Evaluation of ESAT6-CFP10 Skin Test for Mycobacterium tuberculosis Infection among Persons Living with HIV in China.

Recent global guidelines recommend Mycobacterium tuberculosis antigen-based skin tests, such as the ESAT6-CFP10 (EC) skin test, as acceptable alternatives to the tuberculin skin test (TST) and the QuantiFERON-TB Gold In-Tube test (QFT). However, the diagnostic value of these tests among persons living with HIV (PLHIV) is unknown. We aimed to assess the diagnostic accuracy of the EC among a cohort of PLHIV in China. We recruited PLHIV in Jiangsu Province, China, to assess sensitivity and specificity of the EC test. Participants were tested with the QFT, TST, and EC skin test. Results were stratified by age, M. tuberculosis BCG vaccination, and CD4 count. The sensitivity and specificity of the EC skin test was assessed using distinct cutoffs of the QFT and TST. Of 350 PLHIV enrolled in the study, 58 (16.6%), 89 (25.4%), and 59 (16.9%) tested positive with the EC test, the QFT, and the TST, respectively. Positivity increased with CD4 count; however, these trends were similar across tests. At a 5-mm cutoff, EC skin test specificity was high (99.6%, 95% confidence interval [CI] 95% CI = 97.7 to 100.0); however, sensitivity was moderate (81.4%; 95% CI = 66.6 to 91.6). After stratifying by BCG, the sensitivity and specificity were 86.4% (95% CI = 65.1 to 97.1) and 99.1% (95% CI = 95.0 to 100.0) among vaccinated PLHIV and 76.2% (95% CI = 52.8 to 91.8) and 100.0% (95% CI = 97.2 to 100.0) among unvaccinated PLHIV, respectively. Among PLHIV, the diagnostic value of the EC skin test remained high, regardless of BCG vaccination or CD4 count. The EC skin test performed comparably to TST and may be a valid alternative diagnostic test to use in settings or populations with high HIV prevalence and BCG vaccination. To our knowledge, this is the first study to evaluate the novel ESAT6-CFP10 skin test among PLHIV. Among 350 PLHIV, the test displayed high specificity and sensitivity, a finding which did not markedly differ based on BCG vaccination and CD4 count.

Positive rate and risk factors of latent tuberculosis infection among persons living with HIV in Jiangsu Province, China.

Objective: To analyze the latent tuberculosis infection (LTBI) among persons living with HIV(PLWH) in Jiangsu Province, to explore the factors affecting the positive rate of LTBI, and to take appropriate measures to control tuberculosis (TB) infection. Methods: A cross-sectional study was conducted among PLWH in Jiangsu Province from June to July 2021. All PLWH in Jiangsu Province were used as the study population. Currently, the diagnosis of LTBI lacks a "gold standard" and can only be assisted by the immunological method. In this study, Tuberculin skin test (TST), ESAT6-CFP10 test (EC), and QuantiFERON-TB gold in-tube (QFT) were used to detect the positive rate of LTBI among PLWH and to analyze their risk factors. Results: A total of 340 prisoners were included, 89.7% were male, the median age was 38 years [Interquartile Range (IQR):32-46 years], these patients were on Antiviral Therapy (ART), and median CD4 counts was 376 (IQR: 261-496), 103 (30.3%) were positive in at least one test, LTBI by TST was 16.5%, LTBI by EC was 15.9%, LTBI by QFT was 26.2%. Univariate analysis showed the results for TST, EC, and QFT were not affected by CD4 counts (p>0.05), and multivariate analysis showed that a history of incarceration was associated with an increased risk of positive TST (adjusted odds ratio [aOR]=1.98;95% CI,1.03-3.82), EC (aOR=2.65;95% CI,1.37-5.12) and QFT (aOR=2.01;95%CI,1.12-3.57), in addition, female gender was associated with increased risk of positive TST (aOR=3.66;95%CI,1.60-8.37) and EC (aOR=3.43;95%CI,1.46-8.07), and contact history of TB patients was associated with increased risk of TST (aOR= 2.54;95%CI,1.23-5.22) and QFT (aOR=2.03;95%CI,1.03-3.99), and ethnic minorities (aOR=0.26;95%CI,0.12-0.57), longer duration of incarceration was associated with an increased risk of positive QFT (aOR=1.12;95%CI,1.02-1.24). Conclusions Female gender, and ethnic minorities, history of incarceration, longer duration of incarceration, and contact history of TB patients are risk factors for LTBI among PLWH in Jiangsu Province, and attention should be paid to TB control in this population.

Neuroprotection of Exendin-4 by Enhanced Autophagy in a Parkinsonian Rat Model of α-Synucleinopathy.

Glucagon-like peptide-1 (GLP-1) receptor stimulation ameliorates parkinsonian motor and non-motor deficits in both experimental animals and patients; however, the disease-modifying mechanisms of GLP-1 receptor activation have remained unknown. The present study investigated whether exendin-4 (a GLP-1 analogue) can rescue motor deficits and exert disease-modifying effects in a parkinsonian rat model of α-synucleinopathy. This model was established by unilaterally injecting AAV-9-A53T-α-synuclein into the right substantia nigra pars compacta, followed by 4 or 8 weeks of twice-daily intraperitoneal injections of exendin-4 (5 µg/kg/day) starting at 2 weeks after AAV-9-A53T-α-synuclein injections. Positron emission tomography/computed tomography (PET/CT) scanning and immunostaining established that treatment with exendin-4 attenuated tyrosine-hydroxylase-positive neuronal loss and terminal denervation and mitigated the decrease in expression of vesicular monoamine transporter 2 within the nigrostriatal dopaminergic systems of rats injected with AAV-9-A53T-α-synuclein. It also mitigated the parkinsonian motor deficits assessed in behavioral tests. Furthermore, through both in vivo and in vitro models of Parkinson's disease, we showed that exendin-4 promoted autophagy and mediated degradation of pathological α-synuclein, the effects of which were counteracted by 3-methyladenine or chloroquine, the autophagic inhibitors. Additionally, exendin-4 attenuated dysregulation of the PI3K/Akt/mTOR pathway in rats injected with AAV-9-A53T-α-synuclein. Taken together, our results demonstrate that exendin-4 treatment relieved behavioral deficits, dopaminergic degeneration, and pathological α-synuclein aggregation in a parkinsonian rat model of α-synucleinopathy and that these effects were mediated by enhanced autophagy via inhibiting the PI3K/Akt/mTOR pathway. In light of the safety and tolerance of exendin-4 administration, our results suggest that exendin-4 may represent a promising disease-modifying treatment for Parkinson's disease.

Evaluation of Neuropathic Pain in a Rat Model of Total Brachial Plexus Avulsion from Behavior to Brain Metabolism.

BACKGROUND: Approximately 30% to 80% of patients with brachial plexus avulsion (BPA) developed neuropathic pain. It is an intolerable neuropathic pain, which brings heavy burden to family and society. In addition to motor and sensory deficits, neuropathic pain can be another serious sequela that equally influences the patient. The development of a microsurgical technique has promoted the treatment and rehabilitation of brachial plexus injury, but pain relief after BPA is still a difficult problem. OBJECTIVES: The present study aimed to semi-quantify changes in the behavior, spinal cord and cerebral metabolism in a neuropathic pain model following BPA injury in rats. STUDY DESIGN: Controlled animal study. SETTING: Institute of Rehabilitation Medicine, Shanghai, China. METHODS: A total of 15 Sprague-Dawley rats, weighing 200 to 220 g, were randomly divided into 2 groups: experimental group (n = 10) and control group (n = 5). In the experimental group, neuropathic pain induced by BPA was established by directly avulsing the C5, C6, C7, C8, and T1 roots on the right side from the spinal cord. Rats in the control group only received open-close surgery. The autotomic behavior of biting their own digits was recorded and scored at 2 months after the surgery. Small animal positron emission tomography/computed tomography (PET/CT) images after injection of a 2-[18F]-fluoro-2-deoxy-D-glucose (18F-FDG) tracer were acquired to evaluate glucose metabolism in pain-related brain regions before and after the surgery, respectively. Semi-quantitative values of cortical to cerebellum standardized uptake value (SUV) ratios were calculated. Then, the animals were euthanized and the cervical segments of the spinal cord were removed for detection of glial fibrillary acidic protein (GFAP) expression in the astrocytes by immunohistochemical assay. RESULTS: Nine of the 10 rats (90%) in the experimental group showed autotomic behavior at 2 months after the surgery. Slight autotomic behavior was noted only in one of 5 rats (20%) from the control group. The autotomic score in the experimental group was significantly higher than that in the control group (5.4 ± 1.0 vs. 0.2 ± 0.4, P < 0.05). The experimental group showed significantly higher SUV ratio in both the right and left thalamus, compared to the control group (P < 0.05). Immunohistochemical assay demonstrated that GFAP positive astrocytes in the dorsal horn at the injured side significantly increased compared to the control group (P < 0.05). LIMITATIONS: There are differences between small animals and human beings, and the structure and function of the human brain is more complex than in rodents. Therefore, extrapolation of the present conclusion should be cautious. CONCLUSIONS: The present study reported a unique model of neuropathic pain following total BPA in rodents, which was demonstrated by a higher rate and score of autotomic behavior. More astrocytes were found activated in the spinal cord at the corresponding level of C5 and C6 spinal cord. In the small animal PET/CT imaging, significantly higher standardized glucose metabolic activity was found in both the right and left thalamus in the experimental group. The present study semi-quantified the neuropathic pain behavior in rats and explored the plastic changes in the spinal and brain metabolism. KEY WORDS: Brachial plexus avulsion, small animal PET/CT, glucose metabolism, neuropathic pain, astrocyte, 18F-FDG.

A new dinorclerone diterpenoid glycoside from Tinospora sinensis.

A new dinorclerone diterpenoid glycoside, named 1-deacetyltinosposide A (1), was isolated from the stem of Tinospora sinensis together with 10 known compounds. Their structures were elucidated on the basis of extensive spectroscopic techniques (MS, IR, 1D and 2D NMR experiments).

Four new compounds from the leaves of Acer truncatum.

Four new compounds, 3-(4-hydroxy-3,5-dimethoxyphenyl)propyl formate (1), 2,6-dimethoxy-4-[(1S)-3-methoxypropyl]phenol (2), (1R,2R)-4-[(3R)-3-hydroxybutyl]-3,3,5-trimethylcyclohex-4-ene-1,2-diol (3), and (1S,3R,3aR,6S,7S,9aR)-decahydro-1-(hydroxymethyl)-1,7-dimethyl-3a,7-methano-3aH-cyclopentacyclooctene (4) were isolated from the leaves of Acer truncatum, together with twelve known compounds. Their structures were elucidated on the basis of extensive spectroscopic techniques. The absolute configuration of compound 3 was established by the modified Mosher's method. All compounds were evaluated for antibacterial activities.

A new neolignan glycoside from the leaves of Acer truncatum.

A new neolignan glycoside, (7R,8R)-7,8-dihydro-9'-hydroxyl-3'-methoxyl- 8-hydroxymethyl-7-(4-hydroxy-3-methoxyphenyl)-1'-benzofuranpropanol 9'-O-beta-D- glucopyranoside (1) was isolated from the leaves of Acer truncatum along with (7R,8R)-7,8-dihydro-9'-hydroxyl-3'-methoxyl-8-hydroxymethyl-7-(4-O-alpha-L-rhamno- pyranosyloxy-3-methoxyphenyl)-1'-benzofuranpropanol (2), schizandriside (3), lyoniresinol (4), berchemol (5), (-)-pinoresinol-4-O-beta-D-glucopyranoside (6), hecogenin (7), chlorogenic acid (8) and neochlorogenic acid (9). Their structures were elucidated on the basis of extensive spectroscopic data. The absolute configuration of compounds 1 was established by its CD spectrum. The antibacterial activities of compounds 1-7 were evaluated.