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.

Recent progress in the biosynthesis of dicarboxylic acids, a monomer of biodegradable plastics / 生物工程学报

Plastics are one of the most important polymers with huge global demand. However, the downsides of this polymer are that it is difficult to degrade, which causes huge pollution. The environmental-friendly bio-degradable plastics therefore could be an alternative and eventually fulfill the ever-growing demand from every aspect of the society. One of the building blocks of bio-degradable plastics is dicarboxylic acids, which have excellent biodegradability and numerous industrial applications. More importantly, dicarboxylic acid can be biologically synthesized. Herein, this review discusses the recent advance on the biosynthesis routes and metabolic engineering strategies of some of the typical dicarboxylic acids, in hope that it will help to provide inspiration to further efforts on the biosynthesis of dicarboxylic acids.

Geographic Variations in the Prevalence, Awareness, Treatment, and Control of Dyslipidemia among Chinese Adults in 2018-2019: A Cross-sectional Study / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the spatial patterns of the prevalence, awareness, treatment, and control rates of dyslipidemia at the provincial level in China.@*METHODS@#A national and provincial representative cross-sectional survey was conducted among 178,558 Chinese adults in 31 provinces in mainland China in 2018-2019, using a multi-stage, stratified, cluster-randomized sampling design. Subjects, as households, were selected, followed by a home visit to collect information. Both descriptive and linear regression procedures were applied in the analyses.@*RESULTS@#The overall prevalence of dyslipidemia was 35.6%, and wide geographic variations of prevalence, treatment, and control rates of dyslipidemia were identified among 178,558 eligible participants with a mean age of 55.1 ± 13.8 years. The highest-lowest difference regarding the provincial level prevalence rates were 19.7% vs. 2.1% for high low-density lipoprotein cholesterol, 16.7% vs. 2.5% for high total cholesterol, 35.9% vs. 5.4% for high triglycerides, and 31.4% vs. 10.5% for low high-density lipoprotein cholesterol. The treatment rate of dyslipidemia was correlated with the socio-demographic index ( P < 0.001), urbanization rate ( P = 0.01), and affordable basic technologies and essential medicines ( P < 0.001).@*CONCLUSION@#Prevailing dyslipidemia among the Chinese population and its wide geographic variations in prevalence, treatment, and control suggest that China needs both integrated and localized public health strategies across provinces to improve lipid management.

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.

A resting-state functional MRI study on amplitude of low-frequency fluctuation and functional connectivity alteration of parkinson′s disease with apathy / 中华放射学杂志

Objective:To investigate the alterations of amplitude of low frequency fluctuation (ALFF) and functional connectivity (FC) in patients with Parkinson′s disease (PD) with apathy.Methods:From May 2016 to August 2019, PD patients and age-, gender-and education level-matched healthy controls (HC) in the First Affiliated Hospital of Nanjing Medical University were prospectively recruited. The clinical and resting-state functional MRI (rs-fMRI) data of PD patients and HC were analyzed. According to the Starkstein Apathy Scale (SAS) scores, PD patients were divided into PD with apathy (PD-A) group and PD without apathy (PD-NA) group. Rs-fMRI images were processed by DPABI based on MATLAB. ALFF values were calculated and the standard ALFF (zALFF) were obtained. ANOVA and Post-Hoc t test were performed to compare the differences in local brain activity among the three groups. The brain regions with significant different zALFF values were selected as the seeds to calculate the FC values of the whole brain. The associations between FC values and the SAS scores were performed using pearson correlation analyses. Results:A total of 75 PD patients (50 males, 25 females, aged from 44 to 88 years) and 41 HC (25 males, 16 females, aged from 54 to 72 years) were enrolled. There were 42 patients in the PD-A group and 33 patients in the PD-NA group. Significant differences were found in zALFF values among the PD-A, PD-NA and HC groups ( P<0.05). After Post-Hoc t test, compared with the HC group, zALFF values were significantly increased in the right middle frontal gyrus in the PD-A group ( P<0.05) and significantly decreased in the left precuneus in the PD-NA group; The zALFF values of the right middle frontal gyrus and left precuneus in the PD-A group were significantly higher than those in PD-NA group ( P<0.05). Brain regions with different zALFF values were used as seeds for whole-brain FC. Compared with PD-NA group, FC values between the right middle frontal gyrus and bilateral precuneus, left superior frontal gyrus and its medial side, left middle frontal gyrus, left angular, left anterior cingulate gyrus, left posterior cingulate gyrus, left parahippocampal gyrus were significantly decreased in the PD-A group ( P<0.05). Additionally, FC values of PD patients between the right middle frontal gyrus with the left precuneus, the left superior frontal gyrus and its medial side, and the left middle frontal gyrus were negatively correlated with SAS scores ( r=-0.31, -0.30 and -0.34, both P<0.05). Conclusion:PD-A and PD-NA patients have different brain functional activities and connections in the frontal lobe, parietal lobe and limbic system, suggesting that apathy in PD may be associated with the abnormal functional connections of the frontal-parietal cortical circuit and the frontal-limbic-striatal loop.

Triaging patients in the outbreak of COVID-2019 / 中国感染控制杂志

In the outbreak of COVID-19,triage procedures based on epidemiology were implemented in a local hospital in Changsha to control the transmission of SARS-CoV-2 and avoid healthcare-associated infection.This re-trospective study analyzed the data collected during the triage period and found that COVID-19 patients were en-riched 7 folds into the Section A designated for patients with obvious epidemiological history.On the other side,nearly triple amounts of visits were received at the Section B for patients without obvious epidemiological history.8 COVID-19 cases were spotted out of 247 suspected patients.More than 50％of the suspected patients were submi-tted to multiple rounds of nucleic acid analysis for SARS-CoV-2 infection.Of the 239 patients who were diagnosed as negative of the virus infection,188 were successfully revisited and none was reported as COVID-19 case.Of the 8 COVID-19 patients,3 were confirmed only after multiple rounds of nucleic acid analysis.Besides comorbidities,delayed sharing of epidemiological history added complexity to the diagnosis in practice.The triaging experience and strategy will be helpful for the control of infectious diseases in the future.

Viral selection pressure and CD4+T cell epitope in HLA-DRB1 * 11:01 of HCV infected patients / 中国输血杂志

【Objective】 HLA-DRB1 * 11:01, as a class HLA-Ⅱ gene, was reported to be associated with spontaneous clearance of HCV in Han and Li population. Our study was to investigate the effects of viral selection pressure and CD4+T cell epitope on the natural outcome of HCV infection in HLA-DRB1 * 11:01 positive infected patients. 【Methods】 The positive selection sites and population growth of E1E2 and NS3 genes of common HCV 6a in HLA-DRB1 * 11:01 positive and negative groups in Guangdong were respectively analyzed. The peptide library covering the conserved regions of common HCV genotypes was used to stimulate HCV spontaneous clearance group and chronic infection group using ELISPOT method. Reactive peptides were obtained according to the number of spot-forming cells per well and the frequency of occurrence in different groups. 【Results】 The positive selection sites (PSSs) of E1E2 and NS3 of common HCV 6a in HLA-DRB1 * 11:01 negative group were greater than those in HLA-DRB1 * 11:01 positive group. Furthermore, the number of PPSs in CD4+T cell peptide in HLA-DRB1 * 11:01 negative group were also greater than those in HLA-DRB1 * 11:01 positive group; Both groups of HCV 6a had a population growth in Guangdong, and the expansion trend of HLA-DRB1 * 11:01 negative group was significantly higher than that of HLA-DRB1 * 11 :01 positive group. Compared to HCV chronic infection group, the response rate of HCV spontaneous clearance group to five peptides (C-52 E2691-707, C-119 NS31545-1560, C-134 NS4A1669-1684, C-154 NS4B1912-1927, C-159 NS4B1929-1944) was higher. However, the HCV chronic infection group showed a higher response rate to two of the peptides(C-111 NS31497-1512, C-130 NS31650-1665). When HLA-DRB1 * 11:01 typing was considered, there was no significant difference in HCV-specific immune response generated by PBMCs between HLA-DRB1 * 11:01 positive and HLA-DRB1 * 11:01 negative groups. 【Conclusion】 This study revealed the relationship between viral selection pressure of HLA-DRB1 * 11:01 HCV infected persons and CD4+T cell antigen epitopes. At the same time, CD4+ T cell antigen epitopes of HCV pan-genotype were obtained, providing basic data for the development of T cell vaccine suitable for HCV pan-genotype.

Detection and analysis of antibodies against SARS-CoV-2 in blood donors at different periods in Guangzhou / 中国输血杂志

【Objective】 To detect the anti-SARS-CoV-2 antibody levels in blood donors in Guangzhou, so as to provide laboratory data support for the collection and clinical use of convalescent plasma. 【Methods】 Anti-SARS-CoV-2 antibodies were measured by ELISA in qualified donors. Among them, 326 donors who gave blood in February 2023 were tested for IgG antibodies, 444 donors were tested for neutralizing antibodies. In July 2023, 398 donors were tested for IgG and IgM. 【Results】 399 of 724 blood samples diluted with normal saline (1∶160) were IgG reactive, with a reactive rate of 55.11%. Chi-square test showed that there was a significant difference in the reactive rate of IgG among samples collected at different times (25.46% in February vs 79.40% in July, χ2=210.74, P<0.01, 95%CI: 7.97, 15.98), but there was no significant difference in the reactive rate between different genders and different age groups. IgM was detected in 5 of 398 blood samples, with a reactive rate of 1.26%. The IgG test results of these five blood donors were all reactive, whereas the nucleic acid test results were negative. Neutralizing antibody was detected in 440 of 444 blood samples, with a reactive rate of 99.10%, and 71.59% of the reactive donors had a neutralizing antibody level of 10 μg/mL or more. 【Conclusion】 Blood donors in Guangzhou have a high level of SARS-CoV-2 antibody, which is sufficient to provide convalescent plasma for clinical treatment.

Neuroplastic and Pro-cognitive Effects of Granulocyte Colony Stimulating Factor in Healthy Adults: A Pilot Study

Objective@#Granulocyte colony-stimulating factor (G-CSF) is a growth factor used to regulate the mobilization of bone marrow progenitor cells and has been shown to promote brain repair and reduce inflammation. This study aimed to investigate the pro-cognitive and neuroplastic effects of G-CSF in healthy adults. @*Methods@#Sixteen healthy adults or donors of hematopoietic stem cell transplantation received G-CSF injections for 5 consecutive days, and their blood samples were collected before, immediately after, and 3 weeks after the G-CSF injections. Twelve subjects underwent neuropsychological testing before and 12 weeks after the G-CSF injections. @*Results@#The study found that G-CSF administration resulted in significant improvements in cognitive function, as measured by the Rey– Osterrieth Complex Figure test for immediate recall, delayed recall, and recognition score at 12 weeks after the injections. The blood levels of brain-derived neurotrophic factor, interleukin-4, and interleukin-8 were significantly increased immediately after the injections and returned to baseline levels after 3 weeks. There was no significant change in the plasma level of Multimer Detection System-oligomerized amyloid beta. @*Conclusion@#Our results might suggest that G-CSF has neuroplastic and pro-cognitive effects in healthy adults. However, further study containing a larger sample size is needed to confirm our findings.

Functional Connectivity Change Associated With Apolipoprotein E Allotypes Precedes Structural Connectivity and Neurodegeneration in Cognitive Normal Older Adults Without Cerebral Aβ Deposition

Objective@#Apolipoprotein E (APOE) gene is known to influence cerebral functional connectivity (FC) in Alzheimer’s disease continuum. We investigated association between APOE allotypes and FC, structural connectivity, and cortical thickness in amyloid-PET negative cognitive normal older adults (CN). @*Methods@#A total of 188 CN (37 had ε2/ε2 or ε2/ε3 [ε2 group], 113 had ε3/ε3 [ε3 group], and 38 had ε3/ε4 or ε4/ε4 [ε4 group]) were recruited. Voxel-based morphometry and cortical thickness analysis were used to investigate differences in cortical thickness between three APOE allotypes. To investigate integrity of structural connectivity, we analyzed diffusion weighted imaging using fractional anisotropy and mean diffusivity. In terms of FC, differences of FC in default mode network (DMN) among APOE allotypes were measured using functional magnetic resonance imaging. @*Results@#There were no significant differences in age, sex, education, cerebral beta-amyloid (Aβ) deposition severity, or neuropsychological profiles. No significant differences were found in cortical thickness and structural connectivity among the APOE allotypes. However, FC within the DMN was significantly lower in ε4 and ε2 carriers compared to ε3 homozygotes. @*Conclusion@#This study suggests that both ε4 and ε2 exhibit APOE-associated DMN FC changes before Aβ deposition, structural changes, and neurodegeneration.

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.

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.

Effect of Huanglian Ejiaotang on 5-Hydroxytryptamine System and Gut Microbiota in Sleep-deprived Rats / 中国实验方剂学杂志

ObjectiveTo explore the mechanism of Huanglian Ejiaotang in intervening in insomnia based on 5-hydroxytryptamine （5-HT） system and gut microbiota. MethodFifty-five SPF-grade SD rats were randomly divided into normal group， model group， low-， medium-， and high-dose Huanglian Ejiaotang groups （1.925， 3.85， and 7.7 g·kg-1）， and Estazolam group （0.1 mg·kg-1）. Except for those in the normal group， the rats in the other five groups were subjected to sleep deprivation on a narrow platform for 12 hours daily for 21 consecutive days. After 14 days of drug intervention， the sleep， exploratory behavior， and depressive-like behavior of the rats were assessed using the pentobarbital sodium sleep synergistic test， the open field test， and the sugar preference test， respectively. Enzyme-linked immunosorbent assay （ELISA） was used to detect the levels of 5-HT， 5-hydroxyindoleacetic acid （5-HIAA）， tryptophan hydroxylase （TPH）， and monoamine oxidase-A （MAO-A）. Real-time polymerase chain reaction （Real-time PCR） was used to measure the mRNA expression of the 5-HT1A receptor （5-HT1AR） and 5-HT2A receptor （5-HT2AR）. Differences in gut microbiota among the groups were assessed using 16S rRNA sequencing， and the correlation between the 5-HT system and microbiota was revealed using redundancy analysis. ResultCompared with the normal group， the model group showed a prolonged sleep latency （P<0.05）， reduced sleep maintenance （P<0.01）， decreased central area activity time in the open field （P<0.01）， and reduced sugar preference rate （P<0.05）. Moreover， the model group also showed decreased levels of 5-HT， 5-HIAA， TPH， and MAO-A （P<0.01）， decreased 5-HIAA/5-HT ratio （P<0.01）， downregulated mRNA expression of 5-HT1AR （P<0.01）， and upregulated mRNA expression of 5-HT2AR （P<0.05）. The proportion of Firmicutes decreased， while that of Bacteroidetes increased， leading to a decreased Firmicutes/Bacteroidetes （F/B） ratio （P<0.05）. Compared with the model group， the high-dose Huanglian Ejiaotang group exhibited a shortened sleep latency （P<0.01）， and increased sleep maintenance （P<0.01）. The low-dose Huanglian Ejiaotang group showed increased central area activity time （P<0.01） and an increased sugar preference rate （P<0.05）. The high-dose Huanglian Ejiaotang group exhibited increased levels of 5-HT， 5-HIAA， TPH， and MAO-A （P<0.01）， increased 5-HIAA/5-HT ratio （P<0.05）， upregulated mRNA expression of 5-HT1AR （P<0.01）， and downregulated mRNA expression of 5-HT2AR （P<0.05）. The low-dose Huanglian Ejiaotang group displayed an increased proportion of Firmicutes and a decreased proportion of Bacteroidetes， resulting in an increased F/B ratio. At the phylum level， 5-HT， 5-HIAA， and MAO-A were positively correlated with Firmicutes and negatively correlated with Bacteroidetes. At the genus level， 5-HT， 5-HIAA， TPH， and MAO-A were negatively correlated with Prevotella and Lactobacillus and positively correlated with Blautia and Bacteroides. ConclusionHuanglian Ejiaotang can improve sleep deprivation-induced insomnia and depressive-like behavior by regulating the activity of the 5-HT system and the composition of gut microbiota.

Research on the hierarchical supervision of national science and technology programs from the perspective of science and technology ethics / 中华医学科研管理杂志

Objective:This paper analyzed the current situation and issues of ethical supervision of science and technology projects supported by central financial funds and proposed countermeasures to improve project management.Methods:Considering the practical management experience of a key special project during the 13th Five-Year Plan period, this article investigated ethical supervision issues in various stages including guideline preparation, review and approval, process management, and final acceptance, and proposed four levels of review for ethical oversight according to the characteristics of the research projects and the degree of ethical risks involved.Results:Firstly, lower-risk projects should still be reviewed by the Institutional Ethics Committee, and the project implementation unit should primarily assume responsibility for ethical supervision and follow-up on the review. Second, in addition to the review by the Institutional Ethics Committee, the Project Management Institution should strengthen ethical supervision and take risk control measures at different nodes for sensitive projects and higher ethical risk projects. Third, projects with large ethical controversies and high-risk projects should be reviewed by the National Science and Technology Ethics Committee and a public participation discussion mechanism for major ethical issues should be established. Finally, it is suggested to conduct prospective ethical studies for cutting-edge new technologies and new fields.Conclusions:In the process of managing science and technology program projects, strengthening ethical oversight in the management of science and technology projects should both standardize relevant scientific and technological research activities and not impede the growth of scientific and technological innovation. In view of the differences in ethical risks that may be involved in different projects, hierarchical examination, and supervision measures should be taken to effectively guarantee the smooth implementation of science and technology planning projects.

Metabolic regulation of Nod-like receptor protein 3 inflammasome and its role in renal diseases / 中华肾脏病杂志

In recent years, with the development of metabolic reprogramming research, people have changed their understanding of the biological effects of immune cells. Under the stimulation of inflammatory response, immune cells re-regulate their metabolism and bioenergetics, provide energy and substrates for cell survival, and initiate immune effect functions. Nod-like receptor protein 3 (NLRP3) inflammasome, as an important component of the innate immune system, has been shown to sense metabolites such as uric acid and cholesterol crystals, and can be inhibited by metabolites such as ketones. It is also regulated by mitochondrial reactive oxygen species and glycolytic components (such as hexokinase). Recent studies have shown that a variety of metabolic pathways converge as effective regulators of NLRP3 inflammasome. The paper reviews the metabolic regulatory pathways and specificity of NLRP3 inflammasome activation, and its role in renal diseases.