Objective: To analyze the dynamic changes and influencing factors of HIV-1 DNA load in HIV-1 infected individuals under antiretroviral therapy (ART) in Dehong Dai and Jingpo autonomous prefecture, Yunnan province, and provide information support for the clinical use of HIV-1 DNA quantitative detection. Methods: The HIV infection cases in recent infection cohort from Dehong Center for Disease Control and Prevention during 2009-2018 were selected as study subjects. The dynamic curve of HIV-1 DNA load varrying with time was generated and logistic regression analysis was conducted to identify the risk factors for HIV-1 load in the recent follow up after ART and statistical analysis was performed by using SPSS 17.0. Results: Among the 113 HIV infection cases detected from the recent infection cohort, the recent HIV infection rate were 49.6%(56/113) males, sexual transmission cases and drug injection transmission cases accounted for 53.1% (60/113), 80.5% (91/113) and 19.5% (22/113), respectively. The dynamic changes curve showed that HIV-1 DNA load was relatively high (>800 copies /10⁶ PBMCs) before ART, and droped rapidly (<400 copies /10⁶ PBMCs) after ART for 1 year. However, HIV-1 DNA load decreased insignificantly from the second year of ART, and remained to be 269 copies/10⁶ PBMCs after ART for 6 years. Univariable logistic regression analysis indicated that OR (95%CI) of CD8, CD4/CD8 and HIV-1 DNA load were 1.00 (1.00-1.00), 0.30 (0.09-1.05) and 1.01 (1.00-1.01), respectively. Multivariable logistic regression analysis showed that OR value of HIV-1 DNA load base was 1.00 (1.00-1.01). Conclusions: HIV-1 DNA load decreased significantly in the first year of ART, then remained stable for years. HIV-1 DNA load base was the key factor associated with the decrease of HIV-1 DNA load, the lower the HIV-1 DNA load base, the lower HIV-1 DNA load. Therefore, earlier ART can contribute to the decrease of HIV-1 DNA load.
China/epidemiology* ; DNA/therapeutic use* ; HIV Infections/drug therapy* ; HIV Seropositivity ; HIV-1/genetics* ; Humans ; Male ; Viral Load

Background: Management of tumors has become more complex owing to tumor heterogeneity. Fewer studies have been performed on intra-tumor heterogeneity of endometrial cancer (EC) until now. Therefore, it is of great clinical value to explore the intra-tumor heterogeneity of EC based on clinical features and gene expression profiles. Methods: A total of 1688 patients with EC were screened and 114 patients were finally selected, including specimens from 84 patients with primary EC without relapse (PE) and the paired metastases (P-M) specimens, as well as specimens from 30 patients with primary EC with relapse (RPE) and the paired relapsed EC (P-RE) specimens. Microarray and RNA-seq were used to detect gene expression of EC samples. Clinicopathological characteristics and molecular data were compared between PE and P-M groups and between RPE and P-RE groups to explore the intra-tumor heterogeneity of EC. Results: The clinical intra-tumor spatial heterogeneity of pathological type, grade, ER status, and PR status between PE and P-M were 17.9%, 13.1%, 28.6%, and 28.6%, respectively. The clinical intra-tumor spatiotemporal heterogeneity of pathological type, grade, ER status, and PR status between RPE and P-RE were 16.7%, 33.3%, 25.0%, and 37.5%, respectively. Cluster analysis sorts EC samples based on progression type of lesion and their pathological type. There were differentially expressed genes between PE and P-M and between RPE and P-RE, of which gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis were mainly enriched in cell proliferation, the p53 signaling pathway, etc. Conclusions Clinical and molecular data showed that there was spatiotemporal heterogeneity in intra-tumor of EC, which may add to the complexity of diagnosis and therapeutics for EC. Considering the intra-tumor heterogeneity, sequential chemotherapy and precision medicine may be a more suitable treatment plan for EC.

Objective To understand the prevalence and epidemiological characteristics of hepatitis C virus (HCV) co-infection among newly reported HIV-infected patients from 2016 to 2017 in Dehong Prefecture of Yunnan Province. Methods A cross-sectional survey was conducted to detect HCV antibodies in 2 196 newly reported HIV-infected persons in Dehong Prefecture, Yunnan Province, from 2016 to 2017. Results A total of 694 cases(31.6%) were detected antibodies against HCV during HIV-infected persents. The prevalence of HCV co-infection among newly reported HIV-infected patients in Chinese and Burmese was 14.4% (112/780) and 41.1% (582/1 416), respectively. Moreover, the prevalence of HCV co-infection was higher in male, ethnic minorities such as Dai and Jingpo minority, primary school and below and farmers in both Chinese and Burmese. Multivariate Logistic regression model showed that HCV infection was associated with male, Dai minority, HIV infection by injecting drug and famers among Chinese and Burmese reported HIV-infected patients. Conclusions The prevalence of HCV co-infection was high among newly reported in Dehong Prefecture of Yunnan Province. Meanwhile, the epidemiological characteristics of HIV/HCV co-infections in Chinese and Burmese are different, thus different prevention and control measures are needed for patients of different nationalities.

Objective To analyze the prevalence and years lived with disability (YLD) from dental caries among children and adolescents and the time trends over the past two decades in Sichuan province, the largest province in west China. Methods Based on the Global Burden of Disease Study 2015 (GBD2015), which systematically assessed the epidemiological characteristics of major diseases and their transitions by country and region from 1990 to 2015, we extracted the estimated results for China. We then used the Bayesian meta-regression method to estimate the sex- and age-specific prevalences and YLDs from dental caries among children and adolescents under 15 years old in Sichuan province and compared them with global and national indicators for the same period. Results In 2015, there were almost 6 million cases of dental caries in children and adolescents (aged < 15 years) in Sichuan province, accounting for 6% of the total cases in China. For children under 5 years, the prevalence of deciduous caries was 55.9%, and the YLDs value was 10.8 per 100,000, while it was 24.3% and 5.1 per 100,000 respectively among 5- to 14-year-olds; for those aged 5 to 14 years, the prevalence of permanent caries was 21.5%, and the YLDs value was 11.5 per 100,000. From 1990 to 2015, the prevalence of dental caries for children under 5 years increased substantially, by 16.2%, and the YLDs increased by 8.7%. Among those aged 5 to 14 years, the prevalence increased and the YLDs decreased. Conclusion Dental caries remains a huge health burden in Western China. In contrast to the global and national data, the trend has increased rapidly over the past 25 years in this region. This work provides suggestions for the prevention and control for oral health in China with the policy of two-child.

This paper report the development of a new dosage form - self-microemulsifying mouth dissolving films, which can improve the oral bioavailability of water insoluble drugs and have good compliance. A three factor, three-level Box-Behnken design was used for optimizing formulation, investigated the effect of amounts of microcrystalline cellulose, low-substituted hydroxypropyl cellulose and hypromellose on the weight, disintegration time, cumulative release of indomethacin after 2 min, microemulsified particle size and stretchability. Optimized self-microemulsifying mouth dissolving films could fast disintegrate in (17.09 +/- 0.72) s; obtain microemulsified particle size at (28.81 +/- 3.26) nm; and release in vitro at 2 min to (66.18 +/- 1.94)%. Self-microemulsifying mouth dissolving films with broad application prospects have good compliance, strong tensile and can be released rapidly in the mouth through fast self-microemulsifying.
Administration, Oral ; Biological Availability ; Cellulose ; analogs & derivatives ; chemistry ; Drug Compounding ; methods ; Drug Delivery Systems ; methods ; Emulsifying Agents ; chemistry ; Emulsions ; Hypromellose Derivatives ; Indomethacin ; administration & dosage ; Methylcellulose ; analogs & derivatives ; chemistry ; Particle Size ; Solubility ; Surface Properties ; Tensile Strength

Solid carriers had important effects on the properties of solid self-microemulsifying drug delivery systems (S-SMEDDS). In order to make the basis for further development of S-SMEDDS, the influences of silica on the absorption of S-SMEDDS were investigated. An in vitro lipolysis model was used to evaluate the influence of silica on self-microemulsifying drug delivery system digestion from intestinal tract. S-SMEDDS containing silica were prepared by extrusion/spheronization. The drug release and absorption were investigated. The results showed that lipolysis rate and drug concentration in aqueous phase after intestinal lipolysis both increased by adding silica, which was benefit to drug absorption. And silica was not benefit to absorption for slowing drug release. Consistently, there was no significant influence of silica on intestinal absorption. This study implied that the influences of silica on lipolysis rate and drug release were both amount dependent and it is suggested that silica could be used as the solid carrier but the proportion needs to be optimized.
Animals ; Biological Availability ; Drug Delivery Systems ; methods ; Emulsions ; Indomethacin ; administration & dosage ; pharmacokinetics ; Intestinal Absorption ; Lipolysis ; Rats ; Rats, Sprague-Dawley ; Silicon Dioxide ; administration & dosage ; chemistry ; Solubility

A new dynamic in vitro intestinal absorption model for screening and evaluating lipid formulations was established by means of the characteristics of the intestinal digestion and absorption of the lipid formulations. This model was composed of two systems, including intestinal digestion and the intestinal tissue culture, which drew the evaluation method of intestinal absorption into the in vitro lipolysis model. The influence of several important model parameters such as Ca2+, D-glucose, K+ on the two systems of this model has been investigated. The results showed that increasing of Ca2+ concentration could be significantly conductive to intestinal digestion. The increasing of D-glucose concentration could stepped significantly down the decay of the intestinal activity. K+ was able to maintain intestinal activity, but the influence of different concentration levels on the decay of the intestinal activity was of no significant difference. Thus the model parameters were set up as follows: Ca2+ for 10 mmol x L(-1), D-glucose for 15 mmol x L(-1) and K+ for 5.5 mmol x L(-1). Type I lipid formulation was evaluated with this model, and there was a significant correlation between the absorption curve in vitro and absorption curve in vivo of rats (r = 0.995 6, P < 0.01). These results demonstrated that this model can be an attractive and great potential method for the screening, evaluating and predicting of the lipid formulations.
Animals ; Calcium ; metabolism ; Caprylates ; chemistry ; Digestion ; Glucose ; metabolism ; Glycerides ; chemistry ; Indomethacin ; chemistry ; Intestinal Absorption ; Lipids ; chemistry ; Lipolysis ; Models, Biological ; Potassium ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo evaluate the effect and adverse effects of arsenic trioxide (As2O3) in the treatment of primary hepatocarcinoma patients, and conduct the pharmacokinetics study.

METHODSA total of one hundred and eleven advanced primary hepatocarcinoma patients in five centers were treated with As2O3 injection 7 - 8 mg/m(2) i.v. qd for 14 days and was repeated after 7 - 14 days. Evaluation of the clinical response and adverse effects was conducted after two cycles of treatment. The patient who had reached partial PR and SD was treated continuously until disease progression or intolerance.

RESULTSAmong the 102 patients evaluable for clinical efficacy analysis, there were 7 PR, 71 SD and 24 PD, the response rate was 6.9% and the clinical benefit rate was 76.5%. The quality of life was improved in 22.5% of patients. The pain relief rate was 71.7%, time to progress (TTP) was 97 days, and the median survival time (MST) was 195 days. The major adverse effects were reversible WHO I-II grade gastrointestinal reactions and bone marrow suppression. The results of pharmacokinetic study showed that the distribution and elimination characteristics in vivo was found to be a two-compartment model. The plasma elimination half-life was (23.94 ± 18.39) h.

CONCLUSIONSAs2O3 is effective in the management of primary hepatocarcinoma, with a significant analgesic effect. To some extent, it can extend TTP and MST in advanced liver cancer patients, while the treatment is well tolerated in the majority of patients.

Adult ; Aged ; Antineoplastic Agents ; administration & dosage ; adverse effects ; pharmacokinetics ; therapeutic use ; Arsenicals ; administration & dosage ; adverse effects ; pharmacokinetics ; therapeutic use ; Carcinoma, Hepatocellular ; blood ; drug therapy ; pathology ; Disease Progression ; Female ; Follow-Up Studies ; Half-Life ; Humans ; Injections ; Leukopenia ; chemically induced ; Liver Neoplasms ; blood ; drug therapy ; pathology ; Lung Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Nausea ; chemically induced ; Neoplasm Staging ; Oxides ; administration & dosage ; adverse effects ; pharmacokinetics ; therapeutic use ; Quality of Life ; Remission Induction ; Survival Rate ; Vomiting ; chemically induced

The distribution fate and solubilization behavior of indomethacin through the intestinal tract were investigated with in vitro lipolysis model, by comparing the Capmul MCM and Labrafil M 1944 CS type I lipid formulations. The results showed that the more favorable solubilization was in the aqueous digestion phase from each lipid formulations for indomethacin. The lipolysis rate and extent were decided with chemical constitution of the lipid excipients, which meant that less indomethacin was transferred from the long chain polar oil lipid solution into the aqueous digestion phase. Increasing the concentration of indomethacin in the lipid formualitons from a solution to a suspension led to a linear increase in the concentration of indomethacin attained in the aqueous digestion phase from lipid formulations. This study also implied that adverse effects of the lipolysis rate and extent on drug absorption were could be taken into consideration when screening lipid formulations. Lipid suspensions likely had better enhancement of drug absorption. Last, this study demonstrated that a potential basis for optimizing and assessing type I lipid formulations and also researching in vivo-in vitro correlations of lipid formulations were provided by an in vitro lipolysis model.
Caprylates ; chemistry ; Chromatography, High Pressure Liquid ; methods ; Digestion ; Excipients ; Glycerides ; chemistry ; Indomethacin ; administration & dosage ; pharmacokinetics ; Lipolysis ; Models, Biological ; Polyethylene Glycols ; chemistry ; Solubility ; Suspensions

OBJECTIVETo analyze the clinical characteristics of severely and critically ill children with 2009 influenza A (H1N1) infection.

METHODClinical data of 150 cases with 2009 influenza A (H1N1) virus infection confirmed with the use of a real-time polymerase-chain-reaction assay on nasopharyngeal swab specimens were analyzed.

RESULTAmong 150 severely and critically ill children with 2009 influenza A (H1N1) virus infection, 103 were male, 47 were female; the median age was 5 years, 81(55%) were 5 years of age or older; 21 (14%) had underlying chronic diseases. The most common presenting symptoms were fever (95%), cough (89%), vomiting (23%), wheezing (19%), abdominal pain (16%), lethargy (7%), seizures (6%), myalgia (6%), and diarrhea (6%). The common laboratory abnormalities were increased or decreased white blood cells counts (40%), elevated of CRP (33%), LDH (29%), CK (25%) and AST (19%). Clinical complications included pneumonia (65%), encephalopathy (12%), myocarditis (5%), encephalitis (1%) and myositis (1%). All patients had received antibiotics before admission or on admission; 73% of patients had received oseltamivir treatment, 23% of patients had received corticosteroids; 32 (21%) were admitted to an ICU, 13 patients were intubated and mechanically ventilated. Fourteen patients with dyspnea who were irresponsive to the treatment experienced bronchoalveolar lavage with flexible bronchoscopy, and the branching bronchial casts were removed in 5 patients. Totally 145 (97%) patients were discharged, five (3%) died, three previously healthy patients died from severe encephalopathy, one patient died from ARDS, one previously healthy patient died from secondary fungal meningitis.

CONCLUSIONSeverely and critically ill children with 2009 influenza A (H1N1) virus infection may occur mainly in older children without underlying chronic disease. The clinical spectrum and laboratory abnormality of the patients can have a wide range. Neurologic complications may be common and severe encephalopathy can lead to death in previously healthy children. Early use of bronchoalveolar lavage with flexible bronchoscopy may reduce death associated with pulmonary complications.

Child ; Child, Hospitalized ; Child, Preschool ; China ; epidemiology ; Critical Care ; Critical Illness ; Female ; Humans ; Infant ; Influenza A Virus, H1N1 Subtype ; Influenza, Human ; diagnosis ; drug therapy ; epidemiology ; pathology ; Male