Does DRD2 polymorphism influence the clinical characteristics of prolactinoma?

ObjectivesGenetic alterations explaining the clinical variability of prolactinomas still could not be clarified and dopamine D2 receptor (DRD2) polymorphism is a putative candidate for the variable response to dopaminergic treatment. The present study was conducted to investigate the influence of DRD2 TaqI A polymorphism on initial and follow-up characteristics of prolactinoma.Patients and methodsSeventy-two patients with prolactinoma and 98 age and gender matched control subjects were recruited to the case-control study. Serum prolactin levels were assessed by enzyme-linked immunosorbent assay and DRD2 polymorphism was determined by polymerase chain reaction and restriction length polymorphism analysis.ResultsDecrease of prolactin levels and the tumor shrinkage after cabergoline treatment were 93.9 ± 5.9% and 58.3 ± 33.1% in microadenomas and 96.1 ± 6.1% and 51.7 ± 29.3 in macroadenomas (P = 0.02 and P > 0.05, respectively). We observed no significant difference for DRD2 genotypes and the alleles between the patients and healthy group (P > 0.05). Prolactin levels before treatment were correlated with tumor diameter before and after treatment and the percentage of prolactin decrease with treatment (P < 0.001 r = 0.58, P < 0.001 r = 0.40 and P < 0.001 r = 0.47, respectively). Tumor diameter before the treatment was also correlated with the tumor diameter after the treatment (P < 0.001 r = 0.64) and the percentage of prolactin decrease (P = 0.01 r = 0.30). However, no significant association was found between characteristics of prolactinoma and DRD2 genotypes and alleles (P > 0.05).ConclusionThis study revealed that DRD2 TaqI A receptor polymorphism was not associated with the development of prolactinoma and its clinical characteristics. Future studies are needed to clarify the clinical implications of genetic alterations in prolactinoma.     

Relative Bioavailability of Rifampicin in Four Chinese Fixed-dose Combinations Compared with Rifampicin in Free Combinations

Background:

Decreases in the bioavailability of rifampicin (RFP) can lead to the development of drug resistance and treatment failure. Therefore, we investigated the relative bioavailability of RFP from one four-drug fixed-dose combination (FDC; formulation A) and three two-drug FDCs (formulations B, C, and D) used in China, compared with RFP in free combinations of these drugs (reference), in healthy volunteers.

Methods:

Eighteen and twenty healthy Chinese male volunteers participated in two open-label, randomized two-period crossover (formulations A and C) or one three-period crossover (formulations B and D) study, respectively. The washout period between treatments was 7 days. Bioequivalence was assessed based on 90% confidence intervals, according to two one-sided t-tests. All analyses were done with DAS 3.1.5 (Mathematical Pharmacology Professional Committee of China, Shanghai, China).

Results:

Mean pharmacokinetic parameter values of RFP obtained for formulations A, B, C, and D products were 11.42 ± 3.41 μg/ml, 7.86 ± 5.78 μg/ml, 13.05 ± 6.80 μg/ml, and 16.18 ± 3.87 μg/ml, respectively, for peak plasma concentration (C_max), 91.43 ± 30.82 μg·h⁻¹ ·ml⁻¹, 55.49 ± 37.58 μg·h⁻¹ ·ml⁻¹, 96.50 ± 47.24 μg·h⁻¹ ·ml⁻¹, 101.47 ± 33.07 μg·h⁻¹ ·ml⁻¹, respectively, for area under the concentration-time curve (AUC_{0−24 h}).

Conclusions:

Although the concentrations of RFP for formulations A, C, and D were within the reported acceptable therapeutic range, only formulation A was bioequivalent to the reference product. The three two-drug FDCs (formulations B, C and D) displayed inferior RFP bioavailability compared with the reference (Chinese Clinical Trials registration number: ChiCTR-TTRCC-12002451).     

Muscle Oxygenation of the Paretic and Nonparetic Legs During and After Arterial Occlusion in Chronic Stroke

Oxygen delivery and demand are reduced in the paretic leg post-stroke, reflecting decreased vascular function and reduced muscle quantity and quality. However, it is unknown how muscle oxygenation, the balance between muscle oxygen delivery and utilization, is altered in chronic stroke during and after occlusion-induced ischemia.ObjectivesThe objective was to determine muscle oxygen consumption rate, microvascular responsiveness and reactive hyperemia in the paretic and nonparetic legs during and after arterial occlusion post-stroke.Materials and MethodsMuscle oxygen saturation was measured with near-infrared spectroscopy on the vastus lateralis of each leg during 3-minute arterial occlusion and recovery (3 min). Muscle oxygen consumption was derived from the desaturation slope during ischemia, microvascular responsiveness was derived from the resaturation slope after ischemia and reactive hyperemia was derived from the area under the curve above baseline after ischemia. Results: Eleven subjects (91% male; 32.2±6.1 months post-stroke; age 62.9±13.6 years) with a hemiparetic gait pattern participated. There was no significant between-leg muscle oxygenation difference at rest (paretic: 64.9±16.6%; nonparetic: 70.6±15.6%, p = 0.13). Muscle oxygen consumption in the paretic leg (-0.53±0.24%/s) was significantly reduced compared to the nonparetic leg (-0.70±0.36%/s; p = 0.03). Microvascular responsiveness was significantly reduced in the paretic leg compared to the nonparetic leg (paretic: 4.6±1.8%/s; nonparetic: 5.7±1.6%/s, p = 0.04). Reactive hyperemia was not significantly different between legs (paretic:4384±2341%·s; nonparetic: 3040±2216%·s, p = 0.07).ConclusionMuscle oxygen consumption and microvascular responsiveness are impaired in the paretic compared to the nonparetic leg, suggesting both reduced skeletal muscle aerobic function and reduced ability to maximally perfuse muscle tissue.     

Eliminating Mother-to-Child Transmission of Syphilis: Chinese Practice before and during COVID-19 Pandemics

Mother-to-child transmission (MTCT) of syphilis remains a leading cause of stillbirth and death among neonates in many developing countries. In 2007, World Health Orgernization launched the global elimination of MTCT (EMTCT) of syphilis. Given the high burden of congenital syphilis, China subsequently released the specific national EMTCT policies and programs to reduce MTCT of syphilis. The congenital syphilis incidence rate per 100,000 live births in China has markedly decreased from 69.9 in 2013 to 11.9 in 2019. However, due to the global pandemic of COVID-19, the current measures for eliminating MTCT of syphilis are greatly challenged. In this article, we summarize the strategies and measures for the EMTCT of syphilis in China in the past 20 years, the remarkable achievements by the policy support under the leadership of the government. In the context of COVID-19 pandemics, strengthening emergency response to the regional outbreaks of COVID-19, adopting safe, rapid, early and high-quality clinical care for 100% of pregnant women to receive prenatal syphilis testing services, ensuring the availability of Benzathine penicillin for the treatment, and strengthening the closed-loop management of pregnant women and newborns infected with syphilis are the key measures to determine the effectiveness of MTCT for syphilis. Lessons from China may be valuable for other countries that are planning to eliminate MTCT of syphilis.     

Risk of Treatment Failure in Patients with Drug-susceptible Pulmonary Tuberculosis in China

正The objective of this prospective study of the risks of treatment failure in patients with drug-susceptible pulmonary tuberculosis(PTB)was to provide reference data to help develop a disease control strategy.Participants were recruited in eight provinces of China from October 2008 to December2010.A total of 1447 patients with drug-susceptible     

Family Related Factors and Concurrent Heroin Use in Methadone Maintenance Treatment in China

Background: The use of heroin during Methadone Maintenance Treatment (MMT) is a challenging problem that contributes to poor treatment outcomes. Families may play an important role in addressing concurrent heroin use during MMT, especially in collectivist societies such as China. Objectives: In this study, we explored the relationship between family-related factors and concurrent heroin use during MMT in China. Methods: This study was conducted at 68 MMT clinics in five provinces of China. There were 2,446 MMT clients in the analysis. Demographic information, MMT dosage, family members' heroin use status, family support of MMT, family problem, and self-reported heroin use were collected in a cross-sectional survey. The most recent urinalysis of opiate use was obtained from clinical records. Results: Of the 2,446 participants, 533 (21.79%) self-reported heroin use in the previous seven days or had a positive urine morphine test result in the clinic record. Participants whose family member[s] used heroin were 1.59 times (95% CI: 1.17, 2.15) more likely to use concurrently during treatment. Those with family members who totally support them on the MMT were less likely to use (AOR: 0.75, 95% CI: 0.60, 0.94). Having more family problems was positively associated with concurrent heroin use (AOR: 2.01, 95% CI: 1.03, 3.93). Conclusions: The results highlight the importance of the family's role in concurrent heroin use during MMT programs. The study's findings may have implications for family-based interventions that address concurrent heroin use.     

Using NHANES oral health examination protocols as part of an esophageal cancer screening study conducted in a high-risk region of China

Background

The oral health status of rural residents in the People's Republic of China has not been extensively studied and the relationship between poor oral health and esophageal cancer (EC) is unclear. We aim to report the oral health status of adults participating in an EC screening study conducted in a rural high-risk EC area of China and to explore the relationship between oral health and esophageal dysplasia.

Methods

National Health and Nutrition Examination Survey (NHANES) oral health examination procedures and the Modified Gingival Index (MGI) were used in a clinical study designed to examine risk factors for esophageal cancer and to test a new esophageal cytology sampling device. This study was conducted in three rural villages in China with high rates of EC in 2002 and was a collaborative effort involving investigators from the National Institutes of Health and the Cancer Institute of the Chinese Academy of Medical Sciences.

Results

Nearly 17% of the study participants aged 40–67 years old were edentulous. Overall, the mean number of adjusted missing teeth (including third molars and retained dental roots) was 13.8 and 35% had 7 contacts or less. Women were more likely to experience greater tooth loss than men. The average age at the time of first tooth loss for those with no posterior functional contacts was approximately 41 years for men and 36 years for women. The mean DMFT (decayed, missing, and filled teeth) score for the study population was 8.5. Older persons, females, and individuals having lower educational attainment had higher DMFT scores. The prevalence of periodontal disease (defined as at least one site with 3 mm of attachment loss and 4 mm of pocket depth) was 44.7%, and 36.7% of the study participants had at least one site with 6 mm or more of attachment loss. Results from a parsimonious multivariate model indicate that participants with poor oral health wemore likely to have esophageal dysplasia (OR = 1.59; 95% CI 1.06, 2.39).

Conclusion

This report describes the first use of NHANES oral health protocols employed in a clinical study conducted outside of the United States. The extent and severity of poor oral health in this Chinese study group may be an important health problem and contributing factor to the prevalence of EC.     

Assessing outcomes of a stigma-reduction intervention with venue-based analysis

Purpose

A randomized controlled trial with a matched design was conducted during October 2008 and February 2010, aiming at reducing HIV-related stigma in healthcare settings.

Methods

Forty county hospitals in Fujian and Yunnan provinces of China were matched into pairs and randomized to either an intervention condition or a control condition. Forty-four service providers were randomly selected from each hospital, yielding a sample of 1,760. Intervention outcomes were assessed at baseline, 6 and 12 months based on venue-based pair comparisons. We identified and trained 30 popular opinion leaders in each intervention hospital among service providers to disseminate stigma-reduction messages to their peer providers.

Results

Hospital and participant characteristics were comparable between the intervention and control conditions. Thirteen out of twenty pairs of hospitals showed significant reduction in the stigma outcome measure at the 6-month follow-up assessment. For most hospitals, the intervention effects were maintained at the 12-month follow-up assessment. Among the 13 pair of hospitals, which showed intervention effects at 6 months, eight were in Fujian and five were in Yunnan. The non-significant hospitals at 6 months had more beds than significant hospitals. However, the difference did not reach statistical significance.

Conclusions

A matched design and venue-based analysis provide more insight in assessing intervention effects for facility-based intervention trials. The identification of venue-based or hospital characteristics that are associated with intervention efficacy provides additional implications for the adaptation and implementation of future interventions.