Investigation on the pharmacological mechanisms of Shirebi granules in treating gouty arthritis with damp-heat syndrome based on crosstalk of Wnt/β-catenin signaling / 药学学报

Gouty arthritis is a type of metabolic rheumatic disease caused by autoimmune abnormalities. Currently, the use of Western medicine in the clinical treatment of gouty arthritis has been associated with a high risk of adverse reactions. Therefore, there is a growing interest in exploring therapeutic drugs from traditional Chinese medicine as a potential alternative. According to the theory of traditional Chinese medicine, gouty arthritis has been classified as damp-heat arthralgia syndrome. Shirebi granules has been found to have good clinical efficacy in treating gouty arthritis. However, its underlying pharmacological mechanisms remain unclear. To address this problem, the study first established the interaction network of candidate targets for Shirebi granules, which is used to treat damp-heat syndrome of gouty arthritis. Then, the key candidate targets of Shirebi granules for treating gouty arthritis with damp-heat syndrome were screened by calculating the topological features of the network nodes. Then, the functional mining of the key candidate targets revealed that the candidate targets of Shirebi granules may intervene in the biological process of inflammatory response and lipid metabolism through the crosstalk of Wnt/β-catenin signaling. To verify the effectiveness of Shirebi granules in treating gouty arthritis with damp-heat syndrome, a rat model was established. The results demonstrated that the granules significantly improved the severity of arthritis in rats with this condition, reduced joint inflammation, gait score, swelling index, increased mechanical pain threshold (P < 0.05), and reduced the content of serum inflammatory factors IL-1β, IL-6, and TNF-α in gouty arthritis rats with damp-heat syndrome (P < 0.01) gouty. It was also found that Shirebi granules effectively alleviated the symptoms of dampness heat syndrome such as local joint fever and dry mouth by reducing the temperature of the joints in acute gouty arthritis with damp-heat syndrome (AD) rats, increasing the threshold of heat pain, increasing water intake (P < 0.01), and inhibiting abnormal changes in the content of fatty acid oxidation related enzymes (P < 0.01). Western blot analysis showed that Shirebi granules increased the protein expression levels of Wnt and β-catenin (P < 0.01) while decreasing the protein expression of p65, p-p65 and PPARγ (P < 0.01) in rats with gouty arthritis and damp-heat syndrome. The results showed that Shirebi granules may reverse the "inflammation-immune" imbalance and lipid metabolism disorder by regulating the crosstalk of Wnt/β-catenin signaling, and play a role in alleviating the severity of the disease. This study provides a methodological reference for elucidating the pharmacological mechanisms of traditional Chinese medicine formulas. It also presents research ideas for the appropriate clinical use of Chinese patent medicines and the development of new clinical drugs for gouty arthritis therapy. The animal welfare and experiment procedures of this study were performed in accordance with the regulations of the Experimental Animal Ethics Committee of Experimental Research Center, China Academy of Chinese Medical Sciences (grant No. ERCCACMS11-2302-08).

Incidence and prognosis of olfactory and gustatory dysfunctions related to infection of SARS-CoV-2 Omicron strain: a national multi-center survey of 35 566 population / 中华耳鼻咽喉头颈外科杂志

Objective: This cross-sectional investigation aimed to determine the incidence, clinical characteristics, prognosis, and related risk factors of olfactory and gustatory dysfunctions related to infection with the SARS-CoV-2 Omicron strain in mainland China. Methods: Data of patients with SARS-CoV-2 from December 28, 2022, to February 21, 2023, were collected through online and offline questionnaires from 45 tertiary hospitals and one center for disease control and prevention in mainland China. The questionnaire included demographic information, previous health history, smoking and alcohol drinking, SARS-CoV-2 vaccination, olfactory and gustatory function before and after infection, other symptoms after infection, as well as the duration and improvement of olfactory and gustatory dysfunction. The self-reported olfactory and gustatory functions of patients were evaluated using the Olfactory VAS scale and Gustatory VAS scale. Results: A total of 35 566 valid questionnaires were obtained, revealing a high incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain (67.75%). Females(χ2=367.013, P<0.001) and young people(χ2=120.210, P<0.001) were more likely to develop these dysfunctions. Gender(OR=1.564, 95%CI: 1.487-1.645), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), oral health status (OR=0.881, 95%CI: 0.839-0.926), smoking history (OR=1.152, 95%CI=1.080-1.229), and drinking history (OR=0.854, 95%CI: 0.785-0.928) were correlated with the occurrence of olfactory and taste dysfunctions related to SARS-CoV-2(above P<0.001). 44.62% (4 391/9 840) of the patients who had not recovered their sense of smell and taste also suffered from nasal congestion, runny nose, and 32.62% (3 210/9 840) suffered from dry mouth and sore throat. The improvement of olfactory and taste functions was correlated with the persistence of accompanying symptoms(χ2=10.873, P=0.001). The average score of olfactory and taste VAS scale was 8.41 and 8.51 respectively before SARS-CoV-2 infection, but decreased to3.69 and 4.29 respectively after SARS-CoV-2 infection, and recovered to 5.83and 6.55 respectively at the time of the survey. The median duration of olfactory and gustatory dysfunctions was 15 days and 12 days, respectively, with 0.5% (121/24 096) of patients experiencing these dysfunctions for more than 28 days. The overall self-reported improvement rate of smell and taste dysfunctions was 59.16% (14 256/24 096). Gender(OR=0.893, 95%CI: 0.839-0.951), SARS-CoV-2 vaccination status (OR=1.334, 95%CI: 1.164-1.530), history of head and facial trauma(OR=1.180, 95%CI: 1.036-1.344, P=0.013), nose (OR=1.104, 95%CI: 1.042-1.171, P=0.001) and oral (OR=1.162, 95%CI: 1.096-1.233) health status, smoking history(OR=0.765, 95%CI: 0.709-0.825), and the persistence of accompanying symptoms (OR=0.359, 95%CI: 0.332-0.388) were correlated with the recovery of olfactory and taste dysfunctions related to SARS-CoV-2 (above P<0.001 except for the indicated values). Conclusion: The incidence of olfactory and taste dysfunctions related to infection with the SARS-CoV-2 Omicron strain is high in mainland China, with females and young people more likely to develop these dysfunctions. Active and effective intervention measures may be required for cases that persist for a long time. The recovery of olfactory and taste functions is influenced by several factors, including gender, SARS-CoV-2 vaccination status, history of head and facial trauma, nasal and oral health status, smoking history, and persistence of accompanying symptoms.

A multi-center study on evaluation of leukocyte differential performance by an artificial intelligence-based Digital Cell Morphology Analyzer / 中华检验医学杂志

Objective:To evaluate the performance of an artificial intelligent (AI)-based automated digital cell morphology analyzer (hereinafter referred as AI morphology analyzer) in detecting peripheral white blood cells (WBCs).Methods:A multi-center study. 1. A total of 3010 venous blood samples were collected from 11 tertiary hospitals nationwide, and 14 types of WBCs were analyzed with the AI morphology analyzers. The pre-classification results were compared with the post-classification results reviewed by senior morphological experts in evaluate the accuracy, sensitivity, specificity, and agreement of the AI morphology analyzers on the WBC pre-classification. 2. 400 blood samples (no less than 50% of the samples with abnormal WBCs after pre-classification and manual review) were selected from 3 010 samples, and the morphologists conducted manual microscopic examinations to differentiate different types of WBCs. The correlation between the post-classification and the manual microscopic examination results was analyzed. 3. Blood samples of patients diagnosed with lymphoma, acute lymphoblastic leukemia, acute myeloid leukemia, myelodysplastic syndrome, or myeloproliferative neoplasms were selected from the 3 010 blood samples. The performance of the AI morphology analyzers in these five hematological malignancies was evaluated by comparing the pre-classification and post-classification results. Cohen′s kappa test was used to analyze the consistency of WBC pre-classification and expert audit results, and Passing-Bablock regression analysis was used for comparison test, and accuracy, sensitivity, specificity, and agreement were calculated according to the formula.Results:1. AI morphology analyzers can pre-classify 14 types of WBCs and nucleated red blood cells. Compared with the post-classification results reviewed by senior morphological experts, the pre-classification accuracy of total WBCs reached 97.97%, of which the pre-classification accuracies of normal WBCs and abnormal WBCs were more than 96% and 87%, respectively. 2. The post-classification results reviewed by senior morphological experts correlated well with the manual differential results for all types of WBCs and nucleated red blood cells (neutrophils, lymphocytes, monocytes, eosinophils, basophils, immature granulocytes, blast cells, nucleated erythrocytes and malignant cells r>0.90 respectively, reactive lymphocytes r=0.85). With reference, the positive smear of abnormal cell types defined by The International Consensus Group for Hematology, the AI morphology analyzer has the similar screening ability for abnormal WBC samples as the manual microscopic examination. 3. For the blood samples with malignant hematologic diseases, the AI morphology analyzers showed accuracies higher than 84% on blast cells pre-classification, and the sensitivities were higher than 94%. In acute myeloid leukemia, the sensitivity of abnormal promyelocytes pre-classification exceeded 95%. Conclusion:The AI morphology analyzer showed high pre-classification accuracies and sensitivities on all types of leukocytes in peripheral blood when comparing with the post-classification results reviewed by experts. The post-classification results also showed a good correlation with the manual differential results. The AI morphology analyzer provides an efficient adjunctive white blood cell detection method for screening malignant hematological diseases.

Neuroprotection and potential mechanism of xenon on neonatal hypoxic-ischemic encephalopathy / 中华围产医学杂志

Neonatal hypoxic-ischemic encephalopathy often causes long-term adverse effect on neurological system or even death in near-term or full-term infants, but no effective treatment is available currently. Studies have shown that xenon can reduce brain injury caused by hypoxia-ischemia and is promising in clinical practice. The possible mechanisms include antagonism to glutamic acid receptors, anti-apoptosis, promotion of cell repair and xenon preconditioning. This article reviews the mechanism and research progress on neuroprotection effect of xenon in the treatment of neonatal hypoxic-ischemic encephalopathy.

Current situation of parturiophobia and its correlation with prenatal preferred delivery mode in Changning District, Shanghai / 中华围产医学杂志

Objective:To analyze the prevalence of parturiophobia and its association with preferred mode of delivery in pregnant women in Changning District, Shanghai.Methods:A cross- sectional study was conducted among 1 560 pregnant women in the third trimester who had their antenatal examination in Changning Maternity and Infant Health Hospital from September 2020 to March 2021. Fear of childbirth was measured with a validated Chinese version of Wijma Delivery Expectancy/Experience Questionnaire version A (W-DEQ-A). Based on the W-DEQ-A scores, the participants were divided into two groups: non-clinical parturiophobia group [<85 scores, including mild (≤37 scores), moderate (38-65 scores) and severe (66-84 scores) parturiophobia] and clinical parturiophobia group (≥85 scores). Rank-sum test, Chi-square test and t-test were used for univariate analysis. Multivariate binary logistic regression was used to analyze the factors associated with fear of childbirth and its relationship with preferred mode of delivery. Results:The detection rates of mild, moderate, severe and clinical parturiophobia were 18.8% (294/1 560), 44.9% (700/1 560), 31.1% (485/1 560) and 5.2% (81/1 560), respectively. Multivariate binary logistic regression showed that the participants who were supported by relatives and friends to have cesarean section ( OR=3.45, 95% CI: 1.29-9.22) or had antenatal anxiety ( OR=4.73, 95% CI: 2.49-8.97) were more likely to have clinical parturiophobia, while those with planned pregnancy ( OR=0.49, 95% CI: 0.29-0.82), high intensity physical activity ( OR=0.36, 95% CI: 0.18-0.72) or better/well understanding of the delivery process ( OR=0.42, 95% CI: 0.19-0.97) were less likely to develop clinical parturiophobia (all P<0.05). Compared with the non-clinical parturiophobia women, those with clinical parturiophobia were more likely to choose cesarean section ( OR=2.15, 95% CI: 1.22-3.78, P=0.008). Conclusions:The detection rates of severe and clinical parturiophobia are 31.1% and 5.2% in Changning District, Shanghai. The associated factors mainly include the attitudes of relatives and friends towards the mode of delivery, antenatal anxiety, planned pregnancy or not, physical activity level and the understanding of delivery process. Clinical parturiophobia might be an important factor for cesarean section on maternal request.

Focus on genetic modifiers of polyglutamine diseases / 中华神经科杂志

Polyglutamine (PolyQ) diseases are a group of clinically and genetically heterogeneous neurodegenerative diseases, due to an expanded CAG repeat in a coding region of the respective genes leading to neurodegenerative phenotypes by selective neuronal loss. Overall, only part of variance (50%-70%) in age at onset is explained by (CAG)n length, suggesting genetic modifying factors independent of (CAG)n size may contribute to clinical heterogeneity. Here, the research history of genetic modifiers in polyQ diseases is reviewed, and the major findings and current research status are discussed.

Omalizumab for the treatment of 74 patients with chronic spontaneous urticaria accompanied by other allergic diseases: a clinical analysis / 中华皮肤科杂志

Objective:To evaluate the clinical efficacy of omalizumab in the treatment of patients with chronic spontaneous urticaria accompanied by other allergic diseases.Methods:Clinical data were retrospectively collected from 74 patients, who were clinically diagnosed with chronic spontaneous urticaria and other allergic diseases, and received subcutaneous injections of omalizumab in the Department of Allergy, Tianjin Medical University General Hospital from June 2020 to September 2022. Types of allergic diseases, serum total IgE (tIgE) and allergen-specific IgE (sIgE) levels before treatment, treatment outcomes and adverse drug reactions were analyzed. Differences before and after treatment were assessed using paired t-test and Wilcoxon signed-rank sum test. Results:A total of 74 patients with chronic spontaneous urticaria were involved, including 29 with complicated allergic asthma (39.2%) , 61 with complicated allergic rhinitis (82.4%) , 6 with complicated atopic dermatitis (8.1%) , and 4 with food allergy (5.4%) . Before treatment, elevated serum tIgE or sIgE levels were observed in 44 (59.5%) patients. After the first omalizumab treatment, the urticaria control test (UCT) score significantly increased compared with that before treatment (16.00 [13.0.0, 16.00] vs. 6.00 [5.75, 9.00], Z = 7.39, P < 0.001) ; after 4 sessions of the omalizumab treatment, 82.5% (33/40) of the patients achieved complete control of urticaria symptoms or showed complete response. After omalizumab treatment, asthmatic attacks were decreased in 29 patients with allergic asthma, and asthma control test (ACT) scores significantly increased compared with those before treatment (21.07 ± 2.88 points [after the first treatment] vs. 18.48 ± 3.20 points [before treatment], t = 8.87, P < 0.001) ; among 61 patients with allergic rhinitis, global rhinitis symptom-based visual analog scale (VAS) scores (before treatment: 5.89 ± 1.29 points; after the first treatment: 3.28 ±1.46 points) and rhinoconjunctivitis quality of life questionnaire (RQLQ) scores (before treatment: 60.10 ± 20.53 points; after the first treatment: 37.26 ± 18.83 points) both significantly decreased after the first treatment ( t = 15.04, 10.01, respectively, both P < 0.001) , and rhinitis symptoms were relieved at the same time; skin itching was relieved in 4 patients with atopic dermatitis, and allergic symptoms after contact with food allergens were also relieved in the 2 patients with food allergy after omalizumab treatment. During the treatment, only 1 patient experienced erythematous swelling, induration, and pain at the injection site. Conclusions:In the treatment of chronic spontaneous urticaria accompanied by allergic diseases, the use of omalizumab not only effectively improved urticaria symptoms, but also well controlled allergic diseases, with a good safety profile. Multiple benefits may be achieved by the use of omalizumabin in patients with chronic spontaneous urticaria accompanied by other allergic diseases.

Improved ability of demonstrating ocular masses on 3.0 T MR scanner combined with an 8-channel eye surface phased array coil: a multi-center study / 中华放射学杂志

Objective:To investigate the value of the 8-channel eye surface phased array coil in improving image quality and demonstrating ocular masses on 3.0 T MR scanner.Methods:From July 2018 to January 2020, the data of orbital MRI in 692 patients with ocular masses on 6 medical centers were prospectively collected. The patients were simple randomly assigned into 8-channel eye surface phased array coil group (413 patients) or 8-channel head phased array coil group (279 patients), with the same MRI sequences. The signal to noise ratio (SNR) and contrast to noise ratio (CNR) were calculated in orbital anatomy structures and masses (eyelid mass, intraocular mass, lacrimal mass and orbital mass). The image quality scores including motion artifact, mass margin, the relationship between the mass and adjacent structures, and overall image quality were recorded. The differences of image quality between the two groups were compared by two independent sample t-test or Wilcoxon rank test. Results:The SNR and CNR were higher in eye surface coil group than those in head coil group ( P<0.05). The scores of ocular movement artifacts were higher in head coil group than those in surface coil group ( P<0.05). The scores of intraocular mass margin, the relationship between the mass and adjacent structures, and overall image quality were higher in surface coil group than those in head coil group ( P<0.001). There were no significant differences in mass margin, the relationship between the mass and adjacent structures, and overall image quality scores of eyelid, lacrimal gland, and orbital mass between the two groups ( P>0.05). Conclusion:3.0 T MR scanner combined with the 8-channel eye surface phased array coil can improve the SNR and CNR of orbital MR images, the demonstration of the intraocular mass margin and the relationship between the mass and adjacent structures.

Clinical characteristics and risk factors for severe disease of hemorrhagic fever with renal syndrome in underage patients / 中华传染病杂志

Objective:To analyze the clinical characteristics and risk factors for severe disease of hemorrhagic fever with renal syndrome (HFRS) in underage patients, and to construct the severe disease risk model.Methods:A total of 170 HFRS patients (<18 years old) from the Second Affiliated Hospital of Air Force Medical University (153 cases) and the Second Affiliated Hospital of Xi′an Jiaotong University (17 cases) from January 2009 to December 2021 were included. According to the severity of the disease, the patients were divided into mild and severe groups. Baseline demographic data, symptoms, signs, laboratory examination on admission and prognosis were analyzed between the two groups. Statistical comparisons were performed using the Mann-Whitney U test and chi-square test.Binary logistic regression was used to analyze the independent risk factors of patients with severe disease, and the severe disease risk model was built.The receiver operator characteristic curve was used to analyze the value of the risk model in predicting severity of disease. Results:Among the 170 underage patients, 132 (77.6%) were males, aged (14.9±3.1) years, including 124 cases in mild group and 46 cases in severe group. One hundred and sixty-nine cases (99.4%) had fever, 119 cases (70.0%) had headache, 106 cases (62.4%) had lumbago, 158 cases (92.9%) had skin and mucous congestion, and 101 cases (59.4%) had nausea and vomiting. Renal percussive pain was found in 139(81.8%) patients. The incidence of nausea and vomiting and bleeding of skin and mucosa in the severe group were 71.7%(33/46) and 67.4%(31/46), respectively, which were both higher than those in the mild group (54.8%(68/124) and 44.4%(55/124), respectively), and the differences were statistically significant ( χ2=3.97 and 7.12, respectively, both P<0.05). There were significant differences in platelet count, activated partial thromboplastin time (APTT), serum creatinine (SCr), aspartate aminotransferase, alanine aminotransferase, leukocyte count, total bilirubin and albumin levels between the two groups ( Z=-4.14, -4.04, -4.87, -3.90, -4.07, -2.60, -2.78 and t=2.50, respectively, all P<0.05). Binary logistic regression analysis showed that chemosis (odds ratio ( OR)=8.035, 95% confidence interval (95% CI) 2.946 to 21.916), SCr ( OR=1.010, 95% CI 1.006 to 1.015) and APTT ( OR=1.049, 95% CI 1.003 to 1.098) were the independent risk factors for severe HFRS in the underage patients. The risk model was constructed as: Logit(P)=-10.323+ 2.084×chemosis (no=0, grade Ⅰ=1, grade Ⅱ=2, grade Ⅲ=3)+ 0.010×SCr (μmol/L)+ 0.048×APTT (s). The area under the curve to predict severity of disease in underage HFRS patients was 0.868, with an optimal cut-off value of -4.39, with a sensitivity of 73.90% and a specificity of 91.10%. According to the internal verification of the data of the study based on the severe disease risk model, 34 out of 46 patients with severe disease were severe (sensitivity, 73.91%), 113 out of 124 patients with mild disease were mild (specificity, 91.13%). Conclusions:The clinical manifestations of the underage HFRS patients are not typical.The main manifestations are fever, headache and lumbago, nausea and vomiting, and the incidences of skin and mucous congestion and renal percussive pain are high.Chemosis, SCr and APTT are independent risk factors for severe disease in underage patients with HFRS. The severe disease risk model could effectively predict the severity of disease.

Changes of serum CTX-1 and P1NP in patients with skeletal fluorosis in tea-drinking-borne endemic fluorosis area in Qinghai Province / 中华地方病学杂志

Objective:To observe the changes of serum C-terminal peptide of type Ⅰ collagen (CTX-1) and N-terminal lengthening peptide of type Ⅰ collagen (P1NP) in adult patients with skeletal fluorosis in the tea-drinking-borne endemic fluorosis area in Qinghai Province, and to find sensitive indicators for diagnosis of skeletal fluorosis.Methods:From April to August 2019, a case-control study was carried out in tea-drinking-borne endemic fluorosis area in Zhiduo County, Yushu Tibetan Autonomous Prefecture, and Gangcha County, Haibei Tibetan Autonomous Prefecture of Qinghai Province. According to the Diagnostic Standard for Endemic Skeletal Fluorosis (WS/T 192-2008), the clinical diagnosis and X-ray examination of skeletal fluorosis were carried out for permanent residents ≥25 years old and living for more than 10 years in the area, combined with face-to-face inquiry and investigation of past disease history, lifestyle and clinical manifestations. The patients with skeletal fluorosis and healthy people were selected as skeletal fluorosis group and control group, respectively. Randomized urine samples and fasting venous blood from the two groups were collected. The content of fluoride in urine was determined by ion selective electrode method, and the contents of CTX-1 and P1NP in serum were determined by enzyme-linked immunosorbent assay (ELISA).Results:A total of 127 people in the disease area were investigated, including 63 cases in skeletal fluorosis group and 64 cases in control group. There was no statistically significant difference in age and sex ratio between the two groups ( t = 0.42, χ 2 = 0.07, P > 0.05). The X-ray examination results showed that the patients with skeletal fluorosis were mainly mild, accounting for 71.43% (45/63); X-ray changes were mainly ossification of interosseous membrane and tendon. The urinary fluoride in control group and skeletal fluorosis group was 1.62 (1.12, 1.95) and 3.22 (2.38, 4.89) mg/L, respectively, with statistically significant difference between the two groups ( Z = 7.07, P < 0.001). The difference of serum CTX-1 and P1NP contents between the two groups was statistically significant ( Z = 2.00, 4.89, P < 0.05). Conclusions:The levels of serum CTX-1 and P1NP in patients with skeletal fluorosis are higher than those in healthy people. Serum CTX-1 and P1NP may be used as sensitive indicators for diagnosis of skeletal fluorosis.

Mechanism of Ginseng-Rhodiola rosea in treatment of myocardial ischemia-reperfusion injury based on network pharmacology and molecular docking / 中国药理学通报

Aim To investigate the sites and mechanisms of action of Ginseng-Rhodiola rosea in the treat ment of myocardial ischemia-reperfusion injury ( MI-RI) via using network pharmacology approach, molecu¬lar docking techniques and experimental studies. Methods The active ingredients and targets of Gin¬seng-Rhodiola rosea were screened through the TCMSP database and literature supplementation, and the GEN-EC ARDS ,DISGENET and DRUGBANK databases were searched to obtain the targets of MIRI. Functional pro¬tein interaction networks (PPIs) and the STRING database were used to screen out core targets. The DAVID database was also selected for gene ontology functional analysis ( GO) and KEGG signaling pathway enrich¬ment analysis. Lastly, the preliminary validation was performed with the help of molecular docking techniques and experimental studies. Results Forty-three active ingredients and 348 potential targets of Ginseng-Rhodiola were obtained, and targets such as IL-6 , TNF-α and VEGFA were found to be closely related to MIRI, mainly involving TNF, PDK-Akt, HIF-1 and other signaling pathways.The molecular docking results showed that soysterol, ginsenoside rh2 and rhodioloside had good binding effects and high matching with IL-6, TNF-α,Caspase-3,VEGFA,MAPK1 and other targets, among which the best binding was between Caspase-3 and ginsenoside rh2. The results of the experimental study further showed that Ginseng-Rhodiola rosea could improve myocardial tissue necrosis after myocardial ischemia-reperfusion , reduce myocardial cell edema and vascular congestion, and decrease the expression levels of TNF-α and IL-6 in MIRI rats. Conclusions Ginseng-Rhodiola may modulate multiple targets such as IL-6,TNF-α, Caspase-3, VEGFA and MAPK1 through dousterol, ginsenoside rh2 and rhodiol glycosides to inhibit inflammatory response and oxidative stress, reduce cardiomyocyte damage and exert therapeutic effects on MIRI.

Non-canonical STING-PERK pathway dependent epigenetic regulation of vascular endothelial dysfunction via integrating IRF3 and NF-κB in inflammatory response

Inflammation-driven endothelial dysfunction is the major initiating factor in atherosclerosis, while the underlying mechanism remains elusive. Here, we report that the non-canonical stimulator of interferon genes (STING)-PKR-like ER kinase (PERK) pathway was significantly activated in both human and mice atherosclerotic arteries. Typically, STING activation leads to the activation of interferon regulatory factor 3 (IRF3) and nuclear factor-kappa B (NF-κB)/p65, thereby facilitating IFN signals and inflammation. In contrast, our study reveals the activated non-canonical STING-PERK pathway increases scaffold protein bromodomain protein 4 (BRD4) expression, which encourages the formation of super-enhancers on the proximal promoter regions of the proinflammatory cytokines, thereby enabling the transactivation of these cytokines by integrating activated IRF3 and NF-κB via a condensation process. Endothelium-specific STING and BRD4 deficiency significantly decreased the plaque area and inflammation. Mechanistically, this pathway is triggered by leaked mitochondrial DNA (mtDNA) via mitochondrial permeability transition pore (mPTP), formed by voltage-dependent anion channel 1 (VDAC1) oligomer interaction with oxidized mtDNA upon cholesterol oxidation stimulation. Especially, compared to macrophages, endothelial STING activation plays a more pronounced role in atherosclerosis. We propose a non-canonical STING-PERK pathway-dependent epigenetic paradigm in atherosclerosis that integrates IRF3, NF-κB and BRD4 in inflammatory responses, which provides emerging therapeutic modalities for vascular endothelial dysfunction.

Dihydroartemisinin attenuates ischemia/reperfusion-induced renal tubular senescence by activating autophagy / 中国天然药物

Acute kidney injury (AKI) is an important factor for the occurrence and development of CKD. The protective effect of dihydroartemisinin on AKI and and reported mechanism have not been reported. In this study, we used two animal models including ischemia-reperfusion and UUO, as well as a high-glucose-stimulated HK-2 cell model, to evaluate the protective effect of dihydroartemisinin on premature senescence of renal tubular epithelial cells in vitro and in vivo. We demonstrated that dihydroartemisinin improved renal aging and renal injury by activating autophagy. In addition, we found that co-treatment with chloroquine, an autophagy inhibitor, abolished the anti-renal aging effect of dihydroartemisinin in vitro. These findings suggested that activation of autophagy/elimination of senescent cell might be a useful strategy to prevent AKI/UUO induced renal tubular senescence and fibrosis.

Anti-inflammatory effects of acupuncture in the treatment of chronic obstructive pulmonary disease / 中西医结合学报

Numerous randomised controlled trials have suggested the positive effects of acupuncture on chronic obstructive pulmonary disease (COPD). However, the underlying therapeutic mechanisms of acupuncture for COPD have not been clearly summarized yet. Inflammation is central to the development of COPD. In this review, we elucidate the effects and underlying mechanisms of acupuncture from an anti-inflammatory perspective based on animal studies. Cigarette smoke combined with lipopolysaccharide is often used to establish animal models of COPD. Electroacupuncture can be an effective intervention to improve inflammation in COPD, and Feishu (BL13) and Zusanli (ST36) can be used as basic acupoints in COPD animal models. Different acupuncture types can regulate different types of inflammatory cytokines; meanwhile, different acupuncture types and acupoint options have similar effects on modulating the level of inflammatory cytokines. In particular, acupuncture exerts anti-inflammatory effects by inhibiting the release of inflammatory cells, inflammasomes and inflammatory cytokines. The main underlying mechanism through which acupuncture improves inflammation in COPD is the modulation of relevant signalling pathways: nuclear factor-κB (NF-κB) (e.g., myeloid differentiation primary response 88/NF-κB, toll-like receptor-4/NF-κB, silent information regulator transcript-1/NF-κB), mitogen-activated protein kinase signalling pathways (extracellular signal-regulated kinase 1/2, p38 and c-Jun NH2-terminal kinase), cholinergic anti-inflammatory pathway, and dopamine D2 receptor pathway. The current synthesis will be beneficial for further research on the effect of acupuncture on COPD inflammation. Please cite this article as: Jiang LH, Li PJ, Wang YQ, Jiang ML, Han XY, Bao YD, Deng XL, Wu WB, Liu XD. Anti-inflammatory effects of acupuncture in the treatment of chronic obstructive pulmonary disease. J Integr Med. 2023; 21(6): 518-527.

Association between HLA-DRB1 gene polymorphisms and genetic susceptibility of early-onset severe preeclampsia / 中国当代儿科杂志

OBJECTIVES@#To explore the correlation between the single nucleotide polymorphisms (SNP) of rs3135388, rs114293611 and rs142804168 of HLA-DRB1 gene and early-onset severe preeclampsia (sPE).@*METHODS@#Blood samples were collected from 102 early-onset sPE mothers and their neonates (sPE group), as well as 120 normotensive mothers and their neonates (control group). Sanger sequencing was performed to compare the genotype distribution, allele frequencies, and differences in genotype distribution after maternal-infant compatibility between the two groups.@*RESULTS@#Statistically significant differences in genotype distribution at rs114293611 of HLA-DRB1 gene were observed between sPE and control groups in both mothers and neonates (P<0.05). The frequency of the T allele at rs114293611 was higher in the sPE group of neonates than that in the control group (P<0.05), while no significant difference was found between the two groups of mothers (P>0.05). The maternal-infant genotype compatibility analysis showed significant differences in genotype distribution between sPE and control groups (P<0.05). There were no significant differences in genotype distribution and allele frequencies at rs3135388 and rs142804168 of HLA-DRB1 gene between the two groups of mothers and neonates (P>0.05).@*CONCLUSIONS@#The SNP at rs114293611 of HLA-DRB1 gene may be associated with the development of early-onset sPE in mothers. Maternal-infant genotype compatibility abnormality at rs114293611 of HLA-DRB1 gene may be a predisposition factor for the development of sPE.

Conservative treatment of supination and external rotation for type Ⅲ and Ⅳankle fracture by bone setting / 中国骨伤

OBJECTIVE@#To explore curative effect of conservative treatment of supination-lateral rotation (SER) with type Ⅲ and Ⅳ ankle fracture by bone setting technique.@*METHODS@#From January 2017 to December 2019, 64 patients diagnosed with SER with type Ⅲ and Ⅳ ankle fracture were treated with manipulative reduction and conservative treatment (manipulation group) and surgical treatment with open reduction and internal fixation (operation group), 32 patients in each group. In manipulation group, there were 17 males and 15 females, aged from 15 to 79 years old with an average of (51.42±13.68) years old;according to Lauge-Hansen classification, there were 8 patients with supination external rotation type Ⅲ and 24 patients with type Ⅳ. In operation group, there were 13 males and 19 females, aged from 18 to 76 years old with an average of (47.36±15.02) years old;7 patients with type Ⅲ and 25 patients with type Ⅳ. Displacement of ankle fracture was measured by Digimizer software, and compared before treatment, 3 and 12 months after treatment between two groups. Lateral medial malleolus displacement, lateral medial malleolus displacement, lateral malleolus displacement, lateral malleolus displacement, lateral malleolus contraction displacement and posterior malleolus displacement were measured and compared between two groups. Mazur score was used to evaluate ankle joint function.@*RESULTS@#All patients were followed up from 12 to 36 months with an average of (17.16±9.36) months. There were statistical differences in lateral medial malleolus displacement, lateral medial malleolus displacement, lateral malleolus displacement, lateral malleolus displacement, lateral malleolus contraction displacement and posterior malleolus displacement in manipulation group before and after reduction(P<0.05). Compared with operation group, there were no statistically significant differences in lateral malleolus shift, lateral malleolus shift, lateral malleolus contraction shift(P>0.05), while there were statistically significant differences in lateral malleolus shift, posterior malleolus shift up and down (P<0.05). Mazur scores of ankle joint at 3 months after treatment in manipulation group and operation group were 68.84±13.08 and 82.53±7.31, respectively, and had statistical differences(P<0.05), while there was no difference in evaluation of clnical effect(P>0.05). There were no differences in Mazur score and evaluation of clnical effect between two groups at 12 months after treatment (P>0.05).@*CONCLUSION@#Bone setting technique could effectively correct lateral displacement of medial malleolus, lateral displacement of medial malleolus, lateral displacement of lateral malleolus and lateral contraction displacement of lateral malleolus in supination lateral rotation type Ⅲ and Ⅳ ankle fracture, and has good long-term clinical effect, which could avoid operation for some patients and restore ankle function after fracture.

Clinical observation of acupuncture at Huiyin (CV 1) for chronic severe functional constipation / 中国针灸

OBJECTIVE@#To compare the effect of acupuncture at Huiyin (CV 1) and oral administration of western medication in treatment of chronic severe functional constipation (CSFC).@*METHODS@#A total of 64 patients with CSFC were randomly divided into an acupuncture group (32 cases, 5 cases dropped off) and a western medication group (32 cases, 4 cases dropped off). Both groups were given routine basic treatment. The acupuncture group was treated by directly puncture of 20-30 mm at Huiyin (CV 1), once a day for the first 4 weeks, 5 times a week, once every other day for the next 4 weeks, 3 times a week, totally for 8 weeks. The western medication group was treated with 2 mg prucalopride succinate tablets orally before breakfast every day for 8 weeks. The average number of weekly spontaneous bowel movement (SBM) of the two groups were observed before treatment and 1-8 weeks into treatment. The constipation symptom score before and after treatment, and in follow-up of 1 month after treatment, as well as quality of life [patient assessment of constipation quality of life questionnaire (PAC-QOL) score and the proportion of patients of PAC-QOL score difference before and after treatment≥1] before and after treatment were compared in the two groups. The clinical effects of the two groups were evaluated after treatment and in follow-up.@*RESULTS@#Compared before treatment, the average number of weekly SBM in the two groups was increased 1-8 weeks into treatment (P<0.05). The average number of weekly SBM in the acupuncture group was less than that in the western medication group 1 week into treatment (P<0.05), and the average number of weekly SBM in the observation group was more than that in the western medication group 4-8 weeks into treatment (P<0.05). The scores of constipation symptom after treatment and in follow-up and scores of PAC-QOL after-treatment in the two groups were lower than those before treatment (P<0.05), and those in the acupuncture group were lower than the western medication group (P<0.05). The proportion of patients of PAC-QOL score difference before and after treatment≥1 in the acupuncture group was higher than that in the west medication group (P<0.05). The total effective rates after treatment and in follow-up in the acupuncture group were 81.5% (22/27) and 78.3% (18/23), respectively, which were better than 42.9% (12/28) and 43.5% (10/23) in the western medication group (P<0.05).@*CONCLUSION@#Acupuncture at Huiyin (CV 1) can effectively increase the number of spontaneous defecation in patients with CSFC, reduce constipation symptoms, improve the quality of life, and the effect after treatment and in follow-up is better than oral western medication.

A pre-conception cohort study of fertility and its related factors among couples with the intention of conception / 中华预防医学杂志

Objective: To describe fertility and explore factors associated with it among pre-conception couples of childbearing age. Methods: Based on the pre-conceptional offspring trajectory study of the School of Public Health of Fudan University, couples of childbearing age who participated in the pre-conception physical examination in Shanghai Jiading District from 2016 to 2021 were recruited and followed up. Couples' time to pregnancy (TTP) was analyzed and Cox proportional hazards regression model was used to explore the factors associated with TTP. Kaplan-Meier was used to calculate each menstrual cycle's cumulative pregnancy rate. Results: A total of 1 095 preconception couples were included in the analysis, the M(Q1,Q3)of TTP was 4.33 (2.41, 9.78) menstrual cycles. Age of women (FR=0.90, 95%CI: 0.85-0.95, P<0.001), women who were overweight or obese before pregnancy (FR=0.36, 95%CI: 0.24-0.55, P<0.001), women who were exposed to second-hand smoking (FR=0.63, 95%CI: 0.44-0.92, P=0.016), women whose home or office had been renovated in the past 2 years and had a particular smell (FR=0.46, 95%CI: 0.26-0.81, P=0.008) were risk factors for impaired fertility. Regular menstrual cycles (FR=1.64, 95%CI: 1.16-2.31, P=0.005), females who often drank tea/coffee (FR=1.55, 95%CI: 1.11-2.17, P=0.011) and males who took folic acid before conception (FR=2.35, 95%CI: 1.38-4.23, P=0.002) were associated with better fertility. The cumulative pregnancy rate of 3, 6, and 12 menstrual cycles was 37.6%, 64.4%, and 78.4%, respectively. Conclusion: Older couples, overweight or obesity before pregnancy, irregular menstruation, exposure to secondhand smoke and decoration pollutants in females are associated with impaired fertility. Frequent tea/coffee drinking before pregnancy in females and taking folic acid before pregnancy in males are associated with shortened conception time.

Influencing factors of secondary primary cancer in patients with acute lymphoid leukemia / 公共卫生与预防医学

Objective To analyze the influencing factors of second primary cancer (SPC) in patients with acute lymphoblastic leukemia (ALL). Methods The Surveillance, Epidemiology and End Results database of the National Cancer Institute was used to extract data, and SEER*Stat program 8.4.0 was used to calculate the standardized incidence rate ratio (SIR) and absolute excess rate (AER). In addition, Cox regression models were used to estimate the hazard ratio (HR) of different age, race, sex, chemotherapy, and radiation and other factors for secondary tumors by R 4.2.1, and Kaplan-Meier method was used to plot the cumulative incidence. Results A total of 22 407 cases were included, and the person-years of follow-up were 142780.82. There was a total of 436 SPC cases, 32 of which developed multiple cancers. The median time of secondary cancers was 47.5 months. Patients with ALL had a higher risk of SPC than the general population (SIR=2.27; 95% , CI:2.07-2.50), and the most observed SPC was lymphatic and hematopoietic system, with an SIR of 6.96 (95% CI:5.94-8.11). The risk of SPC in ALL patients diagnosed in different time periods showed an upward trend, from 1.98 in 2000 to 2.38 in 2019. With the increase of age, the risk of SPC in ALL patients gradually decreased. Chemotherapy reduced the risk of SPC (HR=0.26; 95%CI: 0.19-0.36), while radiotherapy increased the risk of SPC by 59.60% (HR=1.57; 95% CI: 1.23-2.00). Conclusion In the future, chemotherapy is recommended for ALL patients to reduce radiation exposure during radiotherapy, and more attention should be paid to the health status of ALL patients within 1-5 years after their onset.

Terpinen-4-ol inhibits proliferation of VSMCs exposed to high glucose via regulating KLF4/NF-κB signaling pathway / 中国中药杂志

This study aimed to observe the effect of terpinen-4-ol(T4O) on the proliferation of vascular smooth muscle cells(VSMCs) exposed to high glucose(HG) and reveal the mechanism via the Krüppel-like factor 4(KLF4)/nuclear factor kappaB(NF-κB) signaling pathway. The VSMCs were first incubated with T4O for 2 h and then cultured with HG for 48 h to establish the model of inflammatory injury. The proliferation, cell cycle, and migration rate of VSMCs were examined by MTT method, flow cytometry, and wound healing assay, respectively. The content of inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α) in the supernatant of VSMCs was measured by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to determine the protein levels of proliferating cell nuclear antigen(PCNA), Cyclin D1, KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. The KLF4 expression in VSMCs was silenced by the siRNA technology, and then the effects of T4O on the cell cycle and protein expression of the HG-induced VSMCs were observed. The results showed that different doses of T4O inhibited the HG-induced proliferation and migration of VSMCs, increased the percentage of cells in G_1 phase, and decreased the percentage of cells in S phase, and down-regulated the protein levels of PCNA and Cyclin D1. In addition, T4O reduced the HG-induced secretion and release of the inflammatory cytokines IL-6 and TNF-α and down-regulated the expression of KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. Compared with si-NC+HG, siKLF4+HG increased the percentage of cells in G_1 phase, decreased the percentage of cells in S phase, down-regulated the expression of PCNA, Cyclin D1, and KLF4, and inhibited the activation of NF-κB signaling pathway. Notably, the combination of silencing KLF4 with T4O treatment further promoted the changes in the above indicators. The results indicate that T4O may inhibit the HG-induced proliferation and migration of VSMCs by down-regulating the level of KLF4 and inhibiting the activation of NF-κB signaling pathway.