Chloroquine (CQ) phosphate has been suggested to be clinically effective in the treatment of coronavirus disease 2019 (COVID-19). To develop a physiologically-based pharmacokinetic (PBPK) model for predicting tissue distribution of CQ and apply it to optimize dosage regimens, a PBPK model, with parameterization of drug distribution extrapolated from animal data, was developed to predict human tissue distribution of CQ. The physiological characteristics of time-dependent accumulation was mimicked through an active transport mechanism. Several dosing regimens were proposed based on PBPK simulation combined with known clinical exposure-response relationships. The model was also validated by clinical data from Chinese patients with COVID-19. The novel PBPK model allows in-depth description of the pharmacokinetics of CQ in several key organs (lung, heart, liver, and kidney), and was applied to design dosing strategies in patients with acute COVID-19 (Day 1: 750 mg BID, Days 2-5: 500 mg BID, CQ phosphate), patients with moderate COVID-19 (Day 1: 750 mg and 500 mg, Days 2-3: 500 mg BID, Days 4-5: 250 mg BID, CQ phosphate), and other vulnerable populations (.., renal and hepatic impairment and elderly patients, Days 1-5: 250 mg BID, CQ phosphate). A PBPK model of CQ was successfully developed to optimize dosage regimens for patients with COVID-19.

Objective To analyze the resistance of influenza virus to neuraminidase inhibitors (NAI) in Hebei province during 2018-2019. Methods Virus were collected from the Hebei Influenza Surveillance Network during 2018-2019. A total of 36 confirmed influenza viruses (with 25 H1pdm09 and 11 H3N2) were selected to test resistance to oseltamivir and zanamivi with fluorescence (FL). Results All 36 influenza viruses tested were sensitive to oseltamivir and zanamivir. The median half maximal inhibitory concentration (IC50) for oseltamivir of H1pdm09 and H3N2 were of 0.50 nM (range 0.07-1.14 nM) and 0.25 nM (range 0.09-0.69 nM) respectively, while 0.29 nM (range 0.09-0.85 nM) and 0.87(range 0.17-1.81 nM) for zanamivir, all were within 10 fold IC50 of the reference virus (corresponding type). Conclusion All the tested influenza strains isolated in Hebei province during 2018-2019 were sensitive to NAI.

Objective To evaluate the health education effect of schistosomiasis in Hubei Province after implementing of the Outline of National Mid-Long-Term Plan for Schistosomiasis Prevention and Control (2004–2015). Methods Based on questionnaires and datum review, the data of health education for integrated prevention and control of schistosomiasis in Hubei Province from 2004 to 2015 were collected to evaluate the effect of health education. Results A total of 16 662 499 schistosomiasis health education publicity materials were distributed, 28 712 times of media propaganda were conducted, 174 506 warning signs were established, 185 985 promotional slogans were issued, 1 212 810 pieces of personal protective equipment were distributed, 9 248 village officer training courses were organized, and 5 569 school teacher training courses in primary and secondary schools were conducted in 63 counties (cities, districts) of 13 cities in Hubei Province from 2004 to 2015. A total of 4 815 people were surveyed in 3 counties in 2015. The awareness rate of schistosomiasis control knowledge was 91.62%, and the correct rates of beliefs and attitudes were 89.54% and 96.91% respectively. The overall rate of correct behavior of the population was 91.91%. The related indicators, such as schistosomiasis infection rate, acute infection cases, and others, declined year by year over the same period. Conclusions The schistosomiasis health education in Hubei Province has obvious effects on enhancing the knowledge and attitudes of schistosomiasis control in populations and promoting the formation of correct schistosomiasis control behavior among residents. It has played an active role and is an important mean in comprehensive prevention and control of schistosomiasis.

Hepatocellular carcinoma(HCC) is the most common malignancy in the world. Although there is progress in HCC diagnosis and treatment, it is still the third leading cause of cancer death worldwide because it is not easily diagnosed early and the disease progresses quickly. China is a high-risk area for HCC, and the number of cases is high and on the rise. Its prevention and treatment is a pressing problem. At present, western medicine is still unclear about the complex pathogenesis and clinical treatment of HCC. There are still many shortcomings and huge challenges. Traditional Chinese medicine(TCM) has its unique advantages in the treatment of HCC. With an overall concept, it has unique therapeutic effect and fewer side effect on HCC,it can not only inhibit tumor growth, but also alleviate patients' clinical symptoms and improve their quality of life. Therefore, the study of the effect of TCM in treating HCC has attracted the attention from many clinicians and researchers. However, the chemical composition of TCM formula is complex, with many targets and huge network of pharmacodynamic mechanisms, which greatly limits the research on the development of clinical drugs for the Chinese medicine formula. In recent years, there have been achievements in the studies of anti-hepatocarcinoma efficacy and mechanism of action of Chinese medicine compound, which mainly focused on the compound's effect in inhibiting the proliferation of hepatocarcinoma cells, blocking cell cycle and inducing apoptosis and autophagy, inhibiting liver cancer cell invasion and metastasis, regulating the immune function, synergism and attenuation, and reversing the drug resistance. In this paper, domestic and foreign literatures on the above-mentioned pharmacodynamics and mechanism of anti-liver cancer of TCM compound were studied, analyzed, summarized and summarized. This paper briefly reviews the research progress of its anti-hepatocarcinoma mechanism, and provides scientific ideas and evidence for the future study of the anti-hepatocarcinoma mechanism of TCM compound and its rational clinical application.

Objective To study the serotypes and molecular characteristics of foodborne Salmonella in Yunnan Province using pulsed field gel electrophoresis (PFGE) and to establish PFGE fingerprint database. Methods This study was carried out on the basis of the Serological typing of 322 strains of foodborne Salmonella which was isolated from Yunnan national foodborne disease surveillance from 2013 to 2016. The clustering analysis was conducted on 148 strains of Salmonella DNA restriction enzyme map by using the software of BioNumerics. Fingerprint database was established through the comparison of clustering analysis correlation on bacterial strain. Results The serotype of 322 strains of Salmonella mainly included A, B, C, D, E, F, G and other 7 groups,among which Salmonella typhimurium was the major type, accounting for 11.4% (37/322) . Cluster analysis was applied using BioNumerics software in 148 strains of Salmonella DNA restriction enzyme map. According to the different number and the different positions, electrophoresis strips were divided into 102 different PFGE patterns (Figure 1) , which was categorized into 39 clusters if 90% of the strips was similar. Conclusion Foodborne salmonella molecular classification is complex. Salmonella typhimurium is the major type. PFGE belt type presents diversity.

BACKGROUNDData on the epidemiology of hypertension in Chinese non-dialysis chronic kidney disease (CKD) patients are limited. The aim of the present study was to investigate the prevalence, awareness, treatment, and control of hypertension in the non-dialysis CKD patients through a nationwide, multicenter study in China.

METHODSThe survey was performed in 61 tertiary hospitals in 31 provinces, municipalities, and autonomous regions in China (except Hong Kong, Macao, and Taiwan). Trained physicians collected demographic and clinical data and measured blood pressure (BP) using a standardized protocol. Hypertension was defined as systolic BP ≥ 140 mmHg and/or diastolic BP ≥ 90 mmHg, and/or use of antihypertensive medications. BP < 140/90 mmHg and < 130/80 mmHg were used as the 2 thresholds of hypertension control. In multivariate logistic regression with adjustment for sex and age, we analyzed the association between CKD stages and uncontrolled hypertension in non-dialysis CKD patients.

RESULTSThe analysis included 8927 non-dialysis CKD patients. The prevalence, awareness, and treatment of hypertension in non-dialysis CKD patients were 67.3%, 85.8%, and 81.0%, respectively. Of hypertensive CKD patients, 33.1% and 14.1% had controlled BP to < 140/90 mmHg and < 130/80 mmHg, respectively. With successive CKD stages, the prevalence of hypertension in non-dialysis CKD patients increased, but the control of hypertension decreased (P < 0.001). When the threshold of BP < 130/80 mmHg was considered, the risk of uncontrolled hypertension in CKD 2, 3a, 3b, 4, and 5 stages increased 1.3, 1.4, 1.4, 2.5, and 4.0 times compared with CKD 1 stage, respectively (P < 0.05). Using the threshold of < 140/90 mmHg, the risk of uncontrolled hypertension increased in advanced stages (P < 0.05).

CONCLUSIONSThe prevalence of hypertension Chinese non-dialysis CKD patients was high, and the hypertension control was suboptimal. With successive CKD stages, the risk of uncontrolled hypertension increased.

Adult ; Aged ; Awareness ; Female ; Humans ; Hypertension ; complications ; epidemiology ; therapy ; Male ; Middle Aged ; Prevalence ; Renal Insufficiency, Chronic ; complications

The STandards for Reporting Interventions in Clinical Trials Of Moxibustion (STRICTOM), in the form of a checklist and descriptions of checklist items, were designed to improve reporting of moxibustion trials, and thereby facilitating their interpretation and replication. The STRICTOM checklist included 7 items and 16 sub-items. These set out reporting guidelines for the moxibustion rationale, details of moxibustion, treatment regimen, other components of treatment, treatment provider background, control and comparator interventions, and precaution measures. In addition, there were descriptions of each item and examples of good reporting. It is intended that the STRICTOM can be used in conjunction with the main CONSORT Statement, extensions for nonpharmacologic treatment and pragmatic trials, and thereby raise the quality of reporting of clinical trials of moxibustion. Further comments will be solicited from the experts of the CONSORT Group, the STRICTA Group, acupuncture and moxibustion societies, and clinical trial authors for optimizing the STRICTOM.
Clinical Trials as Topic ; methods ; standards ; Humans ; Moxibustion ; methods ; standards ; Randomized Controlled Trials as Topic ; Research Design ; standards

Objective To investigate the influences of loading time and loading angle on the stress, displacement of human periodontal ligament in dynamic jaw. Methods The three-dimensional assembly model of the mandible front teeth, periodontal ligament and alveolar bone was reconstructed by using the reverse engineering technology. The thickness of periodontal membranes was 0.2 mm. The stress, displacement at different positions of the periodontal ligaments during different jaw cycles were analyzed under dynamic load in the direction from bucca to tongue side with 0°, 15°, 30°, 45°, 60°, 75°, 90° angle to the long axis of the tooth. Results During one jaw cycle, the ratio of the maximum to minimum value of the maximum residual stress due to different loading angles was 5.5, and the ratio of the maximum to minimum value of the maximum displacement was 8.1. The ratio of the maximum to minimum value of the maximum displacement which was caused by five jaw cycles was increased in the range from 1.02 to 1.35 with the increase of loading angles. The ratio of the maximum to minimum value of the maximum residual stress which was caused by different loading angles was increased in the range from 1.86 to 3.00 with the increase of jaw cycles. The location of the maximum stress was at the tongue side of the cervical margin at different loading angles, and the location of the maximum residual stress was distributed at different positions of the cervical margin. Most stress was accumulated at the root of the periodontal ligament under the 0° dynamic load. Conclusions The situation of the accumulated residual stresses and the uncertainties in the distribution of the maximum residual stresses should be observed in the clinical choice of mandible incisors fixed by bridge abutments; large angle force applied to the tooth was harmful to the periodontal ligament and rapid succession of chewing hard food should be avoided as much as possible during the clinical treatment.

OBJECTIVETo analyze the clinical characteristics and the surgical treatment strategy of cervical kyphosis.

METHODSFrom March 2006 to October 2009, 31 cases of cervical kyphosis were treated. According to the clinical features and imaging findings, different treatment methods were used. There were 9 patients in operation group, including 4 male and 5 female patients, aged from 17 to 72 years (average age of 35 years). Among them, 5 cases were idiopathic kyphosis and 4 cases were caused by laminectomy or other reasons. There were 22 patients in conservative treatment group, including 11 male and 11 female patients, aged from 14 to 40 years (average age of 29 years), who were all idiopathic cervical kyphosis. Before and 1 week after operation, clinical assessment were taken for the patients in operation group using Spinal Cord Injuries Classification Standard of American Spinal Injury Association (AISA). During the periodic review, the anteroposterior, normal sagittal films of cervical spine were taken. At 1 week and every 6 months after operation, MRI films were also taken. These films were studied to evaluate the effects of the operations. In the conservative group, assessment of treatment results by studying anteroposterior and normal lateral views of cervical spine were were taken every month. The clinical characteristics and the surgical treatment strategies of these patients were analyzed.

RESULTSIn operation group, 9 cases were followed up for 6 to 18 months, all patients did not failed in internal fixation and fusion. AISA neurological score and neurological function significantly improved. Three days after operation the average Cobb angle was -1.29 ° (preoperative 54.24 °). In conservative group, the average Cobb angle was -5.41 ° (before treatment 11.20 °) 4 months after the treatment. The symptoms of neck shoulder and back pain disappeared, and all patients were followed up for 3 to 24 months, with no recurrence of symptoms.

CONCLUSIONSIn the early period of cervical kyphosis, adopt postural therapy, plaster braces to correct an imbalance in cervical spine biomechanics can prevent deformity development. According to patients' clinical characteristics, choosing individual treatment programs can correct the severe cervical kyphosis and achieve good outcome.

Adolescent ; Adult ; Aged ; Cervical Vertebrae ; surgery ; Female ; Follow-Up Studies ; Humans ; Kyphosis ; surgery ; Male ; Middle Aged ; Spinal Fusion ; Treatment Outcome ; Young Adult

Objective To present the changes of surgical approaches for the resection of juvenile nasopharyngeal angiofibromas(JNA)and the follow-up results.Methods The clinical records of 59 patients with JNA treated under endoscope between 2002 and 2009 were reviewed retrospectively.The patients were divided into two groups:Group A(RadkowskiⅠa-Ⅱb)and Group B(Radkowsik Ⅱc-Ⅲb).The tumor stages,feeding vessels,operating time,complications and recurrence were observed and recorded.Results There were 7 patients with stageⅠa,3 patients with stageⅠb,5 patients with stage Ⅱ a,6 patients with stage Ⅱ b,4 patients with stage Ⅱc,23 patients with stage Ⅲa,11 patients with stage Ⅲb.The average age at diagnosis in Group A(21 cases)was 23.9 years old.The average operating time was(106.0±43.7)min.The follow-up ranged from 3 months to 74 months(median 36 months)except for 3 missing cases.The average age at diagnosis in Group B(38 cases)was 16.2 years old and the average operating time was(152.9±58.0)min.The follow-up ranged from 3 months to 87 months(median 25 months)except for 5 missing cases.During follow-up,6 patients in group B recurred.Infarction of thalamencephalon happened in 1 patient in group B who recovered totally afterwards.The difierence in operating time between two groups was statistically significant(t=-3.232,P=0.002).The life table was used to evaluate the survival curves and Log-rank test showed that the difference of recurrent time between two groups was statistically significant(P=0.03).Conclusions The key techniques to remove tumor are bleeding control,drilling-out the bone that tumor invaded.Transpterygoid or posterolateral wall of maxillary sinus approach are recommended for tumors that extend to infratemporal fossa.Small and intermediate-sized JNA which have no deep invasion of skull base(Radkowski Ⅰ a-Ⅱ b)have a low morbidity.JNA at Radkowski stage Ⅱ c and above have residual and recurrent risk.