Clinical Decision on Disorders of Consciousness After Acquired Brain Injury: Stepping Forward / 神经科学通报·英文版

Major advances have been made over the past few decades in identifying and managing disorders of consciousness (DOC) in patients with acquired brain injury (ABI), bringing the transformation from a conceptualized definition to a complex clinical scenario worthy of scientific exploration. Given the continuously-evolving framework of precision medicine that integrates valuable behavioral assessment tools, sophisticated neuroimaging, and electrophysiological techniques, a considerably higher diagnostic accuracy rate of DOC may now be reached. During the treatment of patients with DOC, a variety of intervention methods are available, including amantadine and transcranial direct current stimulation, which have both provided class II evidence, zolpidem, which is also of high quality, and non-invasive stimulation, which appears to be more encouraging than pharmacological therapy. However, heterogeneity is profoundly ingrained in study designs, and only rare schemes have been recommended by authoritative institutions. There is still a lack of an effective clinical protocol for managing patients with DOC following ABI. To advance future clinical studies on DOC, we present a comprehensive review of the progress in clinical identification and management as well as some challenges in the pathophysiology of DOC. We propose a preliminary clinical decision protocol, which could serve as an ideal reference tool for many medical institutions.

Identification of Human Body Fluid Stains and Non-Biological Stains by Three-Dimensional Fluorescence Spectroscopy / 法医学杂志

OBJECTIVES@#To establish a rapid and nondestructive identification method for human body fluid stains and non-biological stains using three-dimensional fluorescence spectroscopy.@*METHODS@#The collected three-dimensional fluorescence spectrum data of human saliva, 3% blood, coffee and Fanta® stains were processed with dimensionality reduction. After wavelet transform, spectral denoising and feature extraction, the classification formula was established. The Fisher discriminant was used for spectrum matching and recognition to establish the analysis method to distinguish stain types.@*RESULTS@#According to the results of data training and comparison, all the recognition accuracies of Fanta®, coffee, saliva and blood were more than 91.39%. Among them, saliva reached 100% recognition accuracy.@*CONCLUSIONS@#Three-dimensional fluorescence spectroscopy is a potential method for rapid and nondestructive identification of biological and non-biological stains.

Research progress of transcription activating factor 3 in regulating the alveolar macrophages in acute respiratory distress syndrome / 中华危重病急救医学

Acute respiratory distress syndrome (ARDS) refers to acute diffuse lung injury caused by a variety of intrapulmonary and/or extrapulmonary factors such as infection and trauma. Uncontrolled inflammatory response is the main pathological feature. Different functional states of alveolar macrophages have different effects on inflammatory response. Transcription activating factor 3 (ATF3) is a fast response gene in the early stage of stress. In recent years, it has been found that ATF3 plays an important role in regulating the inflammatory response of ARDS by regulating the function of macrophages. This paper reviews the regulatory effects of ATF3 on alveolar macrophage polarization, autophagy and endoplasmic reticulum stress and its effects on the inflammatory process of ARDS, aiming to provide a new research direction for the prevention and treatment of ARDS.

Dissecting Causal Relationships Between Gut Microbiota, Blood Metabolites, and Stroke: A Mendelian Randomization Study / 대한뇌졸중학회지

Background@#and Purpose We investigated the causal relationships between the gut microbiota (GM), stroke, and potential metabolite mediators using Mendelian randomization (MR). @*Methods@#We leveraged the summary statistics of GM (n=18,340 in the MiBioGen consortium), blood metabolites (n=115,078 in the UK Biobank), and stroke (cases n=60,176 and controls n=1,310,725 in the Global Biobank Meta-Analysis Initiative) from the largest genome-wide association studies to date. We performed bidirectional MR analyses to explore the causal relationships between the GM and stroke, and two mediation analyses, two-step MR and multivariable MR, to discover potential mediating metabolites. @*Results@#Ten taxa were causally associated with stroke, and stroke led to changes in 27 taxa. In the two-step MR, Bifidobacteriales order, Bifidobacteriaceae family, Desulfovibrio genus, apolipoprotein A1 (ApoA1), phospholipids in high-density lipoprotein (HDL_PL), and the ratio of apolipoprotein B to ApoA1 (ApoB/ApoA1) were causally associated with stroke (all P<0.044). The causal associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were validated using the weighted median method in an independent cohort. The three GM taxa were all positively associated with ApoA1 and HDL_PL, whereas Desulfovibrio genus was negatively associated with ApoB/ApoA1 (all P<0.010). Additionally, the causal associations between the three GM taxa and ApoA1 remained significant after correcting for the false discovery rate (all q-values <0.027). Multivariable MR showed that the associations between Bifidobacteriales order, Bifidobacteriaceae family and stroke were mediated by ApoA1 and HDL_PL, each accounting for 6.5% (P=0.028) and 4.6% (P=0.033); the association between Desulfovibrio genus and stroke was mediated by ApoA1, HDL_PL, and ApoB/ApoA1, with mediated proportions of 7.6% (P=0.019), 4.2% (P=0.035), and 9.1% (P=0.013), respectively. @*Conclusion@#The current MR study provides evidence supporting the causal relationships between several specific GM taxa and stroke and potential mediating metabolites.

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).

Exploring biological connotation of blood stasis syndrome of rheumatoid arthritis and establishment of improved animal models based on syndrome-symptom mapping / 药学学报

Blood stasis syndrome is one of the core clinical syndrome of rheumatoid arthritis (RA), but the biological connotation of this syndrome is not clear, and there is a lack of disease improved animal models that match the characteristics of this disease and syndrome. The aim of this study was to screen the candidate biomarker gene set of blood stasis syndrome of RA, reveal the biological connotation of this syndrome, and explore and evaluate the preparation method of the improved animal model based on the characteristics of "disease-syndrome-symptom". The study was approved by the ethics committee of Guang'anmen Hospital, Chinese Academy of Traditional Chinese Medicine (No. 2019-073-KY-01) and the First Affiliated Hospital of Tianjin University of Traditional Chinese Medicine (No. TYLL2021[K]018), and the study subjects gave their informed consent. Animal welfare and experimental procedures followed the regulations of the Experimental Animal Ethics Committee of the Chinese Academy of Traditional Chinese Medicine (No. IBTCMCACMS21-2207-01). The whole blood samples were collected clinically from RA patients with blood stasis syndrome (3 cases) or other syndromes (7 types, 3 cases/type), and healthy volunteers (4 cases), and then transcriptome sequencing, KEGG, gene set enrichment analysis (GSEA) and weighted correlation network analysis (WGCNA) analysis were performed. 126 pivotal genes were screened, and their functional annotation results were significantly enriched in "immune-inflammation" related pathways and lipid metabolism regulation (sphingolipids, ether lipid metabolism and steroid biosynthesis). Syndrome-symptom mapping of hub gene set to the TCM primary and secondary symptoms, Western phenotypic symptoms and pathological links showed that joint tingling, abnormal joint morphology, petechiae and abnormal blood circulation are representative of blood stasis syndrome of RA. The results of the improved animal model showed that the rats in the collagen-induced arthritis + adrenaline hydrochloride (CIA+Adr) 3 model group had increased blood rheology, coagulation, platelet function and endothelial function abnormalities compared with the CIA-alone model group, suggesting that the rats with blood stasis syndrome of RA may be in a state of "blood stasis". The results of the study can help to advance the objective study of the evidence of blood stasis syndrome in RA, and provide new ideas for the establishment of an animal model that reflects the clinical characteristics of the disease and syndrome.

Advances in histone epigenetic enzyme inhibitors based on proteomics / 药学学报

As an important component of nucleosomes on the chromatin of eukaryotic cells, histones play an important role in the development and progression of tumour diseases by regulating epigenetic post-translational modifications such as acetylation and methylation. In addition, development of inhibitors targeting methyltransferase and deacetylase provides novel therapeutic strategies for cancer treatment. Mass spectrometry-based proteomics can reveal the global changes of histone modifications under the action of drugs during disease progression, which in turn provides important support for revealing drug action mechanism, drug resistance mechanism, and investigating novel drug combination strategies. This article focuses on the progress and status of proteomic research on a variety of histone modifying enzyme inhibitors, including methyltransferase inhibitors and histone deacetylase inhibitors, which will help to understand the current and further utilization of proteomics in studying histone modifications.

Efficacy observation on prevention of chemotherapy-related anemia by combined therapy of traditional Chinese medicine in malignant tumors / 肿瘤研究与临床

Objective:To explore the effect of combined therapy of traditional Chinese medicine on prevention of chemotherapy-related anemia in malignant tumors.Methods:Seventy-nine patients with malignant tumors diagnosed in Zibo Hospital of Traditional Chinese Medicine from January 2019 to January 2021 were selected, and the patients were divided into experimental group (40 cases) and control group (39 cases) according to the random number table method. The control group received chemotherapy and the experimental group received chemotherapy and combined therapy of traditional Chinese medicine (Wuhong Tang combined with moxibustion). The hemoglobin (Hb) level, Karnofsky score and adverse effects were recorded before and on days 7, 14 and 21 after chemotherapy in the two groups.Results:The Hb level in the experimental group was higher than that in the control group [(117±28) g/L vs. (100±31) g/L] on day 21 after chemotherapy, and the difference was statistically significant ( t = -3.08, P = 0.030). The total effective rate of the experimental group was higher than that of the control group [85% (34/40) vs. 66.7% (26/39)], but the difference was not statistically significant ( χ2 = 4.96, P = 0.084). Karnofsky scores were (77±9) points and (77±12) points before and on day 21 after treatment in the experimental group, with no statistical difference ( t = -0.50, P = 0.623); Karnofsky scores were (78±10) points and (67±9) points in the control group, with statistical difference ( t = 8.32, P < 0.001). There was no statistical difference in Karnofsky score before treatment between the two groups ( t = 1.85, P = 0.068), but the experimental group was higher than the control group on day 21 after treatment ( t = 4.88, P < 0.001). The difference in the incidence of nausea and vomiting between the two groups was not statistically significant ( P > 0.05), and no chemotherapy-related hepatic, renal or cardiac adverse reactions were observed in either group. Conclusions:Combined therapy of traditional Chinese medicine could effectively prevent chemotherapy-related anemia and improve the quality of life of patients.

Analysis of serum allergen-specific immunoglobulin E in 3 051 patients with eczema or dermatitis in an allergy clinic / 中华皮肤科杂志

Objective:To analyze measurement results of serum allergen-specific immunoglobulin E (IgE) in patients with eczema/dermatitis.Methods:A retrospective analysis was conducted on serum allergen-specific immunoglobulin E (IgE) levels in 3 051 patients with eczema/dermatitis, who visited the allergy clinic of Huashan Hospital from April 1, 2021 to March 31, 2022. The serum allergen-specific IgE level was detected by using the Phadia allergen detection system, and positive rates of allergens were calculated to determine common inhaled allergens and food allergens in patients with eczema/dermatitis. Comparisons of enumeration data between groups were performed by chi-square test.Results:Among the 3 051 patients with eczema/dermatitis, there were 1 412 with atopic dermatitis and 1 639 were other eczema/dermatitis. Detection of serum allergen-specific IgE showed that 1 629 (53%) patients were positive for allergens, and the number of positive allergen-specific IgEs in each patient was 3.0 ± 1.6. The top 3 common inhaled allergens in patients with eczema/dermatitis were Dermatophagoides farinae (904/1 522, 59%) , Dermatophagoides pteronyssinus (891/1 513, 59%) and Alternaria alternata (206/1 068, 19%) , and the top 3 common food allergens were shrimps (251/1 432, 18%) , egg white (165/992, 17%) and cow milk (149/994, 15%) . Among the 3 051 patients, 25 (1%) were aged < 2 years, 571 (19%) aged 2 - 12 years, 285 (9%) aged 12 - 18 years, and 2 170 (71%) were aged > 18 years. The most common food allergens were both egg white in the age groups of < 2 years and 2 -12 years (77%, 37%, respectively) , and were both shrimps in the age groups of 12 - 18 years and > 18 years (31%, 17%, respectively) . Dermatophagoides pteronyssinus and Dermatophagoides farina were the top 2 common inhaled allergens in all age groups, with the positive rate ranging from 36% to 84%; in addition, the positive rate of molds was relatively high in the age group of 2 - 12 years (mold mixture: 37%; Alternaria alternata: 27%) . From April 2021 to March 2022, the positive rate of outdoor allergens ranged from 10% to 15% among outpatients in every month; the positive rates of tree pollen and grass pollen increased from April 2021, and peaked in October 2021. The patients with atopic dermatitis showed a significantly increased positive rate of allergens (73%) compared with those with other eczema/dermatitis (37%, χ2 = 389.36, P<0.001) , and the rank of common allergens in the patients with atopic dermatitis was basically the same as that in those with eczema/dermatitis. Conclusions:The common allergens were Dermatophagoides farina, Dermatophagoides pteronyssinus and Alternaria alternata in the patients with eczema/dermatitis. Food allergy was more common in infant patients, and inhalation allergy was more common in child, adolescent and adult patients. The positive rate of allergen-specific IgEs was markedly higher in the patients with atopic dermatitis than in those with other eczema/dermatitis.

Changes of postoperative pulmonary function in lung transplant recipients / 器官移植

Objective To analyze the changes of postoperative pulmonary function in lung transplant recipients. Methods Clinical data of 81 recipients undergoing bilateral lung transplantation and combined heart-lung transplantation were collected, and postoperative status of the recipients was analyzed. Pulmonary ventilation and diffusion function indexes at 1 month, 3 months, every 3 months (3-18 months after lung transplantation) and every 6 months (18-36 months after lung transplantation) were analyzed in the recipients. The characteristics of the optimal pulmonary function in the recipients were assessed. Results Postoperative mechanical ventilation time was 4 (2, 9) d, and the length of postoperative ICU stay was 10 (7, 20) d. Among 81 recipients, 27 recipients developed primary graft dysfunction (PGD) after lung transplantation, with an incidence rate of 33%. Postoperative forced vital capacity (FVC) to predicted value ratio (FVC%pred), forced expiratory volume in one second (FEV1) to predicted value ratio (FEV1%pred), FEV1/FVC to predicted value ratio (FEV1/FVC%pred) and corrected diffusion lung capacity for CO to predicted value ratio (DLCOc%pred) were changed over time (all P<0.001). FVC%pred and FEV1%pred were gradually increased within postoperative 9 months, and DLCOc%pred was gradually elevated within postoperative 3 months (all P<0.05). Thirty-six recipients had FVC%pred≥80%, FEV1%pred≥80% in 41 cases, FEV1/FVC%pred≥92% in 76 cases, FVC%pred≤40% in 1 case and FEV1%pred≤40% in 1 case, respectively. Sixteen recipients had DLCOc%pred≥80%, corrected diffusion lung capacity for CO/alveolar volume to predicted value ratio (DLCOc/VA%pred) ≥80% in 63 cases, DLCOc%pred≤40% in 4 cases and DLCOc/VA%pred≤40% in 1 case, respectively. Postoperative FVC%pred, FEV1/FVC%pred and DLCOc%pred in recipients with a primary disease of obstructive pulmonary disease were significantly higher than those in their counterparts with restrictive pulmonary disease (all P<0.05). Postoperative DLCOc%pred in recipients with PGD was significantly lower than that in those without PGD (P<0.05). Conclusions Pulmonary ventilation function in lung transplant recipients reaches the optimal state and maintains a steady state at postoperative 9 months, and pulmonary diffusion function reaches a steady state at postoperative 3 months. Primary diseases and the incidence of PGD may affect postoperative pulmonary function.

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.

Efficacy of polyetheretherketone rod hybrid surgery in preventing proximal junctional failure after adult spinal deformity surgery / 中华外科杂志

Objective: To investigate the clinical outcome and preventive effect of polyetheretherketone(PEEK) rod hybrid surgery on proximal junction failure(PJF) after long-segment fusion of adult spinal deformity. Methods: A retrospective study was conducted to analyze patients with degenerative scoliosis/kyphosis who underwent long-segment decompression and fusion surgery at Department of Orthopedics, Peking University First Hospital from January 2017 to December 2021. A total of 75 patients were included in the study, including 14 males and 61 females, aged (67.2±6.8)years (range:55 to 84 years). According to the operation method chosen by the patients, the patients were divided into PEEK rod hybrid group (20 cases) and traditional titanium rod group (55 cases). The general information of the patients was collected, and the coronal and sagittal parameters of the spine were measured before operation, at 1 month after operation, and at the last follow-up. The clinical effect of surgery was judged by the visual analogue scale (VAS) and Oswestry disability index (ODI). Whether proximal junctional kyphosis (PJK) and PJF occurred during the follow-up and the time of occurrence were recorded. Comparisons between groups were performed using independent sample t test, Mann-Whitney U test, χ2 test and Fisher's exact probability method. The data before and after surgery in the same group were compared using the paired sample t test and the Wilcoxon test. Results: There were no significant differences in age, gender, body mass index, bone mineral density, distal instrumented vertebrae, surgical segments, osteotomy method, operation time, and intraoperative bleeding between the two groups (all P>0.05). The follow-up time of the PEEK rod group was shorter(M(IQR)16.5(4.8) vs. 25.0(12.0),Z=-4.230,t<0.01). There were no significant differences in coronal, sagittal parameters, VAS, and ODI between the two groups before operation (all P>0.05). Postoperative coronal Cobb angle, pelvic incidence, pelvic tilt, sacral slope, lumbar lordosis, thoracic kyphosis, sagittal vertical axis (SVA), VAS, and ODI were significantly improved in both groups(all P<0.05). At the last follow-up, the SVA of the PEEK rod hybrid group was(3.74±2.40)cm, which was significantly lower than that of the titanium rod group (6.28±4.06)cm (t'=-3.318, P=0.002). At the last follow-up, the ODI of the PEEK rod hybrid group was 30.7±6.1, significantly better than the titanium rod group 39.3±17.2. PJK occurred in 2 patients (10.0%) in the PEEK rod hybrid group, and no PJF phenomenon was observed. In the titanium rod group, 18 patients (32.7%) developed PJK, and 11 patients (20.0%) developed PJF. There was a statistically significant difference in the incidence of PJF between the PEEK rod hybrid group and the titanium rod group (P=0.031). Conclusions: PEEK rod hybrid surgery can achieve good clinical results in the treatment of adult spinal deformities. Compared with traditional titanium rod surgery, it can significantly reduce the incidence of postoperative PJF and improve the clinical function of patients.

Nanocrystals self-stabilized Pickering emulsion loaded with active components of Tongmai prescription: preparation, characterization and evaluation by Caco-2 cell model / 药学学报

It is of great significance to apply the nanocrystals self-stabilized Pickering emulsion (NSSPE) to traditional Chinese medicine (TCM) compounds, and to study the effect of NSSPE on the oral absorption of various components with different solubility and permeability. In the study, NSSPE of Tongmai prescription was prepared by the high pressure homogenization method with nanocrystals of main active components (puerarin, ferulic acid, salvianolic acid B and tanshinone IIA) of Tongmai prescription as solid particle stabilizers and a mixture of Ligusticum chuanxiong essential oil and Labrafil M 1944 CS as oil phase. The NSSPE had better physical stability than nanocrystals suspension and blank emulsion. The adsorption of nanocrystals on the surface of oil droplets was confirmed by scanning electron microscopy and fluorescence microscopy. The surface adsorption rates of puerarin, ferulic acid, salvianolic acid B and tanshinone ⅡA in NSSPE were 15.40% ± 3.19%, 15.39% ± 5.07%, 10.97% ± 3.70% and 31.51% ± 1.60%, respectively. When solid active components were prepared into nanocrystals suspension, the cellular uptake and transport across Caco-2 cells were increased significantly for puerarin and tanshinone IIA. The uptake rates of ferulic acid, ligustilide and tanshinone IIA in NSSPE were further increased compared with the physical mixture of nanocrystals suspension and oil, and the transports of ligustilide and tanshinone IIA were also significantly improved. The main absorption mechanisms of NSSPE were passive diffusion and caveolin-mediated endocytosis, which were determined mainly by the microstructure of NSSPE. In conclusion, NSSPE could be applied to complicated TCM. The "micro" and "nano" synergistic microstructure with drug nanocrystals adsorbed on the surface of micron-sized oil droplets could not only improve the physical stability of NSSPE, but also promote the absorption of various components in NSSPE, which made NSSPE a promising oral drug delivery system for TCM.

Expression pattern of MMP-12 in long-term optic nerve regeneration induced by lens injury / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the expression changes of MMP-12 during the long-term axon regeneration induced by the lens injury after the optic nerve clamp trauma in sprague-dawley(SD)rats.METHODS: The optic nerve injury model and lens injury model of SD rats were established, and the 24 experimental animals were divided into control group; lens injury group; optic nerve injury group; lens injury combined with optic nerve injury group, with 6 rats in each group. Reference transcriptome sequencing was used to analyze the expression changes of differentially expressed genes in the injured optic nerve region, and relevant differentially expressed genes with high expression were screened. Quantitative real-time polymerase chain reaction(qRT-PCR)and enzyme-linked immunosorbent assay(ELISA)were used to quantify the expression changes of matrix metalloproteinase-12(MMP-12)in the injured optic nerve region.RESULTS: The Principal Component Analysis of transcriptome sequencing indicated that lens injury combined with optic nerve injury was the principal component of gene expression change. Analysis of gene expression differences showed that the expression of MMP-12 gene was up-regulated in the lens injury combined with optic nerve injury group. The mRNA expression level of MMP-12 in the lens injury combined optic nerve injury group was up-regulated compared with the control group, the optic nerve injury group and the lens injury group at 14d and 21d after successful modeling(P<0.05). At 7, 28d, there was no difference in expression among all groups. The protein expression level of MMP-12 in the lens injury combined with optic nerve injury group was up-regulated compared with the control group and optic nerve injury group at 7, 14 and 21d after successful modeling(P<0.05), and it was up-regulated in the lens injury group combined with optic nerve injury group compared with optic nerve injury group at 21d(P<0.05). At 28d, there was no difference in expression among all groups.CONCLUSION: The up-regulated expression of MMP-12 may be involved in the long-term regeneration of the optic nerve after lens injury.

Establishment and validation of a preoperative nomogram model for predicting the risk of hepatocellular carcinoma with microvascular invasion / 中华外科杂志

Objective: To establish and validate a nomogram model for predicting the risk of microvascular invasion(MVI) in hepatocellular carcinoma. Methods: The clinical data of 210 patients with hepatocellular carcinoma who underwent hepatectomy at Department of Hepatobiliary and Pancreatic Surgery,the Affiliated Hospital of Qingdao University from January 2013 to October 2021 were retrospectively analyzed. There were 169 males and 41 females, aged(M(IQR)) 57(12)years(range:30 to 80 years). The patients were divided into model group(the first 170 cases) and validation group(the last 40 cases) according to visit time. Based on the clinical data of the model group,rank-sum test and multivariate Logistic regression analysis were used to screen out the independent related factors of MVI. R software was used to establish a nomogram model to predict the preoperative MVI risk of hepatocellular carcinoma,and the validation group data were used for external validation. Results: Based on the modeling group data,the receiver operating characteristic curve was used to determine that cut-off value of DeRitis ratio,γ-glutamyltransferase(GGT) concentration,the inverse number of activated peripheral blood T cell ratio (-aPBTLR) and the maximum tumor diameter for predicting MVI, which was 0.95((area under curve, AUC)=0.634, 95%CI: 0.549 to 0.719), 38.2 U/L(AUC=0.604, 95%CI: 0.518 to 0.689),-6.05%(AUC=0.660, 95%CI: 0.578 to 0.742),4 cm(AUC=0.618, 95%CI: 0.533 to 0.703), respectively. Univariate and multivariate Logistic regression analysis showed that DeRitis≥0.95,GGT concentration ≥38.2 U/L,-aPBTLR>-6.05% and the maximum tumor diameter ≥4 cm were independent related factors for MVI in hepatocellular carcinoma patients(all P<0.05). The nomogram prediction model based on the above four factors established by R software has good prediction efficiency. The C-index was 0.758 and 0.751 in the model group and the validation group,respectively. Decision curve analysis and clinical impact curve showed that the nomogram model had good clinical benefits. Conclusions: DeRitis ratio,serum GGT concentration,-aPBTLR and the maximum tumor diameter are valuable factors for preoperative prediction of hepatocellular carcinoma with MVI. A relatively reliable nomogram prediction model could be established on them.

Clinical efficacy observation of omalizumab on patients with moderate to severe allergic asthma for one year / 中华预防医学杂志

To observe the symptom control, pulmonary function changes and safety of use of omalizumab in patients with moderate to severe allergic asthma for 1 year. A small sample self-controlled study before and after treatment was conducted to retrospective analysis involved 17 patients with moderate to severe asthma who received omalizumab therapy for 12 months in Peking University People's Hospital and Beijing Jishuitan Hospital from January 2020 to December 2021. The clinical symptoms and pulmonary function changes were compared before treatment, after 6 months and 12 months of treatment, and the clinical data such as the use of other drugs and adverse reactions were observed. Statistical data are collected using the median method, and non-parametric paired Wilcoxon analysis was used for pairwise comparison. Before treatment with omalizumab, the patients' FeNO value was 79(58, 121) ppb, and the total serum IgE was 228(150.5, 345.5) IU/ml. After 6 months of omalizumab therapy, the percent predicted value of the forced expiratory volume in 1 second (FEV1%) before inhaled bronchodilator increased from 86.70(82.65, 91.35)% to 90.90(87.70, 95.85)% (Z=-3.626, P<0.001). The FEV1%pred after inhaled bronchodilator increased from 92.60(85.75, 96.90)% to 94.30(89.95, 98.15)% (Z=-2.178, P=0.029). The absolute value of improvement in FEV1 decreased from 150(95, 210)ml to 50(20, 125) ml (Z=-2.796, P=0.005), and the improvement rate decreased from 6.60(3.80, 7.85)% to 1.90(0.75, 4.85)% (Z=-2.922, P=0.003). After 12 months of treatment, the FEV1%pred before inhaled bronchodilator further increased to 92.90 (91.60, 98.15)% (Z=-3.575, -2.818, and P<0.001, 0.005 compared with before treatment and 6 months after treatment, respectively). The FEV1%pred after inhaled bronchodilator increased to 96.80 (91.90, 101.25)% (Z=-3.622, -1.638, and P<0.001, 0.008 compared with before treatment and after 6 months of treatment, respectively). The absolute value of improvement in FEV1 was 70 (35, 120) ml (P=0.004, 0.842 before treatment and 6 months after treatment, respectively), and the improvement rate was 3.0(1.0, 5.0)% (Z=-2.960, -0.166, and P=0.003, 0.868, compared with before treatment and after 6 months of treatment, respectively). After 12 months of treatment, ACT increased from 13 (10.5, 18) before treatment to 24 (23, 25) (Z=-3.626,P<0.001). Only 1 patient experienced an injection site skin reaction during treatment. Therefore, after 6 months and 12 months of treatment with omalizumab, the patient's lung function improved and symptoms were relieved, which could effectively prevent the acute exacerbation of asthma. Omalizumab treatment is safe and well tolerated, and no effect on blood pressure and blood glucose was observed.

Efficacy of glucocorticoid stent implantation in ethmoid sinus after endoscopic sinus surgery for chronic rhinosinusitis with nasal polyps / 临床耳鼻咽喉头颈外科杂志

Objective:To evaluate the efficacy of glucocorticoid sinus stents implanted 2 weeks after functional endoscopic sinus surgery（FESS） for the treatment of chronic rhinosinusitis with nasal polyps（CRSwNP）. Methods:CRSwNP patients with similar bilateral lesions were randomly divided into two groups, with a stent group of 25 patients and a control group of 24 patients. Patients in the stent group had glucocorticoid sinus stents implanted into the bilateral ethmoid sinuses 2 weeks after FESS, while the control group underwent postoperative debridement only. Follow-up assessments occurred at postoperative weeks 2, 4, 8, and 12. Patients were asked to assess their sensation of nasal symptoms using a 10-point visual analog scale. Efficacy was assessed by endoscopic evaluations. Sinus obstruction, crusting/coagulation, polyp formation, middle turbinate position, adhesions, mucosa epithelialization, and postoperative intervention were assessed as efficacy outcomes. GraphPad Prism 9 was applied for statistical analysis. Results:At 4 and 8 weeks postoperatively, the stent group showed significant improvement in VAS scores of nasal congestion and runny nose compared with the control group（P<0.05）. No significant difference was observed in the VAS scores of head and facial stuffiness, loss of smell, or nasal dryness/crusting between the two groups（P>0.05）. Compared with the control group, the stent group had a lower rate of polypoid formation at 4, 8, and 12 weeks postoperatively. At postoperative week 12, the rate of mucosal epithelialization in the ethmoid cavity was significantly higher in the stent group. During the follow-up, the frequency of postoperative intervention was significantly lower in the stent group than in the control group（P<0.05）. Besides, a lower incidence of middle turbinate lateralization was found in the stent group at 8 and 12 weeks postoperatively. At 8 weeks postoperatively, the stent group had a percentage of adhesion lower than that of the control group（all P<0.05）. Conclusion:Implantation of glucocorticoid sinus stents after FESS can maintain sinus cavity patency, improve the inflammatory status of the operative cavity, reduce postoperative interventions, and promote benign regression of the operative cavity.

Polysaccharide Krestin Prevents Alzheimer's Disease-type Pathology and Cognitive Deficits by Enhancing Monocyte Amyloid-β Processing / 神经科学通报·英文版

Deficits in the clearance of amyloid β protein (Aβ) by the peripheral system play a critical role in the pathogenesis of sporadic Alzheimer's disease (AD). Impaired uptake of Aβ by dysfunctional monocytes is deemed to be one of the major mechanisms underlying deficient peripheral Aβ clearance in AD. In the current study, flow cytometry and biochemical and behavioral techniques were applied to investigate the effects of polysaccharide krestin (PSK) on AD-related pathology in vitro and in vivo. We found that PSK, widely used in therapy for various cancers, has the potential to enhance Aβ uptake and intracellular processing by human monocytes in vitro. After administration of PSK by intraperitoneal injection, APP/PS1 mice performed better in behavioral tests, along with reduced Aβ deposition, neuroinflammation, neuronal loss, and tau hyperphosphorylation. These results suggest that PSK holds promise as a preventive agent for AD by strengthening the Aβ clearance by blood monocytes and alleviating AD-like pathology.

Association between the Neutrophil-to-lymphocyte Ratio and New-onset Subclinical Macrovascular and Microvascular Diseases in the Chinese Population / 生物医学与环境科学（英文）

OBJECTIVE@#The association between neutrophil-to-lymphocyte ratio (NLR) with subclinical macrovascular and microvascular diseases has been less investigated. We sought to examine the association between NLR and new-onset subclinical macrovascular and microvascular abnormalities in the Chinese population.@*METHODS@#From a community cohort, we included 6,430 adults aged ≥ 40 years without subclinical macrovascular and microvascular diseases at baseline. We measured subclinical macrovascular and microvascular abnormalities separately using the ankle-brachial index (ABI), brachial-ankle pulse wave velocity (baPWV), and albuminuria.@*RESULTS@#During a mean follow-up of 4.3 years, 110 participants developed incident abnormal ABI, 746 participants developed incident elevated baPWV, and 503 participants developed incident albuminuria. Poisson regression analysis indicated that NLR was significantly associated with an increased risk of new-onset abnormal ABI, elevated baPWV, and albuminuria. Compared to overweight/obese participants, we found a much stronger association between NLR and subclinical vascular abnormalities in participants with normal weight. Furthermore, we found an interaction between the NLR and body mass index (BMI) on the risk of new-onset abnormal ABI ( P for interaction: 0.01).@*CONCLUSION@#NLR was associated with subclinical macrovascular and microvascular diseases in the Chinese population. Furthermore, in participants with normal weight, the association between NLR and subclinical vascular abnormalities was much stronger.

Infection and distribution characteristics of HPV of middle-aged and elderly women from a certain hospital in Guangxi Zhuang Autonomous Region from 2018 to 2020 / 中华预防医学杂志

Objectives: To analyze the type and distribution characteristics of human papillomavirus (HPV) infection along with cervical cytology in middle-aged and elderly women in Guangxi and to provide a basis for the prevention and treatment of cervical cancer in elderly women. Methods: 21 subtypes of HPV and cervical cytology of women over 45-year-old visiting the First Affiliated Hospital of Guangxi Medical University from January 2019 to December 2020 were collected. They were divided into two groups by age, 45-64 years group and over 65 years group. The HPV, HR-HPV, and multiple HPV infection prevalence were analyzed, as well as HPV genotypes, the age distribution of HPV infection rate, and cervical cytology. Results: A total of 6 657 eligible women were included. 6 238 women were in the 45-64 years group, with a HPV prevalence about 20.86% (1 301), while 419 women were in the over 65 years group, with a HPV prevalence about 32.94% (138). The age-associated HPV and HR-HPV prevalence increased with the age, peaking at the age group of 70-74 years (P<0.001). The most prevalent genotype was HPV52, and the infection rate was 5.3% (353), followed by HPV16 and HPV 58, about 4.63% (308) and 3.08% (205) respectively. The majority cytology of HPV-positive middle-aged and elderly women was normal. 8.70% (88) of them were ASC-US, 6.52% (66) for HSIL, 4.55% (46) for LSIL, and 2.96% (30) for ASC-H, and 0.10% (1) for SCC. Compared to middle-aged women, elderly women had a lower negative cytology rate, 69.79% (67) vs. 77.95% (714), but a higher HSIL rate, 13.54% (13) vs. 5.79% (53) (P<0.05). Conclusions: HPV and HR-HPV prevalence of elderly women in a medical center of Guangxi are higher than those of middle-aged women. The most prevalent genotype is HPV16 in elderly women, followed by HPV52 and HPV58.