Identification and semisynthesis of (-)-anisomelic acid as oral agent against SARS-CoV-2 in mice.

(-)-Anisomelic acid, isolated from Anisomeles indica (L.) Kuntze (Labiatae) leaves, is a macrocyclic cembranolide with a trans-fused α-methylene-γ-lactone motif. Anisomelic acid effectively inhibits SARS-CoV-2 replication and viral-induced cytopathic effects with an EC50 of 1.1 and 4.3 µM, respectively. Challenge studies of SARS-CoV-2-infected K18-hACE2 mice showed that oral administration of anisomelic acid and subcutaneous dosing of remdesivir can both reduce the viral titers in the lung tissue at the same level. To facilitate drug discovery, we used a semisynthetic approach to shorten the project timelines. The enantioselective semisynthesis of anisomelic acid from the naturally enriched and commercially available starting material (+)-costunolide was achieved in five steps with a 27% overall yield. The developed chemistry provides opportunities for developing anisomelic-acid-based novel ligands for selectively targeting proteins involved in viral infections.

Association between delayed surgery and survival in early-stage cervical cancer in mainland China: Implications during the coronavirus pandemic (preprint)

Objective: The COVID-19 pandemic has had a significant impact on oncogynecologic patients worldwide, particularly with respect to delayed diagnosis and treatment. During the COVID-19 pandemic, few studies have examined the impact of delayed surgery on survival in early-stage cervical cancer patients. The purpose of this study was to determine the effect of delayed surgical time on survival in patients with early cervical cancer. Design A retrospective cohort study. Setting A single general hospital in Shaanxi, Northwest China. Population A total of 1207women with early cervical cancer were recruited between April 2013 and December 2018 in Mainland China and followed up until 29 Feb 2022. Methods This retrospective cohort study was conducted in a comprehensive tertiary hospital in Shaanxi, Xi’an, China. We used a Cox proportional hazard model with delay time in weeks as a categorical variable to analyse the effect of surgical delay time on survival. Main Outcome Measures The 5-year overall and disease-free survival were used as the primary outcome measures. Results A total of 800 participants were included in the final cohort. In the multivariate Cox regression analysis (median follow-up, 58 months), patients in the long delay time group had DFS (5-year rates, 91.5% versus 90.9%, HR 0.99, 95% CI 0.62~1.59, P=0.98) and OS (5-year rates of 92.9% versus 90.8%, HR 0.68, 95% CI 0.42~1.10, P=0.11) similar to those in the short delay time group. Conclusions Our findings indicate that a 12-week delay in surgery is not associated with long-term survival in women with early-stage cervical cancer.

Benign Clinical and Epidemiological Outcomes-Associated Factors of COVID-19 from a Solved Epidemic with a Low Case Fatality Rate (preprint)

Background: Since December 2019, COVID-19 has been confirmed in more than18.8 million patients and leads to 0.70 million deaths worldwide. The mortality and disease severity predictors of COVID-19 have been investigated in many studies. However, they are based on early or partial datasets from high epidemic areas. Here, we retrospect benign clinical and epidemiological outcomes-associated factors from a solved epidemic in a low epidemic area. Methods: All 98 laboratory-confirmed COVID-19 patients in a local epidemic (Zhuhai, China) from January 17, 2020 to March 10, 2020 were enrolled. Data were updated until all patients having final outcomes. Results: Patients were all hospitalized. The case fatality rate was 1.0%. There were no local secondary infection cases. The median age was 46.3 years. Underlying diseases were found in 33.7% patients. The severe/critical rate was 19.4%. The mean period from disease onset to admission was 4.4 days. Compared with serious/critical cases, mild/common cases on admission were much younger, lacks of comorbidities and normal in functions of vital organs and indicators of secondary bacterial infections. The lymphocyte counts in serious/critical cases began to be significantly lower 3 days before their identification dates. The absence of lymphopenia before the eighth day from disease onset can exclude the possibility of 78.5% to be serious/critical ill. Most patients (88.8%) received antiviral treatments. Early antiviral treatment significantly shortened the viral RNA-negative conversion time. The delayed antiviral treatment was associated with critical patients.Conclusions: Younger age, lack of aging-related diseases and early hospitalization of all patients to conduct antiviral treatment and prevention of secondary epidemic were the important benign clinical and epidemiological outcomes-associated factors of COVID-19. In combating COVID-19, the active intervention strategies are crucial in low epidemic areas and the continuous monitoring of lymphocytes may be useful to sort patients reasonably in high epidemic areas.

Consensus on standardized diagnosis and treatment for osteoporotic vertebral compression fracture patients during epidemic of corona virus disease 2019 / 中华创伤杂志

Since December 2019, the corona virus disease 2019 (COVID-19) caused by the 2019 novel coronavirus (2019-nCoV) has been reported in Wuhan, Hubei Province. Almost 70% of patients susceptible to 2019-nCoV are over age of 50 years, with extremely large proportion of critical illness and death of the elderly patients. Meanwhile, the elderly patients are at high risk of osteoporotic fractures especially osteoporotic vertebral compression fractures (OVCF). During the prevention and control of COVID-19 epidemic, orthopedists are confronted with the following difficulties including how to screen and protect OVCF patients, how to accurately diagnose and assess the condition of OVCF patients with suspected or confirmed COVID-19, and how to develop reasonable treatment plans and comprehensive protective measures in emergency and outpatient clinics. In order to standardize the diagnosis and treatment of patients with OVCF diagnosed with COVID-19, the authors jointly develop this expert consensus. The consensus systematically recommends the standardized emergency and outpatient screening and confirmation procedures for OVCF patients with suspected or confirmed COVID-19 and protective measures for emergency and outpatient clinics. Moreover, the consensus describes the grading and classification of OVCF patients diagnosed with COVID-19 according to the severity of illness and recommends different treatment plans and corresponding protective measures based on the different types and epidemic prevention and control requirements.