mTORC1 Signaling in Brain Endothelial Progenitors Contributes to CCM Pathogenesis.

BACKGROUND: Cerebral vascular malformations (CCMs) are primarily found within the brain, where they result in increased risk for stroke, seizures, and focal neurological deficits. The unique feature of the brain vasculature is the blood-brain barrier formed by the brain neurovascular unit. Recent studies suggest that loss of CCM genes causes disruptions of blood-brain barrier integrity as the inciting events for CCM development. CCM lesions are proposed to be initially derived from a single clonal expansion of a subset of angiogenic venous capillary endothelial cells (ECs) and respective resident endothelial progenitor cells (EPCs). However, the critical signaling events in the subclass of brain ECs/EPCs for CCM lesion initiation and progression are unclear. METHODS: Brain EC-specific CCM3-deficient (Pdcd10BECKO) mice were generated by crossing Pdcd10fl/fl mice with Mfsd2a-CreERT2 mice. Single-cell RNA-sequencing analyses were performed by the chromium single-cell platform (10× genomics). Cell clusters were annotated into EC subtypes based on visual inspection and GO analyses. Cerebral vessels were visualized by 2-photon in vivo imaging and tissue immunofluorescence analyses. Regulation of mTOR (mechanistic target of rapamycin) signaling by CCM3 and Cav1 (caveolin-1) was performed by cell biology and biochemical approaches. RESULTS: Single-cell RNA-sequencing analyses from P10 Pdcd10BECKO mice harboring visible CCM lesions identified upregulated CCM lesion signature and mitotic EC clusters but decreased blood-brain barrier-associated EC clusters. However, a unique EPC cluster with high expression levels of stem cell markers enriched with mTOR signaling was identified from early stages of the P6 Pdcd10BECKO brain. Indeed, mTOR signaling was upregulated in both mouse and human CCM lesions. Genetic deficiency of Raptor (regulatory-associated protein of mTOR), but not of Rictor (rapamycin-insensitive companion of mTOR), prevented CCM lesion formation in the Pdcd10BECKO model. Importantly, the mTORC1 (mTOR complex 1) pharmacological inhibitor rapamycin suppressed EPC proliferation and ameliorated CCM pathogenesis in Pdcd10BECKO mice. Mechanistic studies suggested that Cav1/caveolae increased in CCM3-depleted EPC-mediated intracellular trafficking and complex formation of the mTORC1 signaling proteins. CONCLUSIONS: CCM3 is critical for maintaining blood-brain barrier integrity and CCM3 loss-induced mTORC1 signaling in brain EPCs initiates and facilitates CCM pathogenesis.

Arabidopsis retromer subunit AtVPS29 is involved in SLY1-mediated gibberellin signaling.

KEY MESSAGE: Retromer protein AtVPS29 upregulates the SLY1 protein and downregulates the RGA protein, positively stimulating the development of the root meristematic zone, which indicates an important role of AtVPS29 in gibberellin signaling. In plants, the large retromer complex is known to play roles in multiple development processes, including cell polarity, programmed cell death, and root hair growth in Arabidopsis. However, many of its roles in plant development remain unknown. Here, we show that Arabidopsis trimeric retromer protein AtVPS29 (vacuolar protein sorting 29) modulates gibberellin signaling. The SLEEPY1 (SLY1) protein, known as a positive regulator of gibberellic acid (GA) signaling, exhibited lower abundance in vps29-3 mutants compared to wild-type (WT) plants. Conversely, the DELLA repressor protein, targeted by the E3 ubiquitin ligase SCF (Skp, Cullin, F-box) complex and acting as a negative regulator of GA signaling, showed increased abundance in vps29-3 mutants compared to WT. The vps29-3 mutants exhibited decreased sensitivity to exogenous GA supply in contrast to WT, despite an upregulation in the expression of GA receptor genes within the vps29-3 mutants. In addition, the expression of the GA synthesis genes was downregulated in vps29-3 mutants, implying that the loss of AtVPS29 causes the downregulation of GA synthesis and signaling. Furthermore, vps29-3 mutants exhibited a reduced meristematic zone accompanied by a decreased cell number. Together, these data indicate that AtVPS29 positively regulates SLY1-mediated GA signaling and plant growth.

Arabidopsis COP1 guides stomatal response in guard cells through pH regulation.

Plants rely on precise regulation of their stomatal pores to effectively carry out photosynthesis while managing water status. The Arabidopsis CONSTITUTIVE PHOTOMORPHOGENIC 1 (COP1), a critical light signaling repressor, is known to repress stomatal opening, but the exact cellular mechanisms remain unknown. Here, we show that COP1 regulates stomatal movement by controlling the pH levels in guard cells. cop1-4 mutants have larger stomatal apertures and disrupted pH dynamics within guard cells, characterized by increased vacuolar and cytosolic pH and reduced apoplastic pH, leading to abnormal stomatal responses. The altered pH profiles are attributed to the increased plasma membrane (PM) H+-ATPase activity of cop1-4 mutants. Moreover, cop1-4 mutants resist to growth defect caused by alkali stress posed on roots. Overall, our study highlights the crucial role of COP1 in maintaining pH homeostasis of guard cells by regulating PM H+-ATPase activity, and demonstrates how proton movement affects stomatal movement and plant growth.

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）］

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.

Exosomes from miR-23 Overexpressing Stromal Cells Suppress M1 Macrophage and Inhibit Calcium Oxalate Deposition in Hyperoxaluria Rat Model.

Purpose: To investigate whether ADSC-derived miR-23-enriched exosomes could protect against calcium oxalate stone formation in a hyperoxaluria rat model. Methods: An ethylene glycol- (EG-) induced hyperoxaluria rat model and an in vitro model of COM-induced HK-2 cells coculturing with RAW264.7 cells were established to explore the protective mechanisms of ADSC-derived miR-23-enriched exosomes. Results: The results showed that treatment with miR-23-enriched exosomes from ADSCs protected EG-induced hyperoxaluria rats, and cell experiments confirmed that coculturing with miR-23-enriched exosomes alleviated COM-induced cell autophagy. Overexpressed miR-23 suppressed M1 macrophage polarization by inhibiting IRF1 expression. Furthermore, the predicted binding site between the IRF1 messenger RNA 3'-untranslated region (3'-UTR) and miR-23 was confirmed by the dual-luciferase reporter assay. Conclusion: In conclusion, our research gave the first evidence that ADSC-derived miR-23-enriched exosomes affected the polarization of M1 macrophages by directly inhibiting IRF1 and protecting against calcium oxalate stone formation in a hyperoxaluria rat model.

A decision tree model of hypertension among college students in Yunnan Province, China.

PURPOSE: Previous studies have indicated that the prevalence rate of hypertension in adolescents is high, but it has not received much attention and the influencing factors are unclear, especially in Yunnan Province, China. MATERIALS AND METHODS: A cluster sampling method was used to investigate 4781 freshmen in a college in Kunming, Yunnan Province from November to December. Demographic and lifestyle data were collected using questionnaires, and height, weight and blood pressure were measured. Decision tree model of hypertension in college students was established by Chi-square automatic interactive detection method. RESULTS: Prevalence of prehypertension of systolic blood pressure (SBP) and diastolic blood pressure (DBP) were detected in 33.9% and 32.1%, respectively. Prevalence of hypertension of SBP and DBP was detected in 1.2% and 7.2%, respectively. The hypertension and prehypertension decision tree of SBP has gender (χ2 = 728.64, p < .001) at the first level and body mass index (BMI) (boys: χ2 = 55.98, p < .001; girls: χ2 = 79.58, p < .001) at the second level. The hypertension and prehypertension decision tree of DBP has gender (χ2 = 381.83, p < .001) at the first level, BMI (boys: χ2 = 40.54, p < .001; girls: χ2 = 48.79, p < .001) at the second level, only children (χ2 = 6.43, p = .04) and red wine consumption (χ2 = 8.17, p = .017) at the third level. CONCLUSIONS: The present study suggests that gender, BMI, only children and red wine consumption were the main factors affecting hypertension in college students in southwest border areas of China.

Hypertension in Chinese adolescent is generally ignored. This study first reports the prevalence of hypertension in adolescents in Yunnan Province, China.Four thousand seven hundred and eighty-one freshmen were surveyed and height, weight and blood pressure were measured. A decision tree model was used to analyze the predictors of hypertension.The study demonstrated that gender, BMI, only children and red wine predict hypertension in adolescents.

Treatment persistence of bictegravir/emtricitabine/tenofovir alafenamide and efavirenz + lamivudine + tenofovir disoproxil among HIV-1 patients newly starting treatment in Hunan Province in China.

BACKGROUND: Though bictegravir/emtricitabine/tenofovir (BIC/FTC/TAF) have been regulatory approved and included in the National Reimbursement Drug List in China, due to the affordability concern, generic version of efavirenz + lamivudine + tenofovir (EFV + 3TC + TDF) is still recommended as the first-line therapy in the clinical guideline and widely used in clinical practice. The aim of the study is to assess the persistence with first-line BIC/TAF/TAF and EFV + 3TC + TDF in newly treated HIV-1 patients in the real-world setting in Hunan Province in China. METHODS: A retrospective analysis of the medical records of HIV patients initiating first-line antiretroviral therapy in the First Hospital of Changsha in January 1st, 2021-July 31st, 2022 was conducted. Persistence was assessed as the number of days on the therapy from the index until treatment discontinuation or end of data availability. Kaplan-Meier Curves and Cox Proportional Hazard models were used to evaluate the discontinuation rates. Subgroup analysis was performed excluding BIC/FTC/TAF patients with treatment discontinuation due to economic reason, and EFV + 3TC + TDF patients with a viral load > 500,000 copies/mL. RESULTS: A total of 310 eligible patients were included in the study, with 244 and 66 patients in the BIC/FTC/TAF group and EFV + 3TC + TDF group, respectively. Compared with EFV + 3TC + TDF patients, BIC/FTC/TAF patients were older, more living in the capital city currently, and had significantly higher total cholesterol and low-density level (all p < 0.05). No significant difference was shown in the time to discontinuation between BIC/FTC/TAF patients and EFV + 3TC + TDF patients. After excluding BIC/FTC/TAF patients with treatment discontinuation due to economic reason, EFV + 3TC + TDF group were shown to have a significantly higher risk of discontinuation than BIC/FTC/TAF group (hazard ratio [HR] = 11.1, 95% confidence interval [CI] = 1.3-93.2). After further removing the EFV + 3TC + TDF patients with a viral load > 500,000 copies/mL, the analysis showed similar results (HR = 10.1, 95% CI = 1.2-84.1). 79.4% of the EFV + 3TC + TDF patients discontinued treatment due to clinical reasons, while 83.3% of the BIC/FTC/TAF patients discontinued treatment due to economic reasons. CONCLUSIONS: Compared with BIC/FTC/TAF, EFV + TDF + 3TC patients were significantly more likely to discontinue the first-line treatment in Hunan Province in China.

SRF SUMOylation modulates smooth muscle phenotypic switch and vascular remodeling.

Serum response factor (SRF) controls gene transcription in vascular smooth muscle cells (VSMCs) and regulates VSMC phenotypic switch from a contractile to a synthetic state, which plays a key role in the pathogenesis of cardiovascular diseases (CVD). SRF activity is regulated by its associated cofactors. However, it is not known how post-translational SUMOylation regulates the SRF activity in CVD. Here, we show that Senp1 deficiency in VSMCs increased SUMOylated SRF and the SRF-ELK complex, leading to augmented vascular remodeling and neointimal formation in mice. Mechanistically, SENP1 deficiency in VSMCs increased SRF SUMOylation at lysine 143, which reduced its lysosomal localization concomitant with increased nuclear accumulation. SUMOylation of SRF switched its binding with the contractile phenotype-responsive cofactor myocardin to binding with the synthetic phenotype-responsive cofactor phosphorylated ELK1. Both SUMOylated SRF and phosphor-ELK1 were increased in VSMCs from coronary arteries of CVD patients. Importantly, preventing the shift from SRF-myocardin to SRF-ELK complex by AZD6244 inhibited the excessive proliferative, migratory, and synthetic phenotypes, attenuating neointimal formation in Senp1-deficient mice. Therefore, targeting the SRF complex may have a therapeutic potential for the treatment of CVD.

Endothelial Cell-Pericyte Interactions in the Pathogenesis of Cerebral Cavernous Malformations (CCMs).

Cerebral cavernous malformations (CCMs), consisting of multiple, dilated capillary channels formed by a single layer of endothelium and lacking parenchymal cells, are exclusively to the brain. Patients with inherited autosomal-dominant CCMs carry loss-of-function mutations in one of three genes: CCM1, CCM2, and CCM3. It is not known why CCM lesions are confined to brain vasculature despite the ubiquitous expression of CCM proteins in all tissues, and whether cell types other than endothelial cells (ECs) contribute to CCM lesion formation. The prevailing view is that the primary defects in CCMs in humans are EC-intrinsic, such that EC-specific deletion of any one of the three genes in mice results in similar CCM lesions. An unexpected finding is that Ccm3 deletion in pericytes (PCs) also induces CCM lesions. CCM3 deletion in ECs or PCs destabilizes PC-EC associations, highlighting the importance of these interactions in CCM formation.

A Phase I Study to Evaluate the Safety and Pharmacokinetics of SHR0302 Base Ointment in Healthy Adult Volunteers.

INTRODUCTION: SHR0302 is a highly selective JAK1 inhibitor. This study aimed to investigate the safety, tolerability, and pharmacokinetics of single and multiple-dose topical skin application of SHR0302 base ointment in healthy adult subjects. METHODS: This phase I clinical trial (registration number: CTR20192188) consisted of two parts. Part 1 was a single-dose ascending study with four dose levels in 32 healthy Australian adults (8 subjects in each dose group). All Australian subjects were randomized 3:1 to a single-dose topical skin application of SHR0302 base ointment or placebo. The dose escalated from 1% SHR0302 base ointment on 3% of body surface area (BSA) to 2% SHR0302 base ointment on 20% of BSA. Part 2 combined single and multiple-dose ascension studies with two dose levels in 20 healthy Chinese adults (10 subjects in each dose group). All Chinese subjects were randomized 4:1 to a combination of single and multiple doses for consecutive 10 days of topical application of 1% SHR0302 base ointment on 20% BSA or 2% SHR0302 base ointment on 20% BSA. The safety and pharmacokinetics of the SHR0302 base ointment were evaluated. RESULTS: The incidence of treatment-emergent adverse events (TEAEs) in both parts was comparable between the SHR0302 base ointment group and the vehicle group (part 1: 33.3% vs. 37.5%; part 2: 56.3% vs. 75.0%). All TEAEs were transient, recovered, and equally well-tolerated in the two racial groups. The overall absorption of the SHR0302 base ointment was slow after topical application, with Tmax>10 h. After a single dose of the SHR0302 base ointment, drug exposure in healthy Australian and Chinese subjects increased nonlinearly with the increase in the administration area and drug content. Drug exposure increased in a less-than-dose-proportional manner within the dose range tested. Due to differences in the clinical practice of topical application, the Tmax of the drug in Australian subjects was earlier than in Chinese subjects, but the overall extent of absorption seemed comparable in Australian and Chinese subjects (with comparable AUC0-t). CONCLUSION: The SHR0302 base ointment (either single or multiple doses) was well tolerated and safe, with no racial disparity. KEY MESSAGE: The SHR0302 base ointment (either single or multiples doses) was well tolerated and safe.

The Impact of COVID-19 on Psychiatric Health in the Korean Population

Coronavirus disease 2019 (COVID-19) has multiple negative impacts on the psychiatric health of both those previously infected and not infected with severe acute respiratory syndrome coronavirus 2. Moreover, the negative impacts of COVID-19 are closely associated with geographical region, culture, medical system, and ethnic background. We summarized the evidence of the impact of COVID-19 on the psychiatric health of the Korean population. This narrative review included thirteen research articles, which investigated the impact of COVID-19 on the psychiatric health of Koreans. COVID-19 survivors were reported to have a 2.4 times greater risk of developing psychiatric disorders compared to members of a control group, and anxiety and stress-related disorders were the most common newly diagnosed psychiatric illnesses. Studies also reported that COVID-19 survivors had a 3.33-fold higher prevalence of insomnia, a 2.72-fold higher prevalence of mild cognitive impairment, and a 3.09-fold higher prevalence of dementia compared to the control group. In addition, more than four studies have highlighted that the medical staff members, including nurses and medical students, exhibit a greater negative psychiatric impact of COVID-19. However, none of the articles investigated the biological pathophysiology or mechanism linking COVID-19 and the risk of diverse psychiatric disorders. Moreover, none of the studies were actual prospective studies. Thus, longitudinal studies are needed to more clearly elucidate the effect of COVID-19 on the psychiatric health of the Korean population. Lastly, studies focusing on preventing and treating COVID-19–associated psychiatric problems are needed to provide a benefit in real clinical settings.

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.

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.

Diurnal differences in acute gout attacks: A clinical study of male gout patients / 北京大学学报(医学版)

OBJECTIVE@#To observe the diurnal difference of acute gout attacks in men, and provide reference for accurate clinical prevention and treatment.@*METHODS@#Using a single-center, cross-sectional study design, the patients diagnosed with gout in the outpatient department of Rheumatology and Immuno-logy of PLA Joint Logistic Support Force No.980 Hospital from October 2021 to April 2022 were selected. The information about the patient's current/last acute gout attacks (less than 2 weeks from visit), date and time of attacks, joint symptoms and signs, medication use, and relevant biochemical tests on the day of visit was recorded. The diurnal time difference of acute gout attacks in male patients was analyzed, and univariate comparison and multivariate Logistic regression analyses were conducted to compare the diurnal difference of acute gout attacks with clinical characteristics and biochemical indicators.@*RESULTS@#A total of 100 male gout patients were included, and 100 acute attacks were recorded. Diurnal distribution of acute gout attacks: morning (6:00~11:59, 18, 18%), afternoon (12:00~17:59, 11, 11%), the first half of the night (18:00~23:59, 22, 22%), the second half of the night (0:00~05:59, 49, 49%); During the day (included morning and afternoon, 29, 29%) and at night (included the first half of the night and the second half of the night, 71, 71%). The rate of acute gout attack was significantly higher at night than in the day (about 2.5 ∶1). No matter the first or recurrent gout, no matter the duration of the disease, the number of acute gout attacks had the difference of less in the day and more in the night. Serum urate (SU) level was higher in the patients with nocturnal attack than in those with daytime attack (P=0.044). Comorbidities were significantly different in the day-night ratio of the number of acute gout attack (P=0.028). Multiple Logistic regression analysis showed that SU level (OR=1.005, 95%CI: 1.001-1.009) and comorbidities (OR=3.812, 95%CI: 1.443-10.144) were the correlative factors of nocturnal acute gout attacks.@*CONCLUSION@#No matter the first or recurrent gout, no matter the duration of the disease, it has a diurnal variation characterized by multiple attacks at night, increased SU level and comorbidities are correlative factors for nocturnal acute attack of gout.

Hot water washing processing technology of Euodiae Fructus based on change laws of active components and tastes / 中国中药杂志

In order to establish the standardized processing technology of the hot water washing of Euodiae Fructus, this study, based on the traditional processing method of hot water washing of Euodiae Fructus recorded in ancient works and modern processing specifications of traditional Chinese medicine decoction pieces, took the yield of decoction pieces and the content of main components as the indicators and optimized the processing conditions by orthogonal test based on the results of single factor investigation. At the same time, electronic tongue technology was used to analyze the change law of the taste index of Euodiae Fructus during the hot water washing. The results of the single factor investigation showed that the content of the main components in Euodiae Fructus showed some regular changes during the processing. Specifically, the content of chlorogenic acid, hyperin, isorhamnetin-3-O-rutinoside, isorhamnetin-3-O-galactoside, and dehydroevodiamine decreased significantly, with average decreases of-23.75%,-27.80%,-14.04%,-14.03%, and-13.11%, respectively. The content of limonin increased significantly with an average increase of 19.83%. The content of evodiamine, rutaecarpine, evocarpine, and dihydroevocarpine showed fluctuating changes and generally increased, with average variation amplitudes of 0.54%,-3.78%, 2.69%, and 5.13%, respectively. The orthogonal test results showed that the optimum processing parameters for the hot water washing of Euodiae Fructus were as follows: washing time of 2 min, the solid-to-liquid ratio of 1∶10 g·mL~(-1), washing temperature of 80 ℃, washing once, and drying at 50 ℃. After the hot water washing processing, the average yield of Euodiae Fructus pieces was 94.80%. The content of limonin, evodiamine, and rutaecarpine was higher than those of raw pro-ducts, and the average transfer rates were 102.56%, 103.15%, and 105.16%, respectively. The content of dehydroevodiamine was lower than that of the raw products, and the average transfer rate was 83.04%. The results of taste analysis showed that the hot water washing could significantly reduce the salty, astringent, and bitter tastes of Euodiae Fructus. This study revealed the influence of the hot water washing on the content of main components and taste of Euodiae Fructus, and the processing technology of the hot water was-hing of Euodiae Fructus established in this study was stable, feasible, and suitable for industrial production, which laid a foundation for clarifying its processing principle and improving the quality standard and clinical application value of decoction pieces.

Qualitative and quantitative study of flavonoids in Notoginseng Radix et Rhizoma based on UPLC-Q-TOF-MS and HPLC-DAD / 中国中药杂志

The flavonoids in Panax notoginseng were qualitatively analyzed by ultra-high performance liquid chromatography-quadrupole-time of flight mass spectrometry(UPLC-Q-TOF-MS), and the content of three main flavonoids in P. notoginseng of different specifications and grades collected from different habitats was determined by HPLC-DAD. Flavonoids and anthocyanins were analyzed by UPLC-Q-TOF-MS/MS in the positive and negative ion modes, respectively. Twelve flavonoid glycosides and one anthocyanin glycoside in P. notoginseng were identified, but no flavonoid aglycones were detected. Among them, 12 compounds were identified in the underground part of P. notoginseng for the first time and eight compounds were first reported in this plant. Moreover, six and four compounds were identified in the Panax genus and the Araliaceae family for the first time, respectively. A method for simultaneous determination of three flavonoids in P. notoginseng was established by HPLC-DAD. The content of flavonoids in 721 P. notoginseng samples of 124 specifications and grades collected from 20 different habitats was simultaneously determined. Among three flavonoids determined, the content of quercetin-3-O-(2″-β-D-xylosyl)-β-D-galactoside was the highest with the average content in the tested samples of 161.0 μg·g~(-1). The content of compounds quercetin-3-O-hexosyl-hexoside and kaempferol-3-O-pentosyl-hexoside was relatively low, with the average content of 18.5 μg·g~(-1)(calculated as quercetin-3-O-sophoroside) and 49.4 μg·g~(-1)(calculated as kaempferol-3-O-sangbu diglycoside). There were significant differences in flavonoids content of samples from different production area. The content of flavonoids in spring P. notoginseng was significantly lower than that in winter P. notoginseng when the other influencing factors such as production areas, germplasm resources, and cultivation conditions were fixed. As for P. notoginseng of different specifications, the flavonoid content in the part connecting the taproot and the aboveground stem was significantly higher than that in other parts. The results of large-scale data showed that the flavonoid content gradually increased with the increase in the number of heads. There were significant differences between the flavonoid content in most specifications and grades, especially the 20-head P. notoginseng and countless head P. notoginseng, whose content was significantly lower and significantly higher than that of other specifications and grades, respectively. This study provides a scientific basis for the study of the effective components and quality control of P. notoginseng from the perspective of flavonoids.