Whole-process individualized pharmaceutical care for a case of melioidosis sepsis / 中国药房

OBJECTIVE To provide reference for the adjustment of antibiotic treatment regimens， identification of adverse reactions， and individualized pharmaceutical care for melioidosis sepsis （MS）. METHODS Clinical pharmacists participated in the intensive and eradicating therapeutic processes for an MS patient by using blood concentration and gene detection. Based on the literature， antibiotic treatment regimens of MS were adjusted by determining the blood concentrations of β-lactam and trimethoprim/ sulfamethoxazole （TMP/SMZ） and calculating PK/PD parameters. The causes of adverse drug reactions were analyzed and addressed by detecting drug-related gene polymorphisms through high-throughput sequencing. RESULTS Clinical pharmacists used blood concentration and genetic testing methods to propose adjustments to imipenem-cilastatin sodium dosage and analyze the causes of various adverse drug reactions. PK/PD targets were calculated by measuring the blood concentrations of β-lactam and TMP/SMZ. Clinical pharmacists explained to clinical doctors the compliance status of patients with melioidosis in sepsis and non- sepsis stages through reviewing guidelines and literature； the results of blood concentration and genetic test were used to analyze the correlation of neurotoxicity of MS patients with B14） IMP cmin， and it was found that nephrotoxicity was not related to the cmax of TMP/SMZ， but to the patient’s water intake. After whole-process antibiotic treatment， the patient’s condition improved and was discharged， and the adverse reactions were effectively treated. CONCLUSIONS Clinical pharmacists use blood concentration and genetic tests to assist clinicians in formulating MS treatment regimens， and provide whole-course pharmaceutical care for a MS patient. This method has improved the safety and effectiveness of clinical drug therapy.

Correlation of emotional abnormalities with the effectiveness of bariatric surgery in obese patients / 四川精神卫生

BackgroundBariatric surgery has emerged as an important tool in the management of obesity. Some patients undergoing bariatric surgery are prone to develop emotional abnormalities and have abnormally elevated concentrations of inflammatory factors level in peripheral blood， whereas current domestic research focusing on the impact of preoperative emotional states and peripheral blood inflammatory factors level on weight loss effect remains limited. ObjectiveTo explore the correlation of preoperative emotional abnormalities with the effectiveness of bariatric surgery in obese patients， and to provide theoretical basis for improving the clinical efficacy of bariatric surgery. MethodsEighty-one obese patients scheduled for bariatric surgery at gastrointestinal surgery Department of West China Hospital， Sichuan University from December 30， 2022 to June 30， 2023 were enrolled and assessed using Hamilton Depression Scale-17 item （HAMD-17） and Hamilton Anxiety Scale （HAMA）. Patients who scored 7 or above on HAMD-17 or HAMA or had a history of previous depression or anxiety diagnoses were classified into emotional abnormality group （n=34）， and samples who scored less than 7 on HAMD-17 and HAMA and were free of history of previous depression and anxiety diagnoses were set as non-emotional abnormality group （n=47）. The data were collected by the self made questionnaire. Patients were subjected to complete the assessment of Beck Scale for Suicide Ideation-Chinese Version （BSI-CV）， Eating Disorder Inventory （EDI） and Pittsburgh Sleep Quality Index （PSQI）. Laboratory tests including peripheral blood C-reactive protein （CRP） and interleukin-6 （IL-6）. Body weight and height assessed in the early morning after an overnight fasting period were recorded in all participants at 1- and 6-month after surgery through outpatient clinic visits or telephone follow-up. Pearson correlation coefficient was used to examine relationship among body mass index （BMI）， preoperative emotional states and peripheral blood inflammation mediators. ResultsAmong 81 obese patients， 62 completed the study， including 27 cases in emotional abnormality group and 35 cases in non-emotional abnormality group. Emotional abnormality group scored higher on BSI-CV （current）， BSI-CV （worst）， EDI and PSQI， and detected higher levels of CRP and IL-6 compared with non-emotional abnormality group （Z=2.677， 2.975， t=3.573， 4.035， 1.990， 2.799， P<0.05 or 0.01）. For BMI， there was no significant group effect and time×group interaction effect （P>0.05）， but a significant time effect （F=227.740， P<0.01）. Within emotional abnormality group， BMI at the baseline， 1- and 6-month after surgery showed a positive correlation with IL-6 level （r=0.419， 0.510， 0.559， P<0.05 or 0.01）， BMI at 6-month after surgery was positively correlated with HAMD-17 total score （r=0.390， P<0.05）， and ΔBMI% at 6-month after surgery was negatively correlated with HAMD-17 total score （r=-0.421， P<0.05）. Within non-emotional abnormality group， baseline BMI was positively correlated with IL-6 level （r=0.338， P<0.01）. ConclusionThe short-term effect of bariatric surgery may be comparable in obese patients with or without emotional abnormalities， while it cannot be ruled out whether the outcome of bariatric surgery is related to the severity of preoperative depression.

Study of discrepancy in subjective and objective cognitive function in patients with depressive disorder / 四川精神卫生

BackgroundThere exist differences in the subjective and objective cognitive functions of patients with depressive disorder， ane there are limited research on influencing factors of such phenomenon currently. ObjectiveTo explore the differences in subjective and objective cognitive function in patients with depressive disorder as well as influencing factors， and to provide references for further understanding of cognitive impairment in patients with depressive disorder. MethodsA total of 77 patients with depressive disorder who received outpatient or inpatient treatment in the Fourth People's Hospital of Chengdu from January 13， 2022 to December 11， 2023 were selected for the study. These patients also met the diagnostic criteria of Diagnostic and Statistical Manual of Mental Disorders， fifth edition（DSM-5）. Various tools were employed to assess patients in this study： Montgomery-Asberg Depression Rating Scale （MADRS） for the depressive symptoms， Perceived Deficits Questionnaire for Depression （PDQ-D） and Chinese Version of Brief Neurocognitive Test Battery （C-BCT） for the subjective and objective cognitive function， Sheehan Disability Scale （SDS） for the social function， and Clinical Global Impression-Severity of Illness（CGI-SI） for the severity of patient's condition. Pearson correlation analysis was used to examine the correlation of subjective and objective cognitive function and their differences with age， years of education， MADRS total score， SDS total score， and CGI-SI score. Multiple linear regression was used to explore the influencing factors of the differences between subjective and objective cognitive function. ResultsThere was a statistically significant difference in the total PDQ-D scores and the difference of subjective and objective cognitive function （D value） between depressive patients with and without medication （t=-4.228， -2.392， P<0.05 or 0.01）. There was no statistically significant correlation in subjective and objective cognitive function in patients with depressive disorder （r=-0.148， P>0.05）. Negative correlations can be observed between the PDQ-D total score and age or years of education （r=-0.333， -0.369， P<0.01）. The PDQ-D total score was positively correlated with MADRS total score， SDS total score and CGI-SI score （r=0.487， 0.637， 0.434， P<0.01）. D value was negatively correlated with age and years of education （r=-0.411， -0.362， P<0.01）， while positively correlated with MADRS total score， SDS total score and CGI-SI score （r=0.259， 0.468， 0.299， P<0.05 or 0.01）. Age （β=-0.328， P<0.01） and SDS total score （β=0.409， P<0.01） were two predictive factors for D value. ConclusionThe difference between subjective and objective cognitive function among patients with depressive disorder is related to several factors including age， years of education， severity of symptoms and impairment of social function. ［Funded by Surface Project of National Natural Science Foundation of China （number， 62173069）； Technological Innovation 2030-Major Project of "Brain Science and Brain-Like Research" （number， 2022ZD0211700）； Key R&D Support Program and Major Application Demonstration Project of Chengdu Science and Technology Bureau （number， 2022-YF09-00023-SN）］

Transient elastography technology role assessment during the diagnosis and treatment of patients with chronic hepatitis B virus infection / 中华肝脏病杂志

Objective: To explore the role of transient elastography technology in the assessment of disease staging and treatment in patients with chronic hepatitis B virus (HBV) infection. Methods: Patients who were clinically diagnosed with chronic HBV infection at Beijing Tsinghua Changgung Hospital from January 2018 to December 2021 was collected. Liver stiffness measurement (LSM) examination was performed more than once by transient elastography. The count data were expressed as cases (%) and the χ (2) test was made. Fisher's exact test was used with theoretical frequency less than 5. The measurement data between two groups was compared by t-test. Multiple groups were compared with an analysis of variance. Results: 1 055 patients were included in this study, including 669 (63.4%) males and 386 (36.6%) females. 757 (71.8%) patients were untreated. Among the untreated patients, the LSM value in the immune clearance (10.2 ± 3.8) kPa (187 cases, 40.4%), and the reactivation stages (9.1 ± 3.4) kPa (114 cases, 24.6%) was significantly higher than that in the immune tolerance (8.7 ± 3.6) kPa (78 cases, 16.8%) and immune control stages (8.4 ± 3.5) KPa (84 cases, 18.1%), and the difference between the four groups was statistically significant (F = 5.31 and P = 0.03). With ALT (male: 30 U/L, female: 19 U/L) as defined the normal value, the LSM value in the immune tolerance and the immune control stages were (5.8 ± 0.9) kPa and (7.1 ± 2.5) kPa, respectively, which were significantly lower than those of patients in the immune tolerance and immune control stages, and the difference was statistically significant (P < 0.01). There were 294 (38.8%) patients with uncertain period, excluding patients with fatty liver. Patients with uncertain periods were divided into four gray zone (GZ) groups: immune tolerance stage: LSM (5.1 ± 1.3) kPa was significantly lower than GZ-A (6.5 ± 2.4) kPa, t = 2.06, P = 0.03, and the difference was statistically significant; immune control stage: LSM was (5.6 ± 1.5) kPa, which was also lower than GZ-C (6.8 ± 1.3) kPa, t = 3.08, P = 0.02, and the difference was statistically significant; immune clearance stage: LSM > 8.0 kPa. LSM values showed a year-by-year reduction in patients with expanded indications who started antiviral treatment and were followed up for three years. Conclusion: The LSM value is significantly lower after the decrease of the defined high-normal ALT value in patients with the immune tolerance and immune control stages of chronic HBV infection. The LSM values of GZ-A and GZ-C in the uncertain periods of chronic HBV infection are higher than those of patients in the immune tolerance and immune control stages.

Self-reported quality of life in patients with coronary heart disease and analysis of the associated factors / 中华内科杂志

Objective: To investigate the quality of life and associated factors in patients with coronary heart disease (CHD) in China. Methods: A cross-sectional study of 25 provinces and cities in China was performed from June to September 2020. A questionnaire was used to collect the socio-demographic and clinical information of patients with CHD, while the European Five-dimensional Quality of Life Scale (EQ-5D) was used to assess the quality of life. Multiple linear regression model was performed to analyze the associated factors. Results: The median age of the 1 075 responders was 60 (52, 67) years, and 797 (74.1%) were men. The EQ-5D and EQ-VAS indices were 0.7 (0.5, 0.8) and 60.0 (40.0, 80.0). Among the five dimensions in the quality of life scale, the frequency of anxiety/depression was the highest (59.8%), while problems in self-care was the lowest (35.8%). In the multiple linear regression model, female, increasing age, obesity, comorbidity(ies), anxiety/depression, social media channels, and receiving the CABG therapy were associated with the lower EQ-5D index (all P<0.05). In addition, increasing age, obesity, comorbidity (ies), depression, anxiety and depression, social media channels, and receiving the CABG therapy were associated with lower EQ-VAS index (all P<0.05). Conclusion: Over half of the patients with CHD in China have a low quality of life, which is related to gender, age, obesity, treatment pathway, the presence or absence of comorbidity (ies), and psychological state. In addition to managing the adverse effects of traditional socio-demographic factors on the quality of life, clinical practices should pay attention to the psychological state of patients. Moreover, establishing a WeChat group for doctor-patient communication could improve the quality of life of CHD patients.

Therapeutic efficacy of hematopoietic stem cell transplantation for Wiskott-Aldrich syndrome in 60 children / 中华儿科杂志

Objective: To evaluate the therapeutic efficacy of hematopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome (WAS), and to analyze the factors related to the outcomes. Methods: The clinical data of 60 children with WAS received HSCT in Shanghai Children's Medical Center from January 2006 to December 2020 were retrospectively analyzed. All cases were treated with a myeloablative conditioning regimen with busulfan and cyclophosphamide, and a graft-versus-host disease (GVHD) prevention regimen based on cyclosporine and methotrexate. Implantation, GVHD, transplant-related complications, immune reconstitution and survival rate were observed. Survival analysis was performed by Kaplan-Meier method, and Log-Rank method was used for univariate comparison. Results: The 60 male patients had main clinical features as infection and bleeding. The age at diagnosis was 0.4 (0.3, 0.8) years, and the age at transplantation was 1.1 (0.6, 2.1) years. There were 20 cases of human leukocyte antigen matched transplantation and 40 mismatched transplantation; 35 patients received peripheral blood HSCT, and 25 cord blood HSCT. All cases were fully implanted. The incidence of acute GVHD (aGVHD) was 48% (29/60) and only 2 (7%) developed aGVHD of grade Ⅲ; the incidence of chronic GVHD (cGVHD) was 23% (13/56), and all cases were limited. The incidence of CMV and EBV infection was 35% (21/60) and 33% (20/60) respectively; and 7 patients developed CMV retinitis. The incidence of sinus obstruction syndrome was 8% (5/60), of whom 2 patients died. There were 7 cases (12%) of autoimmune hemocytopenia after transplantation. Natural killer cells were the earliest to recover after transplantation, and B cells and CD4+T cells returned to normal at about 180 days post HSCT. The 5-year overall survival rate (OS) of this group was 93% (95%CI 86%-99%), and the event free survial rate (EFS) was 87% (95%CI 78%-95%). EFS of non-CMV reactivation group is higher than that of CMV reactivation group (95% (37/39) vs.71% (15/21), χ2=5.22, P=0.022). Conclusions: The therapeutic efficacy of HSCT for WAS is satisfying, and the early application of HSCT in typical cases can achieve better outcome. CMV infection is the main factor affecting disease-free survival rate, which can be improved by strengthening the management of complications.

Evaluation of the efficacy and safety of Nocardia rubra cell wall skeleton immunotherapy for cervical high-risk HPV persistent infection / 中华妇产科杂志

Objective: To evaluate the efficacy and safety of Nocardia rubra cell wall skeleton (Nr-CWS) in the treatment of persistent cervical high-risk human papillomavirus (HR-HPV) infection. Methods: A randomized, double blind, multi-center trial was conducted. A total of 688 patients with clinically and pathologically confirmed HR-HPV infection of the cervix diagnosed in 13 hispital nationwide were recruited and divided into: (1) patients with simple HR-HPV infection lasting for 12 months or more; (2) patients with cervical intraepithelial neoplasia (CIN) Ⅰ and HR-HPV infection lasting for 12 months or more; (3) patients with the same HR-HPV subtype with no CINⅡ and more lesions after treatment with CINⅡ or CIN Ⅲ (CINⅡ/CIN Ⅲ). All participants were randomly divided into the test group and the control group at a ratio of 2∶1. The test group was locally treated with Nr-CWS freeze-dried powder and the control group was treated with freeze-dried powder without Nr-CWS. The efficacy and negative conversion rate of various subtypes of HR-HPV were evaluated at 1, 4, 8, and 12 months after treatment. The safety indicators of initial diagnosis and treatment were observed. Results: (1) This study included 555 patients with HR-HPV infection in the cervix (included 368 in the test group and 187 in the control group), with an age of (44.1±10.0) years. The baseline characteristics of the two groups of subjects, including age, proportion of Han people, weight, composition of HR-HPV subtypes, and proportion of each subgroup, were compared with no statistically significant differences (all P>0.05). (2) After 12 months of treatment, the effective rates of the test group and the control group were 91.0% (335/368) and 44.9% (84/187), respectively. The difference between the two groups was statistically significant (χ2=142.520, P<0.001). After 12 months of treatment, the negative conversion rates of HPV 16, 18, 52, and 58 infection in the test group were 79.2% (84/106), 73.3% (22/30), 83.1% (54/65), and 77.4% (48/62), respectively. The control group were 21.6% (11/51), 1/9, 35.1% (13/37), and 20.0% (8/40), respectively. The differences between the two groups were statistically significant (all P<0.001). (3) There were no statistically significant differences in vital signs (body weight, body temperature, respiration, pulse rate, systolic blood pressure, diastolic blood pressure, etc.) and laboratory routine indicators (blood cell analysis, urine routine examination) between the test group and the control group before treatment and at 1, 4, 8, and 12 months after treatment (all P>0.05); there was no statistically significant difference in the incidence of adverse reactions related to the investigational drug between the two groups of subjects [8.7% (32/368) vs 8.0% (15/187), respectively; χ2=0.073, P=0.787]. Conclusion: External use of Nr-CWS has good efficacy and safety in the treatment of high-risk HPV persistent infection in the cervix.

Cardiovascular health status of Chinese adults based on "Life's Essential 8" score / 中华流行病学杂志

Objective: To assess the cardiovascular health status of adults in China by using the "Life's Essential 8" score, and provide reference for the development and improvement of cardiovascular disease prevention and control policies and measures. Methods: Chronic Disease and Nutrition Surveillance was conducted in 298 counties/districts in 2015 in 31 provinces (autonomous regions, municipalities) across China, multi-stage stratified cluster random sampling was used to select 45 households in each village or neighborhood, and 20 households were further selected to conduct dietary surveys. In this study, a total of 70 093 adults aged ≥20 years who completed the dietary survey and had complete information were included, their cardiovascular health status were assessed by using the "Life's Essential 8" score, a cardiovascular health scoring standard released by the American Heart Association in 2022. All results were adjusted using complex design-based sampling weights to achieve a better estimate of the population. Results: In 2015, the overall cardiovascular health score of Chinese adults aged ≥20 years was 73.3±12.6, the score was significantly higher in women (77.9±11.6) than in men (68.7±11.8), and higher in urban area (74.5±12.8) than in rural area (71.9±12.2), the differences were significant (P<0.001). It was estimated that about 0.25% (95%CI: 0.16%-0.33%) of adults in China had cardiovascular health score of 100, and 33.0% (95%CI: 31.6%-34.3%), 63.2% (95%CI: 62.1%-64.3%), and 3.9% (95%CI: 3.5%-4.2%) of adults had high, moderate and low cardiovascular health scores, respectively. The proportion of those with high cardiovascular health scores was relatively low in men, those with low education level, those with low income, those living in rural areas, and those living in southwest China (P<0.001). Of the eight factors, diet had the lowest mean score (46.0, 95%CI: 44.7-47.3), followed by blood pressure (59.4, 95%CI: 58.2-60.6) and tobacco exposure (61.4, 95%CI: 60.6-62.2). Conclusions: The cardiovascular health status of two-thirds of adult population in China needs to be improved. Diet, tobacco exposure, and blood pressure are the factors affecting the cardiovascular health of Chinese population, to which close attention needs to be paid, and men, rural residents, and those with lower socioeconomic status are key groups in cardiovascular health promotion.

Analysis on trend of health examination rate and influencing factors in adults in China, 2010-2018 / 中华流行病学杂志

Objective: To understand the health examination rate and its changing trend in adults in China from 2010 to 2018, identify the main factors affecting the health examination rate and provide data support for decision making of health intervention. Methods: Data from China Chronic Disease and Risk Factor Surveillance in 2010, 2013, 2015 and 2018 were used. After complex weighting of the data, the rates of health examination, its changing trends and reasons for receiving health examination in adults were analyzed. Average annual percent change (AAPC) was used to describe the changing trend. Anderson model was used as the analysis framework. Multivariate logistic regression model was used to identify the influencing factors for the health examination rate. Results: From 2010 to 2018, the health examination rate in adults increased from 28.2% (95%CI: 24.8%-31.6%) to 41.0% (95%CI: 38.9%-43.1%, P for trend <0.001), the AAPC was 5.47%, the annual average increase was more obvious in those with lower education level and lower income level and in those living in rural area and in western China. In 2018, people received health examination mainly due to providing without charge by community (36.7%) and working unit (28.5%). The results of multivariate analysis showed that being women, age ≥45 years, education level of junior high school or above, living in urban areas, medical insurance, annual income ≥24 000 RMB, suffering from multiple chronic diseases, non-smoking, drinking, adequate physical activity were positive factors for receiving health examination. Conclusion: The rate of health examination in adults increased in China during 2010-2018, and the main reason for receiving health examination is free of charge.

Identification and 3D architecture analysis of the LIPC gene mutation in a pedigree with familial hypercholesterolemia-like phenotype / 中华心血管病杂志

Objective: To identify and analyze 3D architecture of the mutational sites of susceptible genes in a pedigree with familial hypercholesterolemia-like phenotype (FHLP). Methods: This is a case series study. A pedigree with suspected familial hypercholesterolemia was surveyed. The proband admitted in Beijing Anzhen Hospital in April 2019. Whole-exome sequencing was performed to determine the mutational sites of susceptible genes in the proband. Polymerase chain reaction (PCR) sequencing was used to verify the pathogenic variant on proband's relatives. The structural and functional changes of the proteins were analyzed and predicted by Discovery Studio 4.0 and PyMol 2.0. Results: The patients in the pedigree showed abnormal lipid profiles, especially elevated levels of total cholesterol(TC). The genetic screening detected the c.1330C>T SNP in the exon 8 of lipase C (LIPC) gene, this mutation leads to an amino acid substitution from arginine to cysteine at position 444 (Arg444Cys), in the proband and proband's father and brother. In this family, members with this mutation exhibited elevated TC, whereas lipid profile was normal from the proband's mother without this mutation. This finding indicated that LIPC: c.1330C>T mutation might be the mutational sites of susceptible genes. The analysis showed that Arg444Cys predominantly affected the ligand-binding property of the protein, but had a limited impact on catalytic function. Conclusion: LIPC: c.1330C>T is a new mutational site of susceptible genes in this FHLP pedigree.

Establishment of leukemia cell model with inducible AML1-ETO expression and its effect on fatty acid metabolism in leukemia cells / 中华血液学杂志

Objective: To investigate the effect of the AML1-ETO (AE) fusion gene on the biological function of U937 leukemia cells by establishing a leukemia cell model that induces AE fusion gene expression. Methods: The doxycycline (Dox) -dependent expression of the AE fusion gene in the U937 cell line (U937-AE) were established using a lentivirus vector system. The Cell Counting Kit 8 methods, including the PI and sidanilide induction, were used to detect cell proliferation, cell cycle-induced differentiation assays, respectively. The effect of the AE fusion gene on the biological function of U937-AE cells was preliminarily explored using transcriptome sequencing and metabonomic sequencing. Results: ①The Dox-dependent Tet-on regulatory system was successfully constructed to regulate the stable AE fusion gene expression in U937-AE cells. ②Cell proliferation slowed down and the cell proliferation rate with AE expression (3.47±0.07) was lower than AE non-expression (3.86 ± 0.05) after inducing the AE fusion gene expression for 24 h (P<0.05). The proportion of cells in the G(0)/G(1) phase in the cell cycle increased, with AE expression [ (63.45±3.10) %) ] was higher than AE non-expression [ (41.36± 9.56) %] (P<0.05). The proportion of cells expressing CD13 and CD14 decreased with the expression of AE. The AE negative group is significantly higher than the AE positive group (P<0.05). ③The enrichment analysis of the transcriptome sequencing gene set revealed significantly enriched quiescence, nuclear factor kappa-light-chain-enhancer of activated B cells, interferon-α/γ, and other inflammatory response and immune regulation signals after AE expression. ④Disorder of fatty acid metabolism of U937-AE cells occurred under the influence of AE. The concentration of the medium and short-chain fatty acid acylcarnitine metabolites decreased in cells with AE expressing, propionyl L-carnitine, wherein those with AE expression (0.46±0.13) were lower than those with AE non-expression (1.00±0.27) (P<0.05). The metabolite concentration of some long-chain fatty acid acylcarnitine increased in cells with AE expressing tetradecanoyl carnitine, wherein those with AE expression (1.26±0.01) were higher than those with AE non-expression (1.00±0.05) (P<0.05) . Conclusion: This study successfully established a leukemia cell model that can induce AE expression. The AE expression blocked the cell cycle and inhibited cell differentiation. The gene sets related to the inflammatory reactions was significantly enriched in U937-AE cells that express AE, and fatty acid metabolism was disordered.

Formulation optimization and analysis of taste-masking effect of licorzine granules based on sensory evaluation and electronic tongue method / 药学学报

Licorzine granules are common preparations for children zinc deficiency. Considering the long course of treatment, the taste of licorzine granules may become a main factor affecting medication adherence. To date there have been no taste evaluation research into licorzine granules yet. In this study, both sensory evaluation and electronic tongue method were utilized to optimize licorzine granules formulations, evaluate the tastes of licorzine, excipients, optimized formulation in vivo and in vitro. As the results show, bitterness and astringency are the main unpleasant tastes generating from licorzine. Xanthan gum is the main taste-masking excipient, lowering down the bitterness and astringency of licorzine by at least one grade. Good correlation exists between the results of sensory evaluation and electronic tongue method, and an integrated combination of the two helps to obtain objective and rational research conclusions. The adult sensory evaluation study was a research-based clinical trial conducted with informed consent from all subjects in accordance with the ethical requirements of Good Clinical Practice.

Advances in Molecular Targeted Drugs for Hepatocellular Carcinoma / 中山大学学报(医学科学版)

Being the most common solid malignant tumor in the digestive system and the third leading cause of cancer-related death worldwide， hepatocellular carcinoma （HCC） is characterized by insidious onset， early recurrence/metastasis and poor prognosis. With the advantages of targeted precision， high specificity， minimal drug resistance， remarkable therapeutic efficacy and fewer side effects， molecular targeted drugs have become the hotspot and focus of tumor therapy research in recent years. As more is learned about the mechanism and clinical efficacy， some molecular targeted drugs have been recommended by HCC treatment guidelines. This paper reviewed the mechanism of HCC targeted therapy， molecular targeted drugs， relevant therapeutic protocols and outcomes so as to provide reference and evidence for subsequent research.

Reliability and validity assessment of Daily Stressors Evaluation Questionnaire for Primary School Students / 中国学校卫生

Objective@#To develop the Daily Stressor Evaluation Questionnaire for Primary School Students and to evaluate the reliability and validity of the questionnaire.@*Methods@#In November 2020, a convenience sampling method was used to conduct semi structured interviews with 10 primary school students in Jiading District, Shanghai. Through literature review, semi structured interviews, and expert consultation, 59 question items were developed, and 138 elementary school students in 2 districts in Shanghai were selected for a pre survey in March 2021, and the formal questionnaire was formed after item screening and parallel analysis. Stratified cluster sampling was used to survey a total of 1 618 fourth and fifth grade students enrolled in five elementary schools in Jiading District, Shanghai from April to May, 2021, to further test the reliability of the questionnaire.@*Results@#The Daily Stressor Evaluation Questionnaire for Primary School Students contained 4 dimensions and 22 items in total. The internal consistency test showed that cronbach α coefficient of the questionnaire was 0.904 and Cronbach α coefficient of each dimension was between 0.689 to 0.803. The Guttman split half reliability was 0.885 and ranged from 0.582 to 0.732 for each dimension. The results of the validation factor analysis showed that the χ 2/df of the questionnaire was less than 4, the root mean square error of approximation was less than 0.08, and the Tueker Lewis index and comparative fit index were above 0.80. The critical value of using the ROC curve to evaluate the questionnaire was 31 points. At this point, the area under the curve was determined to be 0.783, while the sensitivity and specificity were found to be 71.43% and 73.39%, respectively. Additionally, the positive predictive value and negative predictive value were calculated to be 23.26% and 95.79%, respectively.@*Conclusion@#The Daily Stressor Evaluation Questionnaire for Primary School Students developed in this study has good reliability and validity and can be used as an assessment tool for evaluating stressors in primary school students.

Mechanism of Dahuang Zhechongwan in Treating Myocardial Fibrosis of Rats via TGF-β1/Smads/miR29 Pathway / 中国实验方剂学杂志

ObjectiveTraditional Chinese medicine， namely Dahuang Zhechongwan （DHZCW） was used to treat myocardial fibrosis in model rats， observe its effect on myocardial fibrosis in rats， and explore its action mechanism. MethodThirty-six SPF male Kunming rats were divided into blank group， model group， low-， medium-， high-dose groups of DHZCW （0.056， 0.084， 0.168 g·kg-1）， captopril group （10 mg·kg-1）， with six rats in each group. Except for the blank group， the other groups were intraperitoneally injected isoproterenol solution of 5 mg·kg-1 for 15 consecutive days to replicate the myocardial fibrosis model. At the beginning of modeling， the rats in each group took drugs， and they were sacrificed 28 days after administration. Serum and heart tissue were collected for the corresponding detection. Hematoxylin-eosin （HE） staining and Masson staining were used to observe tissue inflammation， cellular degeneration， necrosis， and fibrosis. The contents of hydroxyproline （HYP）， tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β）， interleukin-6 （IL-6）， hyaluronic acid （HA）， laminin （LN）， type-Ⅲ procollagen （PC Ⅲ） in serum of rats and rats were determined by enzyme-related immunosorbent assay （ELISA）. The expression levels of key pathway proteins transforming growth factor-β1 （TGF-β1）， α-smooth muscle actin （α-SMA）， Smad2， Smad3， and Smad7 were detected by Western blot. The expression levels of key pathway genes TGF-β1， α-SMA， Smad2， Smad3， Smad7， miR-29a-5p， miR-29b-2-5p， and miR-29c-5p were detected by Real-time quantitative polymerase chain reaction （Real-time PCR）. ResultCompared with the blank group， the pathological changes of fibrosis in the model group were obvious， the contents of serum HYP， TNF-α， IL-1β， IL-6， HA， LN， and PCⅢ were increased （P<0.01）， the protein expression levels of TGF-β1， α-SMA， Smad2， and Smad3 were increased； the protein expression level of Smad7 was decreased （P<0.01）. The mRNA expression levels of TGF-β1， α-SMA， Smad2， and Smad3 were increased （P<0.05， P<0.01）， while those of Smad7， miR-29a-5p， miR-29b-2-5p， and miR-29c-5p were decreased （P<0.01）. Compared with the model group， after 28 days of administration， serum HYP， TNF-α， IL-1β， IL-6， HA， LN， and PCⅢ in high-， medium-， and low-dose groups of DHZCW and captopril groups were decreased （P<0.01）. Except for the low-dose group， the protein contents of TGF-β1， α-SMA， Smad2， and Smad3 were decreased， while the protein content of Smad7 was increased （P<0.01）. The mRNA expression levels of TGF-β1， Smad2， α-SMA， and Smad3 in high-dose group of DHZCW were decreased （P<0.05，P<0.01）， while those of Smad7， miR-29a-5p， miR-29b-2-5p， and miR-29c-5p were increased （P<0.05）. The mRNA expressions of TGF-β1， Smad2， and Smad3 in the medium-dose group of DHZCW were decreased （P<0.05， P<0.01）， while mRNA expression of Smad7 was increased （P<0.01）. The mRNA levels of TGF-β1 and Smad2 in the low-dose group of DHZCW were decreased （P<0.01）. ConclusionDHZCW can improve myocardial fibrosis in rats， and its action mechanism may be related to the regulation of the TGF-β1/Smads/miR-29 pathway. In addition， there is dose dependence in the range of 0.056-0.168 g·kg-1， and the effect of the high-dose group is more stable.

Association between vitamin D level and blood eosinophil count in healthy population and patients with chronic obstructive pulmonary disease / 南方医科大学学报

OBJECTIVE@#To investigate the prevalence of vitamin D deficiency and its association with blood eosinophil count in healthy population and patients with chronic obstructive pulmonary disease (COPD).@*METHODS@#We analyzed the data of a total 6163 healthy individuals undergoing routine physical examination in our hospital between October, 2017 and December, 2021, who were divided according to their serum 25(OH)D level into severe vitamin D deficiency group (< 10 ng/mL), deficiency group (< 20 ng/mL), insufficient group (< 30 ng/mL) and normal group (≥30 ng/mL). We also retrospectively collected the data of 67 COPD patients admitted in our department from April and June, 2021, with 67 healthy individuals undergoing physical examination in the same period as the control group. Routine blood test results, body mass index (BMI) and other parameters were obtained from all the subjects, and logistic regression models were used to investigate the association between 25(OH)D levels and eosinophil count.@*RESULTS@#The overall abnormal rate of 25(OH)D level (< 30 ng/mL) in the healthy individuals was 85.31%, and the rate was significantly higher in women (89.29%) than in men. Serum 25(OH)D levels in June, July, and August were significantly higher than those in December, January, and February. In the healthy individuals, blood eosinophil counts were the lowest in severe 25(OH)D deficiency group, followed by the deficiency group and insufficient group, and were the highest in the normal group (P < 0.05). Multivariable regression analysis showed that an older age, a higher BMI, and elevated vitamin D levels were all risk factors for elevated blood eosinophils in the healthy individuals. The patients with COPD had lower serum 25(OH)D levels than the healthy individuals (19.66±7.87 vs 26.39±9.28 ng/mL) and a significantly higher abnormal rate of serum 25(OH)D (91% vs 71%; P < 0.05). A reduced serum 25(OH)D level was a risk factor for COPD. Blood eosinophils, sex and BMI were not significantly correlated with serum 25(OH)D level in patients with COPD.@*CONCLUSION@#Vitamin D deficiency is common in both healthy individuals and COPD patients, and the correlations of vitamin D level with sex, BMI and blood eosinophils differ obviously between healthy individuals and COPD patients.

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

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

Comparison of aspirin treatment strategies for primary prevention of cardiovascular diseases: A decision-analytic Markov modelling study / 北京大学学报(医学版)

OBJECTIVE@#To compare the expected population impact of benefit and risk of aspirin treatment strategies for the primary prevention of cardiovascular diseases recommended by different guidelines in the Chinese Electronic Health Records Research in Yinzhou (CHERRY) study.@*METHODS@#A decision-analytic Markov model was used to simulate and compare different strategies of aspirin treatment, including: Strategy ①: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk, recommended by the 2020 Chinese Guideline on the Primary Prevention of Cardiovascular Diseases; Strategy ②: Aspirin treatment for Chinese adults aged 40-59 years with a high 10-year cardiovascular risk, recommended by the 2022 United States Preventive Services Task Force Recommendation Statement on Aspirin Use to Prevent Cardiovascular Disease; Strategy ③: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk and blood pressure well-controlled (< 150/90 mmHg), recommended by the 2019 Guideline on the Assessment and Management of Cardio-vascular Risk in China. The high 10-year cardiovascular risk was defined as the 10-year predicted risk over 10% based on the 2019 World Health Organization non-laboratory model. The Markov model simulated different strategies for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Quality-adjusted life year (QALY) and the number needed to treat (NNT) for each ischemic event (including myocardial infarction and ischemic stroke) were calculated to assess the effectiveness of the different strategies. The number needed to harm (NNH) for each bleeding event (including hemorrhagic stroke and gastrointestinal bleeding) was calculated to assess the safety. The NNT for each net benefit (i.e., the difference of the number of ischemic events could be prevented and the number of bleeding events would be added) was also calculated. One-way sensitivity analysis on the uncertainty of the incidence rate of cardiovascular diseases and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted.@*RESULTS@#A total of 212 153 Chinese adults, were included in this study. The number of people who were recommended for aspirin treatment Strategies ①-③ was 34 235, 2 813, and 25 111, respectively. The Strategy ③ could gain the most QALY of 403 [95% uncertainty interval (UI): 222-511] years. Compared with Strategy ①, Strategy ③ had similar efficiency but better safety, with the extra NNT of 4 (95%UI: 3-4) and NNH of 39 (95%UI: 19-132). The NNT per net benefit was 131 (95%UI: 102-239) for Strategy ①, 256 (95%UI: 181-737) for Strategy ②, and 132 (95%UI: 104-232) for Strategy ③, making Strategy ③ the most favorable option with a better QALY and safety, along with similar efficiency in terms of net benefit. The results were consistent in the sensitivity analyses.@*CONCLUSION@#The aspirin treatment strategies recommended by the updated guidelines on the primary prevention of cardiovascular diseases showed a net benefit for high-risk Chinese adults from developed areas. However, to balance effectiveness and safety, aspirin is suggested to be used for primary prevention of cardiovascular diseases with consideration for blood pressure control, resulting in better intervention efficiency.

The potential targets and mechanisms of modified Baihe dihuang decoction applied in post-stroke depression / 中国药房

OBJECTIVE To explore the potential targets and mechanisms of the modified Baihe dihuang decoction （MBD/ BDD） applied in post-stroke depression （PSD）. METHODS Network pharmacology was used to mine the potential targets and key pathways of MBD/BDD in the treatment of PSD. PSD model rats were induced by focal cerebral ischemia surgery combined with chronic unforeseen mild stress， and then were randomly divided into PSD model group， MBD/BDD group （12.6 g/kg， by raw drug）， and fluoxetine hydrochloride （FLX） group （positive control， 2.3 mg/kg）； a blank control group was also set up， with 8 rats in each group. Each administration group was given a corresponding medication solution by gavage once a day for 21 consecutive days. The intervention effect of MBD/BDD on depression-like symptoms in model rats was evaluated by open field and forced swimming tests. The brain tissues of rats in each group were dissected and total RNA was extracted for transcriptome sequencing and bioinformatics analysis. The mRNA and protein expressions of genes with significant changes and common neurotrophic factors were verified based on the above results. RESULTS A total of 131 MBD/BDD antidepressant-related target genes were obtained （such as IL1B and AKT1， etc.）， which were closely related to neural active ligand-receptor interactions and cyclic adenosine monophosphate signaling pathway. MBD/BDD could significantly prolong or increase the total time spent and distance traveled in the central grid of qiangzhe@cqtcm.edu.cn PSD model rats， and significantly shorten the cumulative immobility time （P＜0.05）. After treatment with MBD/BDD， the number of genes that changed in rat brain tissue was much higher than that in the FLX group， and there were significant differences in gene profiles among the PSD model group， MBD/BDD group， and FLX group. There were 1 351 differentially expressed genes （DEGs） between the MBD/BDD group and the PSD model group， of which 178 were significantly down-regulated and 1 173 were significantly up-regulated （P＜0.05）. Above 1 351 DEGs were involved in neuronal differentiation， chemical synaptic transmission regulation. They were significantly enriched in axonal guidance， cholinergic synapses and neuroactive ligand-receptor interactions. The top 30 genes in terms of up-regulation in the brain tissue of rats of MBD/BDD group were all associated with neuronal proliferation， development， differentiation， and migration. After MBD/BDD intervention， the expressions of Fezf2， Arx， Ostn， Nrgn genes， brain-derived neurotrophic factor and tyrosine kinase receptor B protein in brain tissue of rats were significantly increased （P＜0.05）. CONCLUSIONS The anti-PSD effect of MBD/BDD may be related to the up-regulation of the expression of genes related to neuronal proliferation， development， differentiation and migration， as well as the promotion of neural structural and functional repair.

Effect and Mechanism of Baoshen Prescription in Alleviating Renal Fibrosis in UUO Mice by Regulating ERK/p38 MAPK Signaling Pathway / 中国实验方剂学杂志

ObjectiveTo observe the protective effect of Baoshen prescription against renal fibrosis and explore its underlying mechanism through network pharmacology， molecular docking， and in vivo experiments. MethodAll mice were randomly divided into sham surgery group， model group， low-， medium-， and high-dose Baoshen prescription groups， and a benazepril hydrochloride group. Unilateral ureteral obstruction （UUO） was performed to establish a renal fibrosis model， and the administration of Baoshen prescription at low， medium， and high doses （0.455， 0.91， and 1.82 g·kg-1）， and benazepril hydrochloride （1.68 mg·kg-1） or distilled water began on the same day as model preparation. Mice in the model group and the sham surgery group were given an equal volume of distilled water. The intervention was carried out once daily for 14 days. Mouse serum levels of blood urea nitrogen （BUN） and creatinine （Cr） were measured. Hematoxylin-eosin （HE） staining and Masson staining were used to observe renal pathological changes. Western blot and immunohistochemistry were used to assess the expression of fibronectin （FN）， α-smooth muscle actin （α-SMA）， and E-cadherin， which are related to renal fibrosis. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression of transforming growth factor-β1 （TGF-β1）， tumor necrosis factor-α （TNF-α）， NOD-like receptor protein 3 （NLRP3）， and monocyte chemoattractant protein-1 （MCP-1） in renal tissues. The mechanism of Baoshen prescription in improving renal fibrosis was explored through network pharmacology， molecular docking， and Western blot experiments. ResultCompared with the sham surgery group， the model group showed significantly increased levels of BUN and Cr （P<0.01）. The model group exhibited abnormal renal glomerular morphology， loss of tubular brush borders， tubular dilation， and an enlarged area of blue collagen fibers. Mice in the model group showed significantly elevated levels of FN and α-SMA （P<0.01）， significantly decreased expression of E-cadherin （P<0.01）， and significantly increased expression of TGF-β1， TNF-α， NLRP3， and MCP-1 mRNA （P<0.05， P<0.01）. Compared with the model group， the Baoshen prescription groups showed significantly reduced BUN and Cr levels （P<0.01）， alleviated renal pathological damage， improved fibrosis， reduced expression of FN and α-SMA （P<0.01）， increased E-cadherin expression （P<0.01）， and downregulated mRNA expression of TGF-β1， TNF-α， NLRP3， and MCP-1 （P<0.05， P<0.01）. Network pharmacology and molecular docking predicted that Baoshen prescription could potentially improve renal fibrosis through the extracellular signal-regulated kinase （ERK）/p38 mitogen-activated protein kinase （MAPK） signaling pathway. Pharmacological research showed that compared with the sham surgery group， the model group exhibited significantly increased expression of phosphorylated （p）-ERK and p-p38 （P<0.05， P<0.01）. Compared with the model group， medium- and high-dose Baoshen prescription groups showed significantly downregulated expression of p-ERK and p-p38 proteins （P<0.05， P<0.01）. ConclusionBaoshen prescription can effectively improve renal fibrosis induced by UUO in mice， and its mechanism of action may be related to the ERK/p38 MAPK signaling pathway.