Epidemiological analysis of HPV in Sichuan during 2014-2021.

INTRODUCTION: Cervical cancer is a common malignancy among woman, strong molecular epidemiological data show that high risk HPV infection is the main cause of cervical cancer. MATERIAL AND METHODS: Samples were collected from Sichuan women's and children's hospital based on the relevant guidelines and regulations, HPV DNA was extracted and evaluated by Human Papillomavirus Genotyping Kit for 21 types, according to the manufacturer's guidelines to analyze the epidemic age, mixed infection types, variation trend of HPV types in Sichuan from 2014 to 2021; Results: Out of 51174 samples11165 (21.82 %) HPV positive samples were detected, all belonging to alpha family, 53.32 % HPV positive samples and 61.51 % high-risk (HR) HPV positive samples are alpha-9 genus; The three commonest HR were HPV-52, HPV-16, HPV-58, and the low-risk (LR) HPV were HPV-81, HPV-6, HPV-11; Single infection was absolutely predominant and the age group with the highest HPV detection rate was 26-30 years old. During 2014-2021, HPV-16, HPV-6 and HPV-11 decline, while HPV-58 and HPV-52 increased; Conclusions: The most prevalent age group of HPV in this region was 26-30 years old. The detection rate of HPV-52 increased in the region, overtaking HPV-16 as the commonest type of HPV. α-9 genus HPV with strong pathogenicity is the commonest HR HPV. HPV prevalence systematic comparison in certain areas and continuous time can accurately and intuitively understand its distribution changes, achieve analysis of the epidemic trend, and provide guidance for the prevention, treatment and scientific research of HPV in Sichuan.

Genetically blocking HPD via CRISPR-Cas9 protects against lethal liver injury in a pig model of tyrosinemia type I.

Hereditary tyrosinemia type I (HT1) results from the loss of fumarylacetoacetate hydrolase (FAH) activity and can lead to lethal liver injury (LLI). Therapeutic options for HT1 remain limited. The FAH -/- pig, a well-characterized animal model of HT1, represents a promising candidate for testing novel therapeutic approaches to treat this condition. Here, we report an improved single-step method to establish a biallelic (FAH -/- ) mutant porcine model using CRISPR-Cas9 and cytoplasmic microinjection. We also tested the feasibility of rescuing HT1 pigs through inactivating the 4-hydroxyphenylpyruvic acid dioxygenase (HPD) gene, which functions upstream of the pathogenic pathway, rather than by directly correcting the disease-causing gene as occurs with traditional gene therapy. Direct intracytoplasmic delivery of CRISPR-Cas9 targeting HPD before intrauterine death reprogrammed the tyrosine metabolism pathway and protected pigs against FAH deficiency-induced LLI. Characterization of the F1 generation revealed consistent liver-protective features that were germline transmissible. Furthermore, HPD ablation ameliorated oxidative stress and inflammatory responses and restored the gene profile relating to liver metabolism homeostasis. Collectively, this study not only provided a novel large animal model for exploring the pathogenesis of HT1, but also demonstrated that CRISPR-Cas9-mediated HPD ablation alleviated LLI in HT1 pigs and represents a potential therapeutic option for the treatment of HT1.

Effect of Prepregnancy Obesity on Litter Size in Primiparous Minipigs.

Obesity is a public health problem in both developed and developing countries, and the negative effects of obesity on reproductive physiology have been highlighted recently. We evaluated the effects of porcine obesity index, sex hormones, and peptide hormones on litter size in various breeds of minipigs. Blood samples were collected from sedated 8-,10-, and 12-mo-old minipigs to measure preovulatory levels of sex hormones (follicle-stimulating hormone, luteinizing hormone, estradiol, progesterone, testosterone, and prolactin) and peptide hormones (insulin-like growth factor, glucagon, cortisol, growth hormone, free thyroxine, free triiodothyronine, insulin, and leptin). We also measured weight, abdominal circumference, neck circumference, and body length and then calculated the porcine obesity index. Data were analyzed by one-way ANOVA, and means were compared by least significance difference testing. Pearson correlation between parameters and litter size was analyzed. Prepregnancy porcine obesity index and litter size were negatively correlated in primiparous minipigs. Litter size was influenced by luteinizing hormone, estradiol, progesterone, testosterone, prolactin, follicle-stimulating hormone, cortisol, insulin-like growth factor 1, growth hormone, free thyroxine, insulin, and leptin. In conclusion, prepregnancy obesity reduces litter size in primiparous minipigs.