Large potential of strengthening the land carbon sink in China through anthropogenic interventions.

The terrestrial ecosystem in China mitigates 21%-45% of the national contemporary fossil fuel CO2 emissions every year. Maintaining and strengthening the land carbon sink is essential for reaching China's target of carbon neutrality. However, this sink is subject to large uncertainties due to the joint impacts of climate change, air pollution, and human activities. Here, we explore the potential of strengthening land carbon sink in China through anthropogenic interventions, including forestation, ozone reduction, and litter removal, taking advantage of a well-validated dynamic vegetation model and meteorological forcings from 16 climate models. Without anthropogenic interventions, considering Shared Socioeconomic Pathways (SSP) scenarios, the land sink is projected to be 0.26-0.56 Pg C a-1 at 2060, to which climate change contributes 0.06-0.13 Pg C a-1 and CO2 fertilization contributes 0.08-0.44 Pg C a-1 with the stronger effects for higher emission scenarios. With anthropogenic interventions, under a close-to-neutral emission scenario (SSP1-2.6), the land sink becomes 0.47-0.57 Pg C a-1 at 2060, including the contributions of 0.12 Pg C a-1 by conservative forestation, 0.07 Pg C a-1 by ozone pollution control, and 0.06-0.16 Pg C a-1 by 20% litter removal over planted forest. This sink can mitigate 90%-110% of the residue anthropogenic carbon emissions in 2060, providing a solid foundation for the carbon neutrality in China.

Descending facilitation from rostral ventromedial medulla mu opioid receptor-expressing neurons is necessary for maintenance of sensory and affective dimensions of chronic neuropathic pain.

ABSTRACT: Pharmacological ablation of rostral ventromedial medulla (RVM) mu opioid receptor-expressing cells before peripheral nerve injury prevents the development of neuropathic pain. However, whether these neurons are required for the expression of established neuropathic pain is not known. Male Oprm1Cre heterozygous (MORCre) or wild-type (MORWT) mice received AAV8-hSyn-DIO-hM4D(Gi)-mCherry in the RVM. After partial sciatic nerve ligation (PSNL), we evaluated pain behaviors and descending control of nociception in response to acute or sustained chemogenetic inhibition of RVM-MOR cells expressing hM4D(Gi). A single systemic administration of hM4D(Gi) agonist clozapine-N-oxide (CNO) reversibly inhibited hind paw tactile allodynia and produced conditioned place preference only in MORCre mice with PSNL. Intrathecal CNO also reversibly inhibited PSNL-induced hind paw allodynia, suggesting that the spinal projections from these RVM-MOR cells are critical for manifestation of pain behaviors. Consistent with enhanced descending facilitation from RVM-MOR cells, MORCre-hM4D(Gi) mice with PSNL showed diminished descending control of nociception that was restored by systemic CNO. Sustained CNO in drinking water before PSNL prevented expression of chronic pain without affecting acute surgical pain; however, relief of chronic pain required sustained CNO treatment. Thus, in male mice, activity of spinally projecting RVM-MOR cells is required (1) for expression and manifestation of both sensory and affective dimensions of established neuropathic pain and (2) to promote descending facilitation that overcomes apparently intact descending inhibition to maintain chronic pain. Enhanced descending facilitation likely regulates the output signal from the spinal cord to the brain to shape the pain experience and may provide a mechanism for nonopioid management of pain.

All-cause, cardiovascular, and respiratory mortality and wildfire-related ozone: a multicountry two-stage time series analysis.

BACKGROUND: Wildfire activity is an important source of tropospheric ozone (O3) pollution. However, no study to date has systematically examined the associations of wildfire-related O3 exposure with mortality globally. METHODS: We did a multicountry two-stage time series analysis. From the Multi-City Multi-Country (MCC) Collaborative Research Network, data on daily all-cause, cardiovascular, and respiratory deaths were obtained from 749 locations in 43 countries or areas, representing overlapping periods from Jan 1, 2000, to Dec 31, 2016. We estimated the daily concentration of wildfire-related O3 in study locations using a chemical transport model, and then calibrated and downscaled O3 estimates to a resolution of 0·25°â€ˆ× 0·25° (approximately 28 km2 at the equator). Using a random-effects meta-analysis, we examined the associations of short-term wildfire-related O3 exposure (lag period of 0-2 days) with daily mortality, first at the location level and then pooled at the country, regional, and global levels. Annual excess mortality fraction in each location attributable to wildfire-related O3 was calculated with pooled effect estimates and used to obtain excess mortality fractions at country, regional, and global levels. FINDINGS: Between 2000 and 2016, the highest maximum daily wildfire-related O3 concentrations (≥30 µg/m3) were observed in locations in South America, central America, and southeastern Asia, and the country of South Africa. Across all locations, an increase of 1 µg/m3 in the mean daily concentration of wildfire-related O3 during lag 0-2 days was associated with increases of 0·55% (95% CI 0·29 to 0·80) in daily all-cause mortality, 0·44% (-0·10 to 0·99) in daily cardiovascular mortality, and 0·82% (0·18 to 1·47) in daily respiratory mortality. The associations of daily mortality rates with wildfire-related O3 exposure showed substantial geographical heterogeneity at the country and regional levels. Across all locations, estimated annual excess mortality fractions of 0·58% (95% CI 0·31 to 0·85; 31 606 deaths [95% CI 17 038 to 46 027]) for all-cause mortality, 0·41% (-0·10 to 0·91; 5249 [-1244 to 11 620]) for cardiovascular mortality, and 0·86% (0·18 to 1·51; 4657 [999 to 8206]) for respiratory mortality were attributable to short-term exposure to wildfire-related O3. INTERPRETATION: In this study, we observed an increase in all-cause and respiratory mortality associated with short-term wildfire-related O3 exposure. Effective risk and smoke management strategies should be implemented to protect the public from the impacts of wildfires. FUNDING: Australian Research Council and the Australian National Health and Medical Research Council.

Impacts of land cover changes on summer surface ozone in China during 2000-2019.

China implemented continuous forestation and experienced significant greening tendency in the past several decades. While the ecological project brings benefits to regional carbon assimilation, it also affects surface ozone (O3) pollution level through perturbations in biogenic emissions and dry deposition. Here, we use a coupled chemistry-vegetation model to assess the impacts of land use and land cover change (LULCC) on summertime surface O3 in China during 2000-2019. The LULCC is found to enhance O3 by 1-2 ppbv in already-polluted areas. In contrast, moderate reductions of -0.4 to -0.8 ppbv are predicted in southern China where the largest forest cover changes locate. Such inconsistency is attributed to the background chemical regimes with positive O3 changes over VOC-limited regions but negative changes in NOx-limited regions. The net contribution of LULCC to O3 budget in China is 24.17 Kg/s, in which the positive contribution by more isoprene emissions almost triples the negative effects by the increased dry deposition. Although the LULCC-induced O3 perturbation is much lower than the effects of anthropogenic emissions, forest expansion has exacerbated regional O3 pollution in North China Plain and is expected to further enhance surface O3 with continuous forestation in the future.

Nociceptors are functionally male or female: from mouse to monkey to man.

The prevalence of many pain conditions often differs between sexes. In addition to such quantitative distinctions, sexual dimorphism may also be qualitative reflecting differences in mechanisms that promote pain in men and women. A major factor that influences the likelihood of pain perception is the threshold for activation of nociceptors. Peripheral nociceptor sensitization has been demonstrated to be clinically relevant in many pain conditions. Whether peripheral nociceptor sensitization can occur in a sexually dimorphic fashion, however, has not been extensively studied. To address this fundamental knowledge gap, we used patch clamp electrophysiology to evaluate the excitability of dorsal root ganglion neurones from male or female rodents, non-human primates, and humans following exposure to putative sensitizing agents. Previous studies from our laboratory, and others, have shown that prolactin promotes female-selective pain responses in rodents. Consistent with these observations, dorsal root ganglion neurones from female, but not male, mice were selectively sensitized by exposure to prolactin. The sensitizing action of prolactin was also confirmed in dorsal root ganglion neurones from a female macaque monkey. Critically, neurones recovered from female, but not male, human donors were also selectively sensitized by prolactin. In the course of studies of sleep and pain, we unexpectedly observed that an orexin antagonist could normalize pain responses in male animals. We found that orexin B produced sensitization of male, but not female, mouse, macaque, and human dorsal root ganglion neurones. Consistent with functional responses, increased prolactin receptor and orexin receptor 2 expression was observed in female and male mouse dorsal root ganglia, respectively. Immunohistochemical interrogation of cultured human sensory neurones and whole dorsal root ganglia also suggested increased prolactin receptor expression in females and orexin receptor 2 expression in males. These data reveal a functional double dissociation of nociceptor sensitization by sex, which is conserved across species and is likely directly relevant to human pain conditions. To our knowledge, this is the first demonstration of functional sexual dimorphism in human sensory neurones. Patient sex is currently not a common consideration for the choice of pain therapy. Precision medicine, based on patient sex could improve therapeutic outcomes by selectively targeting mechanisms promoting pain in women or men. Additional implications of these findings are that the design of clinical trials for pain therapies should consider the proportions of male or female patients enrolled. Lastly, re-examination of selected past failed clinical trials with subgroup analysis by sex may be warranted.

Continued Rise in Health Burden from Ambient PM2.5 in India under SSP Scenarios Until 2100 despite Decreasing Concentrations.

Forecasting alterations in ambient air pollution and the consequent health implications is crucial for safeguarding public health, advancing environmental sustainability, informing economic decision making, and promoting appropriate policy and regulatory action. However, predicting such changes poses a substantial challenge, requiring accurate data, sophisticated modeling methodologies, and a meticulous evaluation of multiple drivers. In this study, we calculate premature deaths due to ambient fine particulate matter (PM2.5) exposure in India from the 2020s (2016-2020) to the 2100s (2095-2100) under four different socioeconomic and climate scenarios (SSPs) based on four CMIP6 models. PM2.5 concentrations decreased in all SSP scenarios except for SSP3-7.0, with the lowest concentration observed in SSP1-2.6. The results indicate an upward trend in the five-year average number of deaths across all scenarios, ranging from 1.01 million in the 2020s to 4.12-5.44 million in the 2100s. Further analysis revealed that the benefits of reducing PM2.5 concentrations under all scenarios are largely mitigated by population aging and growth. These findings underscore the importance of proactive measures and an integrated approach in India to improve atmospheric quality and reduce vulnerability to aging under changing climate conditions.

Multi-node wearable optical sensor based on microfiber Bragg gratings.

Flexibly wearable sensors are widely applied in health monitoring and personalized therapy. Multiple-node sensing is essential for mastering the health condition holistically. In this work, we report a multi-node wearable optical sensor (MNWOS) based on the cascade of microfiber Bragg gratings (µFBG), which features the reflective operation mode and ultra-compact size, facilitating the functional integration in a flexible substrate pad. The MNWOS can realize multipoint monitoring on physical variables, such as temperature and pressure, in both static and dynamic modes. Furthermore, the eccentric package configuration endows the MNWOS with the discernibility of bending direction in addition to the bending angle sensing. The multi-parameter sensing is realized by solving the sensing matrix that represents different sensitivity regarding the bending and temperature between FBGs. The MNWOS offers great prospect for the development of human-machine interfaces and medical and health detection.

Acute Effects of Exposure to Fine Particulate Matter and Its Constituents on Sex Hormone Among Postmenopausal Women - Beijing, Tianjin, and Hebei PLADs, China, 2018-2019.

What is already known on this topic?: Exposure to fine particulate matter (PM2.5) was linked to endocrine hormone disruption in the reproductive system. Nonetheless, it was unclear which specific components of PM2.5 were primarily responsible for these associations. What is added by this report?: The study presented the initial epidemiological evidence that brief exposure to PM2.5 can elevate estradiol levels in postmenopausal women. Various particle components had unique effects, with water-soluble ions and specific inorganic elements like Ag, As, Cd, Hg, Ni, Sb, Se, Sn, and Tl potentially playing significant roles in increasing estradiol levels. What are the implications for public health practice?: The study established that the prevalence of air pollution, along with its specific components, has been recognized as a novel risk factor affecting the balance of sex hormones.

The multi-year contribution of Indo-China peninsula fire emissions to aerosol radiation forcing in southern China during 2013-2019.

Fire emissions in Southeast Asia transported to southern China every spring (March-May), influencing not only the air quality but also the weather and climate. However, the multi-year variations and magnitude of this impact on aerosol radiation forcing in southern China remain unclear. Here, we quantified the multi-year contributions of fire emissions in Indo-China Peninsula (ICP) region to aerosol radiation forcing in the various southern Chinese provinces during the fire season (March-May) of 2013-2019 combining the 3-dimension chemical transport model and the Column Radiation Model (CRM) simulations. The models' evaluations showed they reasonably capture the temporal and spatial distribution of surface aerosol concentrations and column aerosol optical properties over the study regions. The fire emissions over the ICP region were found to increase the aerosol optical depth (AOD) value by 0.1 (15 %) and reduce the single scattering albedo (SSA) in three southern regions of China (Yunnan-YN, Guangxi-GX, and Guangdong-GD from west to east), owing to increases in the proportions of black carbon (BC, 0.4 % ± 0.1 %) and organic carbon (OC, 3.0 % ± 0.9 %) within the aerosol compositions. The transported smoke aerosols cooled surface but heated the atmosphere in the southern China regions, with the largest mean reduction of -5 Wm-2 (-3 %) in surface shortwave radiation forcing and the maximum daily contributions of about -15 Wm-2 (-15 %) to the atmosphere radiation forcing in the GX region, followed by the GD and YN regions. The impacts of ICP fire emissions on aerosol optical and radiative parameters declined during 2013-2019, with the highest rate of 0.393 ± 0.478 Wm-2 yr-1 in the GX for the shortwave radiation forcing in the atmosphere. Besides, their yearly changes in the contribution were consistent with the annual fire emissions in the ICP region. Such strong radiative perturbations of ICP fire emissions were expected to influence regional meteorology in southern China and should be considered in the climate simulations.

Wildfire-related PM2.5 and cardiovascular mortality: A difference-in-differences analysis in Brazil.

Brazil has experienced unprecedented wildfires recently. We aimed to investigate the association of wildfire-related fine particulate matter (PM2.5) with cause-specific cardiovascular mortality, and to estimate the attributable mortality burden. Exposure to wildfire-related PM2.5 was defined as exposure to annual mean wildfire-related PM2.5 concentrations in the 1-year prior to death. The variant difference-in-differences method was employed to explore the wildfire-related PM2.5-cardiovascular mortality association. We found that, in Brazil, compared with the population in the first quartile (Q1: ≤1.82 µg/m3) of wildfire-related PM2.5 exposure, those in the fourth quartile (Q4: 4.22-17.12 µg/m3) of wildfire-related PM2.5 exposure had a 2.2% (RR: 1.022, 95% CI: 1.013-1.032) higher risk for total cardiovascular mortality, 3.1% (RR: 1.031, 95% CI: 1.014-1.048) for ischaemic heart disease mortality, and 2.0% (RR: 1.020, 95% CI: 1.002-1.038) for stroke mortality. From 2010 to 2018, an estimation of 35,847 (95% CI: 22,424-49,177) cardiovascular deaths, representing 17.77 (95% CI: 11.12-24.38) per 100,000 population, were attributable to wildfire-related PM2.5 exposure. Targeted health promotion strategies should be developed for local governments to protect the public from the risk of wildfire-related cardiovascular premature deaths.

Selective Electroreduction of 5-Hydroxymethylfurfural to Dimethylfuran in Neutral Electrolytes via Hydrogen Spillover and Adsorption Configuration Adjustment.

5-Hydroxymethylfurfural (HMF), one of the essential C6 biomass derivatives, has been deeply investigated in electrocatalytic reduction upgrading. Nevertheless, the high product selectivity and rational design strategy of electrocatalysts for electrocatalytic HMF reduction is still a challenge. Here, a high selective electro-reduction of HMF to dimethylfuran (DMF) on palladium (Pd) single atom loaded on titanium dioxide (Pd SA/TiO2 ) via hydrogen spillover and adsorption configuration adjustment in neutral electrolytes is achieved. Combining density functional theory calculations and in situ characterization, it is revealed that Pd single atom could weaken the interaction between Pd atoms and adsorbed hydrogen (*H) to promote the *H spillover for increasing *H coverage on the surface and maintain the tilted adsorption configuration to activate C═O bond; thus the selectivity of DMF on Pd SA/TiO2 increases to 90.33%. Besides, it is elaborated that low *H coverage on TiO2 favors the formation of bis(hydroxymethyl)hydro-furoin (BHH), and the flat adsorption configuration of HMF on Pd nanoparticles benefits to form 2,5-dihydroxymethylfuran (DHMF). This work provides a promising approach for modifying electrocatalysts to realize the selective electroreduction of HMF to value-added products.

The carbon budget of China: 1980-2021.

As one of the world's largest emitters of greenhouse gases, China has set itself the ambitious goal of achieving carbon peaking and carbon neutrality. Therefore, it is crucial to quantify the magnitude and trend of sources and sinks of atmospheric carbon dioxide (CO2), and to monitor China's progress toward these goals. Using state-of-the-art datasets and models, this study comprehensively estimated the anthropogenic CO2 emissions from energy, industrial processes and product use, and waste along with natural sources and sinks of CO2 for all of China during 1980-2021. To recognize the differences among various methods of estimating greenhouse emissions, the estimates are compared with China's National Greenhouse Gas Inventories (NGHGIs) for 1994, 2005, 2010, 2012, and 2014. Anthropogenic CO2 emissions in China have increased by 7.39 times from 1980 to 12.77 Gt CO2 a-1 in 2021. While benefiting from ecological projects (e.g., Three Norths Shelter Forest System Project), the land carbon sink in China has reached 1.65 Gt CO2 a-1 averaged through 2010-2021, which is almost 15.81 times that of the carbon sink in the 1980s. On average, China's terrestrial ecosystems offset 14.69% ± 2.49% of anthropogenic CO2 emissions through 2010-2021. Two provincial-level administrative regions of China, Xizang and Qinghai, have achieved carbon neutrality according to our estimates, but nearly half of the administrative regions of China have terrestrial carbon sink offsets of less than 10% of anthropogenic CO2 emissions. This study indicated a high level of consistency between NGHGIs and various datasets used for estimating fossil CO2 emissions, but found notable differences for land carbon sinks. Future estimates of the terrestrial carbon sinks of NGHGIs urgently need to be verified with process-based models which integrate the comprehensive carbon cycle processes.

Health literacy and its influencing factors among residents aged 15-69 years with different chronic disease in Zhejiang Province / 中华健康管理学杂志

Objective:To investigate the level of health literacy and its influencing factors among residents aged 15-69 years with different chronic disease in Zhejiang Province.Methods:In this cross-sectional study, a stratified multistage whole cluster random sampling method was used to select 19 200 permanent residents aged 15-69 years from 30 monitoring sites in Zhejiang Province from June to November 2022, and a household questionnaire survey was carried out with the National Health Literacy Monitoring Questionnaire for the Population. The content of the survey included socio-demographic characteristics, health-related factors and health literacy level. A total of 19 200 questionnaires were distributed and 19 051 were collected, of which 18 857 (98.98%) were valid. The χ2 test was used to compare the health literacy levels of residents with different chronic diseases, and logistic regression was used to analyze the influencing factors of the health literacy levels. Results:The health literacy level of residents aged 15-69 in Zhejiang Province in 2022 was 38.36%. Among them, the health literacy level of patients with multiple chronic diseases was much lower than those with single chronic disease and those without chronic disease (14.70% vs 25.37%, 42.21%) ( χ2=483.05, P<0.001). It was positively associated between having multiple chronic diseases and insufficient health literacy ( OR=1.26, 95% CI: 1.01-1.58); compared with those without chronic disease ( OR=1.00), patients with multiple chronic diseases were significantly more likely to have inadequate health literacy in basic knowledge and concepts ( OR=1.29, 95% CI: 1.03-1.63), health behaviors ( OR=1.24, 95% CI: 1.01-1.53), basic skills ( OR=1.37, 95% CI: 1.11-1.69), and health information literacy ( OR=1.27, 95% CI: 1.08-1.50). Conclusions:The number of chronic diseases is a key factor that affects the residents′ health literacy level, and people with multiple chronic diseases are often associated with a higher risk of inadequate health literacy.

Brief Analysis of Neutral Sweet and Flat Foods in WANG Mengying's Suixiju Diet Spectrum / 浙江中医药大学学报

[Objective]To summarize WANG Mengying's understanding and experience in using neutral sweet and flat foods in Suixiju Diet Spectrum,and analyze the therapeutic characteristics contained in it,so as to better apply the therapeutic and health theory to clinic and life.[Methods]The neutral flavor sweet and flat foods were screened and listed one by one according to food categories,their distribution rules were explored,their efficacy was analyzed,and their clinical application methods were summarized.The theoretical characteristics of food therapy were comprehensively analyzed in combination with the theoretical system of traditional Chinese medicine.[Results]The number of all kinds of food in Suxiju Diet Spectrum was different,and the most were hairy-feather,which not only had the effect of nourishing the five viscera,but also could reduce part of the excess syndrome.The clinical application method was in line with the compatibility of the seven emotions of drugs in formulae,and the therapeutic features contained in it were in line with the theoretical system of traditional Chinese medicine.[Conclusion]WANG Mengying had a unique understanding and indirect opinion on the food with the flavor of sweet and flat in Suxiju Diet Spectrum,and had a variety of use methods,which had a good guiding effect on the use of the food with the flavor of sweet and flat in daily life and clinic.

Efficacy of total laparoscopic radical cystectomy with intracorporeal ileal conduit urinary diversion: a report of 25 cases / 现代泌尿外科杂志

【Objective】 To investigate the efficacy and surgical technique of total laparoscopic radical cystectomy with intracorporeal ileal conduit urinary diversion, so as to provide reference for the selection of surgery for patients with bladder cancer. 【Methods】 Clinical data of 48 patients with bladder cancer who underwent laparoscopic radical cystectomy during Mar.2017 and Aug.2022 in our hospital were retrospectively analyzed, including 23 cases who received traditional laparoscopic radical cystectomy combined with extracorporeal ileal conduit, and 25 who received total laparoscopic radical cystectomy with intracorporeal ileal conduit.The operation time, blood loss, postoperative intestinal function recovery time, drainage tube removal time and hospital stay were compared between the two groups. 【Results】 All procedures were successfully performed, and no Clavien-Dindo>grade 3 complications were observed.The operation time, and amount of estimated blood loss of the traditional group and total laparoscopic radical group were (227.0±46.4) min vs. (253.6±58.9) min, and (131.7±79.8) mL vs. (154.0±93.0) mL, respectively.There were no differences in postoperative intestinal function recovery time and drainage tube removal time (P>0.05).The hospital stay was shorter in the total laparoscopic radical group than in the traditional group (P=0.035). 【Conclusion】 Total laparoscopic radical cystectomy with intracorporeal ileal conduit urinary diversion is safe and feasible.which is comparable to the traditional laparoscopic surgery, while the hospital stay in the total laparoscopic group is shorter, which is conducive to rapid postoperative recovery.

Expression of PLCD3 mRNA in synovium of osteoarthritis and its relationship with immune cell infiltration / 国际检验医学杂志

Objective To investigate the expression of PLCD3 mRNA in the synovium of osteoarthritis(OA)and its relationship with immune cell infiltration.Methods Based on the differentially expressed genes of OA found in the previous study,the expression of phospholipase Cδ3(PLCD3)mRNA was detected by col-lecting synovial samples from OA group and control group.CIBERSORT algorithm was used to analyze the infiltration pattern of immune cells in OA group and control group,and the correlation between PLCD3 and infiltrating immune cells was further analyzed.Results Compared with the control group,the relative expres-sion level of PLCD3 mRNA was significantly increased in synovial samples of OA group(P<0.05).The pro-portions of B cells naive,NK cells activated,M2 macrophages and mast cells activated in synovial tissues of OA group were relatively high(P<0.05).PLCD3 was positively correlated with the proportion of these four immune cells(P<0.05).Conclusion PLCD3 may be a key biomarker for the diagnosis of OA,which may be involved in the pathogenesis of OA by interacting with infiltrating immune cells.

RNA sequencing-based research on the immune regulation mechanism of C-MET in lung cancer / 实用医学杂志

Objective To analyze the immune regulation mechanism of C-MET expression in non-small cell lung cancer by transcriptome sequencing technology.Methods The C-MET expression of lung adenocarci-noma cell line(H1993)and lung squamous cell carcinoma cell line(EBC-1)with high C-MET expression was silenced using siRNA molecular interference technology.The differentially expressed genes(DEGs)before and after C-MET silencing were detected using transcriptome sequencing technology.The signal pathways and related genes of the immune microenvironment in which C-MET may participate in regulation were excavated through bioinformat-ics analysis.Finally,the co-culture technique of human immune cells with H1993 and EBC-1 was used to verify the effect of C-MET on immune factors such as INF-γ,INF-β and CXCL-10.Results We detected 505 DEGs in total using transcriptome sequencing.There were 38 differentially expressed genes in the C-MET regulation group before and after H1993,24 upregulated differentially expressed genes,and 14 downregulated differentially expressed genes,respectively.There are a total of 467 differentially expressed genes in the C-MET regulation group of EBC-1,347 upregulated differentially expressed genes,and 121 downregulated differentially expressed genes,respec-tively.KEGG analysis of differential genes suggested that C-MET expression might participate in the regulation of immune cell regulatory factors through the IL-17 signaling pathway,white blood cell differentiation,cytokine receptor activity,cell cycle,cytokine receptor activity,and cytokine-cytokine receptor interaction.The effect of C-MET on immune factor secretion was verified using the co-culture technique of lung cancer cells and human immune cells,and the results of Rt-qPCR assay suggested,the mRNA transcriptional level of INF-γ in PBMC co-cultured with the C-MET high expression group was 77 times that of the low expression group,and the mRNA transcriptional level of CXCL-10 was 1.6 times that of the low expression group.The mRNA transcriptional level of INF--β was twice as high as that of the low expression group.Conclusion C-MET expression may participate in the regulation of tumor surrounding immune microenvironment through IL-17 signaling pathway,leukocyte differen-tiation,and cytokine receptor activity pathway.

Mechanism by which miR-34a-5p/PLCD3 axis regulates osteoarthritis progression / 中国组织工程研究

BACKGROUND:Molecular mechanisms targeting the miRNA/mRNA axis to regulate osteoarthritis disease process have been studied.We identified the mRNA:phospholipase C delta 3(PLCD3)and its target miRNA(miR-34a-5p)with clinical predictive value through previous bioinformatics studies,while experiments to verify their specific roles and mechanisms in regulating osteoarthritis are still lacking. OBJECTIVE:To investigate the regulatory role and mechanism of miR-34a-5p/PLCD3 axis on osteoarthritis progression. METHODS:The synovium of 15 patients with knee osteoarthritis was selected as the osteoarthritis group,and the synovium of 15 young patients with internal fixation of patellar fracture caused by trauma during the same period was selected as the control group.The expression of PLCD3 and miR-34a-5p in the synovium was detected by real-time PCR.Human fibroblast like synovial cells-osteoarthritis(HFLS-OA)cells were treated by cell transfection and divided into miR-34a-5p mimic group,pCDH-PLCD3 group,miR-34a-5p mimic+pCDH-PLCD3 group,miR-34a-5p inhibitor group,si-PLCD3 group,and miR-34a-5p inhibitor+si-PLCD3 group.The relationship between PLCD3 and miR-34a-5p expression was detected by real-time PCR.The effects of HFLS-OA cell viability and cell migration in each group were detected by CCK-8 assay and cell scratch test.Western blot assay was used to detect the expression level of apoptosis marker protein.The expression of inflammatory factors was detected by ELISA. RESULTS AND CONCLUSION:(1)PLCD3 was a direct target of miR-34a-5p,and the expression levels of PLCD3 and miR-34a-5p were negatively correlated.(2)Upregulation of PLCD3 promoted proliferation of HFLS-OA cells and inhibited cell migration.The up-regulation of miR-34a-5p significantly inhibited the activity of HFLS-OA cells and enhanced cell migration.Overexpression of miR-34a-5p significantly increased the levels of Casp3 and Casp9 proteins in HFLS-OA cells,while overexpression of PLCD3 showed the opposite trend.(3)PLCD3 overexpression significantly increased the expression of interleukin 6 and tumor necrosis factor alpha in HFLS-OA cells,while miR-34a-5p mimics showed protective activity.(4)The miR-34a-5p/PLCD3 axis may affect the progression of osteoarthritis by regulating the inflammatory process or apoptosis of synovial cells.

Application of Acupotomy in a Knee Osteoarthritis Model in Rabbit.

Knee osteoarthritis (KOA) is one of the most frequently encountered diseases in the orthopedic department, which seriously reduces the quality of life of people with KOA. Among several pathogenic factors, the biomechanical imbalance of the knee joint is one of the main causes of KOA. Acupotomology believes that restoring the mechanical balance of the knee joint is the key to treating KOA. Clinical studies have shown that acupotomy can effectively reduce pain and improve knee mobility by reducing adhesion, contracture of soft tissues, and stress concentration points in muscles and tendons around the knee joint. In this protocol, we used the modified Videman method to establish a KOA model by immobilizing the left hindlimb in a straight position. We have outlined the method of operation and the precautions related to acupotomy in detail and evaluated the efficacy of acupotomy in conjunction with the theory of "Modulating Muscles and Tendons to Treat Bone Disorders" through the detection of the mechanical properties of quadriceps femoris and tendon, as well as cartilage mechanics and morphology. The results show that acupotomy has a protective effect on cartilage by adjusting the mechanical properties of the soft tissues around the knee joint, improving the cartilage stress environment, and delaying cartilage degeneration.