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The common data model (CDM) is an important tool to facilitate the standardized integration of multi-source heterogeneous healthcare big data, enhance the consistency of data semantic understanding, and promote multi-party collaborative analysis. The data collections standardized by CDM can provide powerful support for observational studies, such as large-scale population cohort study. This paper provides an in-depth comparative analysis of the data storage structure, term mapping pattern, and auxiliary tools development of the three international typical CDMs, then analyzes the advantages and limitations of each CDM and summarizes the challenges and opportunities faced in the CDM application in China. It is expected that exploring the advanced technical concepts and practical patterns of foreign countries in data management and sharing will provide references for promoting FAIR (findable, accessible, interoperable, reusable) construction of healthcare big data in China and solving the current practical problems, such as the poor quality of data resources, the low degree of semantization, and the inabilities of data sharing and reuse.
Subject(s)
Humans , Big Data , China , Cohort Studies , Data Collection , Information DisseminationABSTRACT
Male reproductive infections are known to shape the immunological homeostasis of the testes, leading to male infertility. However, the specific pathogenesis of these changes remains poorly understood. Exosomes released in the inflammatory microenvironment are important in communication between the local microenvironment and recipient cells. Here, we aim to identify the immunomodulatory properties of inflammatory testes-derived exosomes (IT-exos) and explore their underlying mechanisms in orchitis. IT-exos were isolated using a uropathogenic Escherichia coli (UPEC)-induced orchitis model and confirmed that IT-exos promoted proinflammatory M1 activation with increasing expression of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) in vitro. We further used small RNA sequencing to identify the differential miRNA profiles in exosomes and primary testicular macrophages (TMs) from normal and UPEC-infected testes, respectively, and identified that miR-155-5p was highly enriched in IT-exos and TMs from inflammatory testes. Further study of bone marrow derived macrophages (BMDMs) transfected with miR-155-5p mimic showed that macrophages polarized to proinflammatory phenotype. In addition, the mice that were administrated IT-exos showed remarkable activation of TM1-like macrophages; however, IT-exos with silencing miR-155-5p showed a decrease in proinflammatory responses. Overall, we demonstrate that miR-155-5p delivered by IT-exos plays an important role in the activation of TM1 in UPEC-induced orchitis. Our study provides a new perspective on the immunological mechanisms underlying inflammation-related male infertility.
Subject(s)
Humans , Male , Mice , Animals , Orchitis , Uropathogenic Escherichia coli/metabolism , MicroRNAs/metabolism , Exosomes/metabolism , Macrophages/metabolism , Phenotype , Infertility, Male/metabolismABSTRACT
In the face of a serious occupational disease prevention and control situation, the lack of efficient supervision and regulation methods has become a prominent contradiction. This paper reviewed the progress and application of occupational health grading and classification supervision methods for employers in China in recent years, and analyzed the characteristics and limitations of selected methods. The grading and classification supervision methods have gradually developed from considering only inherent health risk of occupational disease hazards, to considering both inherent attributes of occupational disease hazards and exposure duration. Some regional authorities introduced trial measures for grading and classification of occupational health supervision by embracing exposure level of an occupational disease hazard of interest, associated outcome severity, and occupational health management situation of targeted employers. In October 2022, the National Disease Control and Prevention Bureau issued the Notice on Carrying out Pilot Work of Occupational Health Classification Supervision and Law Enforcement, which further promoted the establishment of a differentiated occupational health supervision model. Grading and classification of occupational health supervision can improve the supervision efficiency of public health administration departments and promote employers to fulfill the main responsibility of occupational disease prevention and control.
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【Objective】 To determine the ELISA kit for screening convalescence plasma with high potency of SARS-CoV-2 IgG by comparing and analyzing the plasma detection results of convalescent plasma collected in different periods via ELISA kits from two manufacturers and the results of mixed plasma with different potency via pseudovirus neutralization experiments. 【Methods】 Two ELISA kits from different manufacturers(named A, B) were used to detect the plasma of 269 convalescent patients collected from Feb.2020~Jan.2022. The correlation and concordance rate of the two results were analyzed to determine the kit preliminarily. According to the titers of diluted series of standard of the preliminary selected kit, 5 mixed plasma samples (G4-G128) with different potency were prepared. The correlation of ELISA IgG results of product A/B, as well as the pseudovirus neutralization test of the original strain, Omicron mutant BA.1 and BA.2 strains were analyzed. Combined with the outside-well dilution mode of the strongly positive samples, the kit for high potency of SARS-CoV-2 IgG screening was determined. 【Results】 When the internal control reference B2 was used as the standard, the detection sensitivity of product A and B was 1∶32 vs 1∶8; the detection sensitivity of product A was 4 times that of product B. The correlation Pearson r between the results given by two kits was 0.944 1(P<0.000 1). Product B with low sensitivity was primarily selected as an alternative kit. The ELISA IgG results of samples from mixed plasma showed that the order of correlation r between product A and B was 0.988. The correlation r between product A and neutralization antibody potency of the three viruses was original strain (0.978)>BA.2(0.970)>BA.1(0.799); the order of correlation r between ELISA IgG results of product B and neutralization antibody potency of the three viruses was original strain(0.994)>BA.2(0.968)>BA.1(0.804). If twice-diluted B2 was taken as the excellent standard, 55.4% of product B met the criterion, while 47.2% of product A met.For positive plasma with high IgG potency, the product B kit required a lower dilution of the sample, which was more convenient to operate. 【Conclusion】 Both of the ELISA IgG kit from product A and B can be used to screen IgG antibodies of SARS-CoV-2, while product B is more suitable for screening positive plasma with high IgG potency.
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【Objective】 To determine the best collection time period of plasma which can be used for human COVID-19 immunoglobulin for intravenous injection through SARS-CoV-2-IgG change and neutralizing antibody distribution against different virus strain in representative mixed plasma before and after Omicron strain infection by ELISA and pseudovirus neutralization test. 【Methods】 An ELISA method for quantitative detection of SARS-CoV-2-IgG was established and its linear range,accuracy and precision was verified. SARS-CoV-2-IgG potency was detected in 25 convalescent plasma which were collected 20-40 days after confirmed Omicron infection, two groups of mixed plasma samples WP1 and WP2 were prepared according to the SARS-CoV-2-IgG results, and pseudovirus neutralization experiments with different virus strain (prototype strain, BA. 1,BA.2, BA.4/5, BF.7, BQ.1.1) were carried out to determine the distribution of neutralizing antibodies against different virus strain. SARS-CoV-2-IgG potency of representative mixed plasma collected from 14 plasma stations subordinate to the company before and after Omicron strain infection was detected, including Omicron convalescent plasma (OP) collected from different plasma stations from December 2022 to May 2023 and normal pool plasma (VN) feed in March 2023 which collected from March 2022 to December 2022. According to the results, the difference and the change rule with time of SARS-CoV-2-IgG before and after Omicron strain infection were analyzed. 【Results】 The linearity of SARS-CoV-2-IgG ranged from 6.25 to 200 EIU/mL, the accuracy in-batch ranged from 81.793% to 106.985%, the precision in-batch ranged from 1. 100% to 13.000%, and the total error in-batch ranged from 2.988% to 22.679%. The accuracy between batches ranged from 90.788%to 96.893%, the precision between batches ranged from 4.870% to 6.272%, and the total error between batches ranged from 9.192% to 15.399%. The results of pseudovirus neutralizing antibody showed that the potency of different virus strain neutralizing antibodies were in the order of prototype strain>BA.2>BA.4/5>BF.7≈ BQ.1.1>BA.1 and the correlation between WP1 and WP2 was high (Pearson r=0. 931 1, P=0.002 3) which indicated that the potency distribution of neutralizing antibodies of different virus strain in Omicron convalescent plasma was basically stable. Compared with the mixed convalescent plasma sample G128 collected in June 2022, the potency of Omicron neutralizing antibodies of WP series were significantly higher, the ratio of BA.2 antibody to prototype antibody increased from 26.9% (before infection) to 82.6%-87.5% (after infection). The results of VN series before Omicron infection were < 100 EIU/mL, and the results of OP series after Omicron infection showed that the plasma collected from the beginning of December 2022 was the peak of antibody in the same month,and then dropped sharply, entering a short plateau in February-March 2023 (potency was about 40% of the peak value),and then dropped sharply again in April (potency was about 20% of the peak value). 【Conclusion】 The potency and proportion of neutralizing antibody against Omicron subtype in convalescent plasma after COVID-19 Omicron strain infection increased significantly. IgG antibody of plasma donors in different regions reached its peak in the month of infection, then continued to dropped sharply. The best collection period of plasma that can be used for human COVID-19 immunoglobulin for intravenous injection was 1 to 2 months after infection.
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Osteochondral lesion of talus (OLT) is a foot and ankle disease characterized by ankle pain, which may impact the joint function and life quality. If managed improperly, it may lead to a further ankle arthritis, severely compromising the prognosis. The therapeutic effect of conservative treatment for OLT is still uncertain. Surgery is still the main treatment modality for OLT with various techniques. However, the optimized surgical technique is still inconclusive, furthermore, regeneration and repair of cartilage after debridement is also a great challenge for the treatment of OLT. Platelet-rich plasma (PRP) with good repair effect on cartilage injury is gradually applied in the treatment of OLT. However, there still lacks the unified understanding of the technique and specification of PRP for the treatment of OLT. Therefore, National Orthopedics Center of Shanghai Sixth People′s Hospital allied Foot Ankle Basic Research & Orthopedics Group, Chinese Association of Orthopedic Surgeons; Foot and Ankle Committee of Chinese Association of Sports Medicine Physicians; and Foot and Ankle Group of Orthopedic Specialized Branch of Shanghai Medical Association to organize related experts to formulate the Expert consensus on platelet- rich plasma treatment for osteochondral lesion of talus ( version2023). Fifteen recommendations were put forward upon PRP preparation, indications, contraindications and treatment methods of PRP for OLT, so as to standardize the PRP treatment for OLT.
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Background Liver damage presented in endemic arsenic poisoning is usually serious. Studies have shown that oxidative stress, proteasome beta 5 subunit (PSMB5), regulatory transcription factor EB (TFEB), and lysosomes are associated with liver injury, but their specific links to arsenic-induced liver injury remain unclear. Objective Using a sodium arsenite (NaAsO2)-induced rat liver injury model established earlier by the research group, the expressions of PSMB5, TFEB, and lysosomal associated membrane protein 1 (LAMP1) in liver tissues were detected. Methods Twenty-four SPF Wistar rats were randomly divided into control group, and low, medium, and high dose groups, with 6 rats in each group, half male and half female. The exposure concentrations were 0, 25, 50, and 100 mg·L−1 NaAsO2 solutions for 24 weeks. At the end of the experiment, liver was dissected after rats were anesthetized. The levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), total bile acid (TBA), and catalase (CAT) in liver tissues were detected by chemical colorimetry, and the levels of lipid peroxide (LPO), 4-hydroxynonenal (4-HNE), LAMP1, and cathepsin D (CTSD) in liver tissues were detected by enzyme-linked immunosorbent assay (ELISA); the transcriptional expression levels of PSMB5 and TFEB in liver tissues were detected by real-time fluorescence quantitative PCR (RT-qPCR), and the protein expressions of PSMB5, TFEB, and phosphorylated TFEB (p-TFEB) in liver tissues were detected by immunohistochemistry. Results The results of chemical colorimetry and ELISA showed that compared with the control group, the liver homogenate levels of ALP, TBA, and LAMP1 of each arsenic-exposed group, the ALT and LPO in the medium and high concentration groups, the 4-HNE and CTSD in the high concentration group were increased, while the CAT activity of each arsenic-exposed group was decreased (P<0.05). The results of real-time fluorescence quantitative PCR showed that the transcription levels of PSMB5 and TFEB in the liver tissues of each arsenic-exposed group were decreased compared with those of the control group (P<0.05). The results of immunohistochemistry showed that compared with the control group, the expression of PSMB5 of each arsenic-exposed group were decreased, the expression of TFEB in the medium and high concentration groups was decreased, while the expression of p-TFEB of each arsenic-exposed group was increased (P<0.05). The expression of TFEB protein gradually decreased in the nucleus, while the expression of p-TFEB protein gradually increased in the cytoplasm, but no expression of p-TFEB was found in the nucleus. The results of Pearson correlation analysis showed that PSMB5 in liver tissues was positively correlated with CAT (r=0.818, P＜0.05), and negatively correlated with 4-HNE and p-TFEB (r=−0.582, r=−0.899; P＜0.05); TFEB was negatively correlated with CTSD and LAMP1 (r=−0.457, r=−0.564; P＜0.05); CTSD was positively correlated with ALT and ALP (r=0.529, r=0.485; P＜0.05). Conclusion Long-term exposure to NaAsO2 can induce oxidative stress, inhibit the expression of PSMB5 and TFEB, promote the accumulation of p-TFEB in the cytoplasm, decrease the nuclear entry of active TFEB, damage the lysosome, and cause liver damage.
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The existing measuring methods of noise exposure on the basis of equal energy hypothesis are applicable to Gaussian noise while not fully applicable to non-Gaussian noise. Studies have shown that temporal structure (kurtosis) combined with noise energy has the potential to quantify non-Gaussian noise exposure effectively. However, there is no unified measuring method adopting this joint metric. In this paper, the measuring method of non-Gaussian noise exposure based on kurtosis adjustment was introduced, detailing measurement indicators, adjustment schemes, applicable objects, instrument requirements, and measurement steps. Adjusting the exposure duration of cumulative noise exposure (CNE) by kurtosis or adjusting the equivalent continuous A-weighted sound pressure level (LAeq) by an adjustment coefficient based on animal or population studies can more accurately quantify workers' exposure to non-Gaussian noise and improve the underestimation of hearing loss caused by non-Gaussian noise. A large number of population studies are warranted in the future to verify the effectiveness of these two adjustment schemes.
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Antibiotic exposure-induced dysbiosis of the intestinal flora increases the risk of developing allergic rhinitis. Hence, regulating the balance of intestinal flora may be useful for preventing and treating allergic rhinitis. However, the underlying mechanism is unclear. Dendrobium nobile (Shihu) exhibits anti-inflammatory and immune activities. Hence, in this study, we investigated the mechanism via which Shihu may improve allergic rhinitis. Mouse models of allergic rhinitis with intestinal flora dysbiosis (Model-D, antibiotics induce intestinal flora dysbiosis with ovalbumin-induced allergy) and normal intestinal flora with allergic rhinitis (Model-N, ovalbumin-induced allergy) were established. The effect of Shihu on intestinal flora and inflammation caused during allergic rhinitis were analyzed. Allergic symptoms, infiltration of hematoxylin and eosin in the lungs and nose, and the release of various factors [interleukin (IL)-2, IL-4, IFN-γ, IL-6, IL-10, and IL-17] in the lungs were evaluated. The results indicate that intestinal flora dysbiosis exacerbated lung and nose inflammation in allergic rhinitis. However, treatment with the Shihu extract effectively reversed these symptoms. Besides, the Shihu extract inhibited the PI3K/AKT/mTOR pathway and increased the level of Forkhead box protein in the lungs. Additionally, the Shihu extract reversed intestinal flora dysbiosis at the phylum and genus levels and improved regulator T cell differentiation. Furthermore, in the Model-D group, the Shihu extract inhibited the decrease in the diversity and abundance of the intestinal flora. Screening was performed to determine which intestinal flora was positively correlated with Treg differentiation using Spearman's correlation analysis. In conclusion, we showed that Shihu extract restored the balance in intestinal flora and ameliorated inflammation in the lungs of allergic rhinitis mice and predicted a therapeutic new approach using Traditional Chinese Medicine to improve allergic rhinitis.
Subject(s)
Animals , Mice , Cytokines/metabolism , Dendrobium , Disease Models, Animal , Drugs, Chinese Herbal/pharmacology , Dysbiosis/drug therapy , Gastrointestinal Microbiome , Inflammation/drug therapy , Mice, Inbred BALB C , Ovalbumin , Phosphatidylinositol 3-Kinases , Pneumonia , Rhinitis, Allergic/metabolismABSTRACT
Background A prominent feature of endemic arsenic poisoning is severe liver damage. Studies have found that liver injury is closely related to oxidative stress, lysosomes, and autophagy. Objective Through establishing a liver injury model of rats by sodium arsenite (NaAsO2)administration in drinking water, this experiment is designed to explore the roles of oxidative stress, lysosomes, and AMP activated protein kinase (AMPK)/Unc-51 like kinase 1 (ULK1) pathway in this model. Methods Twenty-four Wistar rats were randomly divided into four groups with six rats in each group (half male and half female), including control group and 25, 50, 100 mg·L−1 NaAsO2 groups. A rat liver injury model was established by drinking water containing NaAsO2 freely for 24 weeks. Then liver of rats was dissected after sacrificed, and the levels of alanine aminotransferase (ALT), alkaline phosphatase (ALP), and total bile acid (TBA), catalase (CAT), lipid peroxidation (LPO), and total antioxidant capacity (T-AOC) in liver tissues were detected by assay kits. The levels of lysosomal-associated membrane protein 2 (LAMP2), cathepsin B (CTSB), and acid phosphatase (ACP2) were determined by enzyme linked immunosorbent assay. The mRNA transcriptional expressions of AMPK, ULK1, microtubule-associated protein light chain 3 (LC3), and sequestosome 1 (p62) were detected by real-time fluorescence quantitative PCR (RT-qPCR). The protein expressions of p-AMPK, p-ULK1, LC3, and p62 were detected by immunohistochemistry. Results Following the NaAsO2 administration, significant differences were found in the levels of ALT, ALP, and TBA among the designed groups (F=12.09, 72.11, and 23.58, P<0.05). Compared with the control group, the levels of ALT in the 50mg·L−1 and 100 mg·L−1 NaAsO2 groups were increased (P<0.05); the levels of ALP and TBA in the 25, 50, and 100 mg·L−1 NaAsO2 groups were increased (P<0.05); the level of LPO in the 100 mg·L−1 group was increased (P<0.05); the levels of CAT and T-AOC in the 25, 50, and 100 mg·L−1 NaAsO2 groups were decreased (P<0.05). According to the results of enzyme linked immunosorbent assay, the levels of ACP2 in the 25, 50, and 100 mg·L−1 NaAsO2 groups, the level of CTSB in the 100 mg·L−1 NaAsO2 group, and the levels of LAMP2 in the 50 and 100 mg·L−1 NaAsO2 groups were decreased compared with the control group (P<0.05). Based on the results of RT-qPCR and immunohistochemistry, the mRNA transcriptional and protein expressions of AMPK, ULK1, and LC3 in some arsenic groups were elevated to varying degrees compared with the control group, and the increment in the 100 mg·L−1 NaAsO2 group was significant for all the indicators (P<0.05); the mRNA transcriptional expressions of p62 in the three arsenic groups and the protein expressions of p62 in the 50 and 100mg·L−1 NaAsO2 groups also increased compared with the control group (P<0.05). Besides, the results of Pearson correlation analysis showed that there was a positive correlation of T-AOC with LAMP2, CTSB, and ACP2 (r=0.651, 0.673, 0.626; P<0.05), a negative correlation of LPO with CTSB and ACP2 (r=−0468, −0.482; P<0.05), a negative correlation of p62 with LAMP2, CTSB, and ACP2 (r=−0.57, −0.626, −0.591; P<0.05), and a positive correlation of p62 with ALT, ALP, and TBA (r=0.709, 0.897, and 0.857, P<0.05). Conclusion Long-term arsenic exposure may induce oxidative stress, damage lysosomes, and activate the AMPK/ULK1 pathway, which can lead to the blockage of autophagy process, and eventually result in liver damage.
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Objective:To evaluate the medium and long-term clinical efficacy of the treatment of lumbar degenerative diseases in Dynesys dynamic internal fixation combined with decompression.Methods:From March 2008 to March 2015, 145 patients (84 males and 61 females, mean age 55.9±7.1 years old) with symptoms of lumbar degenerative diseases (69 lumbar disc herniation, 53 lumbar spinal stenosis and 23 I grade lumbar degenerative spondylolisthesis) were treated by the lumbar discectomy using Dynesys dynamic internal fixation combined with decompression. The clinical symptoms before and after surgery were assessed by visual analogue scale (VAS), Japanese Orthopaedic Association (JOA) and Oswestry disability index (ODI). Lumbar lateral radiographs were used to measure the height of intervertebral space between the surgical segment and the adjacent segment. The range of motion (ROM) between the surgical segment and the adjacent segment was measured by lumbar dynamic position X-ray. Surgical and adjacent segments degenerative were classified according to the Pfirrmann grade classification.Results:The VAS score, ODI and JOA score of lower back and lower limbs in patients with lumbar disc herniation were improved from 6.6±1.7, 7.1±1.4, 63.1%±10.2%, 12.5±2.4 preoperatively to 2.6±1.0, 2.8±0.9, 30.9%±9.8%, 22.4±2.1 at the latest follow-up. The differences were statistically significant. The VAS score, ODI score and JOA score of lower back and lower limbs in patients with lumbar spinal stenosis were improved from 6.3±2.2, 6.9±1.3, 63.4%±8.5%, 12.8±2.7 preoperatively to 2.4±1.2, 2.8±1.0, 35.1%±12.0%, 22.2±2.2 at the latest follow-up. The differences were statistically significant. The VAS score, ODI score and JOA score of lower back and lower limbs in patients with I degree lumbar degenerative spondylolisthesis were improved from 5.7±2.3, 6.7±0.9, 65.7%±10.0%, 12.5±2.7 preoperatively to 2.2±1.2, 2.7±1.1, 37.0%±11.8%, 22.4±2.6 at the latest follow-up. The differences were statistically significant. Comparing to preoperational value, the height of the operative segment and caudal intervertebral space were decreased at the 1 year postoperatively and last follow-up. But the difference was not significant. As for cranial adjacent segment, the height of intervertebral space preoperatively was decreased from 12.1±1.9 mm preoperatively to 11.7±1.6 mm at 1 year postoperatively, and to 11.3±1.8 mm at the latest follow-up. The difference between them was statistically significant ( F=6.46, P=0.001). The ROM of surgical segments was decreased from 7.6°±2.2° preoperatively to 5.5°±1.6° at 1 year postoperatively, and to 2.9°±1.4° at the latest follow-up. The difference between them was statistically significant ( F=267.9, P<0.001). Conversely, the ROM of cranial and caudal segments was increased from 8.2°±2.4°, 6.5°±1.6° preoperatively to 9.1°±2.1°, 7.1°±1.9° at 1 year postoperatively, and to 10.6°±2.5°, 7.2°±1.8° at the latest follow-up. The difference between them was statistically significant ( F=38.66, 3.81, P<0.001, 0.023). At the latest follow-up, 120 (51.9%) adjacent segments were to be defined adjacent segment degeneration which includes 103 radiological adjacent segment degeneration and 17 symptomatic adjacent segment degenerations. Conclusion:Dynesys dynamic internal fixation combined with decompression could achieve satisfying mid- and long-term therapeutic effect in the treatment of lumbar degenerative diseases. The ROM of surgical segments decreased with time, although part of the ROM was still retained at the latest follow-up. However, it does not seem to avoid the degeneration of adjacent segment.
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Objective:To study the effects of radiotherapy and the prognostic factors in hepatocellular cancer (HCC) patients with cardiophrenic angle or superior diaphragmatic lymph nodes metastasis (LNM).Methods:We retrospectively analyzed 56 HCC patients with cardiophrenic angle or superior diaphragmatic LNM who were treated with or without external beam radiation therapy (EBRT) in Zhongshan Hospital of Fudan University from Jan 2010 to Aug 2020. Patients were divided into two groups according to whether they received radiotherapy, EBRT group and non-EBRT group, and each group had 28 patients. Radiation fields included or excluded primary tumor in EBRT group, and the cardiophrenic angle or superior diaphragmatic LNM did not receive any local treatment in non-EBRT group. The response rate, survival rate, local control rate, prognostic risk factors of the two groups were studied.Results:After EBRT, the partial response rate and complete response rate were 32.1%(9/28) and 32.1%(9/28). The median survival rate of EBRT group was 16.1 months (95% CI 9.00-23.21, RR=3.63) vs. 6.9 months (95% CI 4.63-8.77, RR=1.06) for the non-EBRT group, with statistically significant difference ( χ2=15.53, P<0.05). Cardiophrenic angle or superior diaphragmatic lymph nodes 1-year local control rate for EBRT group and non-EBRT group were 37.0% vs. 10.7%, with statistically significant difference ( χ2=5.28, P<0.05). Since diagnosis of cardiophrenic angle or superior diaphragmatic LNM, 4 patients (14.3%) in the EBRT group vs. 13 patients (46.4%) in the non-EBRT group had higher alpha-fetoprotein (AFP) level after 3 months compared with the AFP before EBRT ( χ2=6.84, P<0.05). Multivariate analysis showed that multiple intrahepatic tumors, maximal diameter of intrahepatic tumors >5 cm, AFP≥400 μg/L, no EBRT were poor prognostic factors. Conclusions:EBRT can prolong overall survival and improve the control rate of lymph node of HCC patients with cardiophrenic angle or superior diaphragmatic LNM. Patients with multiple intrahepatic tumors, maximal diameter of intrahepatic tumors >5 cm, AFP≥400 μg/L and no EBRT have poor prognosis.
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Objective:To explore the effects of Ginkgo biloba on regulating NF-E2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1)-antioxidant response element (ARE) signaling pathway in liver injury induced by coal-burning-borne endemic arsenic poisoning in rats.Methods:Group design method was adopted, according to body weight (80-100 g), a total of 30 Wistar rats were divided into 5 groups (6 rats in each group, half males and half females) by random number table method. The normal control group was fed with normal diet ad libitum for 4.5 months; the Ginkgo biloba control group was fed with Ginkgo biloba (25 mg/kg, 6 d/week) for 1.5 months after normal feeding for 3 months; the drinking water arsenic poisoning group and the arsenic contaminated grain group were fed respectively with 100 mg/L arsenic trioxide (As 2O 3) solution and 100 mg/kg arsenic-containing feed for 3 months, and then fed with normal diet for 1.5 months; the Ginkgo biloba treatment group was fed with 100 mg/kg arsenic-containing feed for 3 months, and then was given Ginkgo biloba (25 mg/kg, 6 d/week) for 1.5 months. After sacrificing the animals, the content of malondialdehyde (MDA), the activity of copper zinc superoxide dismutase (SOD1) and the activity of glutathione peroxidase (GPx) in serum were detected by thiobarbituric acid colorimetry, xanthine oxidase method and dimercaptodinitrobenzoic acid reduction method, respectively. The mRNA and protein expressions of indicator genes of Nrf2-Keap1-ARE signaling pathway in liver tissues were detected by quantitative real-time PCR, immunohistochemistry and Western blotting. Correlation between the indexes was analyzed by Pearson. Results:In drinking water arsenic poisoning group, arsenic contaminated grain group and Ginkgo biloba treatment group, the contents of MDA in serum were (3.54±0.51), (3.83±0.87) and (2.93±0.84) μmol/L, respectively, which were higher than that in normal control group [(1.85±0.36) μmol/L, P < 0.05]; and SOD1 activities [(68.21±4.37), (64.53±9.96), (73.09±5.43) U/ml] and GPx activities [(486.41±40.45), (458.24±42.25), (539.79±79.43) U/L] in serum were lower than those in normal control group [(81.47±5.73) U/ml, (747.86±80.33) U/L, P < 0.05]. Compared with the arsenic contaminated grain group, the content of MDA in serum in Ginkgo biloba treatment group was decreased, the activities of SOD1 and GPx in serum were increased ( P < 0.05). Compared with normal control group, the mRNA expressions of SOD1 and GPx1 in the liver tissues in drinking water arsenic poisoning group, arsenic contaminated grain group and Ginkgo biloba treatment group were significantly higher ( P < 0.05). Compared with arsenic contaminated grain group, the mRNA expressions of SOD1 and GPx1 in the liver tissue in Ginkgo biloba treatment group were increased ( P < 0.05). Compared with the normal control group, the protein expression of SOD1 in liver tissue in arsenic contaminated grain group was decreased ( P < 0.05), the protein expressions of GPx1 were decreased in the liver tissues in drinking water arsenic poisoning group, arsenic contaminated grain group and Ginkgo biloba treatment group ( P < 0.05). Compared with the arsenic contaminated grain group, the protein expressions of SOD1 and GPx1 were increased in the liver tissue in Ginkgo biloba treatment group ( P < 0.05). Compared with the normal control group and arsenic contaminated grain group, the protein expression of Keap1 was decreased in the liver tissue in Ginkgo biloba treatment group ( P < 0.05). Compared with the normal control group, the protein expressions of Nrf2 and phosphorylation of Nrf2 (pNrf2) were increased in the cytoplasm in drinking water arsenic poisoning group, arsenic contaminated grain group and Ginkgo biloba treatment group ( P < 0.05). Compared with the arsenic contaminated grain group, the protein expression of pNrf2 was decreased in the cytoplasm in Ginkgo biloba treatment group ( P < 0.05). The protein expressions of Nrf2 and pNrf2 in the nucleus in drinking water arsenic poisoning group, arsenic contaminated grain group and Ginkgo biloba treatment group were also higher than those in normal control group ( P < 0.05). Compared with the arsenic contaminated grain group, the protein expressions of Nrf2 and pNrf2 were increased in the nucleus in Ginkgo biloba treatment group ( P < 0.05). The results of correlation analysis revealed that the protein expressions of Nrf2 and pNrf2 in the nucleus were negatively correlated with Keap1 protein expression ( r=-0.523,-0.401, P < 0.05), and positively correlated with the mRNA expressions of SOD1 and GPx1 ( r=0.658, 0.530, 0.555, 0.603, P < 0.05). In addition, the protein expressions of SOD1 and GPx1 were positively correlated with their enzyme activities ( r=0.472, 0.629, P < 0.05). Conclusions:Arsenic could induce oxidative stress and liver injury. Ginkgo biloba could reduce the protein expression of Keap1, and promote nuclear translocation of Nrf2, which might induce the up-regulation of mRNA expressions of SOD1 and GPx1, and partially reverse the posttranscriptional regulation of arsenic on SOD1 and GPx1, and then increase their protein expressions and enzyme activities, thereby improve arsenic induced oxidative stress and liver injury.
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Objective:To explore the clinical effect and application value of simultaneous modulated accelerated radiotherapy (SMART) in the suspicious positive lymph nodes of head and neck.Methods:From January 2017 to February 2019, 60 patients with suspected positive lymph nodes in the head and neck in the Hanzhong Central Hospital of Shaanxi Province were divided into experimental group and control group according to different treatment plans, and 30 patients in each group were included. In the experimental group, 63.36 to 66.66 Gy patients were treated with SMART, while in the control group, 54.12 to 60.06 Gy patients were treated with conventional neck prophylactic radiation. In order to evaluate the feasibility of the method, the change of the short diameter of the largest cross section of the suspicious positive lymph nodes in the two groups were observed, and the adverse reactions in the treatment of the two groups were analyzed.Results:There was no significant difference between the two groups before treatment ( P>0.05). After treatment, the size of short diameter of lymph nodes in the two groups was smaller than that before treatment. The maximum short diameter of the largest cross section of lymph nodes in the experimental group was smaller than that before treatment: (0.43 ± 0.07) cm vs. (0.72 ± 0.10) cm, and the difference was statistically significant ( P<0.05). In the control group, the maximum short diameter of the largest cross section of lymph node decreased after treatment, and the difference was not statistically significant ( P>0.05). After treatment, the reduction of the short diameter in the experimental group was more obvious than that in the control group. The maximum short diameter of the largest cross section between the two groups: (0.43±0.07) cm vs. (0.66±0.08)cm was statistically significant ( t = 11.523, P<0.05). Before treatment, hemoglobin (HGB) levels of the two groups were in the normal physiological range, and there was no significant difference between the two groups ( P>0.05); the white blood cell (WBC) levels of the two groups at different time after treatment were compared: in the first week (7.83 ± 2.53) × 10 9/L vs. (8.26 ± 3.16) × 10 9/L, in the third week (7.14 ± 3.65) × 10 9/L vs. (7.08 ± 2.53) × 10 9/L, in the fifth week (5.47 ± 2.81) × 10 9/L vs. (6.41 ± 2.57) × 10 9/L, and in the seventh week (4.36 ± 2.59) × 10 9/L vs. (4.98 ± 1.64) × 10 9/L, and there were statistical differences ( P<0.05), which indicated that the WBC index levels of the two groups were gradually decreased during the treatment, and the decreased degree of the experimental group was higher than that of the control group. The levels of HGB and PLT were maintained in the normal physiological range before and after treatment, and there was no significant difference between the two groups ( P>0.05). The main complications in the treatment of the experimental group were xerostomia and stomatitis. The adverse reactions in the control group were pain in the target area of radiotherapy. There was no significant difference between the two groups ( P>0.05). Conclusions:The application of IMRT is an effective method for the treatment of occult lymph node metastasis, and it is also a therapeutic diagnostic method, which can provide evidence for the study of the law of lymph node metastasis in the head and neck. The safety and tissue tolerance of IMRT in the treatment of suspicious positive lymph nodes in the head and neck are good, which can be used for the suspicious lymph nodes in the head and neck. The treatment of positive lymph nodes and the evaluation of patients′ prognosis provide an effective way of clinical treatment.
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Objective:To compare the effect of SMOF lipids composed of soybean oil, medium chain triglycerides, olive oil, and fish oil with medium-long chain mixed fat emulsions(Lipofundin) on parenteral nutrition-associated cholestasis(PNAC) in premature infants.Methods:Clinical data were collected from premature infants hospitalized in the neonatal intensive care unit of Shanghai Children′s Hospital from January 2018 to December 2019 with gestational age ≤34 weeks, birth weight ≤2 000 g, and duration of parenteral nutrition ≥14 days.They were devided into SMOF lipid group and Lipofundin group, and the incidence of PNAC, neonatal necrotizing enterocolitis(NEC), bronchopulmonary dysplasia(BPD), retinopathy of prematurity(ROP), periventricular-intraventricular hemorrhage(PVH-IVH), late-onset sepsis and liver function were compared between two groups.Results:The incidence of PNAC in the SMOF lipid group was significantly lower than that in Lipofundin group( P=0.042). The average level of ALT and AST in SMOF lipid group were markedly lower than those in Lipofundin group( P<0.05). The time to reach full enteral feeding of SMOF lipid group was shorter than that of Lipofundin group( P=0.005). There was no significant difference in the incidence of NEC, BPD, ROP, PVH-IVH, and late-onset sepsis between two groups( P>0.05). Conclusion:Compared with lipofundin, SMOF lipid can reduce the incidence of PNAC in premature infants, and has no significant effect on the incidence of NEC, BPD, ROP, PVH-IVH and late-onset sepsis.
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Acute lung injury/acute respiratory distress syndrome (ALI/ARDS) is a respiratory disorder with high morbidity and mortality caused by various causes. Exosomes can mediate cell communication through paracrine pathways, transfer proteins, lipids, nucleic acids, etc., and interfere with the biological functions of recipient cells. Various cell-derived exosomes have been reported to play an immunomodulatory role in the ALI/ARDS inflammatory model. This article reviews the mechanism of exosomes involved in immune regulation of ALI/ARDS and possible therapeutic approaches.
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Neonatal intestinal microecology is unstable and susceptible to various factors such as bacterial exposure, conditions that promote and inhibit bacterial growth, and host factors.These factors affect the initial development of the immune system during a critical period known as the "neonatal window of opportunity" . Epidemiological investigations have found a link between the development of the immune system during the "neonatal window of opportunity" and immune-mediated diseases.Recent studies have found that the principal mechanism may be promoting the development and maturation of the intestinal mucosal barrier, influencing the maturation of lymphocytes, and establishing immune tolerance.This review summarizes the effects of neonatal intestinal microecology on immune development during the "neonatal window of opportunity" .
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The gut microbiota play an important role in the bidirectional interactions between the gut and the nervous system, which is called the microbiota-gut-brain axis.The short-chain fatty acids, neurotransmitters, Vagal nerve and the hypothalamus-pituitary-adrenal axis are different ways of affecting neurological diseases, including Alzheimer′s disease, Parkinson′s disease, depression disease; childhood autism and neonatal encephalopathy.Based on the studies of neurological diseases, this paper analyzes the role of gut microbiota in diseases, and provides a modern consideration for the further research and clinical application of microbiota-gut-brain axis.
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With the deepening of study of neonatal intestinal flora metabolomics, the relationship between short-chain fatty acids(SCFA)and neonatal digestive diseases has become the focus of domestic and foreign scholars.Short-chain fatty acids have an important impact on the occurrence and development of digestive diseases such as neonatal necrotizing enterocolitis by inhibiting the immune response, suppressing allergic and inflammatory reactions and affecting intestinal mucosal innate immune function and mucosal development, which providing research ideas for the diagnosis and treatment of such diseases.
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Objective:To investigate the effects of caspase-11 non-canonical inflammasome on the Leptospira interrogans ( L. interrogans)-induced secretion of inflammatory cytokines in J774A.1 cells. Methods:Murine mononuclear macrophage cells (J774A.1) were infected with L. interrogans strain 56601. Expression of caspase-11, IL-1β, IL-1α and IL-18 at mRNA level in J774A.1 cells were detected by real-time RT-PCR. The levels of caspase-11, IL-1β, IL-1α and IL-18 in the culture supernatants of J774A.1 cells were detected by ELISA. Results:Real-time RT-PCR showed that caspase-11 expression at mRNA level was 5.12, 14.21, 8.94, 14.06, 18.58 and 0.93 times of that in uninfected cells after 1, 2, 4, 8, 12 and 24 h of L. interrogans infection, and respectively decreased to 0.10, 0.07, 0.10, 0.09, 0.07 and 0.45 times after caspase-11 inhibitor intervention ( P<0.05). Expression of IL-1β, IL-1α and IL-18 at mRNA level was significantly increased after infection ( P<0.05). After the intervention with caspase-11 inhibitor, IL-1β mRNA decreased to 0.05, 0.03, 0.02, 0.05, 0.06 and 0.02 times ( P<0.05); IL-1α mRNA decreased to 0.14, 0.07, 0.15, 0.10, 0.03 and 0.06 times ( P<0.05); IL-18 mRNA decreased to 0.08, 0.10, 0.16, 0.18, 0.10 and 0.07 times ( P<0.05). ELISA results showed that the expression of caspase-11, IL-1β, IL-1α and IL-18 at protein level was significantly increased. After the intervention with caspase-11 inhibitor, caspase-11 level decreased to 43.07, 41.64, 51.96, 86.56, 105.36, and 129.95 pg/ml ( P<0.05); IL-1β level decreased to 15.01, 14.19, 68.02, 31.20, 173.13 and 104.98 pg/ml ( P<0.05); IL-1α level decreased to 12.14, 15.40, 38.01, 21.97, 24.48 and 27.09 pg/ml ( P<0.05); IL-18 level decreased to 96.27, 102.21, 85.34, 116.28, 155.36 and 114.03 pg/ml ( P<0.05). Conclusions:Caspase-11 non-canonical inflammasome was involved in the mediation of IL-1β, IL-1α and IL-18 secretion in mouse mononuclear macrophages after L. interrogans infection.