Prospects of targeting JAK/STAT signal transduction pathways for vasculitis.

Vasculitis is the inflammation of blood vessels caused by autoimmunity and/or autoinflammation, and its etiology and pathogenesis remain largely unknown. The Janus kinase (JAK) and Signal transduction Transcription Activator (STAT) signal transduction pathways are a group of molecules involved in the major pathways by which many cytokines exert and integrate their functions, and their dysregulation has been implicated in the pathogenesis of a variety of autoimmune diseases. However, current data supporting the role of the JAK/STAT pathway in the development of vasculitis is limited. In terms of treatment, glucocorticoids and immunosuppressants have been the standard therapy. However, because of the huge burden of treatment side effects, people have long waited for new treatment options. JAK inhibitors reduce the production of multiple cytokines and inhibit inflammation by targeting the JAK/STAT pathway, and have the advantage of rapidly acting in oral formulations, reducing glucocorticoid dependence and associated adverse events, especially in refractory cases. Therefore, JAK inhibitors are expected to be a promising drug for the treatment of vasculitis.

[Clinical effects of ultra-pulsed fractional carbon dioxide laser in the treatment of mild to moderate microstomia after burns].

Objective: To investigate the clinical effects of ultra-pulsed fractional carbon dioxide laser (UFCL) in the treatment of mild to moderate microstomia after burns. Methods: A retrospective observational study was conducted on 19 patients with mild to moderate microstomia after burns who were admitted to Inner Mongolia Baogang Hospital from January 2018 to January 2022, including 15 males and 4 females aged (35±14) years. Patients had an average course of 71 d of microstomia, with 8 cases of moderate microstomia and 11 cases of mild microstomia. All the patients received UFCL treatment every 2-3 months until the microstomia was corrected or the treatment bottleneck was reached. The times of UFCL treatment for patients and the time interval from the last treatment to the last follow-up were recorded. Before the first treatment and at the last follow-up, the opening degree of mouth (finger measurement method), oral gap width, and the distance between the upper and lower incisors during mouth opening were recorded. Before the first treatment and at the last treatment, the new Vancouver scar scale (VSS) was used to evaluate the scar. At the last follow-up, the degree of satisfaction was evaluated by the Likert 5 scale by the patients themselves, and the satisfaction ratio was calculated; the adverse reactions such as pigmentation, blisters, infection, and persistent erythema in the treatment area were counted. Data were statistically analyzed with Mann-Whitney rank sum test or paired sample t test. Results: Patients received UFCL treatment of 3 (2, 6) times. The interval from the last treatment to the last follow-up was 26 months at most and 4 months at least. At the last follow-up, the opening degree of mouth of patients was significantly improved than that before treatment (Z=4.68, P<0.01). At the last follow-up, the oral gap width of patients was (35±6) mm, and the distance between upper and lower incisors during mouth opening was (3.2±0.4) cm, which was significantly improved compared with those before treatment (with t values of 10.73 and 18.97, respectively, P<0.01). The VSS score after the last treatment was 4.1±1.6, which was significantly better than that before treatment (t=22.96, P<0.01). At the last follow-up, the satisfaction ratio of patients with treatment was 18/19, and no pigmentation, blisters, infection, persistent erythema, and other adverse reactions of all patients in the treatment area occurred, however, one of the patients reported that the disease recurred about half a year after treatment. Conclusions: UFCL is an effective method for treating mild to moderate microstomia after burns, with which patients are highly satisfied, and it is worth of further study and promotion.

[Research progress on the effects of the interactions between phage and periodontal pathogens on periodontal disease].

Periodontal disease is among the most prevalent oral diseases. As viruses that may infect bacteria, bacteriophages constitute an important component of the oral microbiome. With the advances in bioinformatics and genomics, the relationships among the bacteriophages, oral microbiome and periodontal disease is gradually being elucidated. As a result, phage therapy has become an emerging approach in the fight against super bacteria and has flourished in recent years. This review article discusses the mechanisms involved in the microbial interactions associated with oral phages and periodontal disease, the role of phages in maintaining a normal periodontal environment, the relationship between the imbalance of phages and the occurrence of periodontal disease, and the use of phage in the treatment of periodontal disease in order to provides references for in-depth research on the mechanisms of phage effects on periodontal disease, as well as the further clinical application of phage therapy.

Metallic elements and Pb isotopes in PM2.5 in three Chinese typical megacities: spatial distribution and source apportionment.

Heavy metal pollution in fine particulate matter (PM2.5) is a serious environmental and health concern in China, particularly during winter. Here, we detected 40 elements in 24 h integrated daily PM2.5 samples collected in January 2014 from three typical Chinese metropolises (Beijing, Changchun, and Chengdu) to reflect elemental spatial variations, local sources, and regional transport. The measured elemental concentrations in Changchun were 11.1% and 48.4% higher than those in Beijing and Chengdu, respectively. Thus, PM2.5 from Changchun exhibited high levels and diversity in the elemental profile (characterized by high concentrations of industrial emission elemental markers). The results of elemental ratios and Pb isotopes proved that, except for a coal combustion source, vehicular emissions contributed more to PM2.5 heavy metals in Beijing than in the other two cities; Changchun PM2.5 elements received large contributions from industrial sources, including iron and steel manufacturing, and automobile industry. Moreover, crustal dust from long-range transport of regional air masses from the northwest regions of China played a crucial role in determining elemental levels in Beijing and Changchun, accounting for more than 50% of source intensity. However, a specific dominant source was not determined in Chengdu; the contribution of anthropogenic dust, mainly from construction activities, needs to be paid attention in Chengdu eastern area. This study contributed to enhancing our understanding of elemental spatial distribution characteristics and sources and to setting more judicious standards and strategies for PM2.5 bound heavy metals in China.

Simultaneous non-contrast angiography and intraplaque haemorrhage (SNAP) imaging for cervical artery dissections.

AIM: To evaluate the feasibility of high-resolution magnetic resonance imaging (MRI) with a simultaneous non-contrast angiography and intraplaque haemorrhage (SNAP) sequence in identifying cervical artery dissections (CeAD). MATERIALS AND METHODS: Fifty-three patients with suspected CeAD underwent the SNAP sequence (including non-contrast magnetic resonance angiography [MRA] and heavy T1-weighting vessel wall images simultaneously in a single scan) and conventional MRI sequences (including three-dimensional [3D] time-of-flight MRA and T1-weighted black-blood imaging [T1W BB]) and cervical vascular ultrasound (CVUS). In diagnosis of CeAD, the diagnostic sensitivity and specificity of SNAP, and the diagnostic coherence between SNAP and conventional sequences and between SNAP and CVUS was analysed. At follow-up, the absolute signal (AS) and signal index (SI) of the intramural haematoma (IMH) between vessel wall images on SNAP and T1W-BB images were compared. The image quality of SNAP was analysed by comparing the signal-to-noise ratio (SNR) between vessel wall images from the SNAP and T1W-BB sequences. RESULTS: The SNAP sequence was found to provide good performance in the diagnosis of CeAD (sensitivity 72.2%, specificity 98.2%); good agreement was found between SNAP and conventional sequences (Cohen's κ=0.76, p<0.05); and excellent agreement was found between SNAP and CVUS (Cohen's κ=0.83, p<0.05). There was no significant difference between AS or SI of the IMH of the vessel wall images within the SNAP and T1W-BB sequences during the review. The SNAP sequence had higher SNR of the IMH compared to T1W-BB, T2W-BB, proton-density-weighted volume isotropic turbo-spin-echo acquisition imaging (PD-VISTA) sequences (p<0.05). CONCLUSION: The SNAP sequence holds the potential to be preferred choice for screening of patients with a high suspicion of CeAD and for the follow-up of IMH after treatment.

Gasoline cars produce more carbonaceous particulate matter than modern filter-equipped diesel cars.

Carbonaceous particulate matter (PM), comprising black carbon (BC), primary organic aerosol (POA) and secondary organic aerosol (SOA, from atmospheric aging of precursors), is a highly toxic vehicle exhaust component. Therefore, understanding vehicle pollution requires knowledge of both primary emissions, and how these emissions age in the atmosphere. We provide a systematic examination of carbonaceous PM emissions and parameterisation of SOA formation from modern diesel and gasoline cars at different temperatures (22, -7 °C) during controlled laboratory experiments. Carbonaceous PM emission and SOA formation is markedly higher from gasoline than diesel particle filter (DPF) and catalyst-equipped diesel cars, more so at -7 °C, contrasting with nitrogen oxides (NOX). Higher SOA formation from gasoline cars and primary emission reductions for diesels implies gasoline cars will increasingly dominate vehicular total carbonaceous PM, though older non-DPF-equipped diesels will continue to dominate the primary fraction for some time. Supported by state-of-the-art source apportionment of ambient fossil fuel derived PM, our results show that whether gasoline or diesel cars are more polluting depends on the pollutant in question, i.e. that diesel cars are not necessarily worse polluters than gasoline cars.

Study on the Mechanism Underlying the Regulation of the NMDA Receptor Pathway in Spinal Dorsal Horns of Visceral Hypersensitivity Rats by Moxibustion.

Visceral hypersensitivity is enhanced in irritable bowel syndrome (IBS) patients. Treatment of IBS visceral pain by moxibustion methods has a long history and rich clinical experience. In the clinic, moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints can effectively treat bowel disease with visceral pain and diarrhea symptoms. To investigate the regulatory function of moxibustion on the Tianshu (ST25) and Shangjuxu (ST37) acupoints on spinal cord NR1, NR2B, and PKCε protein and mRNA expression in irritable bowel syndrome (IBS) visceral hypersensitivity rats, we did some research. In the study, we found that moxibustion effectively relieved the IBS visceral hyperalgesia status of rats. Analgesic effect of moxibustion was similar to intrathecal injection of Ro 25-6981. The expression of NR1, NR2B, and PKCε in the spinal dorsal horns of IBS visceral hyperalgesia rats increased. Moxibustion on the Tianshu and Shangjuxu acupoints might inhibit the visceral hypersensitivity, simultaneously decreasing the expression of NR1, NR2B, and PKCε in spinal cord of IBS visceral hyperalgesia rats. Based on the above experimental results, we hypothesized NR1, NR2B, and PKCε of spinal cord could play an important role in moxibustion inhibiting the process of central sensitization and visceral hyperalgesia state.

Reconstruction of atmospheric soot history in inland regions from lake sediments over the past 150 years.

Historical reconstruction of atmospheric black carbon (BC, in the form of char and soot) is still constrained for inland areas. Here we determined and compared the past 150-yr records of BC and polycyclic aromatic compounds (PACs) in sediments from two representative lakes, Huguangyan (HGY) and Chaohu (CH), in eastern China. HGY only receives atmospheric deposition while CH is influenced by riverine input. BC, char, and soot have similar vertical concentration profiles as PACs in both lakes. Abrupt increases in concentrations and mass accumulation rates (MARs) of soot have mainly occurred since ~1950, the establishment of the People's Republic of China, when energy usage changed to more fossil fuel contributions reflected by the variations in the concentration ratios of char/soot and individual PACs. In HGY, soot MARs increased by ~7.7 times in the period 1980-2012 relative to the period 1850-1950. Similar increases (~6.7 times) were observed in CH. The increase in soot MARs is also in line with the emission inventory records in the literature and the fact that the submicrometer-sized soot particles can be dispersed regionally. The study provides an alternative method to reconstruct the atmospheric soot history in populated inland areas.

Inter-annual variability of wintertime PM2.5 chemical composition in Xi'an, China: Evidences of changing source emissions.

Chemical characteristics of PM2.5 in Xi'an in wintertime of 2006, 2008, and 2010 were investigated. Markers of OC2, EC1, and NO3(-)/SO4(2-) ratio were calculated to investigate the changes in PM2.5 emission sources over the 5-year period. Positive matrix factorization (PMF) model was used to identify and quantify the main sources of PM2.5 and their contributions. The results showed that coal combustion, motor vehicular emissions, fugitive dust, and secondary inorganic aerosol accounted for more than 80% of PM2.5 mass. The importance of these major sources to the PM2.5 mass varied yearly: coal combustion was the largest contributor (31.2% ± 5.2%), followed by secondary inorganic aerosol (20.9% ± 5.2%) and motor vehicular emissions (19.3% ± 4.8%) in 2006; the order was still coal combustion emissions (27.6% ± 3.4%), secondary inorganic aerosol (23.2% ± 6.9%), and motor vehicular emissions (20.9% ± 4.6%) in 2008; while coal combustion emission further decreased (24.1% ± 3.1%) with fugitive dust (19.4% ± 5.5%) increasing in 2010. The changes in PM2.5 chemical compositions and source contributions can be attributed to the social and economic developments in Xi'an, China, including energy structure adjustment, energy consumption, the expansion of civil vehicles, and the increase of urban construction activities.

Spatiotemporal distribution of carbonyl compounds in China.

A sampling campaign was carried out at nine Chinese cities in 2010/2011. Fifteen monocarbonyls (C# = 1-9) were quantified. Temperature is the rate-determining factor of the summertime carbonyl levels. The carbonyl emissions in winter are mainly driven by the primary anthropogenic sources like automobile. A molar ratio of propionaldehyde to nonaldehyde is a barometer of the impact of atmospheric vegetation emission which suggesting that strong vegetation emissions exist in summer and high propionaldehyde abundance is caused by fossil fuel combustion in winter. Potential health risk assessment of formaldehyde and acetaldehyde was conducted and the highest cumulative risks were observed at Chengdu in summer and Wuhan in winter. Because of the strong photochemical reaction and large amount of anthropogenic emissions, high concentrations of carbonyl compounds were observed in Chengdu. The use of ethanol-blended gasoline in Wuhan is the key reason of acetaldehyde emission and action should be taken to avoid potential health risks.

Two-stroke scooters are a dominant source of air pollution in many cities.

Fossil fuel-powered vehicles emit significant particulate matter, for example, black carbon and primary organic aerosol, and produce secondary organic aerosol. Here we quantify secondary organic aerosol production from two-stroke scooters. Cars and trucks, particularly diesel vehicles, are thought to be the main vehicular pollution sources. This needs re-thinking, as we show that elevated particulate matter levels can be a consequence of 'asymmetric pollution' from two-stroke scooters, vehicles that constitute a small fraction of the fleet, but can dominate urban vehicular pollution through organic aerosol and aromatic emission factors up to thousands of times higher than from other vehicle classes. Further, we demonstrate that oxidation processes producing secondary organic aerosol from vehicle exhaust also form potentially toxic 'reactive oxygen species'.

Black carbon aerosol characterization in a remote area of Qinghai-Tibetan Plateau, western China.

The concentrations, size distributions, and mixing states of refractory black carbon (rBC) aerosols were measured with a ground-based Single Particle Soot Photometer (SP2), and aerosol absorption was measured with an Aethalometer at Qinghai Lake (QHL), a rural area in the Northeastern Tibetan Plateau of China in October 2011. The area was not pristine, with an average rBC mass concentration of 0.36 µg STP-m(-3) during the two-week campaign period. The rBC concentration peaked at night and reached the minimal in the afternoon. This diurnal cycle of concentration is negatively correlated with the mixed layer depth and ventilation. When air masses from the west of QHL were sampled in late afternoon to early evening, the average rBC concentration of 0.21 µg STP-m(-3) was observed, representing the rBC level in a larger Tibetan Plateau region because of the highest mixed layer depth. A lognormal primary mode with mass median diameter (MMD) of ~175 nm, and a small secondary lognormal mode with MMD of 470-500 nm of rBC were observed. Relative reduction in the secondary mode during a snow event supports recent work that suggested size dependent removal of rBC by precipitation. About 50% of the observed rBC cores were identified as thickly coated by non-BC material. A comparison of the Aethalometer and SP2 measurements suggests that non-BC species significantly affect the Aethalometer measurements in this region. A scaling factor for the Aethalometer data at a wavelength of 880 nm is therefore calculated based on the measurements, which may be used to correct other Aethalometer datasets collected in this region for a more accurate estimate of the rBC loading. The results present here significantly improve our understanding of the characteristics of rBC aerosol in the less studied Tibetan Plateau region and further highlight the size dependent removal of BC via precipitation.

Platelet mitochondrial dysfunction is evident in type 2 diabetes in association with modifications of mitochondrial anti-oxidant stress proteins.

OBJECTIVE: Mitochondrial dysfunction and oxidative stress in insulin responsive tissues is implicated in the pathogenesis of type 2 diabetes. Whether these perturbations extend to other tissues and contribute to their pathophysiology is less well established. The objective of this study was to investigate platelet mitochondria to evaluate whether type 2 diabetes associated mitochondrial dysfunction is evident in circulating cells. METHOD: A pilot study of mitochondrial respiratory function and proteomic changes comparing platelets extracted from insulin sensitive (n=8) and type 2 diabetic subjects (n=7). RESULTS: In-situ platelet mitochondria show diminished oxygen consumption and lower oxygen-dependent ATP synthesis in diabetic vs. control subjects. Mass spectrometric identification and confirmatory immunoblot analysis identifies induction of the mitochondrial anti-oxidant enzymes superoxide dismutase 2 and thioredoxin-dependent peroxide reductase 3 in platelets of diabetic subjects. As oxidative stress upregulates anti-oxidant enzymes we assessed mitochondrial protein carbonylation as an index of oxidative-stress. Platelets of diabetic subjects exhibit significantly increased protein carbonylation compared to controls. CONCLUSIONS: As platelets are anuclear fragments of megakaryocytes, our data suggest that the bone marrow compartment in type 2 diabetic subjects is exposed to increased mitochondrial oxidative stress with upregulation of nuclear-encoded antioxidant mitochondrial enzymes. This 'stress-signature' in platelets of diabetic subjects is associated with a diminution of their mitochondrial contribution to energy production and support that mitochondrial perturbations in type 2 diabetes extends beyond the classical insulin responsive tissues. Platelets, as "accessible human tissue", may be useful to measure the mitochondrial modulatory effects of emerging anti-diabetic therapeutics.

Does iodine gas released from seaweed contribute to dietary iodine intake?

Thyroid hormone levels sufficient for brain development and normal metabolism require a minimal supply of iodine, mainly dietary. Living near the sea may confer advantages for iodine intake. Iodine (I(2)) gas released from seaweeds may, through respiration, supply a significant fraction of daily iodine requirements. Gaseous iodine released over seaweed beds was measured by a new gas chromatography-mass spectrometry (GC-MS)-based method and iodine intake assessed by measuring urinary iodine (UI) excretion. Urine samples were obtained from female schoolchildren living in coastal seaweed rich and low seaweed abundance and inland areas of Ireland. Median I(2) ranged 154-905 pg/L (daytime downwind), with higher values (~1,287 pg/L) on still nights, 1,145-3,132 pg/L (over seaweed). A rough estimate of daily gaseous iodine intake in coastal areas, based upon an arbitrary respiration of 10,000L, ranged from 1 to 20 µg/day. Despite this relatively low potential I(2) intake, UI in populations living near a seaweed hotspot were much higher than in lower abundance seaweed coastal or inland areas (158, 71 and 58 µg/L, respectively). Higher values >150 µg/L were observed in 45.6% of (seaweed rich), 3.6% (lower seaweed), 2.3% (inland)) supporting the hypothesis that iodine intake in coastal regions may be dependent on seaweed abundance rather than proximity to the sea. The findings do not exclude the possibility of a significant role for iodine inhalation in influencing iodine status. Despite lacking iodized salt, coastal communities in seaweed-rich areas can maintain an adequate iodine supply. This observation brings new meaning to the expression "Sea air is good for you!"

Purification, cloning and sequence analyses for pro-metalloprotease-disintegrin variants from Deinagkistrodon acutus venom and subclassification of the small venom metalloproteases.

Acidic and basic hemorrhagic metalloproteases were purified from the venom of Deinagkistrodon acutus (from Fujian Province, China) using gel filtration and anion exchange on FPLC and reversed-phase HPLC. Their hemorrhagic activities and N-terminal sequences were characterized. Extensive screening of the venom gland cDNA after PCR amplification resulted in the identification and sequencing of a total of seven cDNA clones encoding the multidomain precursors of six acidic and one alkaline low molecular mass metalloproteases. Two of the precursors contain a processable disintegrin domain. Disintegrins of 5 kDa were also purified from the venom. The partial amino-acid sequences and molecular masses determined by electrospray ionization mass spectrometry of the purified proteins specifically match those deduced from two of the cDNA sequences. Moreover, phylogenetic analyses based on 30 complete sequences of low molecular mass venom metalloproteases revealed that they may be classified into three functional subtypes: acidic hemorrhagins, basic and moderate hemorrhagins, and nonhemorrhagic enzymes. Subtype-specific amino-acid substitutions in the C-terminal regions of the enzymes were highlighted to explore the structure-activity relationships of the enzymes.

[A simplified emulsification method for antigens with oil adjuvants].

In order to enhance the immune response, people usually add adjuvant to the antigen in immunization. Freund's adjuvant is one of the most used. It can prolong the duration of the antigen staying in the body of the animal, and through continuous stimulation of the antigen the production of antibody is increased. This paper describes a few points in facilitating the emulsification of the antigen and making it more effective. The process can be summarized as follows: (1) Force a small amount of adjuvant from syringe B by pushing it into syringe A filled with antigen solution to mingle with the latter. (2) Push the same volume of the mix from syringe A back to syringe B slowly. (3) Repeat the above mixing process until the mixed portion has become milky white. (4) Gradually increase the volume by small amounts and each time do the same mixing until final completion. After immunization with the mixture, potent sera were always obtained. It has become a routine in this laboratory to use such mixture in its immunization tasks.

[Preparation of toxoid from Taiwan cobra (Naja naja atra) venom].

Potency of sixty antitoxic unit was reached after two immunizations in 2-week intervals of rabbits and horses with 10-25 mg Taiwan cobra (Naja naja atra) venom which was detoxified by 0.125% glutaraldehyde. Now this procedure has become a routine antivenine-producing method by which snake bivalent neurotropic antivenine is produced. The stability test showed that Taiwan cobra toxoid kept at 37 degrees C for 40 days, the antigenicity increased by 24% and toxicity decreased by 10% as compared to the toxoid maintained at 4 degrees C.

[The detoxification of Naja naja atra venom and preparation of potent antivenin].

The 99.2% toxicity of Naja naja atra venom can be detoxified by treatment with 0.25% GA (glutaraldehyde) solution at pH 6.8 and still remains its antigenicity. Using the GA treated venom incorporated with Freund's complete adjuvant as immunogen, the titer of immune horse sera can be enhanced rapidly. The modified immunization method not only shortened the period of immunization (from 180 to 60 days), but also increased the potency of immune sera (from 75 to 170 units). The method also diminished the mortality rate of the horse during the immunization period (from 37 to 0%) and increased the antibody production rate (from 20 to 100%), as compared to Tanaka's method. With the present method, significant economic effects can be achieved. The neutralization antibody titer of Naja naja atra antivenin could be elevated 3.55 times through purification of the antivenin with the pepsin digestion method. The antivenin recovery rate using the pepsin digestion method was about 55.44%. The solubility of lyophilized antivenin was significantly improved by the addition of 2% glycine. In addition to an increase of antivenin potency and purity, the problem of an inadequate production rate has also been resolved. Now lyophilized antivenin can be supplied even to remote areas, thus providing excellent opportunities for clinical application. This Institute has already adopted this new immunization schedule in lieu of the old Tanaka method.