Assessment of Effective Anti-TB Regimens and Adverse Outcomes Related Risk Factors in the Elderly and Senile-Aged TB Patients.

Objective: Compared to younger patients with tuberculosis (TB), elderly and senile-aged patients with TB had a higher incidence of adverse outcomes particularly in terms of lost to follow-up and deaths. Our study aimed to gain insight into the effectiveness of anti-tuberculosis (anti-TB) treatment in the elderly or senile-aged patients and identify the risk factors for adverse outcomes. Methods: The case information was obtained from the "Tuberculosis Management Information System". From January 2011 to December 2021, this retrospective analysis was conducted in Lishui City, Zhejiang Province to observe and record the outcomes of elderly patients diagnosed with TB who agreed to receive anti-TB and(or) traditional Chinese medicine(TCM) treatment. We also employed a logistic regression model to analyze the risk factors for adverse outcomes. Results: Among the 1191 elderly or senile-aged patients with TB who received the treatment, the success rate was 84.80% (1010/1191). Using logistic regression analysis, several risk factors for adverse outcomes (failure, death, loss to follow-up) were identified, including age ≥ 80 years (OR 2.186, 95% CI 1.517~3.152, P<0.001), lesion area ≥ 3 lung fields (OR 0.410, 95% CI 0.260~0.648, P<0.001), radiographic lesions failing to improve after 2 months of treatment (OR 2.048, 95% CI 1.302~3.223, P=0.002), sputum bacteriology failing to turn negative after 2 months of treatment (OR 2.213, 95% CI 1.227~3.990, P=0.008), lack of a standardized treatment plan (OR 2.095, 95% CI 1.398~3.139, P<0.001), and non-involvement of traditional Chinese medicine (OR 2.589, 95% CI 1.589~4.216, P<0.001). Conclusion: The anti-TB treatment success rate in the elderly and senile-aged patients is suboptimal. Contributing factors include advanced age, extensive lesions, and low sputum negative conversion rate during the intensive treatment phase. The results will informative and could be useful for policy maker for to control of reemergence of TB in big cities.

Obesity-induced astrocyte dysfunction impairs heterosynaptic plasticity in the orbitofrontal cortex.

Overconsumption of highly palatable, energy-dense food is considered a key driver of the obesity pandemic. The orbitofrontal cortex (OFC) is critical for reward valuation of gustatory signals, yet how the OFC adapts to obesogenic diets is poorly understood. Here, we show that extended access to a cafeteria diet impairs astrocyte glutamate clearance, which leads to a heterosynaptic depression of GABA transmission onto pyramidal neurons of the OFC. This decrease in GABA tone is due to an increase in extrasynaptic glutamate, which acts via metabotropic glutamate receptors to liberate endocannabinoids. This impairs the induction of endocannabinoid-mediated long-term plasticity. The nutritional supplement, N-acetylcysteine rescues this cascade of synaptic impairments by restoring astrocytic glutamate transport. Together, our findings indicate that obesity targets astrocytes to disrupt the delicate balance between excitatory and inhibitory transmission in the OFC.

Mu-Opioids Suppress GABAergic Synaptic Transmission onto Orbitofrontal Cortex Pyramidal Neurons with Subregional Selectivity.

The orbitofrontal cortex (OFC) plays a critical role in evaluating outcomes in a changing environment. Administering opioids to the OFC can alter the hedonic reaction to food rewards and increase their consumption in a subregion-specific manner. However, it is unknown how mu-opioid signaling influences synaptic transmission in the OFC. Thus, we investigated the cellular actions of mu-opioids within distinct subregions of the OFC. Using in vitro patch-clamp electrophysiology in brain slices containing the OFC, we found that the mu-opioid agonist DAMGO produced a concentration-dependent inhibition of GABAergic synaptic transmission onto medial OFC (mOFC), but not lateral OFC (lOFC) neurons. This effect was mediated by presynaptic mu-opioid receptor activation of local parvalbumin (PV+)-expressing interneurons. The DAMGO-induced suppression of inhibition was long lasting and not reversed on washout of DAMGO or by application of the mu-opioid receptor antagonist CTAP, suggesting an inhibitory long-term depression (LTD) induced by an exogenous mu-opioid. We show that LTD at inhibitory synapses is dependent on downstream cAMP/protein kinase A (PKA) signaling, which differs between the mOFC and lOFC. Finally, we demonstrate that endogenous opioid release triggered via moderate physiological stimulation can induce LTD. Together, these results suggest that presynaptic mu-opioid stimulation of local PV+ interneurons induces a long-lasting suppression of GABAergic synaptic transmission, which depends on subregional differences in mu-opioid receptor coupling to the downstream cAMP/PKA intracellular cascade. These findings provide mechanistic insight into the opposing functional effects produced by mu-opioids within the OFC.SIGNIFICANCE STATEMENT Considering that both the orbitofrontal cortex (OFC) and the opioid system regulate reward, motivation, and food intake, understanding the role of opioid signaling within the OFC is fundamental for a mechanistic understanding of the sequelae for several psychiatric disorders. This study makes several novel observations. First, mu-opioids induce a long-lasting suppression of inhibitory synaptic transmission onto OFC pyramidal neurons in a regionally selective manner. Second, mu-opioids recruit parvalbumin inputs to suppress inhibitory synaptic transmission in the mOFC. Third, the regional selectivity of mu-opioid action of endogenous opioids is due to the efficacy of mu-opioid receptor coupling to the downstream cAMP/PKA intracellular cascades. These experiments are the first to reveal a cellular mechanism of opioid action within the OFC.

Microbial functional traits in phyllosphere are more sensitive to anthropogenic disturbance than in soil.

Soil-plant microbiome plays a critical role in the regulation of terrestrial ecosystem function and service, including biogeochemical cycling and primary production. The lack of knowledge regarding the differences in microbial functional traits, i.e. the functional genes related to carbon (C), nitrogen (N), phosphorus (P) and sulfur (S) cycles, between soil and plant microbiomes hampers our prediction of the terrestrial nutrient cycling processes under the pressure of anthropogenic disturbance. Herein, a quantitative microbial element cycling (QMEC) method and amplicon sequencing was employed to characterize CNPS cycling genes and microbial communities in soil and plant samples collected from peri-urban farmland with high anthropogenic disturbance and forest ecosystem with minimal disturbance. The soil-plant system harbored a diverse array of CNPS cycling genes, which were significantly more abundant in soil than in phyllosphere. The overall CNPS gene profiles in farmland samples was distinct from that of forest samples in both soil and plant phyllosphere. Farmland samples had a lower abundance of CNPS cycling genes than forest samples, indicating that intensive agricultural management practices may consequently compromise the biogeochemical cycling potential of nutrients. Significant positive correlations between the abundance of CNPS cycling genes and microbial diversity were observed in phyllosphere microbiome but not in soil, suggesting that the functional redundancy in soil microbiome may be higher than that of phyllosphere microbiome. Taken together, we provide experimental evidence for the substantial impacts of anthropogenic disturbance on CNPS cycling genes in the soil-plant system and necessitate future efforts to unravel the plant microbiome diversity and functionality under the pressure of global changes.

[Exploration and practice of micro-video teaching of Characteristic Clinical Technology of Acupuncture and Moxibustion].

In this paper, the micro-video teaching mode was explored in the course construction of Characteristic Clinical Technology of Acupuncture and Moxibustion. The micro-video teaching contents include the academic thought, experience in diagnosis and treatment, characteristic technology and clinical manipulation of famous acupuncture experts in the Henan University of CM. Each micro-video film is designed within 15-18 min, including three sections of knowledge, i.e. basic theory, technological application and clinical manipulation. Each section is designed within 5-6 min. The construction of the teaching course of Characteristic Clinical Technology of Acupuncture and Moxibustion is the innovation of practice mode of TCM and the new approach to the inheritance of the experience of experts. The construction of micro-video teaching course propels the reform of teaching mode, improves the learning initiative of students and clinical manipulative ability so as to improve the teaching effect and quality.

Targeting adenosinergic pathway enhances the anti-tumor efficacy of sorafenib in hepatocellular carcinoma.

BACKGROUND: Sorafenib is the most widely used first-line treatment for patients with advanced hepatocellular carcinoma (HCC), but such treatment provides only limited survival benefits that might be related to the immune status of distinct tumor microenvironments. A fundamental understanding of the distribution and phenotypes of T lymphocytes in tumors will undoubtedly lead to the development of novel immunotherapeutic strategies that could possibly enhance the efficacy of sorafenib treatments. METHODS: Flow cytometry, immunohistochemistry and immunofluorescence analyses were performed to detect the infiltration and distribution of various leukocyte populations, and the expression of different immune checkpoint molecules in fresh HCC tumor tissues. Correlations among indicating genes were calculated in 365 patients with HCC from The Cancer Genome Atlas (TCGA) data set, and the cumulative overall survival time was calculated using the Kaplan-Meier method. Moreover, role of adenosinergic pathway on sorafenib anti-tumor efficacy was investigated using both subcutaneous and orthotopic transplantation tumor model in immune competent C57BL/6 mice. RESULTS: We revealed that levels of CD3+ and CD8+ T cells were significantly downregulated in HCC tumor tissue, so were the infiltration of CD169+ cells (a Mφ subpopulation with T cell activation capacities) and their contact with CD8+ cells in tumor milieus. Moreover, levels of PD-1 and CD39 expression were significantly upregulated in human HCC-infiltrating CD4+ and CD8+ T cells, and CD39+CD8+ T cells exhibited a CD69+PD-1+perforinlowIFNγlow "exhausted" phenotype. Levels of both CD39+ T cells infiltration and adenosine receptor ADORA2B expression in tumor tissues were negatively correlated with overall survival of patients with HCC. Accordingly, mice treated with sorafenib in combination with adenosine A2B receptor blockage reagents exhibited significantly reduced tumor progression compared with control groups. CONCLUSIONS: These results suggest that adenosinergic pathway might represent an applicable target for sorafenib-combined-therapies in human HCC.

Projection-Target-Defined Effects of Orexin and Dynorphin on VTA Dopamine Neurons.

Circuit-specific signaling of ventral tegmental area (VTA) dopamine neurons drives different aspects of motivated behavior, but the neuromodulatory control of these circuits is unclear. We tested the actions of co-expressed lateral hypothalamic peptides, orexin A (oxA) and dynorphin (dyn), on projection-target-defined dopamine neurons in mice. We determined that VTA dopamine neurons that project to the nucleus accumbens lateral shell (lAcbSh), medial shell (mAcbSh), and basolateral amygdala (BLA) are largely non-overlapping cell populations with different electrophysiological properties. Moreover, the neuromodulatory effects of oxA and dyn on these three projections differed. OxA selectively increased firing in lAcbSh- and mAcbSh-projecting dopamine neurons. Dyn decreased firing in the majority of mAcbSh- and BLA-projecting dopamine neurons but reduced firing only in a small fraction of those that project to the lAcbSh. In conclusion, the oxA-dyn input to the VTA may drive reward-seeking behavior by tuning dopaminergic output in a projection-target-dependent manner.

A label-free assay for T4 polynucleotide kinase/phosphatase activity and its inhibitors based on poly(thymine)-templated copper nanoparticles.

DNA 3'-phosphatase takes an important role in DNA damage repair, replication and recombination. Here, we present a novel label-free fluorescent assay for T4 polynucleotide kinase/phosphatase (T4 PNKP) activity and its inhibitor screening by using poly(thymine)-templated fluorescent copper nanoparticles (CuNPs) as a fluorescent indicator. In this assay, we designed a simple T-rich hairpin primer with a 3'-phosphoryl end, which can serve as both the substrate for T4 PNKP and DNA template for the formation of fluorescent CuNPs. Once the phosphorylated hairpin primer was hydrolyzed by T4 PNKP, the resulting hairpin primer with a 3'-hydroxyl end was immediately elongated to form a long double-strand product by DNA polymerase, which prohibited the formation of fluorescent CuNPs due to the lack of poly T single-stranded DNA template. This new strategy provides a sensitive, selective, and cost-effective manner for T4 PNKP analysis, which holds a great potential in the study of DNA damage repair mechanisms.

Emodin has a protective effect in cases of severe acute pancreatitis via inhibition of nuclear factor­κB activation resulting in antioxidation.

Severe acute pancreatitis (SAP) accounts for up to 20% of acute pancreatitis (AP) cases. The absence of effective treatment options has resulted in a high rate of morbidity and mortality. Emodin is a major component of the Chinese herb rhubarb, which has been widely used in the treatment of numerous diseases, including inflammation and cancer. There are a limited number of studies however, that have investigated the effectiveness of emodin in the treatment of SAP. The present study used a rat model of SAP, to investigate the effect and molecular mechanisms of emodin treatment. Administration of emodin was identified to significantly attenuate SAP, as determined by serum amylase analysis and histological assessment of edema, vacuolization, inflammation and necrosis (P<0.01). Furthermore, treatment with emodin markedly inhibited nuclear factor (NF)­κB DNA­binding activity (P<0.01) and the serum expression levels of tumor necrosis factor­α, interleukin (IL)­6 and IL­1ß (P<0.05). This attenuation was associated with decreased malondialdehyde and increased superoxide dismutase levels in the pancreatic tissues and serum (P<0.05). This study indicated that administration of exogenous emodin had therapeutic effects on the severity of SAP. The mechanism may be due to inhibition of NF­κB activation resulting in an antioxidation response, which can subsequently suppress the expression of cytokines.

[Effect of banxia xiexin decoction on gastric antral interstitial cells of Cajal and stem cell factor in diabetic rats].

OBJECTIVE: To observe the effect of Banxia Xiexin Decoction (BXD) on expression of the interstitial cells of Cajal (ICCs) and stem cell factor (SCF) in the antrum of rats with diabetes mellitus (DM). METHODS: Totally sixty healthy male SD rats were randomly divided into the control group, the model group, the BXD group, and the Western medicine group (WM, treated by domperidone), 15 in each group. Diabetic rat models were established by a single intraperitoneal injection of streptozotocin (STZ, 55 mg/kg). Those in the BXD group were perfused with BXD at the daily dose of 5.4 g/kg. An equal volume of distilled water was given by gastrogavage to those in the WM group and the control group for 8 successive weeks. The body weight and blood glucose of all rats were detected, and the gastric residual rates were detected with semisolid nutrient paste by gastrogavage. The expression of positive ICCs and SCF were observed by immunohistochemical method and quantified image analyzer. RESULTS: Compared with the control group,the body weight reduced, blood glucose and gastric residual rates increased, and the mean optical density of positive ICCs and SCF significantly decreased in the model group (P < 0.05). Compared with the model group,symptoms such as polydipsia, polyphagia, polyuria were relieved, spirits improved, the body weight and mean optical densities of positive ICCs and SCF significantly increased (P < 0.05), and gastric residual rates significantly decreased in the BXD group and the WM group (P < 0.05). The blood glucose significantly decreased (P < 0.05) in the BXD group. The mean optical density of positive ICCs was higher in the BXD group than in the WM group (P < 0.05). CONCLUSIONS: BXD could promote the expression of positive ICCs and SCF. It could improve the gastric motility in DM rats by partially inverting abnormal changes of gastric antral ICCs and SCF.

Effect of banxia xiexin decoction on gastric antral interstitial cells of Cajal and stem cell factor in diabetic rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Banxia Xiexin Decoction (BXD) on expression of the interstitial cells of Cajal (ICCs) and stem cell factor (SCF) in the antrum of rats with diabetes mellitus (DM).</p><p><b>METHODS</b>Totally sixty healthy male SD rats were randomly divided into the control group, the model group, the BXD group, and the Western medicine group (WM, treated by domperidone), 15 in each group. Diabetic rat models were established by a single intraperitoneal injection of streptozotocin (STZ, 55 mg/kg). Those in the BXD group were perfused with BXD at the daily dose of 5.4 g/kg. An equal volume of distilled water was given by gastrogavage to those in the WM group and the control group for 8 successive weeks. The body weight and blood glucose of all rats were detected, and the gastric residual rates were detected with semisolid nutrient paste by gastrogavage. The expression of positive ICCs and SCF were observed by immunohistochemical method and quantified image analyzer.</p><p><b>RESULTS</b>Compared with the control group,the body weight reduced, blood glucose and gastric residual rates increased, and the mean optical density of positive ICCs and SCF significantly decreased in the model group (P < 0.05). Compared with the model group,symptoms such as polydipsia, polyphagia, polyuria were relieved, spirits improved, the body weight and mean optical densities of positive ICCs and SCF significantly increased (P < 0.05), and gastric residual rates significantly decreased in the BXD group and the WM group (P < 0.05). The blood glucose significantly decreased (P < 0.05) in the BXD group. The mean optical density of positive ICCs was higher in the BXD group than in the WM group (P < 0.05).</p><p><b>CONCLUSIONS</b>BXD could promote the expression of positive ICCs and SCF. It could improve the gastric motility in DM rats by partially inverting abnormal changes of gastric antral ICCs and SCF.</p>

[Study on preparation method of Yueanjian for treatmen of premenstrual syndrome].

OBJECTIVE: To establish the liver-depression and spleen-deficiency syndrome model in rats to screen the optimal extraction method of small compound Yueanjian on the basis of pharmacodynamic and chemical indicators. METHOD: The PMS liver-depression and spleen-deficiency syndrome model were established by the chronic restraint stress method and treatment with Yueanjian extracted by three methods: water-extraction, steam-distillation and alcohol-extraction. Behavioral performances and the contents of estradiol and progestin in serum were determined before and after the administration of the three extracts. The contents of salvianolic acid B in these three extracts were detected by HPLC. The optimal extraction method of Yueanjian was selected according to pharmacodynamic results. RESULT: The contents of estradiol and progestin in groups treated with steam distillations and alcoholic extraction were higher than the model group. In the open field test, the group treated with steam distillations showed much higher scores than the model group. HPLC showed that the content of salvianolic acid B extracted by steam-distillation was higher than the other two extracts. CONCLUSION: On the basis of pharmacodynamic and chemical results, the steam-distillation was proved to be best extraction method of Yueanjian.

Material flow analysis of phosphorus through food consumption in two megacities in northern China.

The key stocks and flows of phosphorus (P) through food consumption in Beijing and Tianjin, two megacities in northern China, were explored using a material flow analysis (MFA) approach to construct a static model of P metabolism. A total of 4498 t P has accumulated with 72% of P flow imported through food consumption eventually remaining in Beijing in 2008. Around 64% of the total inflow of P (2670 t) remained in Tianjin in 2008. P in the uncollected sewage from both urban and rural residents and the effluents from sewage treatment plants has significant negative effects on water quality. An average of 55% the P flow remained in the sewage sludge through urban food consumption. The key problems in P metabolism and management in megacities are identified based on the quantitative analysis of P cycling through food consumption. Relevant solutions for improving P recycling efficiency are also discussed. It is important to link P flows with environmental regulations and to establish a strong coordination between urban and rural areas for nutrient recycling to attain sustainable development of megacities.

[The effect on the differentiation and maturation of dendritic cells by lupane acetate of cortex periplocae].

AIM: To investigate the effect of lupane acetate of cortex periplocae (CPLA) on the differentiation, maturation and immune activity of human peripheral blood mononuclear cell (PBMC)-derived dendritic cells (DCs) in vitro. METHODS: PBMC isolated from human peripheral blood was cultured with GM-CSF, IL-4 for 5 d and stimulated with TNF-alpha (as positive control) or CPLA to induce DCs. The morphological characteristics of DC were observed under inverted microscope and transmisson electron microscope. The expressions of CD1a, CD83, CD80 and CD86 were analyzed by flow cytometry. IL-12, IFN-gamma production in the culture supernatant of DCs was detected by ELISA. MTT method was used to determine the proliferation of T cells stimulated by DCs. RESULTS: After 10-days culture with cytokines and CPLA, PBMC developed into mature DCs with typical morphological characteristics and high expressions of CD1a, CD83, CD80 and CD86 on the cellular surface (P<0.05). CPLA enhanced IL-12 and IFN-gamma production by DCs (P<0.05). CPLA-treated DCs markedly stimulated proliferation of T cells (P<0.05). CONCLUSION: CPLA may induce the differentiation and maturation of DC, up-regulate cytokines production and increase the immune activity of DC.