Mice carrying a null mutation in the Period 1 (mPer1) gene were generated using embryonic stem cell technology. Homozygous mPer1 mutants display a shorter circadian period with reduced precision and stability. Mice deficient in both mPer1 and mPer2 do not express circadian rhythms. While mPER2 regulates clock gene expression at the transcriptional level, mPER1 is dispensable for the rhythmic RNA expression of mPer1 and mPer2 and may instead regulate mPER2 at a posttranscriptional level. Studies of clock-controlled genes (CCGs) reveal a complex pattern of regulation by mPER1 and mPER2, suggesting independent controls by the two proteins over some output pathways. Genes encoding key enzymes in heme biosynthesis are under circadian control and are regulated by mPER1 and mPER2. Together, our studies show that mPER1 and mPER2 have distinct and complementary roles in the mouse clock mechanism.

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To determine the annual incidence and clinically relevant risk factors for foot ulceration in a large cohort study of diabetic foot ulcer (DFU) patients and diabetes mellitus (DM) patients in China. To investigate a cohort of 1,333 patients comprising 452 DFU patients and 881 DM patients, who underwent foot screening, physical examination, and laboratory tests in eight hospitals. The patients were assessed at baseline in terms of their demographic information, medical and social history, peripheral neuropathy disease (PND) screening, periphery artery disease (PAD) screening, assessment of nutritional status, and diabetic control. One year later, the patients were followed up to determine the incidence of new foot ulcers, amputation, and mortality. By univariate analysis, statistically significant differences were found in age, location, gender, living alone (yes/no), occupation, smoking, hypertension, PND, PAD, nephropathy, retinopathy, cataracts, duration of diabetes, Glycosylated hemoglobin A (HbA1c), fasting plasma glucose level, postprandial blood glucose level, insulin level, blood urea nitrogen, creatinine, cholesterol, triglyeride, high density lipoprotein (HDL), serum albumin, white blood cell, and body mass index. A binary logistic regression model was used to examine which of these risk factors were independent risk factors for foot ulceration. A total of 687 (51.5%) of the 1,333 patients were followed up for an average of 12 months; there were 458 DM patients and 229 DFU patients. A total of 46 patients died during the follow-up period; 13 were DM patients, and 33 were DFU patients. Of the 641 patients, 445 (69.4%) patients were DM patients, and 196 (30.6%) were DFU patients. At follow-up, 36/445 DM patients (8.1%), and 62/196 DFU patients (31.6%), developed new ulcers; 10/196 DFU patients underwent an amputation. The annual incidence of ulceration for DM patients and amputation for DFU patients were 8.1 and 5.1%, respectively. The annual mortality of the DM patients and DMF patients were 2.8 and 14.4%, respectively. A binary logistic regression model was used to examine which risk factors were independent risk factors for foot ulceration during the follow-up period, and the final results showed that nephropathy (odds ratio 2.32), insulin level (odds ratio 3.136, 2.629), and decreased HDL (odds ratio 0.427) were associated with increased risks for foot ulceration. Complications of diabetes affecting the feet represent a serious problem in China. The incidence of foot ulcers and amputation are much higher than that of Western countries. More intensive surveillance and aggressive care following a diagnosis of DFU and earlier referral to specialty care might improve the patient outcome.

Overcoming immune tolerance of the growth factors associated with tumor growth should be a useful approach to cancer therapy by active immunity. We used vascular endothelial growth factor (VEGF) as a model antigen to explore the feasibility of the immunogene tumor therapy with a vaccine based on a single xenogeneic homologous gene, targeting the growth factors associated with angiogenesis. To test this concept, we constructed a plasmid DNA encoding Xenopus homologous VEGF (XVEGF-p) and control vectors. We found that immunogene tumor therapy with a vaccine based on XVEGF was effective at both protective and therapeutic antitumor immunity in several tumor models in mice. VEGF-specific autoantibodies in sera of mice immunized with XVEGF-p could be found in Western blotting analysis and ELISA assay. The purified immunoglobulins were effective at the inhibition of VEGFmediated endothelial cell proliferation in vitro, and at antitumor activity and the inhibition of angiogenesis by adoptive transfer in vivo. The elevation of VEGF in the sera of the tumor-bearing mice could be abrogated with XVEGF-p immunization. The antitumor activity and production of VEGF-specific autoantibodies, significantly elevated IgG1 and IgG2b, could be abrogated by the depletion of CD4 ؉ T lymphocytes. The observations may provide a vaccine strategy for cancer therapy through the induction of autoimmunity against the growth factors associated with tumor growth in a cross reaction with single xenogeneic homologous gene and may be of importance in the further exploration of the applications of other xenogeneic homologous genes identified in human and other animal genome sequence projects in cancer therapy.

Coronavirus disease 2019 (COVID-19) has rapidly spread not only in China but throughout the world. Children with kidney failure (chronic kidney disease (CKD) stage 5) are at significant risk for COVID-19. In turn, a set of recommendations for the prevention and control of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and COVID-19 in pediatric hemodialysis (HD) centers and in home peritoneal dialysis (PD) settings have been proposed. The recommendations are based on the epidemiological features of the SARS-CoV-2 virus and COVID-19 disease, susceptibility factors, and preventive and control strategies. These recommendations will be updated as new information regarding SARS-CoV-2 and COVID-19 becomes available.