[Current status of global colorectal cancer prevalence, prevention and control].

Objective: This paper provides a brief overview of the epidemiology of colorectal cancer in China and around the world, and discusses how to prevent colorectal cancer to reduce its disease burden. Method: Using the official database of GLOBOCAN 2020, the China Cancer Registry Annual Report compiled by the National Cancer Center, and data from CONCORD-3.Data management was performed by Microsoft Excel 2016 and R 4.2.1 Relevant graphs were generated using the ggplot2 package for result visualization. Result: An estimated 1 931 590 people were diagnosed with colorectal cancer worldwide in 2020 with an age-standardized incidence rate of 19.5 per 100 000. There were about 935 173 deaths caused by colorectal cancer internationally, with an age-standardized mortality rate of 9.0 per 100 000. Overall, colorectal cancer was the fourth most commonly diagnosed cancer and the third leading cause of cancer-related death worldwide in 2020. In China, the age-standardized incidence rate and mortality rate of colorectal cancer was 17.3 per 100 000 and 7.8 per 100 000, respectively. Gender differences in trends were observed, with a decreasing trend in incidence and mortality among females and an increasing trend in incidence and mortality among males. The primary risk factors for colorectal cancer include age, genetic factors, gastrointestinal disorders, dietary habits, and lifestyle et al. Conclusions: Colorectal cancer poses a significant burden globally and in China. The occurrence of colorectal cancer is closely related to physiology, genetics, behavioral habits, lifestyle, and disease factors. To better control the colorectal cancer burden with the lowest cost, specific measures should be taken to reduce exposure to established risk factors. By combining the disease prevention and control strategies of tertiary prevention in China with the characteristic factors of colorectal cancer, the incidence and mortality of colorectal cancer may be effectively controlled.

[A phase II, single-arm, open-label, multicenter clinical study to evaluate the efficacy and safety of sofosbuvir combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection].

Objective: To evaluate the efficacy and safety of sofosbuvir (Nanjing Zhengda Tianqing Pharmaceutical Co., Ltd.) combined with ribavirin in patients with genotype 2 chronic hepatitis C virus infection. Methods: Treatment-naïve or treatment experienced genotype 2 chronic hepatitis C patients from sixteen research centers of China were screened. All subjects received once-daily dose of sofosbuvir (400 mg) combined with ribavirin (body weight < 75 kg, 1 000 mg/day, 400 mg in the morning and 600 mg in the evening; body weight > 75 kg, 1 200 mg/d, 600 mg in the morning and 600 mg in the evening) for 12 weeks. Patients were followed-up for a period of 12 weeks after discontinuation of treatment. Continuous variables were expressed as mean ± standard deviation. The proportion of subjects with virologic response at different follow-up time points and 95% confidence intervals were estimated by maximum likelihood ratio and Clopper-Pearson interval. Results: 132 cases with genotype 2 chronic hepatitis C virus infection from sixteen research centers of China were included, 12 cases of whom were associated with cirrhosis, and the remaining 120 cases were not associated with cirrhosis. One hundred and thirty-one cases completed the study, and one patient lost to follow-up at week 4 after the end of treatment. The sustained virological response rate was 96.2% (95% confidence interval: 92.37% - 99.16%) after 12 weeks of drug withdrawal. Virological relapse occurred in four cases. Of the 132 subjects enrolled in the study, 119 (90.2%) reported 617 adverse events during treatment, of which 359 (76.5%) were TEAE related to sofosbuvir and/or ribavirin. There were nine TEAEs of grade 3 and above, and six cases (4.5%) of them had six severe adverse events. Only one serious adverse event was associated with sofosbuvir and ribavirin (unstable angina pectoris). There were no adverse events leading to drug discontinuation or death. Conclusion: Sofosbuvir combined with ribavirin has a high SVR rate in the treatment of genotype 2 chronic hepatitis C virus infection, and most of the adverse events occurred were mild with acceptable safety profile.

Tumor suppressor RKIP inhibits prostate cancer cell metastasis and sensitizes prostate cancer cells to docetaxel treatment.

Raf kinase inhibitory protein (RKIP) is a well-established metastasis suppressor that is frequently down-regulated in aggressive cancers. However, the impact of RKIP on cancer cell invasion and metastasis in prostate cancer is still elusive. To this end, we overexpressed RKIP in two prostate cancer cell lines. We found that overexpression of RKIP inhibited prostate cancer cells proliferation, migration and invasion. Mechanistically, we found that RKIP overexpression led to down-regula- tion of the NF-kB signaling pathway and inhibition of the epithelial-to-mesenchymal transition, which is important step for cancer metastasis. In addition, overexpression of RKIP can promote drug effects of docetaxel on prostate cancer cell lines. In conclusion, overexpression of RKIP significantly inhibits prostate cancer cell migration and metastasis, and overexpression of RKIP could aid prostate cancer treatment and therapy.

[Obstetric outcome in pregnancy complained with pulmonary hypertension].

Objective: To identify whether pregnancy outcomes vary by the severity of pulmonary hypertension. Methods: A retrospective study was conducted on 78 cases of pregnancies complained with pulmonary hypertension who delivered in the First Affiliated Hospital, Sun Yat-sen University from 2006 to 2016.The selected cases were divided into three groups according to severity of pulmonary hypertension: mild pulmonary hypertension group (mild PAH group) was defined as a mean pulmonary artery pressure 30-49 mmHg, moderate pulmonary hypertension (moderate PAH group) as mean pulmonary artery pressure 50-69 mmHg and severe pulmonary hypertension (severe PAH group) as mean pulmonary artery pressure 70 mmHg or greater.The clinical features, risk pregnant complication, maternal and neonatal outcomes were described between these three groups.Analysis of variance, Chi-square test was used for statistical analysis. Results: The average age of mild, moderate and severe PAH group were (31±5) years old, (31±5) years old and (27±3) years old, respectively (P=0.050). The rate of natural fertilization (P=0.414), parity (P=0.527) and gestational age (P=0.165) were similar in these three groups. In 78 pregnancies with pulmonary hypertension, 64.9% of pregnancies in mild PAH group was NYHA Ⅰ, 50.0% of moderate PAH group was NYHA Ⅱ and 54.5% of severe PAH group was NYHA Ⅲ(P<0.001). There was no significant difference in the incidence of gestational diabetes mellitus (GDM, P=0.589), preeclampsia (P=0.942), premature rupture of membrane (PROM, P=0.276), scarred uterus (P=0.493) and postpartum hemorrhage (P=0.424). The cesarean section rate was 84.2%, 90.0% and 63.6% in three groups (P=0.208). However, neuraxial anesthesia was performed in 82.5% of cases in mild PAH and 90.0% of cases in moderate PAH, while 27.3% of cases of severe PAH underwent neuraxial anesthesia (P<0.001). The fetal outcome was similar in there groups.But the rate of admission of NICU was significantly different in three groups (P=0.011). Conclusions: Maternal and neonatal outcomes was similar in different severity of pulmonary hypertension.But the severity of pulmonary hypertension affect the type of anesthesia.Close monitoring during pregnancy and timely termination of pregnancy can improve the outcome of pregnancy.

Elevated Ambient Temperature Differentially Affects Virus Resistance in Two Tobacco Species.

Antiviral defense of plants is usually enhanced by an elevated temperature under natural conditions. In order to better understand this phenomenon, we carried out temperature shift experiments with Nicotiana glutinosa plants that were infected with Potato virus X (PVX) or the necrotic strain of Potato virus Y (PVY(N)). The virus titer of the plants was found to be much lower when they were maintained at 30°C compared with 22°C, particularly in the upper leaves. PVX resistance at 30°C persisted for a short period even when temperature was shifted back to 22°C. In contrast, N. benthamiana lost the virus resistance immediately after the temperature dropped to 22°C. Expression analysis of two RNA-dependent RNA polymerases in N. glutinosa (NgRDR) showed that a 12-day treatment at 30°C increased the expression of NgRDR1, while NgRDR6 was not affected. In addition, the NgRDR6 mRNA level correlated with the PVX titer but was unaffected by PVY(N) infection. These observations indicate that PVX and PVY(N), although they are both RNA viruses, might trigger different defense responses at elevated temperatures. Our study provides valuable data for a better understanding of the temperature-regulated host virus interaction.

Update to the Hong Kong Epilepsy Guideline: evidence-based recommendations for clinical management of women with epilepsy throughout the reproductive cycle.

Since the publication of the Hong Kong Epilepsy Guideline in 2009, there has been significant progress in antiepileptic drug development. New AEDs have emerged, and data about their uses have been published. Women require special attention in epilepsy care. Drug teratogenicity, pregnancy, breastfeeding, contraception, reproduction technology, menopause, and catamenial epilepsy are major topics. Antiepileptic drugs should be chosen individually for patients who are pregnant or may become pregnant with consideration of their teratogenicity and seizure control properties. Folate is commonly prescribed for women of childbearing age who are taking antiepileptic drugs. Spontaneous vaginal delivery and breastfeeding are not contra-indicated in most cases but need to be considered individually based on the patient's medical condition and wishes. Serum drug level monitoring of certain antiepileptic drugs during pregnancy and puerperium can guide dosage adjustment. For catamenial epilepsy, intermittent benzodiazepines such as clobazam during the susceptible phase of the menstrual cycle could be a treatment option.

[Interpretation of global lung cancer statistics].

Lung cancer remains one of the leading cause of global cancer-related mortality, posing a significant burden of disease. Tobacco exposure stands as the foremost risk factor for lung cancer. Since the 1960, global efforts have gradually been implemented to control tobacco exposure, consequently reducing tobacco exposure levels within populations. This shift in exposure levels may have altered the epidemiological characteristics of lung cancer globally. This study aims to describe global lung cancer incidence data across five dimensions: age, gender, region, stage at diagnosis, and survival status, using global cancer registry data and relevant research findings. The objective is to elucidate the current epidemiological features of lung cancer worldwide, providing a scientific basis for lung cancer prevention and control. Furthermore, this study offers corresponding measures and recommendations for lung cancer prevention and control, aligning with the three-tiered cancer prevention strategy. Findings indicate that the incidence and mortality burden of lung cancer is significantly higher among the elderly population (aged 65 years and above) compared to the working-age population (aged 15-64 years). The aged-standardized incidence rate of lung cancer remains higher in males than in females, but the overall aged-standardized incidence rate of lung cancer in males shows a declining trend, while that in females shows an increasing trend. Regions with high and very high human development index (HDI) exhibit a substantially higher incidence and mortality burden of lung cancer compared to regions with low and very low HDI. Japan ranks highest in the diagnosis of stage Ⅰ lung cancer, with a diagnosis rate of 38.6%. Its age-standardized 5-year net survival rate is relatively high at 32.9%. Despite improvements in the survival status of lung cancer in certain countries like China and Japan, the overall prognosis for lung cancer remains pessimistic. Given the current epidemiological characteristics of lung cancer, reinforcing tobacco control measures and reducing female-specific lung cancer risk factors stand as significant goals for primary prevention. Promoting low-dose computed tomography screening for high-risk population, minimizing false-positive rates in lung cancer screening, and promoting medical system reforms and standardized treatment constitute principal measures for secondary and tertiary lung cancer prevention, respectively.

Complete sequence and genetic characterization of pigeon avian nephritis virus, a member of the family Astroviridae.

In the current study, the complete genome sequence of a member of the family Astroviridae isolated from pigeons was determined through genetic characterization and phylogeny analysis. The isolated genome sequence was proposed to be that of pigeon avian nephritis virus (ANV), whose genome structure and characteristics were similar to previously reported avian astroviruses. The sequenced ssRNA genome comprises 6928 nucleotides, excluding the poly(A) tail, and contains three open reading frames. Phylogenetic analysis using a partial nucleotide sequence of the polymerase gene and the entire amino acid sequence of the full-length capsid protein revealed that pigeon avian nephritis virus is closely related to the previously published ANV, especially to the Japanese G-4260 and Chinese strains. This investigation provides information on the sequence and genetic characteristics of this virus and contributes to a better understanding of pigeon ANV and the possible occurrence of astrovirus transmission between chickens and pigeons.

Isolation and characterization of canine astrovirus in China.

In this study, we first investigated the prevalence of astrovirus in stools of dogs with and without diarrhea in Shanghai, China. Of all the specimens, 22 (12.02%) from the 183 dogs with diarrhea and none (0%) from the 138 healthy controls were positive for astrovirus. Furthermore, we cloned partial sequences of ORF1b (442 bp) and the entire sequences of ORF2 (2475 bp). Phylogenetic analysis showed that the new isolates were belonged to genus Mamastrovirus and most closely clustered with the Italy strain, based on the ORF2 sequences available. However, the new isolates and the Italy strain were divided into two different clusters. The new isolates may be a new strain of canine astrovirus.

Detection of astrovirus infection in pigeons (Columbia livia) during an outbreak of diarrhoea.

Avian astrovirus infections are widespread in many countries, and infections have been linked to enteritis and increased mortality in young poultry. Although pigeons are treated as an important poultry product in some countries, their diseases are often poorly understood and astrovirus infection in pigeons has not been reported. In the present study, faecal samples were collected during an outbreak of gastrointestinal illness in a population of Shanghai pigeons. The samples were examined for astroviruses by reverse transcription-polymerase chain reaction. Eighty-nine per cent (40/45) and 4% (2/45) were found to be positive for avian nephritis virus (ANV) and chicken astrovirus, respectively. One positive sample indicated a co-infection with both ANV and chicken astrovirus. Phylogenetic analysis based on the partial polymerase gene sequence and full-length capsid protein from published avian astrovirus sequences in GenBank revealed that the pigeon viruses detected in this study were evolutionarily closely related to chicken ANV. The present study provided evidence for the presence of astrovirus in pigeons and suggests that cross-infection between pigeons and commercial chickens was likely. Whether the astroviruses in pigeons were responsible for the diarrhoea remains to be determined.

Sequence analyses of the representative Chinese-prevalent strain of avian nephritis virus in healthy chicken flocks.

Avian nephritis virus (ANV), which belongs to the Astroviridae family, has been associated with acute nephritis in chickens. Cases of ANV infection have been recorded in Japan and in several European countries. However, related studies have never been performed in China. Thus, this study isolated ANV in Chinese chicken flocks. ANV RNA was detected by reverse transcription-PCR in stool samples collected from healthy layer chickens in the Sichuan Province of China in 2009. Of the 192 stool specimens collected, 32.3% (62/192) were positive for ANV infection. The whole genome of ANV-Sichuan54, the first representative Chinese strain, was 6941 nucleotides in length, including the 5' untranslated region, three open reading frames (ORFs), a 3' UTR, and a poly-(A) tail. Comparative and phylogenetic analyses based on partial RNA-dependent RNA polymerase (ORF1b) demonstrated that the majority of ANV investigations were more closely related to the U.S. ANV strain (DQ324827-324836) than to the G-4260 (AB033998).

Mutation in Cys662 of Escherichia coli DNA topoisomerase I confers temperature sensitivity and change in DNA cleavage selectivity.

Cys662 is one of the 12 cysteine residues proposed to be co-ordination sites for binding of three Zn(II) in Escherichia coli DNA topoisomerase I. Oligonucleotide-directed mutagenesis was used to convert Cys662 to either serine or histidine. The mutant enzymes were overexpressed and purified to homogeneity. Analysis of the purified enzymes demonstrated that the mutations resulted in loss of one tightly bound Zn(II). In vivo complementation tests and in vitro relaxation activity assays at different temperatures showed that the partial relaxation activities retained in the two mutant enzymes were temperature sensitive. Fluorescence measurements indicated that the wild-type and mutant enzymes have structural differences. When DNA cleavage specificity was examined, the mutant enzymes were found to have altered cleavage site preferences. The preferred cleavage sites of the wild-type enzyme all had a cytosine residue four nucleotides to the minus side of the break. The cleavage sites produced by the mutant enzymes did not show a preference for cytosine at that position.

Induction of NADPH-diaphorase activity in the forebrain in a model of intracerebral hemorrhage and its inhibition by the traditional Chinese medicine complex Nao Yi An.

Induction of NADPH-diaphorase (NDP) activity in the rat cerebral cortex was studied after autologous blood injection into the internal capsule as experimental model of intracerebral hemorrhage. The potential inhibitory effect on NDP induction by Nao Yi An (NYA), a complex derived from materials of animal and plant origin used in the treatment of intracerebral hemorrhage in traditional Chinese medicine, was also investigated. In animals without therapeutic treatment 2 and 4 days after injection of autologous blood, NDP activity was highly induced in pyramidal neurons in the neocortex, piriform, and entorhinal cortices, in astrocytes and in phagocytes in the hematoma and the area surrounding it, as well as in the subcortical white matter, and in endothelial cells in both the cortex and subcortical white matter bilaterally. Oral administration of NYA failed to inhibit NDP induction in endothelial cells but demonstrated a strong inhibitory effect on NDP activity induced in pyramidal neurons and astrocytes. NDP induction in phagocytes was also inhibited by the administration of NYA. Altogether the present results suggest that intracerebral hemorrhage in the internal capsule may induce nitric oxide synthase activity in different cell populations in the cortex and that administration of NYA can selectively inhibit such induction and, thus, potentially play a neuroprotective role.

Effects of K salt or a potassium blocker on gossypol-related hypokalemia.

Gossypol was found to be an effective male contraceptive. The most serious side effect of gossypol contraception was the presumed lowering of serum potassium levels. The purpose of this present randomized and controlled study was to evaluate the merit of ingesting K salt or a potassium blocker while using gossypol. Results indicated that supplementation of K salt does not cause a reversal of the effect of gossypol on serum potassium levels and the blocker triamterene does not prevent loss of serum potassium.

[Effects of intracerebroventricular injections of thyrotropin releasing hormone on gastrointestinal propulsive motility in rats].

The effect of intracerebroventricular (ICV) injections of thyrotropin releasing hormone (TRH) on the propulsive motility of the gastrointestinal tract was examined in rats. The distance travelled by charcoal meal through the small intestine, measured in terms of percentage of its total length, was recorded as the index of propulsive motility. The results were as follows: (1) The propulsive distance of charcoal meal was significantly reduced in a dose-dependent manner after ICV injections of TRH (1 microgram/10 microliters, 5 micrograms/10 microliters or 10 micrograms/10 microliters) (P less than 0.01-0.001) The effects were abolished by injection of atropine (5 micrograms/10 microliters ICV). (2) The gastrointestinal propulsive motility decreased markedly (P less than 0.01) after injection of a larger dose of TRH (50 micrograms/100 g) into the hypodermis. The effects were not completely blocked by subcutaneous injections of propranolol (5 mg/kg). (3) No effects (P greater than 0.05) were found on the inhibition of gastrointestinal propulsive motility after ICV injections of regitine (2.5 mg/kg im, 50 micrograms/50 microliters ICV) or propranolol (5 mg/kg im, 50 micrograms/50 microliters ICV). The results indicate that TRH has an inhibitory effect on the propulsive motility of gastrointestinal tract, which may be mediated via the non-adrenergic inhibitory nerve of the vagal nerves.

[Analysis of nucleotide level of human erythrocytes in patients with liver-fire exuberance syndrome].

Level of erythrocytes in 30 patients with Liver-Fire Exuberance Syndrome (LFES) was observed, and that of 30 healthy persons was determined in the meantime as control by high-performance liquid chromatography. It was found that the adenosine triphosphate in erythrocytes of LFES patients was lower and level of adenosine monophosphate was higher than that of healthy persons. While, the levels of adenylate pool and energy load ratio were lower than that of control. These results showed the metabolism was exuberant, the energy consumption increased and the energy storage reduced in patients of LFES.

In situ electron holography study of charge distribution in high-κ charge-trapping memory.

Charge-trapping memory with high-κ insulator films is a candidate for future memory devices. Many efforts with different indirect methods have been made to confirm the trapping position of the charges, but the reported results in the literatures are contrary, from the bottom to the top of the trapping layers. Here we characterize the local charge distribution in the high-κ dielectric stacks under different bias with in situ electron holography. The retrieved phase change induced by external bias strength is visualized with high spatial resolution and the negative charges aggregated on the interface between Al2O3 block layer and HfO2 trapping layer are confirmed. Moreover, the positive charges are discovered near the interface between HfO2 and SiO2 films, which may have an impact on the performance of the charge-trapping memory but were neglected in previous models and theory.

Molecular detection of Torque teno sus virus from tissues samples of sick pigs in China.

In the present study, Torque teno sus virus (TTSuV) was detected from different tissues, stool and serum samples of 25 sick pigs. The total prevalence of TTSuV1 and TTSuV2 were 64% (16/25) and 28% (7/25), 24% (6/25) were co-infected with both TTSuV1 and TTSuV2. The prevalence of TTSuV infection in spleen is a slightly higher, with positive rates of 52% (13/25) for TTSuV1 and 24% (6/25) for TTSuV2. Phylogenetic analysis of TTSuV1 showed that 21 isolates were distributed into two clusters (genotype TTSuV1a and TTSuV1b), with genotype TTSuV1b was the dominant genotype. Phylogenetic analysis of TTSuV2 showed that the nine isolates shared 80.9-99.2% nucleotide homology with each other, and were distributed in different genotypes (TTSuV2a-TTSuV2f). TTSuV2d was the most prevalent genotype in this study, which contained five Spanish strains and nine Chinese strains, and shared 94.2-96.8% homology.

Segmentation expression of capsid protein as an antigen for the detection of avian nephritis virus infection in chicken flocks.

Subclinical pathological changes in the kidneys of broiler chickens and suppression of growth caused by the avian nephritis virus (ANV) affect poultry flocks worldwide. A test for detection of virus-specific antibodies in serum would be useful for epidemiological investigations, however the poor propagation in cell cultures has restricted the development of serological tests based on the use of ANV particles as antigens. An enzyme-linked immunosorbent assay (ELISA) was developed for detection of ANV-specific antibodies in chicken serum, using a recombinant protein antigen prepared by segmentation expression of the capsid protein antigen epitope of ANV (HM029238) transfected into Escherichia coli. The expressed fusion protein was detected by Western blotting with ANV-positive serum, and the optimal immunoreactive fusion P1 protein was determined. Using the optimized P1-ELISA, ANV-specific antibodies were detected in commercial chicken flocks aged 10-25 days obtained from the Liaoning Province, China. Out of 960 serum samples, 459 (47.8%) were positive for infection with ANV. These results indicate that the P1-ELISA is helpful for preliminary serological diagnosis of ANV infection, and could be used to for screening in ANV infection and for determining antibodies against ANV.

Highly efficient virus resistance mediated by artificial microRNAs that target the suppressor of PVX and PVY in plants.

MicroRNAs (miRNAs) processed from nuclear-encoded transcripts control expression of target transcripts by directing cleavage or translational inhibition. Artificial miRNAs (amiRNAs) that exploit this endogenous gene silencing mechanism can be designed to target any gene of interest and provide a highly specific approach for effective post-transcriptional gene silencing (PTGS) in plants. Here, using Arabidopsis thaliana miR159a, miR167b and miR171a precursors as backbones, we designed two types of amiRNA targeting sequence that encode the silencing suppressor HC-Pro of Potato virus Y (PVY) and the TGBp1/p25 (p25) of Potato virus X (PVX). The detected amiRNAs efficiently inhibited HC-Pro and p25 gene expression and conferred highly specific resistance against PVY or PVX infection in transgenic Nicotiana tabacum; this resistance was also maintained under conditions of increased viral pressure. Moreover, resistance was strongly influenced by the complementarity between the target sequence and amiRNA, and was well correlated to amiRNA expression level; the expression level of amiRNAs was also well related to the precursor backbones. We further showed that transgenic N. tabacum developed highly effective resistance to both PVY and PVX through expression of a dimeric amiRNA precursor. Together, our findings indicate that transgenic plants with multiple virus-specific resistance can be obtained through co-expression of several amiRNAs targeting multiple viruses.