Detection and Analysis of Blood Dexmedetomidine in Drug-Facilitated Cases / 法医学杂志

OBJECTIVES@#To establish a simple and rapid qualitative and quantitative detection method of dexmedetomidine in blood.@*METHODS@#Blood was separated on the Allure PFP Propyl liquid chromatography column with isocratic elution after it was precipitated by acetonitrile and filtered. Qualitative and quantitative analysis of dexmedetomidine was performed using positive ion scan mode and multi-reaction monitoring mode.@*RESULTS@#The limit of detection of dexmedetomidine in blood was 0.2 ng/mL and the limit of quantification was 0.5 ng/mL. The linearity of the method was good in the range of 0.5-1 000 ng/mL, and the correlation coefficient was greater than 0.99. The accuracy of the method was 90.34%-112.67% and the extraction recovery was 50.05%-91.08%, with no significant matrix effect.@*CONCLUSIONS@#This method is simple, selective and suitable for the qualitative and quantitative analysis of dexmedetomidine in blood, which can provide a reference for drug-facilitated cases involving dexmedetomidine.

Evaluation of the application value of seven tumor-associated autoantibodies in non-small cell lung cancer based on machine learning algorithms / 中华预防医学杂志

Objective: Based on the diagnostic model established and validated by the machine learning algorithm, to investigate the value of seven tumor-associated autoantibodies (TAABs), namely anti-p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE antibodies in the diagnosis of non-small cell lung cancer (NSCLC) and to differentiate between NSCLC and benign lung nodules. Methods: This was a retrospective study of clinical cases. Model building queue: a total of 227 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from November 2018 to June 2021 were collected as the NSCLC group, and 120 cases of benign lung nodules, 122 cases of pneumonia and 120 healthy individuals were selected as the control groups. External validation queue: a total of 100 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from May 2022 to December 2022 were collected as the NSCLC group, and 36 cases of benign lung nodules, 32 cases of pneumonia and 44 healthy individuals were selected as the control groups. In addition, NSCLC was divided into early (stage 0-ⅠB) and mid-to-late (stage ⅡA-ⅢB) subgroups. The levels of 7-TAABs were detected by enzyme immunoassay, and serum concentrations of CEA and CYFRA21-1 were detected by electrochemiluminescence. Four machine learning algorithms, XGBoost, Lasso logistic regression, Naïve Bayes, and Support Vector Machine are used to establish classification models. And the best performance model was chosen based on evaluation metrics and a multi-indicator combination model was established. In addition, an online risk evaluation tool was generated to assist clinical applications. Results: Except for p53, the levels of rest six TAABs, CEA and CYFRA21-1 were significantly higher in the NSCLC group (P<0.05). Serum levels of anti-SOX2 [1.50 (0.60, 10.85) U/ml vs. 0.8 (0.20, 2.10) U/ml, Z=2.630, P<0.05] and MAGEA1 antibodies [0.20 (0.10, 0.43) U/ml vs. 0.10 (0.10, 0.20) U/ml, Z=2.289, P<0.05], CEA [3.13 (2.12, 5.64) ng/ml vs. 2.11 (1.25, 3.09) ng/ml, Z=3.970, P<0.05] and CYFRA21-1 [4.31(2.37, 7.14) ng/ml vs. 2.53(1.92, 3.48) ng/ml, Z=3.959, P<0.05] were significantly higher in patients with mid-to late-stage NSCLC than in early stages. XGBoost model was used to establish a multi-indicator combined detection model (after removing p53). 6-TAABs combined with CYFRA21-1 was the best combination model for the diagnosis of NSCLC and early NSCLC. The optimal diagnostic thresholds were 0.410, 0.701 and 0.744, and the AUC was 0.828, 0.757 and 0.741, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in model building queue, and the AUC was 0.760, 0.710 and 0.660, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in external validation queue. Conclusion: In the diagnosis of NSCLC, 6-TAABs is superior to that of traditional tumor markers CEA and CYFRA21-1, and can compensate for the shortcomings of traditional tumor markers. For the differential diagnosis of NSCLC and benign lung nodule, "6-TAABs+CYFRA21-1" is the most cost-effective combination, and plays an important role in prevention and screening for early lung cancer.

Evaluation of the application value of seven tumor-associated autoantibodies in non-small cell lung cancer based on machine learning algorithms / 中华预防医学杂志

Objective: Based on the diagnostic model established and validated by the machine learning algorithm, to investigate the value of seven tumor-associated autoantibodies (TAABs), namely anti-p53, PGP9.5, SOX2, GAGE7, GBU4-5, MAGEA1 and CAGE antibodies in the diagnosis of non-small cell lung cancer (NSCLC) and to differentiate between NSCLC and benign lung nodules. Methods: This was a retrospective study of clinical cases. Model building queue: a total of 227 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from November 2018 to June 2021 were collected as the NSCLC group, and 120 cases of benign lung nodules, 122 cases of pneumonia and 120 healthy individuals were selected as the control groups. External validation queue: a total of 100 primary patients who underwent radical lung cancer surgery in the Department of Thoracic Surgery, Shengjing Hospital of China Medical University, from May 2022 to December 2022 were collected as the NSCLC group, and 36 cases of benign lung nodules, 32 cases of pneumonia and 44 healthy individuals were selected as the control groups. In addition, NSCLC was divided into early (stage 0-ⅠB) and mid-to-late (stage ⅡA-ⅢB) subgroups. The levels of 7-TAABs were detected by enzyme immunoassay, and serum concentrations of CEA and CYFRA21-1 were detected by electrochemiluminescence. Four machine learning algorithms, XGBoost, Lasso logistic regression, Naïve Bayes, and Support Vector Machine are used to establish classification models. And the best performance model was chosen based on evaluation metrics and a multi-indicator combination model was established. In addition, an online risk evaluation tool was generated to assist clinical applications. Results: Except for p53, the levels of rest six TAABs, CEA and CYFRA21-1 were significantly higher in the NSCLC group (P<0.05). Serum levels of anti-SOX2 [1.50 (0.60, 10.85) U/ml vs. 0.8 (0.20, 2.10) U/ml, Z=2.630, P<0.05] and MAGEA1 antibodies [0.20 (0.10, 0.43) U/ml vs. 0.10 (0.10, 0.20) U/ml, Z=2.289, P<0.05], CEA [3.13 (2.12, 5.64) ng/ml vs. 2.11 (1.25, 3.09) ng/ml, Z=3.970, P<0.05] and CYFRA21-1 [4.31(2.37, 7.14) ng/ml vs. 2.53(1.92, 3.48) ng/ml, Z=3.959, P<0.05] were significantly higher in patients with mid-to late-stage NSCLC than in early stages. XGBoost model was used to establish a multi-indicator combined detection model (after removing p53). 6-TAABs combined with CYFRA21-1 was the best combination model for the diagnosis of NSCLC and early NSCLC. The optimal diagnostic thresholds were 0.410, 0.701 and 0.744, and the AUC was 0.828, 0.757 and 0.741, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in model building queue, and the AUC was 0.760, 0.710 and 0.660, respectively (NSCLC vs. control, NSCLC vs. benign lung nodules, early NSCLC vs. benign lung nodules) in external validation queue. Conclusion: In the diagnosis of NSCLC, 6-TAABs is superior to that of traditional tumor markers CEA and CYFRA21-1, and can compensate for the shortcomings of traditional tumor markers. For the differential diagnosis of NSCLC and benign lung nodule, "6-TAABs+CYFRA21-1" is the most cost-effective combination, and plays an important role in prevention and screening for early lung cancer.

Genetic variants, circulating levels of monocyte chemoattractant protein-1 with risk of breast cancer: a case-control study and Mendelian randomization analysis / 中华预防医学杂志

Objective: To assess the association of genetic polymorphisms and circulating levels of chemokine monocyte chemoattractant protein-1 (MCP1) with risk of breast cancer. Methods: A total of 820 patients with pathologically confirmed breast cancer and 900 age-and area-of-residence-matched healthy controls who visited the hospital for routine health screening during the same period were included in this case-control study. Mendelian randomization analysis was performed using three widely followed functional single nucleotide polymorphisms (SNPs) of the MCP1 gene rs1024611, rs2857656 and rs4586 to construct instrumental variables . Results: MCP1 rs1024611 (OR=1.26, P=0.002), rs2857656 (OR=1.23, P=0.006) and rs4586 (OR=1.23, P=0.003) were significantly associated with increased risk of breast cancer. SNP rs1024611 (β=1.194, P<0.001), rs2857656 (β=1.221, P<0.001) and rs4586 (β=1.137, P<0.001) were positively correlated with higher circulating level of MCP1. The case-control study showed that an increase of 23.7 pg/ml of circulating levels of MCP1 was associated with a 0.25-fold increased risk of breast cancer. MR analysis confirmed that the genetic predicted circulating levels of MCP1 were associated with an increased risk of breast cancer, and the risk of breast cancer increased by 0.20 times with an increase of 23.7 pg/ml in MCP1. Conclusion: Genetic variants and circulating levels of MCP1 are significantly associated with the risk of breast cancer and can be used as a biomarker for early prediction of breast cancer.

A case report of macro-AST with isolated elevated aspartate aminotransferase in a child / 中华检验医学杂志

We need to consider the macro-AST when the elevated AST activity cannot be explained. A 3-year-old child was found to have an increase in serum AST activity, but no obvious abnormality be found ofter examination. The PEG precipitation assay showed that the activity was 98.7%, which was diagnosed as macro-AST.

Large- scale prospective clinical study on prophylactic intervention of COVID-19 in community population using Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules / 中国中药杂志

To scientifically evaluate the intervention effect of Chinese medicine preventive administration(combined use of Huo-xiang Zhengqi Oral Liquid and Jinhao Jiere Granules) on community population in the case of coronavirus disease 2019(COVID-19), a large cohort, prospective, randomized, and parallel-controlled clinical study was conducted. Total 22 065 subjects were included and randomly divided into 2 groups. The non-intervention group was given health guidance only, while the traditional Chinese medicine(TCM) intervention group was given two coordinated TCM in addition to health guidance. The medical instructions were as follows. Huoxiang Zhengqi Oral Liquid: oral before meals, 10 mL/time, 2 times/day, a course of 5 days. Jinhao Jiere Granules: dissolve in boiling water and take after meals, 8 g/time, 2 times/day, a course of 5 days, followed up for 14 days, respectively. The study found that with the intake of medication, the incidence rate of TCM intervention group was basically maintained at a low and continuous stable level(0.01%-0.02%), while the non-intervention group showed an overall trend of continuous growth(0.02%-0.18%) from 3 to 14 days. No suspected or confirmed COVID-19 case occurred in either group. There were 2 cases of colds in the TCM intervention group and 26 cases in the non-intervention group. The incidence of colds in the TCM intervention group was significantly lower(P<0.05) than that in the non-intervention group. In the population of 16-60 years old, the incidence rate of non-intervention and intervention groups were 0.01% and 0.25%, respectively. The difference of colds incidence between the two groups was statistically significant(P<0.05). In the population older than 60 years old, they were 0.04% and 0.21%, respectively. The incidence of colds in the non-intervention group was higher than that in the intervention group, but not reaching statistical difference. The protection rate of TCM for the whole population was 91.8%, especially for the population of age 16-60(95.0%). It was suggested that TCM intervention(combined use of Huoxiang Zhengqi Oral Liquid and Jinhao Jiere Granules) could effectively protect community residents against respiratory diseases, such as colds, which was worthy of promotion in the community. In addition, in terms of safety, the incidence of adverse events and adverse reactions in the TCM intervention group was relatively low, which was basically consistent with the drug instructions.

Real-world study on syndrome distribution and medication characteristics of colonic malignant tumors / 中国中药杂志

In order to explore the characteristics of traditional Chinese medicine(TCM) syndromes and medications in patients with colonic malignant tumors in China, the clinical data of patients with colonic malignant tumors from the information system of 33 Grade-A tertiary hospitals in China from 2001 to 2016 were extracted and a descriptive analysis was conducted on their disease characteristics, syndrome distribution, drug characteristics and treatment status. A total of 22 691 patients with colonic malignancies nationwide were included in the analysis, with male to female ratio of 1.59∶1, median age of 62 years, susceptible age of 50-79 years. Postoperative patients with colonic malignant tumors accounted for 47.10%, and patients with liver metastases reached 36.02%. Among the 520 patients with colonic malignant tumors, the top three TCM syndromes were: spleen deficiency syndrome(21%), Qi and Yin deficiency syndrome(17%) and liver and stomach disharmony syndrome(15%). The most frequently used Western medicine for patients with colonic malignant tumors was anti-metabolite cytotoxicity(61.23%), most frequently used in combination with platinum-based cytotoxic drugs(support degree 42.40%).The top three Western medicines were oxaliplatin(42.26%), leucovorin injection(38.58%) and dexamethasone(34.67%). The most frequently used traditional Chinese medicine type was heat-clearing and detoxifying drugs(39.59%), most frequently used in combination with Qi replenishing and body resistance strengthening drugs(support degree 12.72%). The top three traditional Chinese medicines were compound Kushen Injection(14.62%), Shenqi Fuzheng Injection(10.18%) and Aidi Injection(6.48%). This study shows that spleen and Qi deficiency may be the dominant syndrome of colonic malignant tumor, and chemotherapy is one of the main treatment methods. Traditional Chinese medicine has shown unique advantages in alleviating the toxic and side effects of chemotherapy and preventing recurrence and metastasis, so integrated TCM and Western medicine can significantly improve the clinical efficacy.

Relationship between Maternal PBMC HBV cccDNA and HBV Serological Markers and its Effect on HBV Intrauterine Transmission / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the relationship between maternal peripheral blood mononuclear cells (PBMC) hepatitis B virus (HBV) covalenty closed circular deoxyribonucleic acid (cccDNA) and other HBV serological markers and its effects on HBV intrauterine transmission.@*METHODS@#We enrolled 290 newborns and their hepatitis B surface antigen (HBsAg) positive mothers. HBV cccDNA in PBMC and HBV DNA in serum were detected by a real-time PCR-TaqMan probe while HBV serological markers were detected with an electrochemiluminescence immunoassay.@*RESULTS@#There was a positive correlation between the levels of PBMC HBV cccDNA and serum HBV DNA and HBeAg (r = 0.436 and 0.403, P < 0.001). The detection rate of pattern A ['HBsAg (+), HBeAg (+), and anti-HBc (+)'] was significantly higher in the PBMC HBV cccDNA positive group than in the control group (χ2 = 48.48, P < 0.001). There was a significant association between HBV intrauterine transmission and PBMC HBV cccDNA (χ2 = 9.28, P = 0.002). In the presence of serum HBV DNA, HBeAg, and PBMC HBV cccDNA, the risk of HBV intrauterine transmission was three times higher (OR = 3.69, 95% CI: 1.30-10.42) than that observed in their absence. The risk of HBV intrauterine transmission was the greatest (OR = 5.89, 95% CI: 2.35-14.72) when both PBMC HBV cccDNA and pattern A were present. A Bayesian network model showed that maternal PBMC HBV cccDNA was directly related to HBV intrauterine transmission.@*CONCLUSION@#PBMC HBV cccDNA may be a direct risk factor for HBV intrauterine transmission. Our study suggests that serological markers could be combined with PBMC-related markers in prenatal testing.

Effect of PBMC HBV cccDNA in HBsAg-positive mothers on neonatal Th1/Th2 cytokines / 中华疾病控制杂志

Objective To explore the effect of PBMC HBV cccDNA in HBsAg-positive mothers on neonatal Th1, Th2 cytokines and the ratio of Th1/Th2. Methods HBsAg-positive mothers and their neonates delivered in the Third People’s Hospital of Taiyuan between June 2011 and July 2013 were recruited. Questionnaires on general information were collected by an in-person interview. Electrochemiluminescence immunoassay (ECLIA) were utilized to detect HBV serological markers.HBV cccDNA in PBMC was detected with real-time PCR-TaqMan Probe method, Th1 cytokines (interleukin 2, interferon-γ and tumor necrosis factor-α) and Th2 cytokines (interleukin 4, interleukin 6 and interleukin 10) were detected with Procarta Plex Multiplex Immunoassays. Results Univariate analysis showed that the levels of IL-2, IL-6 and IL-10 in the positive group were significantly higher than those in the negative group, while the ratio of Th1/Th2 was lower than that in the negative group (P=0.034, P=0.007, P=0.048, P=0.029). The levels of IL-6 and IL-10 in neonates delivered by vagina were significantly higher than those by cesarean section, while the ratio of Th1/Th2 was lower than that by cesarean section (P<0.001). The level of IL-10 in positive group of neonatal HBsAg was significantly higher than that in negative group, while TNF-α and Th1/Th2 ratio were lower than negative group (P=0.011, P<0.001, P=0.027). The degree of Th2 predominant response was reflected by ratio of Th1/Th2. After adjusting potential confounding factors in non-conditional logistic regression analysis, compared to those born to mothers with PBMC HBV cccDNA negative, neonates whose mother with PBMC HBV cccDNA positive had an increased risk of having a strong Th2 predominant response (OR=2.42,95% CI:1.16-5.04, P=0.018). The risk of a strong Th2 predominant response in neonates delivered by vagina was 5.49 times higher than those by cesarean section (OR=5.06, 95% CI: 2.95-8.67, P<0.001). Conclusion HBsAg-positive mothers’ PBMC HBV replication and vaginal delivery may increase the risk of having a Th2 predominant response in neonates. It is suggested that we should pay attention to the effect of maternal PBMC HBV replication and the mode of delivery on neonatal Th1/Th2 cytokines.

Therapeutic effect of in vitro 5-aza-2'-deoxycytidine combined with imatinib on gastrointestinal stromal tumor / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the impact of 5-aza-2'-deoxycytidine(5-aza-CdR) combined with imatinib on the proliferation, motility, invasion, and apoptosis of gastrointestinal stromal tumors(GIST) cells in vitro.</p><p><b>METHODS</b>MTT assay was used to investigate the effect of the two agents on proliferation of GIST882. Plate colony forming assay was used to determine the number of colony-forming. Motility and invasion abilities were tested to evaluate the inhibitory effect of each agent. Flow cytometry was used to observe apoptosis and cell cycle.</p><p><b>RESULTS</b>5-aza-CdR or imatinib effectively inhibited the growth of GIST882 cells in concentration- and time-dependent manner. The inhibitory rate of combined treatment using 5-aza-CdR and imatinib was significantly higher than that of 5-aza-CdR or imatinib alone(P<0.05). After treatment for 48 h, the apoptosis rates of 5-aza-CdR group (1000 μg/L) and imatinib group (100 μmol/L) were (11.7±1.2)% and (14.6±0.8)%, respectively. Compared with the control group (2.8±0.3)%, the difference was statistically significant(P=0.000). Furthermore, the difference in apoptosis rate was significant between combined treatment group (19.4±1.1)% and single drug treatment group(vs. 5-aza-CdR group, P=0.000, vs. imatinib group, P=0.013). 5-aza-CdR raised G0/G1 ratio and reduced S ratio of GIST882. Imatinib and combined group had no apparent influence on the cell cycle of GIST882 cells.</p><p><b>CONCLUSION</b>5-aza-CdR may be a potential agent of GIST treatment in the near future.</p>

Clinical observation on treatment of radiative pneumonia in patients with lung cancer by integrative Chinese and Western medicine / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the effect of integrative Chinese and Western medical therapy for radiative pneumonia (RP).</p><p><b>METHODS</b>Eighty patients were randomly assigned to two groups. The treated group (48 patients) was treated by Shenqi Fuzheng Injection (SFI), antibiotics and short-term pulse therapy with high efficient hormone, while the control group (32 patients) was treated only by antibiotic and hormone pulse therapy. Changes of symptoms, signs, quality of life and subsets of T-lymphocytes (CD3+, CD4+, CD8+ and CD4+/CD8+ ratio) were observed before and after 20-day treatment.</p><p><b>RESULTS</b>The chief symptom disappearance time was shorter (P < 0.05), Karnofsky performance score was better (P < 0.05) in the treated group after treatment as compared with those in the control group. Moreover, the immune function was improved in the treated group after treatment (P < 0.01).</p><p><b>CONCLUSION</b>SFI combined with antibiotics and short-term pulse therapy with high efficient hormone has a good effect for radiative pneumonia, it could also increase patients' quality of life as well.</p>