Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

OBJECTIVE: To evaluate pharmacokinetics (PK), efficacy, and safety of atezolizumab (anti-PD-L1) in high interest cancers in China, including esophageal cancer (EC), gastric cancer (GC), hepatocellular carcinoma (HCC), nasopharyngeal cancer (NPC), and non-small cell lung can-cer (NSCLC). METHODS: This phase I, open-label study was conducted at 6 Chinese sites from August 4, 2016 to April 15, 2019. The patients were ≥18 years old with a histologically documented incurable or metastatic solid tumor that was advanced or recurrent and had progressed since the last anti-tumor the-rapy. The PK phase characterized PK and safety of atezolizumab following multiple-dose administration when atezolizumab was administered as a single agent. The extension phase studied safety and efficacy of atezolizumab, as monotherapy (EC, GC, HCC, NPC) and with chemotherapy (NSCLC). RESULTS: This study enrolled 120 patients (PK phase: n=20; extension phase: n=20/cohort). Fourty-two patients (42.0%) were PD-L1 positive in atezolizumab monotherapy group (100 patients), of the 9 patients (9.0%) with microsatellite instability-high (MSI-H) tumors. Atezolizumab clearance was 0.219 L/d, and steady state was reached after 6 to 9 weeks (2-3 cycles) of repeated dosing. Objective response rates (ORRs) in EC, GC, HCC, NPC, and NSCLC were 10.0%, 15.0%, 10.0%, 5.0%, and 40.0%, respectively. In the patients with PD-L1 positive tumors, ORR was 11.9% with atezolizumab and 46.2% with atezolizumab plus gemcitabine and cisplatin. Two GC patients achieved durable response after pseudo-progression. The most common treatment-related adverse events in the atezolizumab monotherapy group were fatigue, anemia, fever, and decreased white blood cell count. The most common treatment-related adverse events in the combination group were anemia, decreased white blood cell count, and decreased appetite. No new safety signals were identified. CONCLUSION Atezolizumab's PK, efficacy, and safety were similar in Chinese patients vs. global patients in previous studies.
Adolescent ; Antibodies, Monoclonal, Humanized ; Antineoplastic Agents/therapeutic use* ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use* ; Carcinoma, Hepatocellular/drug therapy* ; Cisplatin/therapeutic use* ; Humans ; Liver Neoplasms/drug therapy* ; Lung Neoplasms/pathology* ; Nasopharyngeal Neoplasms/drug therapy*

"The Expert Group on Tumor Ablation Therapy of Chinese Medical Doctor Association, The Tumor Ablation Committee of Chinese College of Interventionalists, The Society of Tumor Ablation Therapy of Chinese Anti-Cancer Association and The Ablation Expert Committee of the Chinese Society of Clinical Oncology" have organized multidisciplinary experts to formulate the consensus for thermal ablation of pulmonary subsolid nodules or ground-glass nodule (GGN). The expert consensus reviews current literatures and provides clinical practices for thermal ablation of GGN. The main contents include: (1) clinical evaluation of GGN, (2) procedures, indications, contraindications, outcomes evaluation and related complications of thermal ablation for GGN and (3) future development directions.
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Aortic Valve/surgery* ; Aortic Valve Stenosis/surgery* ; China/epidemiology* ; Heart Valve Prosthesis Implantation ; Humans ; Severity of Illness Index ; Treatment Outcome

Animals ; Chemical and Drug Induced Liver Injury ; drug therapy ; Diabetes Mellitus, Experimental ; drug therapy ; Diabetes Mellitus, Type 2 ; drug therapy ; Dyslipidemias ; drug therapy ; Glycemic Load ; drug effects ; Male ; Protective Agents ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Specific Pathogen-Free Organisms ; Stilbenes ; pharmacology

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.

A questionnaire survey of 1 000 clinicians having experience in treating uncomplicated lower urinary tract infections from different levels of hospitals was conducted to mainly evaluate the applicability and effectiveness of clinical application of clinical practice guideline on traditional Chinese medicine therapy alone or combined with antibiotics for uncomplicated lower urinary tract infection(hereinafter referred to as Guideline). The research was conducted with the three-level quality control strictly throughout the process, and the data was real and reliable. The survey's results showed that: most clinicians considered that the Guideline had good clinical applicability. The availability and price of the recommended medicine were moderate. Traditional Chinese medicine had obvious features and advantages in treating lower urinary tract infection for it could reduce the usage of antibiotics and shorten the course of antibiotic application. In the recommendation section, clinicians proposed increasing medication guidance, updating the Guideline timely, as well as increasing treating methods and techniques, strengthen propaganda and promotion, and improve the use of evidence-based methods. In the evaluation of effectiveness, the majority of clinicians agreed that the definition in both traditional Chinese medicine (TCM) and Western medicine and differential diagnosis in the Guideline were accurately described and the basic principle of treatment as well as the treating method of TCM were recommended appropriately. The TCM formulas and Chinese patent medicine had good effect. Some clinicians suggested refining the syndrome differentiation of stranguria. Some clinicians considered that the formulas and herbs recommended in Guideline didn't have obvious effect and some had doubts about the manipulation of fumigation and washing in the part of other methods recommended in Guideline. Moreover, specification and procedure of manipulation of fumigation and washing using herbs and the acupuncture included in characteristic TCM therapy treating uncomplicated lower urinary tract infection remained to be developed.
Acupuncture Therapy ; Anti-Bacterial Agents ; Diagnosis, Differential ; Drugs, Chinese Herbal ; Humans ; Medicine, Chinese Traditional ; Urinary Tract Infections

Objective: To analyze and compare the epidemiological features of prevalent influenza A viruses in children in Beijing during 13 consecutive surveillance seasons from 2004 to 2017. Methods: This was a repeated cross section study. Throat swabs were collected weekly from children with influenza-like illnesses (ILI) who presented to the outpatient/emergency department of Children's Hospital, Capital Institute of Pediatrics during the period from September, 2004 to August, 2017. All of the specimens were inoculated into Madin Darby canine kidney (MDCK) cells to isolate influenza viruses followed by identifying different types of influenza viruses with reference antisera by hemagglutination-inhibition assay. Descriptive statistics, t test and chi-square test were used to analyze the characteristics of prevalent influenza and characteristics of children infected with different types of influenza viruses. Results: Out of 10 984 specimens from ILI tested for influenza viruses, 1 052 (9.6%) were positive for influenza A viruses, and the positive rate was higher than that of influenza B viruses (6.7%, 741/10 984). Out of 1 052 cases positive for influenza A viruses, 70 cases of seasonal H1N1, 302 cases of 2 009 pandemic H1N1 and 680 cases of H3N2 were identified. The mean age of children with influenza A was (4.2±2.9) years, in whom 55.5% (584/1 052) were male. The mean age of children infected with seasonal H1N1, 2009 pandemic H1N1 and H3N2 was (4.6±2.1) , (4.3±3.1) and (4.2±2.9) years, respectively. There was no significant difference in the mean age among children infected with different subtypes of influenza A viruses (seasonal H1N1 vs. H3N2: t=1.139, P=0.255; 2009 pandemic H1N1 vs. H3N2: t=0.631, P=0.528; seasonal H1N1 vs. 2009 pandemic H1N1: t=0.720, P=0.472), while the mean age of children with influenza B was higher than that of the patients with influenza A ((5.2±2.7) vs. (4.2±2.9) years, t=7.120, P=0.000). The infection rate of influenza A in children with each age group was significantly different from that of influenza B. The infection rate of 2009 pandemic H1N1 and H3N2 increased with age, except for the patients of 0-6 months. Meanwhile, the infection rate of H3N2 in children aged 6 months to 12 years was higher than that of seasonal H1N1 and 2009 pandemic H1N1 (all P<0.05). The influenza A epidemic peaked earlier than that of influenza B when the positive rate of influenza A was higher than that of influenza B, and vice versa. After 2009, circulating strain was substituted by 2009 pandemic H1N1 virus with higher positive rate, while previous seasonal H1N1 had not been detected. The 2009 pandemic H1N1 circulated at high level in two consecutive seasons, which was followed by low level in next season. H3N2 epidemic peaked mostly in winter and spring each year, however, the epidemic wave of H3N2 with high virulence occurred so early in the summer in the year of 2009 H1N1 pandemic. Conclusions The characteristics of prevalent influenza A viruses in children were different among 13 surveillance seasons from 2004 to 2017 in Beijing. The 2009 pandemic H1N1 and H3N2 became the predominant strains of influenza A virus.

BACKGROUNDIt remains controversial whether patients with Stage II colorectal cancer would benefit from adjuvant chemotherapy after radical resection. The aim of this study was to establish two mathematical models to identify the suitable patients for adjuvant chemotherapy.

METHODSThe current study comprised of two steps. In the first step, 353 patients with Stage II colorectal cancer who underwent surgical procedures at the Third Affiliated Hospital of Sun Yat-sen University between June 2006 and December 2015 were entered and followed up for 6-120 months. Their clinical data were collected and enrolled into the database. We established two mathematical models by univariate and multivariate Cox regression analysis to identify the target patients; in the second step, 230 patients under the same standard between January 2012 and December 2016 were entered and followed up for 3-62 months to verify the two models' validation.

RESULTSIn the first step, totally 340 surgical patients with Stage II colorectal cancer were finally enrolled in this study. Statistical analysis showed that tumor differentiation (TD) (P < 0.001), lymphovascular invasion (LVI) (P < 0.001), uncertain or positive margins (UPM) (P < 0.001), and fewer lymph nodes (LNs) (<12) retrieved (P < 0.001) were correlated with the overall survival (OS) and disease free survival (DFS). We obtained two models: (1) OS risk score = 1.116 × TD + 2.202 × LVI + 3.676 × UPM + 1.438 × LN - 0.493; (2) DFS risk score = 0.789 × TD + 2.074 × LVI + 3.183 × UPM + 1.329 × LN - 0.432. According to the models and cutoff points [(0.07, 1.33) and (-0.04, 1.30), respectively], patients can be divided into three groups: low-risk, moderate-risk, and high-risk. Moreover, the high-risk group patients could benefit from adjuvant chemotherapy. In the second step, totally 221 patients were finally used to verify the models' validation. The results proved that the models were accurate and feasible (P< 0.05).

CONCLUSIONSAccording to the predictive models, patients with Stage II colorectal cancer in the high-risk group are strongly recommended for adjuvant chemotherapy, thus facilitating the individualized and precise treatment.