Transcranial Direct Current Stimulation for Knee Osteoarthritis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

OBJECTIVE: The effects of transcranial direct current stimulation (tDCS) in the treatment of knee osteoarthritis (KOA) is still unclear. The objective is to evaluate the efficacy and safety of tDCS in improving symptoms in patients with KOA. METHODS: The following electronic databases were searched for eligible randomized controlled trials (RCTs): PubMed, Embase, Web of Science, and the Cochrane Library. The search was performed from the inception dates to April 30, 2023. Data extraction and quality assessment were performed by two independent reviewers. Standard mean differences (SMDs) with 95% confidence intervals (95% CIs) for pooled data were calculated. A random-effects model was used for the data analyses. The primary outcomes were pain and physical function. Secondary outcomes included stiffness, mobility performance, quality of life, pressure pain tolerance, and plasma levels of brain-derived neurotrophic factor (BDNF). RESULTS: This meta-analysis included 13 RCTs. tDCS was significantly associated with pain decrease compared with sham tDCS (SMD = -0.62, 95% CI -0.87 to -0.37, P < 0.00001). When comparing tDCS plus other non-tDCS with sham tDCS plus other non-tDCS, there was no longer a significant association with pain decrease (SMD = -0.45, 95% CI -1.08 to 0.17, P = 0.16). The changes in physical function were not significantly different between the tDCS and sham tDCS groups (SMD = -0.09, 95% CI -0.56 to 0.38, P = 0.71). When comparing tDCS plus other non-tDCS with sham tDCS plus other non-tDCS, there was still no significant association with improvement in physical function (SMD = -0.66, 95% CI -1.63 to 0.30, P = 0.18). There was no significant difference with improvement in stiffness (SMD = -0.21, 95% CI -0.77 to 0.34, P = 0.45), mobility performance (SMD = 4.58, 95% CI -9.21 to 18.37, P = 0.51), quality of life (SMD = -7.01, 95% CI -22.61 to 8.59, P = 0.38), and pressure pain tolerance (SMD = 0.30, 95% CI -0.09 to 0.69, P = 0.13). There was a statistically significant reduction in plasma levels of BDNF (SMD = -13.57, 95% CI -24.23 to -2.92, P = 0.01). CONCLUSION: In conclusion, tDCS could significantly alleviate pain, but it might have no efficacy in physical function, stiffness, mobility performance, quality of life, and pressure pain tolerance among patients with KOA.

Therapeutic outcomes of early and delayed endoscopic retrograde cholangiopancreatography and percutaneous transhepatic cholangial drainage in patients with obstructive severe acute biliary pancreatitis.

Background: Obstructive severe acute biliary pancreatitis (SABP) is a clinical emergency with a high rate of mortality that can be alleviated by endoscopic retrograde cholangiopancreatography (ERCP) and percutaneous transhepatic cholangial drainage (PTCD) selectively. However, the optimal timing of ERCP and PTCD requires elucidation. Aim: The aim of this study was to evaluate outcome parameters in patients with SABP subjected to ERCP and PTCD compared to SABP patients who were not subjected to any form of invasive intervention. Methods: A total of 62 patients with obstructive SABP who had been treated from July 2013 to July 2019 were included in this retrospective case-control study and stratified into a PTCD group (N = 22), ERCP group (N = 24), and conservative treatment group (N = 16, control). Patients in the PTCD and ERCP groups were substratified into early (≤72 h) and delayed (>72 h) treatment groups based on the timing of the intervention after diagnosis. Clinical chemistry, hospitalization days, liver function, abdominal pain, and complications were determined to assess the treatment efficacy and safety of each modality and to establish the optimal timing for PTCD and ERCP. Results: The average hospitalization time, time to abdominal pain relief, and time to normalization of hematological and clinical chemistry parameters (leukocyte count, amylase, alanine transaminase [ALT], and total bilirubin [TBiL]) were shorter in the PTCD and ERCP groups compared to the conservative treatment group (p < 0.05). The average hospitalization time in the ERCP group (16.7 ± 4.0 d) was shorter compared to the PTCD group (19.6 ± 4.3 d) (p < 0.05). Compared to the conservative treatment group (62.5%), there were more complications in patients treated with ERCP and PTCD (p < 0.05). In the early ERCP group, the average hospitalization time (13.9 ± 3.3 d) and the time to normalization of leukocyte count (6.3 ± 0.9 d) and TBiL (9.1 ± 2.0 d) were lower than in the delayed ERCP group (18.6 ± 4.1 d, 9.9 ± 2.4 d, 11.8 ± 2.9 d, respectively) and early PTCD group (16.4 ± 3.7 d, 8.5 ± 2.1 d, 10.9 ± 3.1 d, respectively) (p < 0.05). In the delayed ERCP group, the average hospitalization time (18.6 ± 4.1 d) and ALT recovery time (12.2 ± 2.6 d) were lower than in the delayed PTCD group (21.9 ± 4.3 d and 14.9 ± 3.9 d, respectively) (p < 0.05). Conclusions: ERCP and PTCD effectively relieve SABP-associated biliary obstruction with comparable overall incidence of complications. It is recommended that ERCP is performed within 72 h after diagnosis; and PTCD drainage may be considered an alternative approach in cases where patients are unable or unwilling to undergo ERCP, or when ERCP is unsuccessful. Relevance for Patients: ERCP and PTCD in patients with obstructive SABP can resolve biliary obstruction and delay progression of the disease. Performing ERCP and PTCD within 72 h (i.e., optimal treatment time window) can be beneficial to patients, especially in terms of post-operative recovery. Visual biliary endoscopy (oral or percutaneous transhepatic) may be used for concomitant therapeutic interventions in the biliary system.

A feasibility study for objective evaluation of visual acuity based on pattern-reversal visual evoked potentials and other related visual parameters with machine learning algorithm.

BACKGROUND: To develop machine learning models for objectively evaluating visual acuity (VA) based on pattern-reversal visual evoked potentials (PRVEPs) and other related visual parameters. METHODS: Twenty-four volunteers were recruited and forty-eight eyes were divided into four groups of 1.0, 0.8, 0.6, and 0.4 (decimal vision). The relationship between VA, peak time, or amplitude of P100 recorded at 5.7°, 2.6°, 1°, 34', 15', and 7' check sizes were analyzed using repeated-measures analysis of variance. Correlations between VA and P100, contrast sensitivity (CS), refractive error, wavefront aberrations, and visual field were analyzed by rank correlation. Based on meaningful P100 peak time, P100 amplitude, and other related visual parameters, four machine learning algorithms and an ensemble classification algorithm were used to construct objective assessment models for VA. Receiver operating characteristic (ROC) curves were used to compare the efficacy of different models by repeated sampling comparisons and ten-fold cross-validation. RESULTS: The main effects of P100 peak time and amplitude between different VA and check sizes were statistically significant (all P < 0.05). Except amplitude at 2.6° and 5.7°, VA was negatively correlated with peak time and positively correlated with amplitude. The peak time initially shortened with increasing check size and gradually lengthened after the minimum value was reached at 1°. At the 1° check size, there were statistically significant differences when comparing the peak times between the vision groups with each other (all P < 0.05), and the amplitudes of the vision reduction groups were significantly lower than that of the 1.0 vision group (all P < 0.01). The correlations between peak time, amplitude, and visual acuity were all highest at 1° (rs = - 0.740, 0.438). VA positively correlated with CS and spherical equivalent (all P < 0.001). There was a negative correlation between VA and coma aberrations (P < 0.05). For different binarization classifications of VA, the classifier models with the best assessment efficacy all had the mean area under the ROC curves (AUC) above 0.95 for 500 replicate samples and above 0.84 for ten-fold cross-validation. CONCLUSIONS: Machine learning models established by meaning visual parameters related to visual acuity can assist in the objective evaluation of VA.

Association between long-term green space exposure and mortality in China: A difference-in-differences analysis of national data in 2000, 2010 and 2019.

BACKGROUND: Effects of green space on human health have been well-documented in western, high-income countries. Evidence for similar effects in China is limited. Moreover, the underlying mechanisms linking green space and mortality are yet to be established. We therefore conducted a nation-wide study to assess the association between green space and mortality in China using a difference-in-difference approach, which applied a causal framework and well controlled unmeasured confounding. In addition, we explored whether air pollution and air temperature could mediate the association. METHODS: In this analysis, we collected data on all-cause mortality and sociodemographic characteristics for each county in China from the 2000 and 2010 censuses and the 2020 Statistical Yearbook. Green space exposure was assessed using county-level normalized difference vegetation index (NDVI) and the percentage of green space (forest, grasslands, shrub land and wetland). We applied a difference-in-differences approach to evaluate the association between green space and mortality. We also performed mediation analysis (by air pollution and air temperature). RESULTS: Our sample consisted of 2726 counties in 2000 and 2010 as well as 1432 counties in 2019. In the 2000 versus 2019 comparison, a 0.1 unit increase in NDVI was associated with a 2.4 % reduction in mortality [95 % confidence interval (CI) 0.4-4.3 %], and a 10 % increase in percentage of green space was associated with a 4.7 % reduction (95 % CI 0-9.2 %) in mortality. PM2.5 and air temperature mediated 0.3 % to 12.3 % of the associations. CONCLUSIONS: Living in greener counties may be associated with lower risk of mortality in China. These findings could indicate the potential of a population-level intervention to reduce mortality in China, which has important public health implications at the county level.

Duloxetine for rehabilitation after total knee arthroplasty: a systematic review and meta-analysis.

OBJECTIVE: The aim was to evaluate the efficacy and safety of duloxetine for postoperative recovery after total knee arthroplasty. METHODS: The following electronic databases were searched for eligible trials: PubMed, EMBASE, Web of Science, Cochrane Library, VIP, Wanfang Data, and China National Knowledge Infrastructure (CNKI). The search was performed from the inception dates to 10 August 2022. Data extraction and quality assessment were performed by two independent reviewers. Standard mean differences or mean differences with 95% CIs for pooled data were calculated. The primary outcomes were pain, physical function, and analgesic consumption. Secondary outcomes included range of motion (ROM) of the knee, depression, and mental health. RESULTS: This meta-analysis included 11 studies, reporting on a total of 1019 patients. Results of analyses indicated that duloxetine showed a statistically significant reduction in pain at rest at 3 days, 1 week, 2, and 6 weeks and pain on movement at 5 days, 1 week, 2, 4, 6, and 8 weeks. However, there was no statistical significance in pain at rest and on movement at 24 h, 12 weeks, 6 months, and 12 months. Additionally, duloxetine had a significant improvement in physical function, ROM of the knee at 6 weeks, and emotional function (depression and mental health). Moreover, the cumulative opioid consumption at 24 h in the duloxetine groups was lower than in the control groups. But there was no statistical significance for the cumulative opioid consumption over 7 days between the duloxetine groups and controls. CONCLUSIONS: In conclusion, duloxetine might reduce pain mainly over a time span of 3 days-8 weeks and lower cumulative opioid consumption within 24 h. In addition, it improved physical function, ROM of the knee with a time span of 1-6 weeks and emotional function (depression and mental health).

π-Extended BTD Derivatives: Synthesis, Photophysical Properties, and Applications in Biological Systems Imaging for Discriminating Living and Dead Cells.

Here, π-Extended BTD derivatives were successfully synthesized by Heck coupling reaction, which exhibited the the advantages of simplicity and efficiency, wild substrate scope, easily available substrates and high yield. The fluorescent probe PEG-BTDAr targeting LDs was successfully prepared by the nucleophilic substitution reaction between the Heck coupling reaction product 3 h and Amino polyethylene glycol monomethyl ether (Mn=2000). PEG-BTDAr exhibited the advantages of high selectivity, good stability and pH resistance. The use of PEG as a substrate gave PEG-BTDAr good biocompatibility. It was worth mentioning that PEG-BTDAr could not only track LDs in cells under different physiological conditions, but also distinguish between living and dead cells in biological systems.

Performance and degradation mechanism of phycocyanin by Cu-TiO2 photocatalytic treatment.

The efficiency, transformation products, and mechanism of phycocyanin removal from water by simulated sunlight/Cu-decorated TiO2 photocatalyst treatment were studied. After 360 min of photocatalytic degradation, the removal rate of PC was higher than 96%, about 47% of DON was oxidized into NH4+-N, NO3- and NO2-. ·OH was the main active species in the photocatalytic system, which contributes about 55.7% to PC degradation efficiency, H+ and ·O2- also contributed to the photocatalytic activity. The degradation process of phycocyanin is firstly caused by the attack of free radicals, which leads to the disintegration of the chromophore group PCB and the apoprotein, and then apoprotein peptide chain was broken to generate small molecule dipeptides, amino acids, and their derivatives. Amino acid residues sensitive to free radical action in phycocyanin peptide chain include most hydrophobic amino acids such as leucine, isoleucine, proline, valine, phenylalanine, and some hydrophilic amino acids which are easily oxidized such as lysine and arginine. Small molecular peptides (dipeptides), amino acids, and their derivatives are broken off and released into water bodies for further reaction and degradation into smaller molecular weight substances. During this process, part of organic nitrogen was transferred to inorganic nitrogen. When photocatalytic oxidation lasts for 300 min, NH4+ increases from 0.41 mg/L to 2.21 mg/L, and DON removal rate reaches 47%. The Cu-TiO2 photocatalyst was found to decrease the CHCl3 formation potential; however, it exacerbated the production of dichloroacetamide (DCAcAm) and dichloroacetonitrile (DCAN) beyond their initial levels. The divergent trends of these disinfection by-products are due to the fundamental differences in the precursor material.

Global, regional, and national burden of preterm birth attributable to ambient and household PM2.5 from 1990 to 2019: Worsening or improving?

BACKGROUND: Maternal exposure to fine particular matter (PM2.5) during pregnancy, including ambient and household PM2.5, has been linked with increased risk of preterm birth (PTB). However, the global spatio-temporal distribution of PTB-related deaths and disability-adjusted life years (DALYs) attributable to PM2.5 is not well documented. We estimated the global, regional, and national patterns and trends of PTB burden attributable to both ambient and household PM2.5 from 1990 to 2019. METHODS: Based on the Global Burden of Disease Study (GBD) 2019 database, we obtained the numbers of deaths and DALYs as well as age-standardized mortality rate (ASMR) and age-standardized DALY rate (ASDR) of PTB attributable to total, ambient, and household PM2.5 by socio-demographic index (SDI) and sex during 1990-2019. The average annual percentage changes (AAPCs) were calculated to assess the temporal trends of attributable burdens. RESULTS: In 2019, 126,752 deaths and 11.3 million DALYs related to PTB worldwide (two-thirds in Western Sub-Saharan Africa and South Asia) could be caused by excess PM2.5 above the theoretical minimum-risk exposure level (TMREL), of which 39 % and 61 % were attributable to ambient PM2.5 and household PM2.5, respectively. From 1990 to 2019, the global ASMR due to ambient PM2.5 increased slightly by 7.08 % whereas that due to household PM2.5 decreased substantially by 58.81 %, although the latter still dominated the attributable PTB burden, especially in low and low-middle SDI regions. Similar results were also observed for ASDRs. In addition, PTB burden due to PM2.5 was higher in male infants and in lower SDI regions. CONCLUSIONS: Globally in 2019, PM2.5 remains a great concern on the PTB burden, especially in Western Sub-Saharan Africa and South Asia. Between 1990 and 2019, age-standardized burden of PTB due to ambient PM2.5 increased globally, while that due to household PM2.5 decreased markedly but still dominated in low and low-middle SDI regions.

Simulated vestibular spatial disorientation mouse model under coupled rotation revealing potential involvement of Slc17a6.

Spatial disorientation (SD) is the main contributor to flight safety risks, but research progress in animals has been limited, impeding a deeper understanding of the underlying mechanisms of SD. This study proposed a method for constructing and evaluating a vestibular SD mouse model, which adopted coupled rotational stimulation with visual occlusion. Physiological parameters were measured alongside behavioral indices to assess the model, and neuronal changes were observed through immunofluorescent staining. The evaluation of the model involved observing decreased colonic temperature and increased arterial blood pressure in mice exposed to SD, along with notable impairments in motor and cognitive function. Our investigation unveiled that vestibular SD stimulation elicited neuronal activation in spatially associated cerebral areas, such as the hippocampus. Furthermore, transcriptomic sequencing and bioinformatics analysis revealed the potential involvement of Slc17a6 in the mechanism of SD. These findings lay a foundation for further investigation into the molecular mechanisms underlying SD.

Current Status of Objectification of Four Diagnostic Methods on Constitution Recognition of Chinese Medicine.

Chinese medicine (CM) has thousands of years of experience in prevention of diseases. As for CM, people's constitution is closely related to their health status, thus recognition of CM constitution is the fundamental and core content of research on constitution types. With development of technologies such as sensors, artificial intelligence and big data, objectification of the four diagnostic methods of CM has gradually matured, bringing changes in the mindset and innovations in technical means for recognition of CM constitution. This paper presents a systematic review of the latest research trends in constitution recognition based on objectification of diagnostic methods in CM.

Cellular senescence: a promising therapeutic target in colorectal cancer.

Colorectal cancer is one of the most malignant cancers worldwide, and efforts have been made to elucidate the mechanism of colorectal carcinogenesis. Cellular senescence is a physiological process in cell life, but it is also found in cancer initiation and progression. Lines of evidence show that senescence may influence the development and progression of colorectal carcinogenesis. Here, the authors review the characteristics of senescence and the recent findings of a relationship between senescence and colorectal cancer.

Cancer is a leading cause of death worldwide; out of the top ten most common cancers in 2020, the incidence and mortality rate of colorectal cancer (CRC) ranked third and second, respectively. Based on statistics, it was estimated that more than 1.9 million CRC cases occurred in 2020. In terms of CRC, a prominent risk factor is age, and studies suggest that the aging process plays a role in CRC initiation and progression. This review discusses how aging contributes to CRC carcinogenesis and summarizes recent findings on potential therapeutics.

Involvement of the SIRT1/PGC-1α Signaling Pathway in Noise-Induced Hidden Hearing Loss.

Objective: To establish an animal model of noise-induced hidden hearing loss (NIHHL), evaluate the dynamic changes in cochlear ribbon synapses and cochlear hair cell morphology, and observe the involvement of the SIRT1/PGC-1α signaling pathway in NIHHL. Methods: Male guinea pigs were randomly divided into three groups: control group, noise exposure group, and resveratrol treatment group. Each group was divided into five subgroups: the control group and 1 day, 1 week, 2 weeks, and 1 month post noise exposure groups. The experimental groups received noise stimulation at 105 dB SPL for 2 h. Hearing levels were examined by auditory brainstem response (ABR). Ribbon synapses were evaluated by inner ear basilar membrane preparation and immunofluorescence. The cochlear morphology was observed using scanning electron microscopy. Western blotting analysis and immunofluorescence was performed to assess the change of SIRT1/PGC-1α signaling. Levels of superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), ATP and SIRT1 activity were measured using commercial testing kits. Results: In the noise exposure group, hearing threshold exhibited a temporary threshold shift (TTS), and amplitude of ABR wave I decreased irreversibly. Ribbon synapse density decreased after noise exposure, and the stereocilia were chaotic and then returned to normal. The expression and activity of SIRT1 and PGC-1α protein was lower than that in the control group. SOD, CAT and ATP were also influenced by noise exposure and were lower than those in the control group, but MDA showed no statistical differences compared with the control group. After resveratrol treatment, SIRT1 expression and activity showed a significant increase after noise exposure, compared with the noise exposure group. In parallel, the PGC-1α and antioxidant proteins were also significantly altered after noise exposure, compared with the noise exposure group. The damage to the ribbon synapses and the stereocilia were attenuated by resveratrol as well. More importantly, the auditory function, especially ABR wave I amplitudes, was also promoted in the resveratrol treatment group. Conclusion: The SIRT1/PGC-1α signaling pathway and oxidative stress are involved in the pathogenesis of NIHHL and could be potential therapeutical targets in the future.

A novel and fast-responsive two-photon fluorescent probe with modified group for monitoring endogenous HClO accompanied by a large turn-on signal and its application in zebrafish imaging.

Hypochlorous acid (HClO) plays a critical role in physiological activities of maintaining the stable oxidation balance of organisms, which was proved to relate to some serious diseases. In this work, 4-nitrobenzenesulfonylhydrazide based fast-responsive two-photon fluorescent probe CoPh-ClO was designed and synthesized reasonably, which possessed low cytotoxicity, good anti-interference characteristics, a large Stokes shift (85 nm), and good two-photon performance. In addition, probe CoPh-ClO was successfully applied to detect exogenous HClO in living HeLa cells and endogenous HClO in living RAW264.7 cells respectively. Moreover, we successfully achieved tissues imaging with a deep penetration depth of 65 µm and zebrafish imaging accompanied with a high contrast (about 45-fold). Interestingly, the introduce of benzene ring between fluorophore and reaction site made probe CoPh-ClO more sensitive (only 20 s) with a large turn-on signal. The probe CoPh-ClO was modified and possessed better stability (more than 10 mins) even in excessive HClO. All of mentioned above merits demonstrated that CoPh-ClO could be a promising imaging tool for monitoring HClO in various physiological processes, and the introduction of benzene ring would provide a new perspective for the development of multi-function probes.

Multi-Dimensional and Objective Assessment of Motion Sickness Susceptibility Based on Machine Learning.

Background: As human transportation, recreation, and production methods change, the impact of motion sickness (MS) on humans is becoming more prominent. The susceptibility of people to MS can be accurately assessed, which will allow ordinary people to choose comfortable transportation and entertainment and prevent people susceptible to MS from entering provocative environments. This is valuable for maintaining public health and the safety of tasks. Objective: To develop an objective multi-dimensional MS susceptibility assessment model based on physiological indicators that objectively reflect the severity of MS and provide a reference for improving the existing MS susceptibility assessment methods. Methods: MS was induced in 51 participants using the Coriolis acceleration stimulation. Some portable equipment were used to digitize the typical clinical manifestations of MS and explore the correlations between them and Graybiel's diagnostic criteria. Based on significant objective parameters and selected machine learning (ML) algorithms, several MS susceptibility assessment models were developed, and their performances were compared. Results: Gastric electrical activity, facial skin color, skin temperature, and nystagmus are related to the severity of MS. Among the ML assessment models based on these variables, the support vector machine classifier had the best performance with an accuracy of 88.24%, sensitivity of 91.43%, and specificity of 81.25%. Conclusion: The severity of symptoms and signs of MS can be objectively quantified using some indicators. Multi-dimensional and objective assessment models for MS susceptibility based on ML can be successfully established.

A covalent organic framework as a photocatalyst for window ledge cross-dehydrogenative coupling reactions.

A benzothiadiazole-involving donor-acceptor (D-A) covalent organic framework (COF), which has high crystallinity and strong light-harvesting capability (ranging from 300 to 800 nm), can serve as a highly effective photocatalyst for window ledge aerobic cross-dehydrogenative coupling (CDC) reactions (such as Mannich and aza-Henry reactions) even at a gram level.

Consistency-Driven Methodology to Manage Incomplete Linguistic Preference Relation: A Perspective Based on Personalized Individual Semantics.

In linguistic decision-making problems, there may be cases when decision makers will not be able to provide complete linguistic preference relations. However, when estimating unknown linguistic preference values in incomplete preference relations, the existing research approaches ignore the fact that words mean different things for different people, that is, decision makers have personalized individual semantics (PISs) regarding words. To manage incomplete linguistic preference relations with PISs, in this article, we propose a consistency-driven methodology both to estimate the incomplete linguistic preference values and to obtain the personalized numerical meanings of linguistic values of the different decision makers. The proposed incomplete linguistic preference estimation method combines the characteristic of the personalized representation of decision makers and guarantees the optimum consistency of incomplete linguistic preference relations in the implementation process. Numerical examples and a comparative analysis are included to justify the feasibility of the PISs-based incomplete linguistic preference estimation method.

Consistency Improvement With a Feedback Recommendation in Personalized Linguistic Group Decision Making.

Consistency is an important issue in linguistic decision making with various consistency measures and consistency improving methods available in the literature. However, existing linguistic consistency studies omit the fact that words mean different things for different people, that is, decision makers' personalized individual semantics (PISs) over their expressed linguistic preferences are ignored. Therefore, the aim of this article is to propose a novel consistency improving approach based on PISs in linguistic group decision making. The proposed approach combines the characteristics of personalized representation and integrates the PIS-based model in measuring and improving the consistency of linguistic preference relations. A detailed numerical and comparative analysis to support the feasibility of the proposed approach is provided.

[Optimization of extraction of flavonoids from Lonicera rupicola and analysis of its effects in resisting inflammation, relieving pain, enhancing immunity, and inhibiting pyroptosis].

The present study optimized the extraction of flavonoids from Lonicera rupicola Hook. f. et Thoms(LRH) and explored its pharmacological effects, such as resisting inflammation, relieving pain, enhancing immunity, and inhibiting pyroptosis, aiming to provide data support and scientific basis for the development and utilization of LRH. Response surface methodology(RSM) was applied to optimize the extraction of flavonoids from LRH based on the results of single-factor experiments. Anti-inflammatory and analgesic effects of LRH flavonoids were evaluated via inflammation and pain models in mice, such as xylene-induced ear swelling, carrageenan-induced footpad swelling, writhing caused by acetic acid, and paw licking. The effect of LRH flavonoids on the carbon clearance index of monocytes and serum immunoglobulin A(IgA) and IgM levels was analyzed on the immunosuppression model induced by cyclophosphamide in mice. The anti-oxidative effect in vivo of LRH flavonoids on liver superoxide dismutase(SOD), catalase(CAT), and malondialdehyde(MDA) levels was determined based on the chronic/subacute aging model in mice induced by D-galactose. The levels of cysteinyl aspartate specific proteinase-1(caspase-1), interleukin-1ß(IL-1ß), and IL-18 in the supernatant of J774 A.1 mononuclear phagocytes were detected to evaluate the effect of LRH flavonoids on the pyroptosis of mononuclear phagocytes in mice induced by the combination of lipopolysaccharide(LPS) and adenosine triphosphate(ATP). Meanwhile, the effect of LRH flavonoids on the cAMP-PKA signaling pathway was also explored. The optimum conditions for the extraction of LRH flavonoids are listed below: extraction temperature of 65 ℃, the ethanol concentration of 50%, extraction time of 60 min, a material-liquid ratio at 1∶25, and the yield of LRH flavonoids of 0.553%. RSM determined the multiple quadratic regression equation model of response value and variables as follows: the yield of LRH flavonoids=0.61-0.48A+0.1B+0.029C-0.014D+0.32AB+0.04AC-0.012AD-0.02BC+0.037BD-0.031CD-0.058A~2-0.068B~2-0.069C~2-0.057D~2. LRH flavonoids could effectively inhibit ear swelling and footpad swelling, reduced acetic acid-induced writhing, and delayed the paw licking response time in mice. Additionally, LRH flavonoids could improve the carbon clearance index in immunosuppressed mice, potentiate the activities of SOD and CAT and reduce MDA levels in the liver of aging mice induced by D-galactose, and effectively inhibit macrophage pyroptosis by decreasing the levels of caspase-1, IL-1ß, and IL-18. The results reveal that LRH flavonoids possess excellent pharmacological activities such as resisting inflammation and oxidation, relieving pain, and enhancing immunity. They can inhibit pyroptosis by enhancing the cAMP-PKA signaling pathway. The results of this study can underpin the pharmacological research, development, and utilization of LRH.

Hemorrhagic fever with renal syndrome complicated with aortic dissection: A case report.

BACKGROUND: Hemorrhagic fever with renal syndrome is caused by hantaviruses presenting with high fever, hemorrhage, and acute kidney injury. Microvascular injury and hemorrhage in mucus were often observed in patients with hantavirus infection. Infection with bacterial and virus related aortic aneurysm or dissection occurs sporadically. Here, we report a previously unreported case of hemorrhagic fever with concurrent aortic dissection. CASE SUMMARY: A 56-year-old man complained of high fever and generalized body ache, with decreased platelet counts of 10 × 109/L and acute kidney injury. The enzyme-linked immunosorbent assays test for immunoglobulin M and immunoglobulin G hantavirus-specific antibodies were both positive. During the convalescent period, he complained sudden onset acute chest pain radiating to the back, and the computed tomography angiography revealed an aortic dissection of the descending aorta extending to iliac artery. He was diagnosed with hemorrhagic fever with renal syndrome and Stanford B aortic dissection. The patient recovered completely after surgery with other support treatments. CONCLUSION: Hemorrhagic fever with renal syndrome complicated with aortic dissection is rare and a difficult clinical condition. Hantavirus infection not only causes microvascular damage presenting with hemorrhage but may be risk factor for acute macrovascular detriment. A causal relationship has yet to be confirmed.

Metallothionein-2 is associated with the amelioration of asthmatic pulmonary function by acupuncture through protein phosphorylation.

BACKGROUND: Acupuncture has long been used for asthma treatment but the underlying mechanism remains unclear. Previous study showed that metallothionein-2 (MT-2) was significantly decreased in asthmatic lung tissue. However, the relationship between acupuncture treatment and MT-2 expression during asthma is still unknown, and the detailed effect analysis of MT-2 on phosphorylation in airway smooth muscle cells (ASMCs) is also unclear. METHODS: The acupuncture effect on pulmonary resistance (RL) was investigated in a rat model of asthma, and the mRNA and protein levels of MT-2 in lung tissue were detected. Primary ASMCs were isolated and treated with MT-2 recombinant protein to study the MT-2 effects on ASMC relaxation. A Phospho Explorer antibody microarray was applied to detect protein phosphorylation changes associated with MT-2-induced ASMC relaxation. Bioinformatic analysis were performed with PANTHER database, DAVID and STRING. Phosphorylation changes in key proteins were confirmed by Western blot. RESULTS: Acupuncture significantly reduced RL at 2-5 min (P < 0.05 vs asthma) in asthmatic rats. Acupuncture continued to increase MT-2 mRNA expression in lung tissue for up to 14 days (P < 0.05 vs asthma). The MT-2 protein expression was significantly decreased in the asthmatic rats (P < 0.05 vs control), while MT-2 protein expression was significantly increased in the asthmatic model group treated with acupuncture (P < 0.05 vs asthma). Primary ASMCs were successfully isolated and recombinant MT-2 protein (100, 200, 400 ng/ml) significantly relaxed ASMCs (P < 0.05 vs control). MT-2 induced phosphorylation changes in 51 proteins. Phosphorylation of 14 proteins were upregulated while 37 proteins were downregulated. PANTHER classification revealed eleven functional groups, and the phosphorylated proteins were identified as transferases (27.8 %), calcium-binding proteins (11.1 %), etc. DAVID functional classification showed that the phosphorylated proteins could be attributed to eight functions, including protein phosphorylation and regulation of GTPase activity. STRING protein-protein interaction network analysis showed that Akt1 was one of the most important hubs for the phosphorylated proteins. The phosphorylation changes of Akt1 and CaMK2ß were consistent in both the Phospho Explorer antibody microarray and Western blot. CONCLUSION: Acupuncture can significantly ameliorate RL, and the MT-2 mRNA and protein levels in lung tissue are increased during treatment. MT-2 significantly relaxes ASMCs and induces a series of protein phosphorylation. These phosphorylation changes, including Akt1 and CaMK2ß, may play important roles in the therapeutic effects of acupuncture on asthma.