Response of Scalp and Skull Metastasis to Anti-PD-1 Antibody Combined with Regorafenib Treatment in a Sorafenib-Resistant Hepatocellular Carcinoma Patient and a Literature Review.

Background: Scalp and skull metastasis of hepatocellular carcinoma (HCC) is extremely rare. Modalities for the treatment of this disease include craniotomy, radiotherapy and chemotherapy, which are unsatisfactory. We report a case of HCC with scalp and skull metastasis and review similar cases from the literature to accumulate experience for better management of this type of HCC metastasis. Case Presentation: A 54-year-old female was diagnosed with advanced HCC with posterior portal vein tumor thrombus (PVTT) at admission. She received laparoscopic microwave therapy for a large tumor in Segment 6, which was then followed by sorafenib therapy. One year later, sorafenib resistance developed, metastasis occurred in the scalp and skull, left sacroiliac joint, and lung; PVTT extended into the main portal vein and alpha-feta protein (AFP) levels exceeded 65,000 ng/mL. Systemic therapy was then substituted by regorafenib combined with sintilimab. Three months later, AFP decreased to 2005 ng/mL; meanwhile, skull and lung metastatic lesions shrank significantly. Furthermore, both lump and limp disappeared. One year after the combination of regorafenib and sintilimab, skull and lung metastasis, and PVTT were completely relieved. Moreover, primary liver lesions showed no sign of activity. With comprehensive therapy, the patient has survived for 5 years and 7 months. Conclusion: Sorafenib-regorafenib sequential treatment combined with sintilimab is safe and effective when used to treat HCC skull metastasis, for which high-level evidence is needed to support this treatment strategy.

Ancient Adaptative Evolution of ACE2 in East Asians.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been posing an unprecedented challenge to global public health. SARS-CoV-2 and several other coronaviruses utilize angiotensin-converting enzyme 2 (ACE2) as their entry receptors. The ACE2 gene has been found to experience episodic positive selection across mammals. However, much remains unknown about how the ACE2 gene evolved in human populations. Here, we use population genetics approaches to investigate the evolution of the ACE2 gene in 26 human populations sampled globally. We find the ACE2 gene exhibits an extremely low nucleotide diversity in the East Asian populations. Strong signals of selective sweep are detected in the East Asian populations, but not in the other human populations. The selective sweep in ACE2 is estimated to begin in East Asian populations ∼23,600 years ago. Our study provides novel insights into the evolution of the ACE2 gene within human populations.