Coordinated surveillance, vaccination and public information efforts have brought the Chinese rabies epizootic under control, but significant numbers of fatalities are still reported annually with some cases occurring in previously rabies free regions. Tibet has remained virtually rabies free for 16 years, but since 2015 one human rabies case has been reported each year. To better understand the origins of these cases, we sequenced three human samples and an additional sample isolated from a dog in 2012. Three genomes were sequenced from brain samples: human case 1 (reported in 2015), human case 3 (2017), and the 2012 dog case. For human case 2 (2016), the rabies N gene was sequenced from a limited saliva sample. Phylogenetic analysis shows that Case 1 (CXZ1501H) and the dog case (CXZ1201D) belong to China IV lineage (equivalent to Arctic-like-2 in global rabies), suggesting an association with a wildlife spillover event. However, Case 2 (CXZ1601H) is placed within the dominant lineage China I, and was most similar with recent strains from neighboring Yunnan province, indicating the current epizootic has finally reached Tibet. Most surprisingly however, was the finding that Case 3 (CXZ1704H) is distinct from other Chinese isolates. This isolate is placed in the Indian Subcontinent clade, similar to recent Nepal strains, indicating that cross-border transmission is a new source for rabies infections. Thus, the complex mixture of the rabies epizootic in Tibet represents a major new challenge for Tibet and national rabies control.

In recent years, the number of human rabies cases in China has decreased annually. However, some western provinces with no human cases for more than 10 years have begun to report rabies cases, and all of the rabies lineages that circulated in western China were found in Inner Mongolia as well. In this study, we generated a phylogenetic tree with all the Inner Mongolia rabies strains available in GenBank and our laboratory, as well as strains from western China and representative viruses from neighboring countries, based on the N gene sequence. Furthermore, the possible relationships underlying the spread of the virus within Inner Mongolia and neighboring regions were analyzed. Three of six rabies lineages of China (China I-VI) were shown to exist in Inner Mongolia, and a spatial cluster analysis supported that the China I lineage, the dominant cluster of China, likely spread to Ningxia from Inner Mongolia. Wild raccoon dog rabies (China IV/Arctic-like-2) may have spread to Inner Mongolia from Russia and likely continued to spread to Qinghai and Tibet. The red fox lineage (China III/Cosmopolitan), which likely spread from Russia and Mongolia, has been shown to circulate in Inner Mongolia and was a serious threat to Xinjiang, which is adjacent to Inner Mongolia. Thus, Inner Mongolia likely became a location where national and international rabies viruses collected and developed into a potential portal for the spread of rabies to western China. To effectively control the spread of rabies in China, both prevention and control of dog and wild animal rabies in Inner Mongolia should be a top priority.

Extramammary Paget’s disease (EMPD) is a rare cutaneous neoplasm with distant metastases and a poor prognosis. We report the case of a 63-year-old male patient exhibiting stage IV primary EMPD with neuroendocrine differentiation, and harboring a somatic mutation in AMER1. After four cycles of Anlotinib combined with Tislelizumab, the patient achieved partial response for the metastatic lesions according to mRECIST1.1 criteria. Total positron emission tomography and computed tomography (PET-CT) scans revealed a significant reduction in SUV from 18.9 to 5.3, and the serum CEA decreased to normal levels after the treatment regimen. However, the patient developed fractures of the fourth and fifth thoracic vertebrae during the treatment. Therefore, percutaneous vertebroplasty was performed, and the patient experienced severe postoperative pneumonia and died from pulmonary encephalopathy and respiratory failure in June 2021. The overall and progression-free survival of the patient after diagnosis were 9 and 8 months, respectively. During the systemic treatment, the patient suffered grade 1 rash in the back and thigh and grade 1 hypertension. Nevertheless, the combination treatment of anlotinib and tislelizumab had a favorable clinical outcome and provided a survival advantage, and should be considered a therapeutic option for patients with AMER1-mutant metastatic EMPD.