Genetic polymorphism of WNT9A is functionally associated with thumb osteoarthritis in the Chinese population

Abstract Background In a recent genome-wide association study, novel genetic variations of WNT9A were reported to be involved in the etiopathogenesis of thumb osteoarthritis (TOA) in Caucasians. Our purposes were to replicate the association of WNT9A with the development of TOA in the Chinese population and to further unveil the functional role of the risk variants. Methods SNP rs11588850 of WNT9A were genotyped in 953 TOA patients and 1124 healthy controls. The differences of genotype and allele distributions between the patients and healthy controls were evaluated using the Chi-square test. Luciferase Reporter Assay was performed to investigate the influence of variant on the gene expression. Results There was significantly lower frequency of genotype AA in TOA patients than in the controls 74.9% vs. 81.9%, p < 0.001). The frequency of allele A was remarkably lower in the patients than in the controls (86.3% vs. 90.5%, p < 0.001), with an odds ratio of 0.66 (95% CI = 0.54-0.80). Luciferase Reporter Assay showed that the construct containing mutant allele G of rs11588850 displayed 29.1% higher enhancer activity than the wild allele A construct (p < 0.05). Conclusions Allele G of rs11588850 was associated with the increased risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA. Key Points Genetic variants of WNT9A were associated with the incidence and severity of TOA. Allele G of rs11588850 was associated with an increased transcriptional activity of WNT9A promoter. Allele G of rs11588850 may add to the risk of TOA possibly via up-regulation of WNT9A expression. Further functional analysis into the regulatory role of rs11588850 in WNT9A expression can shed new light on the genetic architecture of TOA.

A survey of symptoms after thoracoscopic lung cancer resection based on patient-reported outcomes / 中国胸心血管外科临床杂志

@#Objective     To analyze the changes of perioperative symptoms of lung cancer patients by using patient-reported outcomes at different time points. Methods    A total of 109 patients who underwent thoracoscopic lung cancer resection in the department of thoracic surgery of our hospital from March to April 2021 were selected, including 55 (50.46%) males and 54 (49.54%) females. The mean age was 55.19±12.12 years. The postoperative symptom scale for lung cancer patients was used to investigate the changes of symptoms before surgery, 1 day after surgery, the day of discharge, and 30 days after surgery. Results     The mean hospital stay was 6.89±2.25 days. None of the patients reported any clinical symptoms related to lung cancer before surgery. The most prominent symptoms 1 day after surgery were pain (3.33±0.96 points), nausea (2.81±1.18 points), dizziness (2.00±0.85 points), fatigue (1.89±0.79 points) and shortness of breath (1.79±1.37 points). The patients with dizziness, nausea, fatigue and other symptoms gradually decreased, and the symptoms were relieved significantly (P<0.05). However, the symptoms of conscious pain, cough and shortness of breath lasted for a long time. At 30 days after surgery, 70.64%, 64.22% and 33.03% of patients felt pain, cough and shortness of breath, respectively, and the degree of cough was aggravated (P<0.001). Conclusion     Pain, cough, dizziness, shortness of breath and fatigue are the core postoperative symptoms of lung cancer patients. Most postoperative adverse symptoms can be effectively controlled in a short period of time, but pain, cough and shortness of breath still present persistent characteristics, which deserve further study.

Advantages and suggestions on the development of "Internet+nursing service" / 中国实用护理杂志

This paper summarized the development of "Internet + nursing service" in the first six provinces and cities, analyzed its characteristics and advantages, combed the existing problems, so as to further promote and develop "Internet + nursing service", so that the service can truly benefit the people.

One case report of adrenal crisis with difficulty in weaning after lumbar spinal canal decompression surgery / 中华内分泌外科杂志

Adrenocortical crisis (AC) is a kind of endocrine emergency, often occurs in infection, shock, trauma, or postoperative, if the processing is not handling timely, can endanger patient's life.But as the disease is not common and the clinical symptoms are not typical,so it is easy to be misdiagnosis and missed diagnosis.This case was a "lumbar spinal canal decompression surgery" patient, who appeared postoperative confusion, oxygenation decline,and could not seperated from breathing machine, clinical manifestations were atypical.

Anti-pyroptosis effect of Albiziae Cortex-Tribuli Fructus combination on hepatic stellate cell line LX2: based on network pharmacology / 中国中药杂志

Based on network pharmacology, molecular docking, and in vitro experimental verification, this study aims to explore the effect of Albiziae Cortex-Tribuli Fructus combination on HSC-LX2 pyroptosis. Specifically, the targets of Albiziae Cortex, Tribuli Fructus, and hepatic fibrosis were retrieved from an online database and CNKI, and "drug-component-target" network and "drug-component-target-disease" network were constructed. Protein-protein interaction(PPI) network was established based on STRING. Metascape was employed for Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment, and the mechanism of Albiziae Cortex-Tribuli Fructus combination against liver fibrosis was predicted. Molecular docking was used to verify some of the results of network pharmacology, and in vitro experiment was carried out to further verify the above conclusions. According to the results of network pharmacological analysis, 25 active components and 439 targets of Albiziae Cortex-Tribuli Fructus combination and 152 anti-liver fibrosis targets were screened out, including nucleotide-binding oligomerization domain and leucine-rich-repeat-and pyrin-domain-containing 3(NLRP3) and caspase-1. The key targets were involved in 194 KEGG pathways in which the NOD-like receptor signaling pathway topped. The binding common targets were related to pyroptosis. The results of in vitro experiment showed that the pair-containing serum reduced the proliferation rate of HSC-LX2 and the content of reactive oxygen species(ROS), interleukin-18(IL-18), and interleukin-1β(IL-1β)(P<0.05). Western blot and qRT-PCR suggested that the protein and gene expression of NLRP3, caspase-1, α-smooth muscle actin(α-SMA), and gasdermin D(GSDMD) in HSC-LX2 increased after AngⅡ stimulation, and the expression decreased after the intervention of pair-containing serum(P<0.05). In summary, the pair-containing serum can inhibit the classic pathway of pyroptosis, which may be the anti-liver fibrosis mechanism. This is consistent with the predicted results of network pharmacology.

Transcriptome analysis of Aedes aegypti larvae before and after treatment with fipronil / 中国热带医学

@#Abstract: Objective　In order to explore the application prospects of the phenyl pyrazole insecticide fipronil for mosquito control and identify potential target genes involved in the resistance of Aedes aegypti to fipronil, and lay the foundation for an in-depth study of the resistance mechanism of Aedes aegypti to fipronil. Methods　Using Aedes aegypti sensitive strains as experimental materials, Aedes aegypti larvae were treated with fipronil, and the differences in gene expression of Aedes aegypti larvae before and after drug administration were compared at the transcriptome level using transcriptome sequencing combined with bioinformatics analysis, and the differential genes were analyzed. Results　A total of 757 differentially expressed genes were identified between the fipronil-treated group and control group, including 217 and 540 up- and down-regulated genes, respectively. Among these, the expression of glutamate-gated chloride channel (GluCls) genes varied significantly before and after treatment. Gene ontology analysis revealed that differentially expressed genes were enriched in catalytic activity, binding, metabolic processes, and membrane-related functions, while KEGG pathway analysis indicated enrichment in biosynthesis, metabolism, and life regulation processes, while the glutathione metabolic pathway was enriched in 15 differentially expressed genes. Conclusions The transcriptome results revealed that GST gene expression was significantly upregulated in fipronil-treated Aedes aegypti larvae, indicating that GST gene is involved in the development of fipronil resistance in Aedes aegypti larvae. In addition, GluCls gene expression was also significantly different before and after treatment, suggesting that GluCls migh be a potential target receptor for fipronil resistance in Aedes aegypti. As GluCls is an ideal target receptor found only in invertebrates, this discovery provides a reference and basis for further exploration of the toxicological mechanism of fipronil on Aedes aegypti.

Failure mode and effect analysis for risk management of unplanned extubation after esophageal cancer surgery / 中国胸心血管外科临床杂志

@#Objective 聽 聽 To explore the application value of failure mode and effect analysis (FMEA) in the risk management of unplanned extubation after esophageal cancer surgery. Methods 聽 聽 A total of 1 140 patients who underwent esophageal cancer surgery in our department from January 2015 to May 2017 were selected as a control group, including 948 males and 192 females with an average age of 64.45卤4.53 years. FMEA was used to analyze the risk management process of unplanned extubation. The potential risk factors in each process were found by calculating the risk priority number (RPN) value, and the improvement plan was formulated for the key process with RPN>125 points. Then 1 117 patients who underwent esophageal cancer surgery from June 2017 to December 2019 were selected as a trial group, including 972 males and 145 females with an average age of 64.60卤5.22 years, and the FMEA risk management mode was applied. Results 聽 聽 The corrective measures were taken to optimize the high-risk process, and the RPN values of 9 high-risk processes were reduced to below 125 points after using FMEA risk management mode. The rate of unplanned extubation in the trial group was lower than that in the control group (P<0.05). Conclusion 聽 聽 The application of FMEA in the risk management of unplanned extubation after esophageal cancer surgery can reduce the rate of unplanned extubation, improve the quality of nursing, and ensure the safety of patients.

Evaluation of intervention effect of health education on overweight and obesity among middle school students in Guangzhou / 中国学校卫生

Objective@#To explore the effect of the comprehensive intervention on overweight and obesity among middle school students at the population level (health education lecture and official account push) and individual level (personalized dietary guidance), so as to provide a reference for preventing and controlling their overweight and obesity.@*Methods@#Three junior high schools and three senior high schools were randomly selected in Guangzhou in 2018 by convenience sampling. Through physical examination, 1 457 overweight and obese students aged from 12 to 18 years old were screened. Intervention was administered through "Student Personalized Dietary Guidance" manual, health tweets on the official accounts, and health education lectures from September 2018 to December 2019. The Chi square test was used to compare the difference in overweight and obesity constituent ratio between the two groups before and after the intervention. And intervention effect was evaluated by analyzing the number needed to treated(NTT).@*Results@#The proportion of overweight before the intervention was 66.71% (972/1 457), and decreased to 59.92% (873/1 457) after the intervention; the proportion of obesity before the intervention was 33.29% (485/1 457), which decreased to 26.63% (388/1 457) after the intervention. Among obese students, the smallest NNT was seen in the girl group aged 12-13 years (NNT=2.6, 95% CI =1.9-4.1), while the largest NNT in the boy group aged 14-18 years (NNT=5.9, 95% CI =4.7-8.1). The NNT of the girls aged 12-13 years was the smallest (NNT=2.7, 95% CI =2.2-3.5), and the NNT of the boys aged 14-18 years was the largest (NNT=7.4, 95% CI =6.0-9.7).@*Conclusion@#Health education at population level (health education lectures, official account push) with individual level (personalized dietary guidance) can effectively intervene overweight and obesity among middle school students in Guangzhou.

Research progress on the effects of ionizing radiation exposure on cardiovascular systems / 中国辐射卫生

With the rapid development and widespread application of medical imaging technologies, ionizing radiation has become unavoidable in human lives. Accurate assessment of healthy effects of ionizing radiation is of great significance to reduce the risk of exposure to radiation. Increasing evidence has proven the impact of ionizing radiation on cardiovascular systems. This article reviews the effects of ionizing radiation on heart, blood pressure, and blood vessels and the possible mechanisms, so as to provide insights into implementation of targeted protective interventions and reduction of ionizing radiation hazard.

Serological and molecular biological analysis of RhD--: a case report / 中国输血杂志

【Objective】 To study the blood group serology and molecular biology of patients with RhD--, so as to guide clinical blood use. 【Methods】 The EDTA-K2 anticoagulant blood of the patient was detected for Rh antigens and antibodies. Meanwhile, DNA was extracted, and the 1-10 exon of RHCE and RHAG gene was sequenced by Sanger sequencing. 【Results】 The serological test showed O type RhD--, and all spectral cells were positive. RHCE gene sequencing showed RHCE*02/RHCE*02, RHAG gene sequencing showed mutations at site 808 G > A and site 861 G > A of exon 6. 【Conclusion】 When patients were with RhD--, and related immune conditions such as pregnancy and/or transfusion history were present, autologous blood transfusion or plasma exchange could be an option for emergency blood use.

An acute kidney injury risk prediction model for elderly patients with sepsis based on the intensive care medicine information database-Ⅳ / 中华老年医学杂志

Objective:To explore the risk factors of acute kidney injury(stage 3)developed within 48 hours in elderly patients with sepsis, and to use them to develop a risk prediction model and then evaluate and externally validate the model.Methods:Clinical data of all elderly patients(age≥ 60 years)with sepsis in the intensive care medicine information database(MIMIC-Ⅳ v1.0)were extracted.Independent risk factors were determined by multivariate logistic regression analysis.A risk prediction model was constructed, a nomogram was drawn, and the receiver operating characteristic curve(ROC)and the Hosmer-Lemeshow(H-L)test were used to evaluate the model's prediction accuracy and R-squared.Clinical data of elderly patients(age≥ 60 years)with sepsis admitted to the Department of Critical Care Medicine of the Second People's Hospital of Hefei from May 2019 to October 2021 were retrospectively collected and fed into the prediction model to conduct external validation.Results:A total of 1 977 elderly patients with sepsis were screened out from the MIMIC-IV database and included in the training set, of whom, 544 developed AKI-stage 3 within 48 hours.Univariate analysis was performed for factors that might be associated with acute kidney injury in elderly patients with sepsis.Compared with the normal group that did not progress to AKI stage 3, there were statistically significant differences in 28 indicators, such as the duration of ICU stay, intravenous fluid intake in 24 hours, and use of vasoactive drugs[5(3, 9)d vs.7(4, 12)d; 2.05(1.17, 3.27)ml·kg -1·h -1vs.2.37(1.47, 4.10)ml·kg -1·h -1; 761(53.11%) vs.375(68.93%), P<0.001]. Based on the results of multivariate logistic regression analysis, a prediction model was finally constructed with 9 variables: albumin( OR=0.983, 95% CI: 0.966-0.999, P=0.040), aspartate transaminase( OR=1.000, 95% CI: 1.000-1.000, P<0.001), APTT( OR=1.005, 95% CI: 1.001-1.009, P=0.028), total bilirubin( OR=1.003, 95% CI: 1.001-1.004, P=0.001), serum creatinine( OR=1.005, 95% CI: 1.004~1.007, P<0.001), Charlson score( OR=1.117, 95% CI: 1.061-1.177, P<0.001), intravenous fluid intake in 24 hours( OR=1.101, 95% CI: 1.034-1.173, P=0.003), weight( OR=1.023, 95% CI: 1.018-1.029, P<0.001), and mechanical ventilation( OR=2.412, 95% CI: 1.843-3.157, P<0.001). Then a nomogram was generated.The area under the ROC curve(AUC)of the prediction model was 0.755(95% CI: 0.731-0.780), and the H-L test was conducted( χ2=10.89, P=0.208>0.05), indicating a good fit.Data from 102 elderly patients were included in the validation set, with 27 cases that had developed AKI-stage3 within 48 hours, and were fed into the prediction model, with an AUC of 0.778(95% CI: 0.676-0.880)and χ2=3.72 and P=0.882>0.05 from the H-L test, consistent with the results of the training set. Conclusions:The model has some predictive value for acute kidney injury in elderly patients with sepsis.

Analysis of the risk factors of acute gastrointestinal injury above grade II in elderly patients with severe pneumonia / 中国医师杂志

Objective:To establish a prediction model of acute gastrointestinal injury (AGI) above grade II in elderly patients with severe pneumonia, and to evaluate and validate the model internally.Methods:A retrospective analysis was performed on 268 patients aged >65 years with severe pneumonia admitted to the Second People′s Hospital of Hefei from June 2019 to May 2022 (207 cases in the training set and 61 cases in the verification set). Sixteen indicators, including age, sex, underlying disease, pneumonia Severity index (PSI) score, dosage of sedative and analgesic drugs, and mechanical ventilation time of all patients were collected. After logistic regression analysis in the training set, a model was established to predict AGI above grade Ⅱ in elderly patients with severe pneumonia. Receiver operating characteristic (ROC) curve was drawed and correction curve was used to evaluate the reliability of the model. The model was internally validated by validation set data.Results:Among 207 patients with severe pneumonia in the training set, 50 patients developed AGI above grade Ⅱ during treatment. The prediction model was established by logistic regression analysis as follows: When L=Sequential Organ Failure Assessment (SOFA)×0.181+ PSI score×0.066+ propofol dosage×0.607+ reifentanil dosage×1.187, L>19.288, it can be considered that patients with severe pneumonia have a 93.24% chance of developing grade Ⅱ or above AGI. The ROC curve showed that the model was well differentiated, AUC=0.960. H-L test indicated (χ 2=7.39, P=0.496>0.05) the model fit was good. The sensitivity and specificity of the model were 82.00% and 96.82% respectively. AUC=94.58% (sensitivity 81.25%, specificity 93.33%), H-L test indicated ( χ 2=4.51, P=0.808>0.05) the prediction accuracy was 90.16%. Conclusions:The prediction model for AGI after severe pneumonia in elderly patients can be used clinically to help predict the occurrence of AGI in elderly patients with multiple injuries.

Relationship between arterial blood partial pressure of carbon dioxide and prognosis of neurological function after cardiopulmonary resuscitation / 中国基层医药

Objective:To investigate the relationship between arterial blood partial pressure of carbon dioxide and neurological outcome after cardiopulmonary resuscitation.Methods:The clinical data of 116 patients who underwent cardiopulmonary resuscitation admitted to the Intensive Care Unit and Emergency Department of the Second People's Hospital of Hefei from January 2018 to January 2020 were retrospectively analyzed. According to the average arterial blood partial pressure of carbon dioxide within 24 hours after admission, patients were divided into normal (35 mmHg ≤ PaCO 2 ≤ 55 mmHg, 1 mmHg = 0.133 kPa, n = 44), hypercapnia (PaCO 2 > 55 mmHg, n = 51), and hypocapnia (PaCO 2 < 35 mmHg, n = 21) groups. ICU stay, in-hospital mortality, and neurological outcome at discharge were compared among groups. A logistic regression analysis model was established. The relationship between PaCO 2 and neurological outcome was determined. Results:There were no significant differences in age, sex, cardiac arrest time, acute physiological and chronic health evaluation II score at admission, 1-hour mean arterial pressure, location of cardiac arrest, and initial heart rhythm among the three groups (all P > 0.05). ICU stay in the normal group [(7.23 ± 2.55) days] was significantly higher than that in the hypercapnia [(12.21 ± 4.12) days] and hypocapnia [(11.78 ± 4.72) days] groups ( t = 6.48, 4.59, both P < 0.01). In-hospital mortality in the normal group was 38.6% (17/44), which was significantly lower than 60.8% (31/51) in the hypercapnia group and 66.7% (14/21) in the hypocapnia group ( χ2 = 4.63, 4.47, both P < 0.05). The good neurological outcome rate in the normal group was 55.6% (15/44), which was significantly higher than 25.0% (5/51) in the hypercapnia group and 28.6% (2/21) in the hypocapnia group ( χ2 = 8.38, 5.14, both P < 0.05). Multivariate logistic regression analysis showed that cardiac arrest time, 1-hour mean arterial pressure, acute physiological and chronic health evaluation II score, and PaCO 2 are important factors for neurological outcomes of resuscitated patients at discharge (all P < 0.01). Conclusion:Within 24 hours after cardiopulmonary resuscitation, maintaining a normal PaCO 2 level can help improve the neurological outcome of patients at discharge.

Decitabine combined with chemotherapy in treatment of relapsed T lymphoblastic lymphoma/leukemia with TP53 mutation after allogeneic hematopoietic stem cell transplantation: report of 1 case and review of literature / 白血病·淋巴瘤

Objective:To observe the efficacy and safety of decitabine combined with chemotherapy in treatment of relapsed/refractory T lymphoblastic lymphoma/leukemia (T-LBL/ALL) with TP53 mutation.Methods:The clinical data of a T-LBL/ALL patient with TP53 mutation who had recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) treated with decitabine combined with chemotherapy in the First Affiliated Hospital of Soochow University in June 2018 were retrospectively analyzed and the relevant literature was reviewed.Results:The patient, a 42-year-old male, diagnosed as T-LBL/ALL with TP53 mutation by comprehensive examination underwent sibling-matched donor allo-HSCT after a second complete remission. The patient relapsed 8 months later and was treated with decitabine combined with CLAG regimen to achieve complete remission again. And then, he had leukemia-free survival until now through maintenance treatment with decitabine.Conclusion:Decitabine combined with chemotherapy may be a safe and effective treatment option for relapsed T-LBL/ALL patients with TP53 mutation after allo-HSCT.

Cumulative Meta analysis of the association between obesity and autism spectrum disorders in children and adolescents / 中国学校卫生

Objective@#This study conducts a Meta analysis on the epidemiological studies of obesity and autism spectrum disorder (ASD) in order to explore the relationship between autism spectrum disorder and obesity in children and adolescents, and to provide some guidance for improving the quality of daily life of children and adolescents with ASD.@*Methods@#PubMed and CNKI (January,2010-January,2022) were systematically searched for literature related to autism spectrum disorders reported the or value by Meta analysis, and compared the weight, BMI acquisition method.@*Results@#A total of 11 literatures were selected for analysis. The total sample included 336 830 participants, including 58 187 patients with ASD and 278 643 patients with normal development. Through Meta analysis, children and adolescents with ASD had a higher risk of obesity than normal people ( OR=1.80, 95%CI = 1.74 -1.86). when stratified by BMI acquisition, autistic patients with BMI obtained from objective measurement, medical records and parents reports had a higher risk of obesity than normal people, and the OR value (95% CI ) was 1.43(1.04-1.96),5.23( 4.44- 6.16),2.57(1.79-3.69). When stratified by age, children and adolescents with ASD aged 14 to 20 years had a higher risk of obesity than normal people. The OR value (95% CI ) was 2.19(1.21-3.94).@*Conclusion@#Compared with healthy peers, children and adolescents with ASD have a higher risk of obesity. ASD patients need guidance in diet and physical activity, especially in adolescence, to prevent obesity or diseases caused by obesity.

Uniportal thoracoscopic decortication in the treatment of chronic tuberculous empyema / 中华胸心血管外科杂志

Objective:To investigate the surgical procedure and outcome of uniportal thoracoscopic decortication in the treatment of chronic tuberculous empyema.Methods:From March 2019 to December 2019, the clinical data of 53 patients with chronic tuberculous empyema, who underwent uniportal thoracoscopic decortication in the Surgical Department of Wuhan Pulmonary Hospital were retrospectively analyzed. There were 40 males and 13 females. Age ranged from 16 to 69, averaged 36 years old.36 cases were on the right side and 17 cases on the left side, 38 cases were complicated with pulmonary tuberculosis. All cases had been diagnosed as tuberculous empyema by pathogeny and pathology test in preoperative or postoperative, and received tuberculosis management treatment between 2 and 12 months prior to surgery.The surgical procedure and clinical efficacy of uniportal thoracoscopic decortication were expounded in treatment of chronic tuberculous empyema.Results:Among the 53 patients, 49(92.45%) cases underwent uniportal thoracoscopic decortication, and 4(7.55%) cases changed to thoracotomy. The duration of surgery was 100-370 min, mean(234.53±56.06)min. Intraoperative hemorrhage was 50-1 400 ml, median value 300(175.0, 402.5)ml. Catheter retention time was 3-22 days, median value 8(6.00, 11.25)days. The incidence of surgical complications was 1.89%(1/53), the cure rate was 92.45%(49/53).Conclusion:If the perioperative evaluation and treatment are appropriate, and the operator is experienced, the uniportal thoracoscopic decortication is feasible, safe and effective in the therapy of chronic tuberculous empyema.

The mechanism of proprotein convertase subtilisin/kexin type 9 in the inflammatory response induced by Helicobacter pylori infection / 中华消化杂志

Objective:To explore the mechanism of proprotein convertase subtilisin/kexin type 9 (PCSK9) in the inflammatory response induced by Helicobacter pylori ( H. pylori) infection. Methods:From May 1, 2020 to January 31, 2021, 60 patients with gastritis (30 H. pylori positive and 30 H. pylori negative)and 30 healthy individuals, who initially visited the Department of Gastroenterology, Shiyan Taihe Hospital were collected, and their serum PCSK9 levels were detected. Normal gastric epithelial cell line GES-1 and macrophages induced from THP-1 cells, and GES-1 infected with H. pylori were selected to prepare different supernatant media. Phosphate buffer saline empty medium (negative control group), normal GES-1 cell supernatant medium ( H. pylori-uninfected GES-1 group), H. pylori infected GES-1 cell supernatant medium ( H. pylori infected GES-1 group), H. pylori infected GES-1 cell supernatant + PCSK9 neutralizing antibody medium (anti PCSK9 group), H. pylori infected GES-1 cell supernatant+ human immunoglobulin G medium (isotype control group) were established. The differences between H. pylori infected GES-1 group and H. pylori-uninfected GES-1 group, negative control group, anti PCSK9 group and isotype control group in number of migrated macrophages, relative expression level of CC chemokine receptor ( CCR2), the levels of released interleukin(IL)-6 and cell necrosis factor (TNF)- α, level of CD8 + T cell membrane phosphorylation, and the number of macrophage colonies were determined by Transwell assay, real time fluorescence quantitative polymerase chain reaction, plate colony assay, H. pylori and phagocytosis lysosome co-localization assay. The regulating mechanism of PCSK9 in H. pylori infection induced inflammation was analyzed. Independent sample t test was used for statistical analysis. Results:The serum level of PCSK9 of patients with H. pylori positive gastritis was higher than that of patients with H. pylori negative gastritis and healthy individuals ((384.00±57.57) g/L vs. (208.80±48.89) and (176.10±47.14) g/L), and the differences were statistically significant ( t=12.71 and 15.31; both P<0.001). Compared with negative control group, H. pylori standard strain and 4 isolated H. pylori strains could stimulate GES-1 to secrete PCSK9 ((1 267.00±287.50) g/L vs.(2 717.00±199.20), (4 858.00±302.40), (3 167.00±334.20), (6 075.00±597.30), (4 283.00±331.20) g/L), and the differences were statistically significant( t=10.15, 21.09, 10.56, 17.77, 16.85, all P<0.001). The number of migrated macrophages, CCR2 mRNA expression level in macrophage, expression levels of IL-6 and TNF-α, and the number of macrophage colonies of H. pylori-infected GES-1 group were all higher than those of H. pylori-uninfected GES-1 group and negative control group (132.20±5.67 vs.84.83±4.62, 39.83±4.12; 8.66±0.94 vs. 6.52±0.47 and 1.00±0.09, (281.00±8.56) ng/L vs. (115.00±7.72) and (64.00±5.44) ng/L, (619.80±18.47) ng/L vs.(373.30±12.85)and (225.70±6.44) ng/L, (357.00±16.31) colony forming unit (CFU) vs. (134.80±8.64) and (74.17±9.68) CFU), and the differences were statistically significant ( t=15.85, 32.27; 4.96, 19.79; 35.28, 52.43; 26.84, 49.37; 29.49, 36.53; all P<0.001). The percentage of co-localization of H. pylori and phagocytosis lysosome, and the expression of cell membrane CD3ζ Tyr142, granzyme B and perforin in CD8 + T cell of H. pylori-infected GES-1 group were lower than that of H. pylori-uninfected GES-1 group ((15.33±1.86)% vs. (34.50±3.72)% and (65.67±3.56)%, 464.20±120.80 vs. 1 924.00±262.10 and 2 390.00±484.10; (6.41±0.42)% vs.(17.37±0.73)% and (26.60±1.57)%; (6.84±1.37)% vs.(14.53±0.48)% and (26.22±1.21)%), and the differences were statistically significant( t=11.27 and 30.70, 12.39 and 9.45, 30.50 and 31.90, 25.96 and 13.00; all P<0.001). The number of migrated macrophages, the relative expression level of CCR2 mRNA, the expression levels of IL-6 and TNF-α, and the number of macrophage colonies of anti-PCSK9 group were all lower than those of isotype control group (72.50±4.97 vs. 128.30±6.74, 0.82±0.06 vs. 1.00±0.08, (85.50±4.37) ng/L vs. (277.70±8.98) ng/L, (291.80±13.69) ng/L vs. (615.30±12.65) ng/L, (111.50±10.21) CFU vs. (346.20±18.04) CFU), and the differences were statistically significant ( t=16.33, 4.40, 47.13, 42.50 and 27.73, all P<0.001). The percentage of co-localization of H. pylori and phagocytosis lysosome, the expression levels of CD3ζ Tyr142, granzyme B and perforin of anti-PCSK9 group were all higher than those of isotype control group ((51.05±3.03)% vs. (16.71±1.91)%, 2 948.00±384.00 vs. 1 156.00±178.60, (53.88±3.86)% vs. (5.88±0.93)%, (32.80±2.07)% vs. (6.83±0.54)%), and the differences were statistically significant ( t=23.49, 10.36, 29.60 and 29.76, all P<0.001). Conclusions:H. pylori can inhibit CD8 + T activation and cytotoxicity by inducing the release of PCSK9 from gastric epithelial cells, and can also recruit macrophages, activate nuclear factor-κB signal axis to up-regulate the level of released inflammatory factors from macrophages, inhibit the phagocytosis and killing effects of macrophages, so as to regulate the inflammatory response.

Clinical significance of prognostic serum marker expression in older adult patients with sepsis-associated encephalopathy / 中国基层医药

Objective:To investigate the clinical significance of prognostic serum marker expression in older adult patients with sepsis-associated encephalopathy (SAE).Methods:The clinical data of 79 older adult patients with SAE who received treatment in The Second People's Hospital of Hefei from June 2019 to February 2021 (study group) and 121 sepsis patients without encephalopathy concurrently (control group) were retrospectively analyzed. The indexes with statistically significant difference between the two groups were subjected to multivariate binary logistic regression. Survival curve was plotted.Results:There were no significant differences in neuron specific enolase [NSE, (10.69 ± 4.31) μg/L vs. (24.84 ± 3.28) μg/L, t = 26.25, P < 0.01], S100β [(0.25 ± 0.06) μg/L vs. (0.53 ± 0.09) μg/L, t = 22.45, P < 0.01], monocyte chemoattractant protein-1 [MCP-1, (99.33 ± 4.87) ng/L vs. (179.99 ± 6.02) ng/L, t = 99.94, P < 0.01], malondialdehyde [MDA, (4.22 ± 0.08) nmol/L vs. (6.78 ± 0.11) nmol/L, t = 33.76, P < 0.01], glial fibrillary acidic protein [GFAP, (0.21±0.08) μg/L vs. (2.03 ± 0.47) μg/L, t = 33.76, P < 0.01], procalcitonin [(7.04 ± 2.50) ng/L vs. (16.23 ± 2.48) ng/L, t = 25.47, P < 0.01], interleukin-6 [(29.91 ± 4.51) ng/L vs. (69.22 ± 6.79) ng/L, t = 45.51, P < 0.01], Acute Physiology and Chronic Health Evaluation II (APACHE II) score [(18.33 ± 2.12) points vs. (28.89 ± 5.09) points, t = 17.53, P < 0.01], and sequential organ failure assessment score [(7.69 ± 1.50) points vs. (14.05 ± 1.55) points, t = 28.92, P < 0.01] between the control and study groups. N-terminal pro B-type natriuretic peptide was (868.38 ± 25.28) ng/L and (1 037.19 ± 25.34) ng/L in the control and study groups, respectively. Logistic regression analysis revealed that NSE, MCP-1, MDA, and GFAP were the independent risk factors for developing SAE in older adults (NSE: t = 8.42, P < 0.01; MCP-1: t = 4.16, P < 0.01; MDA: t = 18.4, P < 0.01; GFAP: t = 2.88, P < 0.01). The survival curve indicated that survival rate was significantly lower in the study group than in the control group. Conclusion:NSE, MCP-1, MDA, and GFAP are independent risk factors for developing SAE in older adults.

Improvement of Quality Control Standard of Bufonis Venenum in Shexiang Baoxin Pills / 中国实验方剂学杂志

ObjectiveTo develop a quantitative analysis of multi-components by single marker （QAMS） for determination of bufalin， cinobufagin and resibufogenin in Shexiang Baoxin pills， and to provide a method for improving the national standard of the pills. MethodHigh performance liquid chromatography （HPLC） was developed for simultaneous determination of bufalin， cinobufagin and resibufogenin in Shexiang Baoxin pills and the methodology validation was carried out. The chromatographic separation was performed on a Nucleosil 100-5 C18 column （4.6 mm×250 mm， 5 μm） with the mobile phase of acetonitrile -0.1% potassium dihydrogen phosphate aqueous solution （pH adjusted to 3.2 with phosphoric acid） （48∶52）， and the flow rate was 0.6 mL·min-1， the detection wavelength was set at 296 nm and the column temperature was 35 ℃. Taking cinobufagin as the internal standard， the relative correction factors （RCFs） of bufalin and resibufogenin were calculated， and the key influencing factors of RCFs were investigated. Relative retention time was used for the chromatographic peak location of the analyte， combining with the on-line ultraviolet spectroscopy and accurate relative molecular weight obtained by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry （UPLC-QTOF/MS）. The external standard method was used to verify the contents of three components obtained by QAMS. ResultQAMS was established for the determination of bufalin， cinobufagin and resibufogenin in the samples， and RCFs of cinobufagin to bufalin and resibufogenin were 0.922 and 1.01， respectively. The total content of the three marker compounds in 11 batches of Shexiang Baoxin pills was 33.7-36.0 µg per pill. There was no significant difference between the quantitative results of QAMS and external standard method. ConclusionThe established method can be used for the quality control of bufalin， cinobufagin and resibufogenin in Shexiang Baoxin pills. It is suggested that bufalin should be considered as one of three marker compounds， and the sum of bufalin， cinobufagin and resibufogenin should be used for the content limit of this preparation.

Cerebrospinal Fluid β2-Microglobulin for Prognostic Evaluation of Patients with Central Nervous System Infiltration in Acute Lymphoblastic Leukemia / 中国实验血液学杂志

OBJECTIVE@#To investigate the prognostic value of serum and cerebrospinal fluid β2-microglobulin (β2-MG) in acute lymphoblastic leukemia (ALL) with central nervous system invasion after chemotherapy.@*METHODS@#40 patients with leukemia who had been confirmed to have central nervous system infiltration were selected for treatment at the Second Affiliated Hospital of Chongqing Medical University from January 2015 to May 2017, and the serum levels of β2-MG and CSF-β2MG were dynamically monitored and performed statistical analysis.@*RESULTS@#After chemotherapy, the changes in serum β2-MG were not statistically significant (P>0.05); the absolute level of CSF-β2MG and the percentage of relative baseline changes were statistically different in different clinical outcome groups(P<0.05), and the decreasing CSF-β2MG levels suggest a better prognosis, with cut-off values of 1.505 and -25%, respectively.@*CONCLUSION@#The best cut-off point may be a predictor of complete remission; the reduction of the absolute and relative levels of CSF-β2MG can suggest a good prognosis for patients.