC and GC derivatives represent a new class of potent, specific, noncytotoxic, and nonsubstrate P-gp modulators.

[Changes of dynamic visual acuity after phacoemulsification combined with intraocular lens implantation].

OBJECTIVE: To compare the spatial resolutions of dynamic optotypes at different speed levels among age-related cataract patients, older people with clear crystalline lenses and senile individuals implanted with intraocular lenses (IOL). METHODS: The control study recruited 24 patients (48 eyes) with age-related cataract scheduled for phacoemulsification surgery in our hospital between Jul. 2011 and Dec. 2011 in the cataract group. Twenty-three older volunteers (46 eyes) with clear crystalline lenses were enrolled in the normal group. The postoperative group consisted of 23 contemporary cases implanted with spherical monofocal non-yellow-tinted IOL and followed up for 3 months postoperatively, of which 5 cases undertook unilateral surgery for normal visual acuity of the contralateral eye. Monocular and binocular best corrected visual acuity at static condition and binocular spatial resolution of optotypes at speeds of 15, 30, 60 and 90 degrees per second (dps) were measured by a logarithmic visual acuity chart. Statistical analysis was performed with student's t test (with Bonferroni correction). RESULTS: Binocular spatial resolutions at speeds of 15, 30, 60 and 90 dps were (0.29 ± 0.16), (0.34 ± 0.17), (0.47 ± 0.19) and (0.52 ± 0.17), respectively, in the cataract group, and (0.04 ± 0.06), (0.06 ± 0.06), (0.12 ± 0.09) and (0.15 ± 0.11), respectively, in the normal group. Resolution of dynamic optotypes at the four speed levels were statistically lower in the cataract group than in the normal group (t = -6.952, -7.558, -8.235, -8.737; P < 0.01). Velocity dependent spatial resolution changes manifested statistically higher values in the cataract group than in the normal group, with (0.14 ± 0.13) versus (0.03 ± 0.05) at the interval between static and 15 dps (t0-15 dps = -3.874, P = 0.001) and (0.13 ± 0.09) versus (0.06 ± 0.07) at the interval between 30 dps and 60 dps (t30-60 dps = -3.113, P = 0.003). In the postoperative group, resolutions of dynamic optotypes at speeds of 15, 30, 60 and 90 dps were (0.03 ± 0.05), (0.05 ± 0.07), (0.11 ± 0.10) and (0.16 ± 0.11), respectively. Dynamic visual acuities at all the four speed levels were statistically higher in the postoperative group than in the cataract group (t = -7.336, -7.673, -8.328, -8.583; P < 0.01) and compatible to that in the normal group (t = 0.669, 0.400, 0.372, -0.504; P > 0.05). Visual acuity differences between consecutive speed levels were comparable between the postoperative group and the normal group (t = 0.586, -0.326, 0.133, -1.600; P > 0.05), while at the interval between static and 15 dps and the interval between 30 dps and 60 dps, the postoperative group exhibited lower visual acuity changes than the cataract group, with (0.03 ± 0.04) versus (0.14 ± 0.13) (t0-15 dps = -4.182, P < 0.01) and (0.05 ± 0.06) versus (0.13 ± 0.09) (t30-60 dps = -3.334, P = 0.002), respectively. CONCLUSIONS: As the optotype's moving speed increased, spatial resolutions declined more rapidly in patients with age-related cataract. Phacoemulsification combined with IOL implantation could effectively restore the spatial resolution of dynamic optotypes.

[Randomly sampling survey of dry eye awareness in general eye clinic].

OBJECTIVE: To determine the dry eye awareness in the populations visiting general eye clinic. METHODS: This was a cross-sectional study. A questionnaire about dry eye was designed and administrated to Peking University Third Hospital General Eye Clinic patients (n = 804) from June 2010 to June 2011. The questionnaire contents included general demographic characteristics, experience of health-related work, past medical history, medication history and ocular surface symptoms associated with dry eye, contact lens wearing, ocular operation history, etc. Chi-square and Binary logistic regression analysis was used to determine the influence of demographic and clinical features on awareness of dry eye. RESULTS: Awareness of "dry eye" in the general eye clinical patients was relatively low (26.9%, 216/804). Participants whose age were between 40 and 60 years had better dry eye awareness (41.7%, 73/175) (χ(2) = 27.365, P = 0.000). Dry eye awareness of female was better than that of male [female: 33.8% (151/447), male: 18.2% (65/357), χ(2) = 24.500, P = 0.000]. Those who had been in health-related work (71.4%, 30/42), and whose friends or relatives were ophthalmologists (54.7%, 52/95) had better dry eye awareness (χ(2) = 31.582, 36.400; both P < 0.01). Participants with a history of rheumatoid arthritis (7/10) or diabetes mellitus (63.0%, 17/27) had better dry eye awareness (χ(2) = 32.301, 29.887;both P < 0.01). Those who had been using artificial tears (77.5%, 31/40), oral contraceptives (9/14), diuretics (10/18), sedatives (70.4%, 19/27) and anti-depression drugs (4/4) had better dry eye awareness (χ(2) = 54.928, 10.154, 7.713, 26.912, 10.943; all P < 0.01). Except frequently blinking (29.5%), participants who had ocular irrigating symptoms (all > 33.0%) had better awareness than those who had not (χ(2) = 7.831 - 32.522, all P < 0.01). Those who were allergic to environment irritating factors (all > 30.0%) had better awareness (χ(2) = 5.033 - 24.564, all P < 0.01). Participants who had medical history of ocular surgery (47.2%, 34/72), experience of wearing contact lens (33.2%, 94/283), who were diagnosed as dry eye (100.0%, 45/45) and who had regular ocular examinations (31.0%, 96/310) had better awareness (χ(2) = 4.321 - 129.763, all P < 0.01). Those who had visited general practitioners (14.8%, 16/108) had lower awareness than those who went to hospital of higher level (28.7%, 200/696) (χ(2) = 9.324, P = 0.002). The result of binary logistic regression analysis showed that gender, health-related working experience, relatives or friends working as Ophthalmologists, using artificial tears, oral contraceptives and sedatives, ocular irritations or environment sensitivity, eye surgeries and wearing contact lens were factors that affected dry eye awareness (OR > 1.000, P < 0.10). CONCLUSIONS: Dry eye awareness in the population who visit general eye clinic is low. The knowledge of dry eye should be added to the patient education and public popularization.

Polymorphism of A133S and promoter hypermethylation in Ras association domain family 1A gene (RASSF1A) is associated with risk of esophageal and gastric cardia cancers in Chinese population from high incidence area in northern China.

BACKGROUND: The role of tumor suppressor gene RASSF1A in the esophageal and gastric cardia carcinogenesis is still inconclusive. In this study, the polymorphism, promoter methylation and gene expression of RASSF1A were characterized in esophageal squamous cell carcinoma (ESCC) and gastric cardia adenocarcinoma (GCA). METHODS: We firstly analyzed the prevalence of RASSF1A A133S in a total of 228 cancer patients with ESCC (n=112) and GCA (n=116) and 235 normal controls by polymerase chain reaction (PCR) and restriction enzyme-digestion assay. Then, the promoter methylation status of the RASSF1A in ESCC (n=143), GCA (n=92) and corresponding adjacent normal tissues were further investigated using methylation-specific PCR (MSP) approach. Finally, the RASSF1A protein expression were determined in ESCC (n=27), GCA (n=24) and the matched adjacent normal tissues by immunohistochemical method. RESULTS: The frequency of 133Ala/Se and Ser/Ser genotype was significantly higher in GCA patients than in normal controls (19.0% vs. 10.2%, P=0.02). Compared with Ala/Ala genotype, Ala/Se and Ser/Ser genotype significantly increased susceptibility to GCA (OR=2.06, 95% CI=1.09-3.97). However, this polymorphism had no association with ESCC (P=0.69). The promoter methylation of RASSF1A gene was significantly increased the risk to both ESCC (OR=5.90, 95% CI=2.78-12.52) and GCA (OR=7.50, 95% CI= 2.78-20.23). Promoter methylation of RASSF1A gene in ESCC was also associated with age and cancer cell differentiation (for age: OR=3.11, 95% CI=1.10-8.73; for differentiation: OR=0.29, 95% CI=0.12-0.69). RASSF1A positive expression was significantly decreased the risk of GCA (OR=0.16, 95% CI=0.03-0.83). In contrast, there was no statistical significance between RASSF1A positive expression and ESCC. The expression of RASSF1A protein trend to be positively related with older GCA patients (OR=16.20, 95% CI=1.57-167.74). CONCLUSIONS: The present findings suggest that alterations of RASSF1A may play an important role in gastric cardia carcinogenesis in terms of polymorphism, promoter hypermethylation and protein expression. Whereas, RASSF1A hypermethylation may probably also be involved in esophageal squamous cell carcinogenesis.

Duodenum-preserving pancreatic head resection vs. pancreatoduodenectomy for benign lesions and low-grade malignancies of the pancreatic head.

BACKGROUND/AIMS: To compare the postoperative results of duodenum-preserving pancreatic head resection (DPPHR) techniques with those of conventional pancreatoduodenectomy (PD). METHODOLOGY: We retrospectively reviewed the records of 58 patients who underwent DPPHR or PD at Jinhua central hospital between May 1998 and May 2011. RESULTS: Eighteen patients underwent DPPHR (Group 1) and 40 conventional PD (Group 2). They were followed up for more than 6 months. Operation time in Group 1 was longer (290±18 min vs 269±14 min, p=0.001). Estimated blood loss in Group 1 was more (633±88 mL vs. 495±131 mL, p=0.003). Intraoperative transfusion in Group 1 was more (533±88 mL vs. 335±218 mL, p=0,001). However, postoperative transfusion was Iess (141±162 mL vs. 440±193 mL, p=0.000). Group 1 had a lower short-term complication rate (16.67% vs. 50.0%, p=0.0 16) and long-term complication rate (11.11% vs. 45.0%, p=0.012). Hospital mortality of both groups were 0. CONCLUSIONS: DPPHR for benign or premalignant lesions is a difficult procedure, but with a lower complication rate than conventional PD. Preserving the entire duodenum and a normal biliary tree allows better short-term and long-term results. DPPHR will be suitable for only a small group of patients and should be performed by experienced surgeons.

[Exploration of the association of H. pylori and EBV infection with cardiac and distal gastric adenocarcinoma among residents in Cixian County, a high-risk area of esophgeal cancer in Hebei province].

OBJECTIVE: To evaluate the H. pylori and Epstein-Barr virus infection in cardiac and distal gastric adenocarcinoma tissues in residents in Cixian county, a high risk area of esophageal cancer in Hebei province, and to explore the putative role of H. pylori and Epstein-Barr virus infection in the carcinogenesis of adenocarcinoma at different subsites of stomach. METHODS: H. pylori and Epstein-Barr virus latent membrane protein 1 (EBV-LMP1) immunopositivities were determined by Elivision(TM) plus immunohistochemical staining in 190 gastric adenocarcinoma tissues including 144 cases of cardiac adenocarcinoma and 46 cases of distal gastric adenocarcinoma. The relationship between H. pylori and Epstein-Barr virus infection and the subsite, Laurén type as well as other clinicopathological features of gastric adenocarcinoma were analyzed. RESULTS: No significant difference was found between the H. pylori detection rates in cardiac and distal gastric adenocarcinomas(56.9% vs. 65.2%, P > 0.05). The detection rate of H. pylori in intestinal type was significantly higher than that in the diffuse type distal gastric adenocarcinomas (71.8% vs. 28.6%, P < 0.05). No positive expression of EBV-LMP1 was found in the gastric adenocarcinomas in this study. CONCLUSIONS: No significant differences in H. pylori and EBV-LMP1 infections were found between cardiac and distal gastric adenocarcinomas in Cixian county. H. pylori infection is related with the intestinal type of distal gastric adenocarcinoma.