Clinical efficacy of adjunctive perampanel in focal epilepsy patients≥12 years old / 中华神经医学杂志

Objective:To evaluate the clinical efficacy, tolerability and safety of adjunctive perampanel in focal epilepsy patients≥12 years old.Methods:One hundred and nineteen focal epilepsy patients≥12 years old accepted adjunctive perampanel in Department of Neurology, First Affiliated Hospital of Guangxi Medical University from July 2020 to December 2022 were chosen. At 1-3 months, 4-6 months, 7-9 months and 10-12 months after adjunctive perampanel, seizure frequency changes every 28 d, medication retention rate and adverse reactions were recorded to evaluate the clinical efficacy (a reduction in seizure frequency≥50% from baseline was defined as overall valid treatment), tolerability and safety of adjunctive perampanel. According to efficacy results after adjunctive perampanel of 4-6 months (short-term) and 10-12 months (long-term), these patients were divided into valid group and invalid group; and the influencing factors for short-term and long-term efficacy were analyzed.Results:At 1-3, 4-6, 7-9, 10-12 months after adjunctive perampanel, reduction in seizure frequency every 28 d was 66.7% (24.3%, 97.2%), 77.5% (48.6%, 100%), 94.6% (50%, 100%), 100% (70.9%, 100%), enjoying overall valid rate of 60.2% (59/98), 75.0% (7/76), 78.9% (45/57), 86.5% (32/37). The retention rate at 3, 6, 9 and 12 months after adjunctive perampanel was 85.2% (98/115), 67.9% (76/112), 54.3% (57/105), 41.1% (37/90). Adverse reactions were reported in 33 patents (27.7%), mainly with dizziness and secondly with mental symptoms. After short-term and long-term adjunctive perampanel, no significant difference was noted in gender, initial age of adjunctive perampanel, course of disease, etiology, EEG results, imaging results, number and type of combined anti-seizure drugs, or maximum dose of pirampanel between the valid group and invalid group ( P>0.05). Conclusion:Perampanel has good efficacy, tolerability and safety in adolescents and adults≥12 years old with focal epilepsy; no clear influencing factors for pirampanel valid treatment is found so far.

Study on the mechanism of Yishen daluo decoction in alleviating nervous system inflammation in EAE model mice / 中国药房

OBJECTIVE To study the effects of Yishen daluo decoction on inflammatory factors and cyclic adenosine monophosphate（cAMP）/protein kinase A （PKA）/cAMP response element binding protein （CREB） signal pathway in experimental autoimmune encephalomyelitis （EAE） model mice by inhibiting the expressions of β-arrestin1， and to explore the mechanism of Yishen daluo decoction in the treatment of EAE. METHODS Sixty mice were randomly divided into normal group， model group， TCM group （Yishen daluo decoction 20 g/kg）， positive control group （prednisone acetate 3.9 mg/kg）， β-arrestin1 siRNA adeno- associated virus （AAV-β） group， AAV-β+TCM group， with 10 mice in each group. Except for normal group， EAE model was made in other groups. AAV-β group and AAV-β+TCM group were injected with AAV-β via tail vein to interfere with the expression of β -arrestin1 protein. Starting from the 8th day of modeling， they were given corresponding drug solution/normal saline intragastrically， once a day， for consecutive 14 days. The neurological function score of mice was detected； the pathological and morphological changes were observed in the brain and spinal cord tissues of mice； the serum levels of inflammatory factors [interleukin-2 （IL-2）， IL-23， interferon-γ （IFN-γ）] in mice were determined； the expressions of β-arrestin1， cAMP， PKA and CREB in brain and spinal cord were detected. RESULTS Compared with normal group， neurological function scores， serum levels of inflammatory factors， and protein expressions of β-arrestin1 in brain and spinal cord were significantly increased （P＜0.05 or P＜ 0.01）； protein expressions of PKA， CREB and cAMP in brain and spinal cord were decreased significantly（P＜0.05 or P＜0.01）. The deep staining of cellular shrinkage and aggregation of inflammatory cells were observed in most neurons of the brain and spinal cord， with varying degrees of demyelinating. Compared with model group， the neurological function scores， pathological changes in brain and spinal cord tissues， and most indicators （except for CREB and cAMP proteins in the brain tissue of AAV-β group） were significantly reversed （P＜0.05 or P＜0.01）.Compared with AAV- β group， the neurological function scores， the levels of IFN-γ in serum and β-arrestin1 in spinal cord were significantly decreased （P＜0.05 or P＜0.01）， PKA and cAMP in brain and spinal cord tissues were significantly increased in AAV- β +TCM group （P＜0.05 or P＜0.01）. CONCLUSIONS Yishen daluo decoction can inhibit the expression of β-arrestin1 in the central nervous system thus activating the cAMP/PKA/CREB signaling pathway， relieving nervous system inflammation， and ultimately alleviates the symptoms of EAE.

Research on the Correlation between Hospital Ethical Atmosphere and Work Engagement of Emergency Department Nurses / 中国医学伦理学

【Objective:】 To explore the correlation between hospital ethics atmosphere and work engagement of nurses in emergency department, and provide a basis for reasonably solving ethical issues and improving nurses’ work engagement. 【Methods:】 From May 2019 to May 2021, the convenient sampling method was used to select 350 nurses from emergency departments of four tertiary or above hospitals in Xi’an as the research subjects. The Ethical Climate Cognitive Scale and the Work Engagement Scale were used to evaluate the hospital ethical atmosphere and work engagement of nurse, and analyze their correlation. The univariate factor analysis and multiple factor analysis were used to explore the influencing factors. 【Results:】 The work engagement score of emergency department nurses was (51.69±11.09) points, and the ethical atmosphere score was (72.78±11.45) points. The results of univariate analysis showed that there were statistically significant differences in the work engagement scores among emergency department nurses with different educational backgrounds, hospital grades, hospital employment methods, and whether they had received ethics training (P<0.05). The results of multiple factor analysis indicated that the cognition of hospital ethical atmosphere, hospital employment methods, and whether they had received ethics education and training were all factors that affected work engagement (P<0.05). 【Conclusion:】 The hospital ethical atmosphere is positively correlated with the work engagement of emergency department nurse. The ethical atmosphere and work engagement of nurses are both at a moderate level, with significant room for improvement. Therefore, it is necessary to continue to strengthen the management support of emergency nursing work and improve the perceived level of recognition and respect among emergency department nurses in the organization.

Study on the features of Clostridioides difficile infection among diarrhea patients in Kunming from 2018 to 2020 / 中华流行病学杂志

Objective: We analyze the characteristics of Clostridioides difficile (C. difficile) infection among diarrhea patients in Kunming from 2018 to 2020 and provide evidence for follow-up surveillance and prevention. Methods: A total of 388 fecal samples of diarrhea patients from four sentinel hospitals in Yunnan Province from 2018 to 2020 were collected. Real-time quantitative PCR was used to detect the fecal toxin genes of C. difficile. The positive fecal samples isolated the bacteria, and isolates were identified by mass spectrometry. The genomic DNA of the strains was extracted for multi-locus sequence typing (MLST). The fecal toxin, strain isolation, and clinical patient characteristics, including co-infection with other pathogens, were analyzed. Results: Among the 388 fecal samples, 47 samples with positive reference genes of C. difficile were positive, with a total positive rate of 12.11%. There were 4 (8.51%) non-toxigenic and 43 (91.49%) toxigenic ones. A total of 18 strains C. difficile were isolated from 47 positive specimens, and the isolation rate of positive specimens was 38.30%. Among them, 14 strains were positive for tcdA, tcdB, tcdC, tcdR, and tcdE. All 18 strains of C. difficile were negative for binary toxins. The MLST results showed 10 sequence types (ST), including 5 strains of ST37, accounting for 27.78%; 2 strains of ST129, ST3, ST54, and ST2, respectively; and 1 strain of ST35, ST532, ST48, ST27, and ST39, respectively. Fecal toxin gene positive (tcdB+) results were statistically associated with the patient's age group and with or without fever before the visit; positive isolates were only statistically associated with the patient's age group. In addition, some C. difficile patients have co-infection with other diarrhea-related viruses. Conclusions: The infection of C. difficile in diarrhea patients in Kunming is mostly toxigenic strains, and the high diversity of strains was identified using the MLST method. Therefore, the surveillance and prevention of C. difficile should be strengthened.

Establishment of PCR assays and genetic polymorphism analysis of genes encoding Clostridium perfringens β2 toxin from different sources / 中华流行病学杂志

Objective: To establish and optimize PCR methods for the gene encoding of Clostridium perfringens β2 toxin (cpb2) and atypical-cpb2 (aty-cpb2), analyze the epidemiological characteristics and genetic polymorphism of the cpb2 of Clostridium perfringens in 9 Chinese areas from 2016 to 2021. Methods: The cpb2 of 188 Clostridium perfringens strains were examined by PCR; the cpb2 sequences were acquired by whole-genome sequencing to analyze the genetic polymorphism. Using Mega 11 and the Makeblastdb tool, a phylogenetic tree, and cpb2-library based on 110 strains carrying the cpb2 were produced. Using the Blastn technique, a comparison was made to discover sequence similarity between consensus-cpb2 (con-cpb2) and aty-cpb2. Results: The specificity of PCR assay for the cpb2 and aty-cpb2 was verified. The PCR results for cpb2 amplification were highly consistent with the whole-genome sequencing approach (Kappa=0.946, P<0.001). A total of 107 strains from nine regions in China carried cpb2, 94 types A strains carried aty-cpb2, 6 types A strains carried con-cpb2, and 7 types F strains carried aty-cpb2. The nucleotide sequence similarity between the two coding genes was 68.97%-70.97%, and the similarity between the same coding genes was 98.00%-100.00%. Conclusions: In this study, a specific PCR method for cpb2 toxin was developed, and the previous PCR method for detecting aty-cpb2 was improved. aty-cpb2 is the primary gene encoding of β2 toxin. There is a significant nucleotide sequence variance between the various cpb2 genotypes.

Investigation on medical security and quality of life of migrant workers with pneumoconiosis / 中华劳动卫生职业病杂志

Objective: To investigate and understand the medical security and quality of life of migrant workers with pneumoconiosis, so as to provide scientific basis for the prevention and control countermeasures of migrant workers with pneumoconiosis and targeted poverty alleviation. Methods: Using a stratified random sampling method, 200 migrant workers diagnosed with pneumoconiosis at the Shandong Academy of Occupational Health and Occupational Medicine from January 2016 to December 2021 were selected as the observation group, while 200 non migrant workers diagnosed with pneumoconiosis were selected as the control group. St. George's Respiratory Questionnaire (SGRQ) and Pneumoconiosis Questionnaire were used to collect and compare information on the age, working age of dust exposure, economic sources, employment status, income, medical security and quality of life of two groups of patients. Results: The age of migrant worker pneumoconiosis patients in the observation group was (58.1±8.1) years old, and the working age of dust exposure was (19.3±10.1) years. The main source of income was children support (85.5%, 171/200), employment status was mainly wait for employment or unemployed (69.0%, 138/200), personal monthly income was mainly non income (90.0%, 180/200), and family annual income was mainly less than 10000 yuan (48.0%, 96/200). The average personal annual medical expenditure of 5000-<10000 yuan accounted for 42.0% (84/200). The age of pneumoconiosis patients in the control group was (59.2±8.9) years old, and the working age of dust exposure was (20.2±10.5) years. The main source of income was retirement pension or salary (99.0%, 198/200), with retirement as the main employment status (66.0%, 132/200), the main personal monthly income was 2000-<4000 yuan (61.5%, 123/200), the main family annual income was 20000-<40000 yuan (44.0%, 88/200), and the average personal annual medical expenditure was mostly non-expenditure (92.0%, 184/200). There were statistically significant differences in the distribution of economic sources, employment status, personal monthly income, family annual income and average personal annual medical expenditure between the two groups (P<0.001). The main type of insurance for the observation group was rural cooperative medical care (68.5%, 137/200), and 87.0% (174/200) had no medical reimbursement and a proportion less than 50%. There were statistically significant differences in insurance type and medical reimbursement proportion between the two groups (P<0.001). The respiratory symptoms, activity ability, daily life influence and total quality of life scores of pneumoconiosis patients in the observation group were significantly higher than those in the control group, the differences were statistically significant (P<0.001) . Conclusion: Migrant workers with pneumoconiosis have low income, high medical expenditure, low medical reimbursement proportion and poor quality of life. Therefore, it is necessary to draw high attention from relevant departments and provide timely attention and assistance to improve the quality of life of migrant workers with pneumoconiosis.

Efficacy and safety of neoadjuvant chemotherapy combined with PD-1 antibody for esophageal squamous cell carcinoma in the real world / 中华肿瘤杂志

Objective: To evaluate the efficacy and safety of neoadjuvant chemotherapy combined with programmed death-1 (PD-1) antibody in operable, borderline or potentially resectable locally advanced esophageal squamous cell carcinoma(ESCC) in the real world. Methods: The study retrospectively analyzed 28 patients with operable or potentially resectable locally advanced ESCC patients treated with preoperative chemotherapy combined with PD-1 inhibitor in Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School from April 2020 to March 2021. According to the clinical TNM staging system of the 8th edition of the American Joint Committee on Cancer, there were 1, 15, 10, 1 and 1 case of stage Ⅱ, Ⅲ, ⅣA, ⅣB and unknown stage respectively. The treatment was two cycle of dual drug chemotherapy regimen including taxane plus platinum or fluorouracil combined with PD-1 antibody followed by tumor response assessment and surgery if the patient was eligible for resection. Results: Of the 28 patients, 1, 2, 3 and 4 cycles of chemotherapy combined with PD-1 antibody treatment completed in 1, 21, 5, and 1 patient, respectively. Objective response rate (ORR) was 71.4% (20/28), and disease control rate (DCR) was 100% (28/28). The incidence of adverse events exceeding grade 3 levels was 21.4% (6/28), including 3 neutropenia, 1 leukopenia, 1 thrombocytopenia and 1 immune hepatitis. There was no treatment-related death. Of the 23 patients underwent surgery, R0 resection rate was 87.0% (20/23), 13 patients had down staged to the T1-2N0M0 I stage, the pCR rate was 17.3% (4/23), and the pCR rate of primary tumor was 21.7% (5/23). Four patients received definitive chemoradiotherapy. One patient rejected surgery and other treatment after achieved PR response. Conclusion: Neoadjuvant chemotherapy combined PD-1 inhibitor is safe and has high efficacy in operable, borderline or potentially resectable locally advanced ESCC, and it is a promising regimen.

Update on the role and mechanism of erythropoietin receptor in acute kidney injury and repair or fibrosis / 生理学报

Acute kidney injury (AKI) is a common critical disease clinically with high morbility and mortality and some survival patients also progress to chronic kidney disease. Renal ischemia-reperfusion (IR) is one of the main causes of AKI, in which, its repair and potential fibrosis, apoptosis, inflammation and phagocytosis play important roles. During the progression of IR-induced AKI, the expression of erythropoietin homodimer receptor (EPOR)2 and EPOR and β common receptor formed heterodimer receptor (EPOR/βcR) is changed dynamically. Moreover, (EPOR)2 and EPOR/βcR may synergistically participate in renoprotection at the stage of AKI and early repair, whereas at the late stage of AKI, the (EPOR)2 induces renal fibrosis and the EPOR/βcR facilitates repair and remodelling. The underlying mechanism, signaling pathways and the different effect turning point of (EPOR)2 and EPOR/βcR have not been well defined. It has been reported that EPO, according to its 3D structure, derived helix B surface peptide (HBSP) and cyclic HBSP (CHBP) only bind to EPOR/βcR. Synthesized HBSP, therefore, provides an effective tool to distinguish the different roles and mechanisms of both receptors, with the (EPOR)2 promoting fibrosis or the EPOR/βcR leading to repair/remodelling at the late stage of AKI. This review discusses the similarities and differences of (EPOR)2 and EPOR/βcR in their impacts on apoptosis, inflammation and phagocytosis in AKI, repair and fibrosis post IR, associated mechanisms, signaling pathways and outcomes.

Analysis of risk factors of mortality in infants and toddlers with moderate to severe pediatric acute respiratory distress syndrome / 中华儿科杂志

Objective: To identify the risk factors in mortality of pediatric acute respiratory distress syndrome (PARDS) in pediatric intensive care unit (PICU). Methods: Second analysis of the data collected in the "efficacy of pulmonary surfactant (PS) in the treatment of children with moderate to severe PARDS" program. Retrospective case summary of the risk factors of mortality of children with moderate to severe PARDS who admitted in 14 participating tertiary PICU between December 2016 to December 2021. Differences in general condition, underlying diseases, oxygenation index, and mechanical ventilation were compared after the group was divided by survival at PICU discharge. When comparing between groups, the Mann-Whitney U test was used for measurement data, and the chi-square test was used for counting data. Receiver Operating Characteristic (ROC) curves were used to assess the accuracy of oxygen index (OI) in predicting mortality. Multivariate Logistic regression analysis was used to identify the risk factors for mortality. Results: Among 101 children with moderate to severe PARDS, 63 (62.4%) were males, 38 (37.6%) were females, aged (12±8) months. There were 23 cases in the non-survival group and 78 cases in the survival group. The combined rates of underlying diseases (52.2% (12/23) vs. 29.5% (23/78), χ2=4.04, P=0.045) and immune deficiency (30.4% (7/23) vs. 11.5% (9/78), χ2=4.76, P=0.029) in non-survival patients were significantly higher than those in survival patients, while the use of pulmonary surfactant (PS) was significantly lower (8.7% (2/23) vs. 41.0% (32/78), χ2=8.31, P=0.004). No significant differences existed in age, sex, pediatric critical illness score, etiology of PARDS, mechanical ventilation mode and fluid balance within 72 h (all P>0.05). OI on the first day (11.9(8.3, 17.1) vs.15.5(11.7, 23.0)), the second day (10.1(7.6, 16.6) vs.14.8(9.3, 26.2)) and the third day (9.2(6.6, 16.6) vs. 16.7(11.2, 31.4)) after PARDS identified were all higher in non-survival group compared to survival group (Z=-2.70, -2.52, -3.79 respectively, all P<0.05), and the improvement of OI in non-survival group was worse (0.03(-0.32, 0.31) vs. 0.32(-0.02, 0.56), Z=-2.49, P=0.013). ROC curve analysis showed that the OI on the thind day was more appropriate in predicting in-hospital mortality (area under the curve= 0.76, standard error 0.05,95%CI 0.65-0.87,P<0.001). When OI was set at 11.1, the sensitivity was 78.3% (95%CI 58.1%-90.3%), and the specificity was 60.3% (95%CI 49.2%-70.4%). Multivariate Logistic regression analysis showed that after adjusting for age, sex, pediatric critical illness score and fluid load within 72 h, no use of PS (OR=11.26, 95%CI 2.19-57.95, P=0.004), OI value on the third day (OR=7.93, 95%CI 1.51-41.69, P=0.014), and companied with immunodeficiency (OR=4.72, 95%CI 1.17-19.02, P=0.029) were independent risk factors for mortality in children with PARDS. Conclusions: The mortality of patients with moderate to severe PARDS is high, and immunodeficiency, no use of PS and OI on the third day after PARDS identified are the independent risk factors related to mortality. The OI on the third day after PARDS identified could be used to predict mortality.

Preliminary Results of Single-cell Transcriptome Sequencing in Renal Arterial Lesions of Takayasu Arteritis / 中国医学科学院学报

Objective To explore the preliminary application of single-cell RNA sequencing (scRNA-seq) in the renal arterial lesions in Takayasu arteritis (TA) patients. Methods This study included 2 TA patients with renal artery stenosis treated by bypass surgery in the Department of Vascular Surgery,Beijing Hospital.The obtained 2 renal artery samples were digested with two different protocols (GEXSCOPE kit and self-made digestion liquid) before scRNA-seq and bioinformatics analysis. Results A total of 2920 cells were obtained for further analysis.After unbiased cluster analysis,2 endothelial cell subsets,2 smooth muscle cell subsets,1 fibroblast subset,2 mononuclear macrophage subsets,1 T cell subset,and 1 undefined cell subset were identified.Among them,the two subsets of smooth muscle cells were contractile and secretory,respectively.The results of scRNA-seq indicated that enzymatic hydrolysis with GEXSCOPE kit produced a large number of endothelial cells (57.46%) and a small number of immune cells (13.21%).However,immune cells (34.64%) were dominant in the cells obtained by enzymatic hydrolysis with self-made digestive liquid. Conclusion scRNA-seq can be employed to explore the cellular heterogeneity of diseased vessels in TA patients.Different enzymatic digestion protocols may impact the proportion of different cells.

Inhibitory effects of simeprevir on Staphylococcusepidermidis and itsbiofilm in vitro / 中南大学学报(医学版)

OBJECTIVES@#Staphylococcus epidermidis (S. epidermidis) is a Gram-positive opportunistic pathogen that often causes hospital infections. With the abuse of antibiotics, the resistance of S. epidermidis gradually increases, and drug repurposing has become a research hotspot in the treating of refractory drug-resistant bacterial infections. This study aims to study the antimicrobial and antibiofilm effects of simeprevir, an antiviral hepatitis drug, on S. epidermidis in vitro.@*METHODS@#The micro-dilution assay was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of simeprevir against S. epidermidis. Crystal violet staining assay was used to detect the biofilm inhibitory effect of simeprevir. The antimicrobial activity of simeprevir against S. epidermidis and its biofilm were explored by SYTO9/PI fluorescent staining. The combined effect between simeprevir and gentamycin was assessed by checkerboard assay and was confirmed by time-inhibition assay.@*RESULTS@#Simeprevir showed significant antimicrobial effects against S. epidermidis type strains and clinical isolates with the MIC and MBC at 2-16 μg/mL and 4-32 μg/mL, respectively. The antimicrobial effects of simeprevir were confirmed by SYTO9/PI staining. Simeprevir at MIC could significantly inhibit and break the biofilm on cover slides. Similarly, simeprevir also significantly inhibit the biofilm formation on the surface of urine catheters either in TSB [from (0.700±0.020) to (0.050±0.004)] (t=54.03, P<0.001), or horse serum [from (1.00±0.02) to (0.13±0.01)] (t=82.78, P<0.001). Synergistic antimicrobial effect was found between simeprevir and gentamycin against S. epidermidis with the fractional inhibitory concentration index of 0.5.@*CONCLUSIONS@#Simeprevir shows antimicrobial effect and anti-biofilm activities against S. epidermidis.

Platelet RNA enables accurate detection of ovarian cancer: an intercontinental, biomarker identification study

Platelets are reprogrammed by cancer via a process called education, which favors cancer development. The transcriptional profile of tumor-educated platelets (TEPs) is skewed and therefore practicable for cancer detection. This intercontinental, hospital-based, diagnostic study included 761 treatment-naïve inpatients with histologically confirmed adnexal masses and 167 healthy controls from nine medical centers (China, n = 3; Netherlands, n = 5; Poland, n = 1) between September 2016 and May 2019. The main outcomes were the performance of TEPs and their combination with CA125 in two Chinese (VC1 and VC2) and the European (VC3) validation cohorts collectively and independently. Exploratory outcome was the value of TEPs in public pan-cancer platelet transcriptome datasets. The AUCs for TEPs in the combined validation cohort, VC1, VC2, and VC3 were 0.918 (95% CI 0.889-0.948), 0.923 (0.855-0.990), 0.918 (0.872-0.963), and 0.887 (0.813-0.960), respectively. Combination of TEPs and CA125 demonstrated an AUC of 0.922 (0.889-0.955) in the combined validation cohort; 0.955 (0.912-0.997) in VC1; 0.939 (0.901-0.977) in VC2; 0.917 (0.824-1.000) in VC3. For subgroup analysis, TEPs exhibited an AUC of 0.858, 0.859, and 0.920 to detect early-stage, borderline, non-epithelial diseases and 0.899 to discriminate ovarian cancer from endometriosis. TEPs had robustness, compatibility, and universality for preoperative diagnosis of ovarian cancer since it withstood validations in populations of different ethnicities, heterogeneous histological subtypes, and early-stage ovarian cancer. However, these observations warrant prospective validations in a larger population before clinical utilities.

Hydrogen intervenes early inflammation of silicosis through the NF-κB/NLRP3 signaling pathway / 中国职业医学

{L-End}Objective To study the intervention effect of hydrogen on early inflammation in a rat silicosis model and its mechanism. {L-End}Methods Wistar rats of specific pathogen free were randomly divided into the control group, model group, tetrandrine group, hydrogen group and combined intervention group, with 10 rats in each group. The rats in the last four groups were treated with a dose of l.00 mL silica suspension with a mass concentration of 50.0 g/L by a one-time non-exposed tracheal method. The rats in the control group were given 0.9% sodium chloride solution in equal volume. After 24 hours of dust exposure, rats of the tetrandrine group were given 30 mg/kg body mass tetrandrine by gavage daily, rats of the hydrogen group were given 66.6% hydrogen inhalation continuously for four hours daily, rats of the combined intervention group were given the same interventions as the rats in the tetrandrine group and the hydrogen group, rats in the control group and model group were given 0.9% sodium chloride solution in equal volume by gavage. After 14 days of treatment, the lung coefficient of rats was determined, and lung histopathology was performed. The level of malondialdehyde in serum was detected by colorimetry. The level of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) in serum were detected by enzyme-linked immunosorbent assay. The relative expression of nucleotide-binding oligomerization domain-like receptor thermal protein domain associated protein 3 (NLRP3), nuclear factor-κB (NF-κB) p65, NF-κB phosphorylated p65 (NF-κB p-p65), cysteinyl aspartate specific proteinase1 (Caspase1) and apoptosis-associated speck-like protein containing a CARD (ASC) in serum were detected in lung tissues by Western blot. The relative expression of NLRP3 and NF-κB p65 in lung tissues were detected by immunohistochemistry. {L-End}Results The result of pulmonary histopathology showed that the model group had obvious alveolar rupture and fusion, interstitial lymphocyte and macrophage infiltration, and alveolar wall thickening, collagen fibre deposition, and mild fibrotic hyperplasia, compared with the control group. The pathological outcomes of lung tissues in the three treated groups were alleviated compared with the model group, and the alveolar structure was more complete and the alveolar wall was thinner and the fewer collagen fibres in the rats of combined intervention group, compared with tetrandrine group and hydrogen group. The lung coefficient and Szapiel score of rats of the tetrandrine group, hydrogen group and combined intervention group were lower than those of the model group (all P<0.05). The levels of serum malondialdehyde, TNF-α and IL-1β in lung tissues, and the relative expression of NLRP3, NF-κB p65, NF-κB P-p65, Caspase1 and ASC in lung tissues increased in the model group, compared with the control group (all P<0.05). The indexes above decreased in the three treated groups than those in the model group (all P<0.05). The indexes above decreased in the combined intervention group than those in the tetrandrine group and hydrogen group (all P<0.05), except for the level of malondialdehyde in serum and the relative expression of NF-κB p-p65 in lung tissue. {L-End}Conclusion Hydrogen can intervene the early inflammation of silicosis through NF-κB/ NLRP3 signaling pathway.

Chr9∶52042693|52047844⁃miR⁃351⁃5p⁃Pten Is Involved in the Development and Progression of Obstructive Sleep Apnea Syndrome through a ceRNA Mechanism / 中国生物化学与分子生物学报

Intermittent hypoxia (IH) is an important pathophysiological feature of obstructive sleep apnea (OSA), but its molecular mechanism is still unclear. We aim to investigate the role of endogenous competing endogenous RNA (ceRNA) regulatory network in the development of IH in OSA rats. An intermittent hypoxic rat model of OSA was constructed by hypoxic and reoxygenation cycles. CircRNAs and mRNAs were detected in rat bronchial tissues, and 230 up-regulated and 181 down-regulated circRNAs and 1238 up-regulated and 608 down-regulated mRNAs were analyzed and screened. The results of Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the differential circRNAs and mRNAs suggested that they were mainly associated with metabolic pathways and PI3K-Akt signaling pathways. The key circRNAs (the top six circRNAs with the largest differences) were further validated by quantitative real-time polymerase chain reaction (qRT-PCR), chr9:52042693| 52047844 and chr4: 64889575|64899587 were expressed in bronchial tissues consistent with the sequencing results, which were used to further construct the ceRNA regulatory network. Four potential ceRNA regulatory networks were identified by TargetScan and miRanda database, combined with the results of differential circRNA and mRNA. The expression of molecules in the four potential ceRNA regulatory networks was detected by qRT-PCR in bronchial and lung tissues, and the results suggested that the expression of this regulatory network, chr9:52042693|52047844-miR-351-5p-Pten, was consistent with the sequencing results. The findings indicate that chr9:52042693 | 52047844-miR-351-5p-Pten may be involved in the development and progression of obstructive sleep apnea syndrome through a ceRNA mechanism.

Role of Flow Cytometry in the Diagnosis of Chronic Myeloid Leukemia / 中国实验血液学杂志

OBJECTIVE@#To analyze the immunological phenotype of chronic myeloid leukemia (CML), and explore its characteristics and significance.@*METHODS@#The immunophenotypes of 40 CML children and 40 controls were analyzed by multicolor flow cytometry. CD45/SSC, as the basic gate, was used to delineate neutrophils. Then, the distribution of cluster differentiation (CD) molecules on the surface of granulocytes was analyzed in three ranges (≥1%, ≥5%, and ≥20%), and the expression rates of CD molecules (≥1% included in the statistical analysis) and the mean fluorescence intensity (MFI) were compared between the two groups.@*RESULTS@#The proportion of granulocytes in the CML group was (82.1±6.4)%, which was significantly higher than (57.8±11.8)% in the control group (P <0.001). The expression rates of CD15/CD11b/CD33/CD13 in CML and control groups were high, and both distributed in the range of ≥20%. The differentiation trajectory of CD33/CD13 was normal and there were no significant differences in the expression rate and MFI between the two groups. However, both the expression rate of CD11b and CD15 MFI in the CML group were significantly lower than those in the control group (P <0.001). There were no significant differences in the expression rate and MFI of CD10 between the two groups, and the expression levels of CD10 between the two groups were consistent in different distributions. In the CML group, there was a large number of cases with abnormal high expression of CD56, 52.5% of the cases had a CD56 expression rate of ≥5%, and 42.5% had a CD56 expression rate of ≥20%, while the control group did not express CD56 (<1%). The expression distribution of CD117 was different between the two groups. In the range of expression rate ≥5%, there were 35.0% cases in the CML group, while only 2.5% in the control group. The expression rate of CD117 in the CML group was higher than that in the control group (P <0.001), though there was no significant difference in MFI.@*CONCLUSION@#The immunophenotyping of CML is characterized by increased proportion of mature neutrophils, decreased CD15 MFI, decreased proportion of CD11b and abnormal high expression of CD56 and CD117. Flow cytometric analysis of immunophenotype can effectively distinguish normal granulocytes from chronic granulocytes, and help in the diagnosis of CML.

Preparation of vitexin albumin nanoparticles and its pharmacokinetic study / 中国中药杂志

This study aims to prepare vitexin albumin nanoparticles(VT-BSA-NPs) to alleviate the low bioavailability of vitexin(VT) in vivo due to its poor water solubility. VT micro powders were prepared by the antisolvent crystallization method, and the morphology, size, and physicochemical properties of VT micro powders were studied. The results showed that the VT micro powder had a particle size of(187.13±7.15) nm, an approximate spherical morphology, and a uniform size distribution. Compared with VT, the chemical structure of VT micro powders has not changed. VT-BSA-NPs were prepared from VT micro powders by desolvation-crosslinking curing method. The preparation process was screened by single factor test and orthogonal test, and the quality evaluation of the optimal prescription particle size, PDI, Zeta potential, EE, and morphology was performed. The results showed that the average particle size of VT-BSA-NPs was(124.33±0.47) nm; the PDI was 0.184±0.012; the Zeta potential was(-48.83±2.20) mV, and the encapsulation rate was 83.43%±0.39%, all of which met the formulation-related requirements. The morphological results showed that the VT-BSA-NPs were approximately spherical in appearance, regular in shape, and without adhesion on the surface. In vitro release results showed a significantly reduced release rate of VT-BSA-NPs compared with VT, indicating a good sustained release effect. LC-MS/MS was used to establish an analytical method for in vivo analysis of VT and study the plasma pharmacokinetics of VT-BSA-NPs in rats. The results showed that the specificity of the analytical method was good, and the extraction recovery was more than 90%. Compared with VT and VT micro powders, VT-BSA-NPs could significantly increase AUC, MRT, and t_(1/2), which was beneficial to improve the bioavailability of VT.

Research progress on the correlation between autism spectrum disorder and food allergy / 中华实用儿科临床杂志

The incidences of both autism spectrum disorder and food allergy have been on the rise in the past few decades, which have become global public health problems.Autism spectrum disorder is a complex neurodevelopmental disorder commonly associated with gastrointestinal problems.The exact etiology and pathogenesis are unclear, and immune dysfunction has been shown associated with autism spectrum disorder.Food allergy is an immune-mediated disease that often causes gastrointestinal symptoms.Some studies have reported a possible link between food allergy and autism spectrum disorder.This reviews describes the correlation between food allergy and autism spectrum disorder, aiming to provide information for the study of etiology and treatment of autism spectrum disorder.

Research progress on the regulation and mechanism of reactive oxygen species on tumor immune checkpoints / 药学学报

Immune checkpoints (ICs) are immunosuppressive molecules expressed on immune cells, which can regulate immune cells' activation. Immune checkpoint inhibitors (ICIs) which can block the interaction of immune checkpoints and their ligands, improve the cytotoxic effect of the immune system on tumor cells. Immunotherapy such as employing ICIs has gradually become a conventional therapeutic strategy for cancer treatment. However, the low response rate and the emergence of drug resistance have seriously affected the clinical efficacy of ICIs. Reactive oxygen species (ROS) are electronic reduction products of active oxygen, as well as natural by-products of cell metabolism, which can be used as regulators of intercellular signals. Tumor microenvironment (TME) is often in the state of oxidative stress (OS), which is the imbalance between oxidative system and antioxidant system. ROS can affect the interaction with its ligands by regulating the expression and activity of immune checkpoints in TME, thus affecting the anti-tumor effect of immune cells. Accumulating studies have shown that ROS could regulate tumor immune checkpoints through several pathways. Due to different types and stages of tumor, it would be clinical beneficial to understand the mechanistic link of ROS on tumor immune checkpoint, and choose appropriate ROS regulators combined with immune checkpoint inhibitors to maximize anti-tumor effects. This article reviews the common metabolic sources and characteristics of ROS, the regulatory effect and mechanism of ROS on tumor immune checkpoints and its therapeutic application.

Progress in probiotics for treating Clostridioides difficile infection / 中华微生物学和免疫学杂志

Clostridioides difficile infection (CDI) is an infectious disease with fever, abdominal pain and diarrhea as the main clinical manifestations. At present, CDI is mainly treated with antibiotics and faecal microbiota transplantation. As recurrent and refractory CDI continues to increase, it is important to seek a more effective alternative therapy. However, many of the studies on the prevention and control of CDI by probiotics are still in the early stage. This paper summarized the research on the types, mechanisms and technical means of probiotics in the treatment of CDI.

Molecular epidemiological characteristics and antibiotic resistance of Clostridioides difficile in a tertiary hospital in Shaanxi Province / 中华微生物学和免疫学杂志

Objective:To investigate the molecular epidemiological characteristics and antibiotic resistance of Clostridioides difficile ( Cd) in hospitalized diarrhea patients in a tertiary hospital in Shaanxi Province. Methods:This study collected 425 stool samples of hospitalized diarrhea patients from October 2018 to December 2021 for isolation and identification of Cd. Toxin genes carried by the isolates were detected. Multilocus sequence typing (MLST) was performed to analyze the phylogenetic profile. Antibiotic susceptibility was analyzed by E-test. Results:Forty-nine strains of Cd were isolated from the 425 samples, including 37 strains of toxigenic Cd (75.5%, 37/49). The detection rate of Cd was 14.0% (25/179) in diarrhea patients aged ≥65 years old and 36.4% (4/11) in Nephrology Department. In the 37 toxigenic Cd strains, A -B + CDT -Cd, A + B + CDT -Cd and A + B + CDT +Cd accounted for 18.9% (7/37), 78.4% (29/37) and 2.7% (1/37), respectively. There were 24 ST types, among which ST2, ST3 and ST54 were the predominant types, each accounting for 12.2% (6/49). All strains were sensitive to metronidazole and vancomycin, with a high resistance rate of 93.9% (46/49) to ciprofloxacin and a low resistance rate of 12.2% (6/49) and 10.2% (5/49) to rifampicin and meropenem, respectively. Conclusions:The main type of toxigenic strains was A + B + CDT -. ST2, ST3 and ST54 were the predominant types and the distribution of ST types was scattered. All isolates were sensitive to metronidazole and vancomycin and most of them were resistant to ciprofloxacin.