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The Wisconsin upper respiratory symptom survey (WURSS) is a validated English questionnaire to evaluate the quality of life and severity of upper respiratory tract infections (URTIs). We aimed to develop a Mandarin Chinese version of WURSS-24 (WURSS-24-C) and evaluate its reliability, validity and minimal important difference (MID). The WURSS-24-C was developed using the forward-backward translation procedure. People with URTIs’ symptoms within 48 h of onset were recruited and asked to fill in the WURSS-24-C daily for up to 14 d. Exploratory and confirmatory factor analyses were used to suggest domains. The 8-Item Short Form Health Survey (SF-8) assessing general mental and physical health was used to assess validity. Reliability estimated by Cronbach’s alpha and mean day-to-day change for those indicating minimal improvement as MID were evaluated. The WURSS-24-C was found to be acceptable, relevant, and easy to complete in cognitive debriefing interviews. A total number of 300 participants (age 28.4 ± 9.3, female 70%) were monitored for 2500 person-days. Four domains (activity and function, systemic symptoms, nasal symptoms and throat symptoms) of the WURSS-24-C were confirmed (comparative fit index [CFI] = 0.93). The reliability of this 4-domain-structure is good (Cronbach’s alphas varied from 0.849 to 0.943). Convergent validity is moderate (Pearson correlation coefficients between daily WURSS-24-C and the SF-8 were −0.780 and −0.721, for the SF-8 physical and mental health, respectively). Estimates of MID for individual items varied from −0.41 to −1.14. The WURSS-24-C is a reliable and valid questionnaire for assessing illness-specific quality-of-life health status in Chinese-speaking patients with URTIs.Key messagesThe Wisconsin upper respiratory symptom survey (WURSS) series are patient-oriented questionnaire instruments assessing the quality of life and severity of upper respiratory tract infections (URTIs).The WURSS-24 was translated into Mandarin Chinese using the forward-backward translation procedure, and evaluated its validity, reliability and minimal important difference (MID) in 300 Chinese participants with URTIs.The WURSS-24 Chinese version (WURSS-24-C) seems to be a reliable and valid questionnaire for assessing illness-specific quality-of-life health status in Chinese patients with URTIs. The Wisconsin upper respiratory symptom survey (WURSS) series are patient-oriented questionnaire instruments assessing the quality of life and severity of upper respiratory tract infections (URTIs). The WURSS-24 was translated into Mandarin Chinese using the forward-backward translation procedure, and evaluated its validity, reliability and minimal important difference (MID) in 300 Chinese participants with URTIs. The WURSS-24 Chinese version (WURSS-24-C) seems to be a reliable and valid questionnaire for assessing illness-specific quality-of-life health status in Chinese patients with URTIs.

The kidney tropism of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has been well‐validated clinically and often leads to various forms of renal damage in coronavirus disease‐2019 (COVID‐19) patients. However, the underlying mechanisms and diagnostic approaches remain to be determined. We interrogated the expression of virus‐related host factors in single‐cell RNA sequencing (scRNA‐seq) datasets of normal human kidneys and kidneys with pre‐existing diseases and validated the results with urinary proteomics of COVID‐19 patients and healthy individuals. We also assessed the effects of genetic variants on kidney susceptibility using expression quantitative trait loci (eQTLs) databases. We identified a subtype of tubular cells, which we named PT‐3 cells, as being vulnerable to SARS‐CoV‐2 infections in the kidneys. PT‐3 cells were enriched in viral entry factors and replication and assembly machinery but lacked antiviral restriction factors. Immunohistochemistry confirmed positive staining of PT‐3 cell marker SCL36A2 on kidney sections from COVID‐19 patients. Urinary proteomic analyses of COVID‐19 patients revealed that markers of PT‐3 cells were significantly increased, along with elevated viral receptor angiotensin‐converting enzyme 2. We further found that the proportion of PT‐3 cells increased in diabetic nephropathy but decreased in kidney allografts and lupus nephropathy, suggesting that kidney susceptibility varied among these diseases. We finally identified several eQTLs that regulate the expression of host factors in kidney cells. PT‐3 cells may represent a key determinant for the kidney tropism of SARS‐CoV‐2, and detection of PT‐3 cells may be used to assess the risk of renal infection during COVID‐19., Through single‐cell analysis, we identified PT‐3 cells, a proximal tubule epithelial cell subtype in human kidney, that are highly susceptible to severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection. We validated these results using immunostaining and urinary proteomics in coronavirus disease‐2019 (COVID‐19) patients. Our findings provide not only new insights into the mechanism involving SARS‐CoV‐2 infection of the kidney cells, but also a potential strategy for risk assessment of kidney infection among COVID‐19 patients.

BACKGROUND: Radix Scutellariae (RS) has been used to treat influenza for thousands of years in China. However, its mechanisms of action remain unclear. The aim of the present study was to use a network pharmacology and molecular docking-based approach to explore active components and potential molecular mechanisms of RS for influenza A. METHODS: Target genes of RS and influenza A were attained by accessing network databases. We then determined the intersection of both genes through bioinformatics using R and Perl language. The protein-protein interaction (PPI) network was constructed by the STRING website (https://cn.string-db.org). The network analysis was done using Cytoscape software. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were applied for the above genes. Effective components as core targets were screened out based on the condition that the interaction must come first. These core targets were combined with 3D structures of main RNA coding proteins of influenza A virus. Molecular docking was used to visualize drug–target interaction via AutoDock Vina and PyMOL. RESULTS: Twenty-eight active components and 40 target genes were acquired through the regulatory network of active components of RS and the PPI network. Seventy-one bioinformatics expressions were obtained through GO enrichment analysis (P

Signaling pathway alterations in COVID-19 of living humans as well as therapeutic targets of the host proteins are not clear. We analyzed 317 urine proteomes, including 86 COVID-19, 55 pneumonia and 176 healthy controls, and identified specific RNA virus detector protein DDX58/RIG-I only in COVID-19 samples. Comparison of the COVID-19 urinary proteomes with controls revealed major pathway alterations in immunity, metabolism and protein localization. Biomarkers that may stratify severe symptoms from moderate ones suggested that macrophage induced inflammation and thrombolysis may play a critical role in worsening the disease. Hyper activation of the TCA cycle is evident and a macrophage enriched enzyme CLYBL is up regulated in COVID-19 patients. As CLYBL converts the immune modulatory TCA cycle metabolite itaconate through the citramalyl-CoA intermediate to acetyl-CoA, an increase in CLYBL may lead to the depletion of itaconate, limiting its anti-inflammatory function. These observations suggest that supplementation of itaconate and inhibition of CLYBL are possible therapeutic options for treating COVID-19, opening an avenue of modulating host defense as a means of combating SARS-CoV-2 viruses.

Background The coronavirus disease 2019 (COVID-19) has turned into a pandemic and resulted in huge death tolls and burdens. Integrating Chinese and western medicine has played an important role in the fight against the COVID-19 pandemic. Purpose We aimed to develop a living evidence-based guideline of integrating Chinese and western medicine for COVID-19. Study design Living evidence-based guideline. Methods This living guideline was developed using internationally recognized and accepted guideline standards, dynamically monitoring the release of new clinical evidence, and quickly updating the linked living systematic review, evidence summary tables, and recommendations. Modified Delphi method was used to reach consensus for all recommendations. The certainty of the evidence, resources, and other factors were fully considered, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of evidence and the strength of recommendations. Results The first version of this living guidance focuses on patients who are mild or moderate COVID-19. A multidisciplinary guideline development panel was established. Ten clinical questions were identified based on the status of evidence and a face-to-face experts' consensus. Finally, nine recommendations were reached consensus, and were formulated from systematic reviews of the benefits and harms, certainty of evidence, public accessibility, policy supports, feedback on proposed recommendations from multidisciplinary experts, and consensus meetings. Conclusion This guideline panel made nine recommendations, which covered five traditional Chinese medicine (TCM) prescription granules/decoction (MXXFJD, QFPD, XFBD, TJQW, and JWDY), three Chinese patent medicines (LHQW granules/capsule, JHQG granules, and LHQK granules), and one Chinese herbal injection (XBJ injection). Of them, two were strongly recommended (LHQW granules/capsule and QFPD decoction), and five were weakly recommended (MXXFJD decoction, XFBD decoction, JHQG granules, TJQW granules, and JWDY decoction) for the treatment of mild and moderate COVID-19; two were weakly recommended against (XBJ injection and LHQK granules) the treatment of mild and moderate COVID-19. The users of this living guideline are most likely to be clinicians, patients, governments, ministries, and health administrators.

Background The coronavirus disease 2019 (COVID-19) epidemic is still ongoing, but the optimal treatment remains unclear. China adopted a series of measures, including widespread screening, strict quarantine and early treatment, combining western medicine with Chinese medicine, leading to rapid control of its spread. Nevertheless, the effects of ( combined ) Chinese medicine in reducing the toll of COVID-19 lack proof from statistics. Objective We conducted a retrospective data analysis to determine whether ( combined ) Chinese medicine is able to affect patient outcomes and to decrease the risk of death in COVID-19 patients. Methods The data were acquired by outputting the formatting information from the HIS system and then extracting and recording it in the database for complete cases. The demographics, disease onset, treatment, survival/death and all of the clinical classifications, groups and definitions were verified by specialists in the clinic, along with the research methodology and statistics, before conducting the statistical analysis. The characteristics of the cohort and the clinical symptoms and signs, prescriptions and outcomes were described and analyzed by the mean ± SD, median, interquartile range and composition ratio. Analysis of variance was used for comparisons between the measurement data sets; otherwise, the rank sum test was used. Counting data were compared between groups using the chi square test and Fisher’s exact test. Tendency matching was adopted to make the general data balance between groups. A Cox proportional hazard model was used to compare the risk of death among the different groups. Results Four centers were included in our study, and a total of 6,076 patients' clinical records were obtained after combining the data. We included 4567 cases for the descriptive statistics, and the crude case fatality rate was 3.0%. Compared with using only western medicine, (combined) Chinese medicine reduced the risk of death from COVID-19 after adjusting for other prognostic risk factors (HR = 0.135, 95% CI (0.088, 0.208)). Multivariate Cox regression also indicated that when applying the clinical classification of severe/critical, age ≥ 65 years old, coronary heart disease or chronic kidney disease and a time from onset to hospital admission of fewer than 14 days, all of these factors increased the risk of death. Conclusion (Combined) Chinese medicine can significantly reduce the risk of death from COVID-19, but the specific strategy/solution, effects and amount need further exploration in future studies.

Three-dimensional visualization technology converts engineering design drawings and data into graphics or images, realizes virtual reality perception of simulated users in future construction scene, enhances the interaction between project management and technical personnel and engineering construction achievement, and provides intuitive, flexible and strong realistic experience for project management. It can effectively improve the level of project communication, and assist the needs of project construction planning management, training, exhibition, etc. As a tool to help improve project management skills, it has good application effect and prospects.

Background: COVID-19 is a multi-systemic disease that is highly contagious and pathogenic. The long-term consequences of it are not yet clear, as is whether society and life can return to a healthy state. Long-term assessment of their health-related quality of life (HRQoL) is essential. This study aimed to investigate HRQoL and its risk factors in COVID-19 survivors at a follow-up of 6-month. Methods: A multicenter cross-sectional survey was conducted among 192 COVID-19 patients with confirmed age ≥ 18 years who were discharged from various hospitals in Wuhan from January to April 2020. The demographic characteristics, clinical characteristics, and laboratory results of the study subjects were obtained from the hospital's medical records. Survivors' HRQoL was assessed using the Short Form 36 (SF-36), cognition was assessed using the ascertain dementia eight-item informant questionnaire (AD8), and survivors' pulmonary function were examined. All participants in this study completed the survey and testing at Hubei Provincial Hospital of Chinese and Western Medicine. SF-36 scores were compared with the Chinese norm, and logistic regression and multivariate analysis were used to investigate the factors affecting HRQoL in COVID-19 survivors. Results: SF-36 showed significant differences in HRQoL between COVID-19 survivors and the general Chinese population ( P< 0.05).Multiple linear regression demonstrated that age was negatively correlated with physical functioning (PF), role-physical limitation (RP) and social functioning (SF) ( P

Objectives: To describe the clinical sequelae and immunological features of COVID-19 survivors who have been discharged from the hospital for 5-8 months. Methods: This study is a cross-sectional study of confirmed COVID-19 patients aged ≥18 years who were discharged from hospitals in Wuhan from January to April 2020. The demographics, clinical features, and laboratory findings of the participants were collected from medical records in the hospital. The participants from the study completed an investigation of clinical sequelae, blood tests, a pulmonary function examination and an unarmed rehabilitation evaluation at Hubei Provincial Hospital of Traditional Chinese & Western Medicine. A group of volunteers who were free of COVID-19 and lived in Wuhan during the outbreak were recruited as the comparison group. Results: The average age of the 574 COVID-19 survivors was 57.7±11.4 years, and 348 (60.6%) survivors were female. The average number of days from the onset of symptoms was 241.79±16.16. The average number of days from discharge was 194.3±14.4. Clinical sequelae were common, including general symptoms (n=321, 55.9%), respiratory symptoms (n=265, 46.2%), digestive symptoms (n=84, 14.6%), nervous symptoms (n=75,13.1%) and psychosocial symptoms (n=201, 35%). A total of 190 (33.7%) survivors reported reduced exercise capacity. Through the results of pulmonary function examination, anomalies were noted in carbon monoxide diffusion capacity (DLCO)% in 110 cases (32.4%), maximal mid-expiratory flow (MMEF)% in 105 cases (30.7%), forced expired flow at 50% of forced vital capacity (FEF 50 )% in 128 cases (37.4%), and forced expired flow at 75% of forced vital capacity (FEF 75 )% in 240 cases (70.2%). The counts of T lymphocyte, CD4+ T lymphocyte counts, CD8+ T lymphocyte counts, B lymphocyte and NK cell in the survival group was significantly lower than that in the comparison group(all P 0.05). The T lymphocyte counts, CD4+ T lymphocyte counts and CD8+ T lymphocyte counts of the patients before discharge were significantly higher than those in the early stage of admission (P < 0.025). There were 319 (55.6%) survivors with positive or weakly positive IgG antibodies and 17 (2.9%) survivors with positive or weakly positive IgM antibodies. Conclusion: Even after 5 to 8 months of discharge, many survivors still have clinical sequelae, and some of them have impaired immune function. Therefore, the long-term rehabilitation of COVID-19 survivors remains a concern. Funding Statement: This study was funded by the National Key R&D Plan of China (2020YFC0841600), Guangdong Provincial Key Laboratory of Research on Emergency in TCM (2017B030314176), R&D plan in key areas of Guangdong Province (2020B1111300005), and National Administration of Traditional Chinese Medicine (2020ZYLCYJ05-11). Declaration of Interests: The authors declare that they have no competing interests. Ethics Approval Statement: This study was approved by the ethical committees of Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, China (GPHCM; No. BF2020-205-01). All participants signed informed consent forms.

A 39-year-old woman who was maintained on peritoneal dialysis (PD) for 25 years was admitted to ED with a 2-week history of abdominal pain and vomiting. She had been taking midodrine for several years because of low blood pressure but she had no medical history of diabetes or hypercholesterolaemia. On clinical examination, she presented with middle abdominal tenderness, no rebound tenderness and negative Murphy’s and McBurney’s signs. The laboratory examination showed that her leucocyte count was 9.45×10 …

Clear cell sarcoma of the kidney (CCSK) is a rare paediatric renal malignant tumour. The majority of CCSKs have internal tandem duplications (ITDs) of the BCOR gene, whereas a minority have the YWHAE-NUTM2 gene fusion. A third 'double-negative' (DN) category comprises CCSKs with neither BCOR ITDs nor YWHAE-NUTM2 fusion. The aim of this study was to characterise 11 histologically diagnosed CCSKs immunohistochemically (with CCND1, BCOR and CCNB3 stains) and genetically.By next-generation sequencing, 10 cases (90.9%) had BCOR exon 15 ITDs, with positive BCOR immunoreactivity being found in four (36%) or eight (72%) cases, depending on the antibody clone. By reverse transcription polymerase chain reaction, none had the YWHAE-NUTM2 fusion. The DN case had a BCOR-CCNB3 fusion and strong nuclear CCNB3 and BCOR immunoreactivity. Quantitative polymerase chain reaction showed markedly elevated BCOR expression in this case, whereas BCOR ITD cases had lower levels of elevated BCOR expression.The majority of the CCSKs in our cohort had BCOR ITDs, and none had the YWHAE-NUTM2 fusion. We verified the strong, diffuse cyclin D1 (CCND1) immunoreactivity in CCSKs described in recent reports. BCOR immunoreactivity was not consistently positive in all CCSKs with BCOR ITDs, and therefore cannot be used as a diagnostic immunohistochemical stain to identify BCOR ITD cases. The DN case was a BCOR-CCNB3 fusion sarcoma. BCOR-CCNB3 sarcoma is typically a primary bone sarcoma affecting male adolescents, and this is the first report of it presenting in a kidney of a young child as a CCSK. The full spectrum of DN CCSKs awaits more comprehensive characterisation.

Traditional Chinese medicine has been used for the treatment of many diseases including acute infections often associated with public health emergencies for thousands of years. However, clinical evidence supporting the use of these treatments is insufficient, and the mechanism for using Chinese medicine therapy in the public health setting has not been fully established. In this report, the Evidence-based Traditional and Integrative Chinese medicine Responding to Public Health Emergencies Working Group proposed five recommendations to facilitate the inclusion of Chinese medicine as part of our responses to public health emergencies. It is expected that the Working Group’s proposals may promote the investigation and practice of Chinese Medicine in public health settings.

Background Chinese herbal medicine (CHM) has been used for severe illness caused by coronavirus disease 2019 (COVID-19), but its treatment effects and safety are unclear. Purpose This study reviews the effect and safety of CHM granules in the treatment of patients with severe COVID-19. Methods We conducteda single-center, retrospective study on patients with severe COVID-19 in a designated hospital in Wuhan from January 15, 2020 to March 30, 2020. The propensity score matching (PSM) was used to assess the effect and safety of the treatment using CHM granules. The ratio of patients who received treatment with CHM granules combined with usual care and those who received usual care alone was 1:1. The primary outcome was the time to clinical improvement within 28 days, defined as the time taken for the patients’ health to show improvement by decline of two categories (from the baseline) on a modified six-category ordinal scale, or to be dischargedfrom the hospital before Day 28. Results Using PSM, 43 patients (45% male) aged 65.6 (57–70) yearsfrom each group were exactly matched. No significant difference was observed in clinical improvement of patients treated with CHM granules compared with those who received usual (p = 0.851). However, the use of CHM granules reduced the 28-day mortality (p = 0.049) and shortened the duration of fever (4 days vs. 7 days, p = 0.002). The differences in the duration of cough and dyspnea and the difference in lung lesion ratio on computerized tomography scans were not significant.Commonly,patients in the CHM group had an increased D -dimer level (p = 0.036). Conclusion Forpatients with severe COVID-19, CHM granules, combined with usual care, showed no improvement beyond usual care alone. However, the use of CHM granules reduced the 28-day mortality rate and the time to fever alleviation. Nevertheless, CHM granules may be associated with high risk of fibrinolysis.

In many countries afflicted with dengue fever, traditional medicines are widely used as panaceas for illness, and here we describe the systematic evaluation of a widely known natural product, luteolin, originating from the “heat clearing” class of herbs. We show that luteolin inhibits the replication of all four serotypes of dengue virus, but the selectivity of the inhibition was weak. In addition, ADE-mediated dengue virus infection of human cell lines and primary PBMCs was inhibited. In a time-of-drug-addition study, luteolin was found to reduce infectious virus particle formation, but not viral RNA synthesis, in Huh-7 cells. During the virus life cycle, the host protease furin cleaves the pr moiety from prM protein of immature virus particles in the trans-Golgi network to produce mature virions. Analysis of virus particles from luteolin-treated cells revealed that prM was not cleaved efficiently. Biochemical interrogation of human furin showed that luteolin inhibited the enzyme activity in an uncompetitive manner, with Ki value of 58.6 μM, suggesting that treatment may restrict the virion maturation process. Luteolin also exhibited in vivo antiviral activity in mice infected with DENV, causing reduced viremia. Given the mode of action of luteolin and its widespread source, it is possible that it can be tested in combination with other dengue virus inhibitors. NMRC (Natl Medical Research Council, S’pore) MOH (Min. of Health, S’pore) Accepted version

Taxol (paclitaxel) is one of the taxane class of anticancer drugs as a first-line chemotherapeutic agent against many cancers including colorectal cancer, breast cancer, non-small cell lung cancer, ovarian cancer and so on. It is verified to induce cytotoxicity in a concentration and time-dependent manner. Numerous novel formulations of Taxol have been remanufactured for better therapeutic effect. Though Taxol works as a common anticancer drug for a long time in clinical practice, drug resistance is a major limitation of its long-term administration. In-depth research on drug resistance is still in progress and researchers have made some achievements, however, the mechanism or key molecule related to Taxol resistance in colorectal cancer still remains to be explored. In the present study, we observed that the high expression of TXNDC17 (thioredoxin domain containing 17) was associated with Taxol resistance in colorectal cancer cells. And TXNDC17 mediated Taxol resistance was related with increased basal autophagy level. Taxol exposure induced high levels of phospho-STAT3 (Tyr 705) and TXNDC17; and increase of basal autophagy in colorectal cancer cells. TXNDC17 overexpression cells obtained Taxol resistance and a high level of autophagy, and it is not surprising that stable downregulation of TXNDC17 accordingly reversed these phenomena. Interestingly, STAT3 could similarly work as TXNDC17 in spite of slighter effect compared to TXNDC17. And it has been proved that phospho-STAT3 (Tyr 705) possesses transcriptional regulation activity through forming dimmers. Many research revealed that transcription factor STAT3 affected more than 1000 gene products, and TXNDC17 is predicted to be a target gene of STAT3 at UCSC database. For the first time, we found STAT3 could bind promoter region of TXNDC17 (− 623 bp to − 58 bp relative to the transcription start site (TSS)) for regulating its expression. These results suggest the possibility that TXNDC17 could play an important role in Taxol resistance via enhancing autophagy in human colorectal cancer cells. TXNDC17 may become a potential target of colorectal cancer therapeutics.

Background: Sudden cardiac arrest (SCA) is one of the most common critical illnesses encountered in clinical practice. Shenfu injection (SFI) has received extensive attention as an alternative therapy that can effectively maintain the autonomic circulation function after cardiopulmonary resuscitation. However, the mechanism of SFI is not yet fully understood. In addition, there has been no systematic review or meta-analysis of SFI in the treatment of patients with return of spontaneous circulation after SCA. Herein, we describe the protocol of a proposed study based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines that aims to systematically evaluate the efficacy and safety of SFI in patients with return of spontaneous circulation after SCA. Methods: Two researchers will search 9 electronic databases (PubMed, Medline, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Chinese VIP Information, Wanfang, and Chinese Biomedical Database) to identify all studies that meet the inclusion criteria and were published before July 2018. After information extraction and methodological quality evaluation, we will use Stata 13.0 software (STATA Corporation, College Station, TX, USA) to synthesize the data. The primary outcomes will be the survival rate and Glasgow Coma Scale. Results: The data synthesis results will objectively illustrate the efficacy and safety of SFI in patients with return of spontaneous circulation after SCA. Conclusion: The findings will provide a reference for the use of SFI in the treatment of patients with return of spontaneous circulation after SCA. Registration: PROSPERO (registration number: CRD42018104230).

In the big data era, learning-based techniques have attracted more and more attentions in many industry areas. The sport injury prediction is one of the most critical issues in data analysis of soccer teams.However, learning-based methods have not been widely used due to the poor data quality and computational capacity. In this paper, we propose a learning-based model to forecast sport injuries according to the data from various information systems. We first reduce the attributes that have significant impact on the injury risk by using learning-based methods.Then, we provide an algorithm based on the random forest method to prevent the over-fitting problem. We have evaluated the proposed model with the real-world data. The experimental results show that our model works efficiently and achieves low error rates.

BACKGROUND: Tumor suppressor genes were studied in gallbladder disease including cancer for correlation. VEGF (vascular endothelial growth factor) expression was assessed against Nevin staging and metastasis of gallbladder carcinoma. The importance of p53, p16, and VEGF in gallbladder cancer was estimated. STUDY DESIGN: Twenty-four gallbladder carcinomas, 20 gallbladder adenomas, and 18 chronic cholecystitis specimens were immunohistochemically and histopathologically investigated for the relation of p53, p16, and VEGF to Nevin staging and pathologic grading. RESULTS: The expression rate of abnormal p53 in gallbladder carcinomas was significantly higher than that in gallbladder adenoma and chronic cholecystitis (p = 0.003, p=0.014). The expression rate of abnormal p53 in Nevin staging S 1 , S 2 , S 3 gallbladder carcinoma was significantly higher than that in S 4 , S 5 (p = 0.01). Abnormal p16 was highest in carcinoma, next in adenoma, and lowest in chronic cholecystitis (p = 0.031, p=0.017). Gallbladder carcinoma expressed VEGF far more often than adenoma or cholecystitis (p = 0.001); VEGF-positive rates were lower in S 1 , S 2 , S 3 than S 4 , S 5 by Nevin staging of gallbladder cancer (p = 0.044). CONCLUSIONS: Mutation of p53 and p16 genes might correlate with progression of of gallbladder carcinoma. Analysis of p53 and p16 can estimate the prognosis of gallbladder cancer. VEGF expression correlates with Nevin staging in gallbladder cancer.