Stability study of umbilical cord mesenchymal stem cells formulation in large-scale production / 药学学报

Umbilical cord mesenchymal stem cells (UC-MSCs) have been widely used in regenerative medicine, but there is limited research on the stability of UC-MSCs formulation during production. This study aims to assess the stability of the cell stock solution and intermediate product throughout the production process, as well as the final product following reconstitution, in order to offer guidance for the manufacturing process and serve as a reference for formulation reconstitution methods. Three batches of cell formulation were produced and stored under low temperature (2-8 ℃) and room temperature (20-26 ℃) during cell stock solution and intermediate product stages. The storage time intervals for cell stock solution were 0, 2, 4, and 6 h, while for intermediate products, the intervals were 0, 1, 2, and 3 h. The evaluation items included visual inspection, viable cell concentration, cell viability, cell surface markers, lymphocyte proliferation inhibition rate, and sterility. Additionally, dilution and culture stability studies were performed after reconstitution of the cell product. The reconstitution diluents included 0.9% sodium chloride injection, 0.9% sodium chloride injection + 1% human serum albumin, and 0.9% sodium chloride injection + 2% human serum albumin, with dilution ratios of 10-fold and 40-fold. The storage time intervals after dilution were 0, 1, 2, 3, and 4 h. The reconstitution culture media included DMEM medium, DMEM + 2% platelet lysate, 0.9% sodium chloride injection, and 0.9% sodium chloride injection + 1% human serum albumin, and the culture duration was 24 h. The evaluation items were viable cell concentration and cell viability. The results showed that the cell stock solution remained stable for up to 6 h under both low temperature (2-8 ℃) and room temperature (20-26 ℃) conditions, while the intermediate product remained stable for up to 3 h under the same conditions. After formulation reconstitution, using sodium chloride injection diluted with 1% or 2% human serum albumin maintained a viability of over 80% within 4 h. It was observed that different dilution factors had an impact on cell viability. After formulation reconstitution, cultivation in medium with 2% platelet lysate resulted in a cell viability of over 80% after 24 h. In conclusion, the stability of cell stock solution within 6 h and intermediate product within 3 h meets the requirements. The addition of 1% or 2% human serum albumin in the reconstitution diluent can better protect the post-reconstitution cell viability.

Based on LC-MS technology explored the metabolomics of Agrimonia pilosa intervening in non-small cell lung cancer A549 cells / 药学学报

The objective of this study was to analyze the effects on cell viability, apoptosis, and cell cycle of non-small cell lung cancer (NSCLC) A549 cells after intervention with Agrimonia pilosa (AP) and investigate Agrimonia pilosa anti-tumor activity in vitro. Meanwhile, liquid chromatography mass spectrometry (LC-MS) metabolomics technology was used to analyze the changes of cellular metabolites and metabolic pathways. The results of this study will provide a theoretical and experimental basis for investigating the mechanism of the effect of Agrimonia pilosa on non-small cell lung cancer A549 cells. The results showed that the cell nucleus of A549 cells crumpled and apoptosis occurred with the increase of drug concentration. The survival rate of the cells decreased, and the inhibition rate reached 21.5% and 91.74% under the low and high dose conditions, respectively. Lactate dehydrogenase (LDH) content increased (P < 0.05). Metabolomics results showed significant differences in metabolism between groups, thirty-three distinct metabolites including LysoPC(24:0/0:0), LysoPC(17:0/0:0) and PC(O-40:5) were deduced. The pathway enrichment showed that the Agrimonia pilosa plays an anti-tumor role mainly by regulating the metabolism of glycerophosphate and purine in A549 cells, in which the effect on glycerophosphate metabolism pathway was most significant. The results of combined pharmacodynamics suggested that Agrimonia pilosa might induce apoptosis and inhibit the growth of A549 cells by regulating LysoPC(24:0/0:0), LysoPC(17:0/0:0) and PC(O-40:5) metabolites in A549 cells.

Clinicopathologic Characteristics and Prognosis of Oligodendroglioma with IDH Mutation and 1p/19q Codeletion / 肿瘤防治研究

Objective To analyze the clinicopathological characteristics and prognosis of oligodendroglioma with IDH mutation and 1p/19q codeletion. Methods We collected the data of 54 oligodendroglioma patients with IDH mutation and 1p/19q codeletion.The patients'clinicopathological data, including age, histological grade, and tumor site, were analyzed for the effects on progression-free and overall survival. Results Among the 54 patients, 46 cases were with tumor sites in one lobe, and eight cases involved tumor sites in more than two lobes.A total of 12 and 42 cases had WHO grades 2 and 3 oligodendroglioma, respectively.Detection by fluorescence in situ hybridization showed 1p/19q co-deletion in all cases.Immunohistochemical tests revealed diffuse and strong positive results for Olig2.All glial fibrillary acidic proteins were positive.p53 was strongly positive in six cases.ATRX was expressed in all 48 cases.Ki-67 proliferation index ranged from 5% to 60%.Sanger sequencing showed that all 54 cases had IDH gene mutations (40 cases were IDH1 mutations, and 14 were IDH2 mutations), and 33 cases had telomerase reverse transcriptase promoter mutations.Relapse and metastasis occurred in 16 patients during treatment.Univariate analysis indicated that the postoperative recurrence and metastasis interval of more than two years can prolong the progression-free and overall survival of patients.All 54 patients had a mean progression-free survival of 33.5 months and the mean overall survival of 40.7 months. Conclusion For oligodendroglioma with IDH mutation and 1p/19q codeletion, precision chemoradiotherapy after surgery can reduce the risk of progression, and the postoperative recurrence and metastasis interval is associated with the prognosis.

Characteristics and relationship between the development of gross motor skills and executive function in children with attention deficit hyperactivity disorder / 中国康复理论与实践

ObjectiveTo investigate the developmental characteristics of gross motor skills and executive functions, and the correlation between them in school-age children with attention deficit hyperactivity disorder (ADHD). MethodsFrom November, 2020 to May, 2021, 90 children with ADHD were recruited from Peking University Sixth Hospital and Beijing Haidian Wanquan Primary School, and other 90 children with normal development from this primary school were recruited matched their age and gender. Gross motor skills were assessed with the Test of Gross Motor Development in Children, Third Edition (TGMD-3), and inhibitory control, working memory, and cognitive flexibility were assessed with Stroop Color Words Test (SCWT), Rey-Osterrich Complex Figure Test (ROCFT) and Trail Making Test (TMT), respectively. ResultsThe TGMD-3 score was significantly lower in children with ADHD than in normal children (t = -6.275, P < 0.001), while the test results of SCWT, ROCFT and TMT were worse (|t| ≥ 1.986, P ≤ 0.05). The TGMD-3 score of children with ADHD was negatively correlated with the word sense reaction time (r = -0.261), the number of word sense errors (r = -0.404) and the number of color errors (r = -0.326) (P < 0.05), positively correlated with the delayed structural memory scores (r = 0.228) (P < 0.05), and negatively correlated with the TMT-A reaction time (r = -0.255), the number of TMT-A errors (r = -0.329), TMT-B reaction time (r = -0.214) and the number of TMT-B errors (r = -0.474) (P < 0.05). Stratified linear regression analyses showed that the TGMD-3 score of children with ADHD was significant only in predicting test results for inhibitory control and cognitive flexibility (P < 0.05), with explanations of 8.7% and 22.5%, respectively. ConclusionDevelopments of both gross motor skills and executive function delay in children with ADHD, and there is a relation between them, especially the level of gross motor skills relating to the developments of inhibitory control and cognitive flexibility.

Research progress on mTOR signaling pathway and regulatory T cell nutrition metabolic regulation mechanism / 细胞与分子免疫学杂志

In the tumor microenvironment, metabolic reprogramming can impact metabolic characteristics of T cells, thus inducing immunosuppression to promote tumor immune escape. The mammalian target of rapamycin (mTOR) signaling pathway plays an important role in regulating diverse functions of various immune cells. This review mainly focuses on the molecular mechanism of mTOR signaling in regulating cellular energy metabolism process, and the activation status of mTOR signaling under different nutritional environments. In addition, it also summarizes the role of the mTOR signaling in regulatory T cell (Tregs) metabolism and function in current studies, and evaluates the potential of mTOR as a clinical immunotherapeutic target and its current application challenges.

An evaluation of carrier detection for Spinal muscular atrophy using digital PCR assay / 中华医学遗传学杂志

OBJECTIVE@#To assess the effectiveness and feasibility of carrier detection for Spinal muscular atrophy (SMA) by using digital PCR assay.@*METHODS@#Peripheral blood samples were collected from 214 pregnant women who were routinely screened for SMA carriers, of which 204 were randomly selected samples and 10 were samples with known copy numbers of SMN1 exons 7 and 8. Samples with known copy numbers of SMN1 exons 7 and 8 were randomly mixed into the experiment to validate the performance of the digital PCR assay.@*RESULTS@#The copy numbers of SMN1 exons 7 and 8 and SMN2 exons 7 and 8 in peripheral blood samples were detected by digital PCR assay. The results of SMN1 exons 7 and 8 were compared with those of the quantitative PCR method to assess the reliability and clinical performance of the digital PCR assay. Among the 204 random samples, digital PCR has detected five samples with simultaneous heterozygous deletion of SMN1 exons 7 and 8, three samples with heterozygous deletion of SMN1 exon 8 only, and 196 samples with no deletion of SMN1 exons 7 and 8. Ten samples with known SMN1 exons 7 and 8 copy numbers were detected with the expected values. The digital PCR test results were fully consistent with that of the quantitative PCR.@*CONCLUSION@#The results of digital PCR for the detection of copy number variation of SMN1 exons 7 and 8 were consistent with qPCR. Digital PCR assay was able to clearly distinguish the copy number of the target genes, therefore can be used for SMA carrier screening. Moreover, it can also detect copy number of SMN2 exons 7 and 8, which can provide more information for genetic counseling.

Meta-analysis of the role of fibular fixation in tibiofibular fractures / 中国骨伤

OBJECTIVE@#To compare the role and importance of fibular fixation in tibiofibular fractures by Meta-analysis.@*METHODS@#The literature related to the comparison of the efficacy of fixation of the fibula with or without fixation on the treatment of tibiofibular fractures was searched through the databases of China Knowledge Network, Wipu, Wanfang, The Cochrane Library, Web of science and Pubmed, and statistical analysis was performed using RevMan 5.3 software. The rates of malrotation, rotational deformity, internal/external deformity, anterior/posterior deformity, non-union, infection, secondary surgery and operative time were compared between the fibula fixation and non-fixation groups.@*RESULTS@#A total of 11 publications were included, six randomised controlled trials and five case-control trials, eight of which were of high quality. A total of 813 cases were included, of which 383 were treated with fibula fixation and 430 with unfixed fibulae.Meta-analysis results showed that fixation of the fibulae in the treatment of tibiofibular fractures reduced the rates of postoperative rotational deformity[RR=0.22, 95%CI(0.10, 0.45), P<0.000 1] and internal/external deformity[RR=0.34, 95%CI(0.14, 0.84), P=0.02] and promoted fracture healing [RR=0.76, 95%CI(0.58, 0.99), P=0.04]. In contrast, the rates of poor reduction [RR=0.48, 95% CI(0.10, 2.33), P=0.36], anterior/posterior deformity[RR=1.50, 95%CI(0.76, 2.96), P=0.24], infection[RR=1.43, 95%CI(0.76, 2.72), P=0.27], secondary surgery[RR=1.32, 95%CI(0.82, 2.11), P=0.25], and operative time[MD=10.21, 95%CI(-17.79, 38.21), P=0.47] were not statistically significant (P>0.05) for comparison.@*CONCLUSION@#Simultaneous fixation of the tibia and fibula is clinically more effective in the treatment of tibiofibular fractures.

MiR⁃31 Promotes the Proliferation and Migration of Human Dental Pulp Mesenchymal Stem Cells / 中国生物化学与分子生物学报

Pulpitis and periapical inflammation are two common diseases in stomatology today. Existing treatment options primarily include root canal therapy and pulp revascularization, which can effectively control inflammation and preserve the affected tooth while also causing permanent deactivation of the pulp tissue, structural failure, and secondary infection. In recent years, research on dental pulp regeneration has progressively entered the public consciousness because of tissue engineering technology that combines stem cells and biomaterials. Due to their multi⁃differentiation and high proliferation, dental pulp stem cells (DPSCs) isolated from permanent or deciduous teeth have emerged as a significant stem cell source for dentin or pulp tissue regeneration. However, the number and survival time of live cells in the dam⁃ aged area are impacted, which significantly limits the efficacy of stem cells since they are unable to efficiently be recruited to the injured area. The ability of DPSCs to migrate and multiply must therefore be enhanced. This study sought to determine if miR⁃31 (miR⁃31) may significantly enhance the proliferative and migratory capacities of DPSCs. The tissue block enzyme digestion method was used to successfully separate and culture DPSCs from dental pulp tissues, and the miR⁃31 levels in dental pulp tissues and DPSCs from normal and inflammatory teeth were compared. The results of real⁃time fluorescence quanti⁃ tative PCR (RT⁃qPCR) revealed that the expression level of miR⁃31 in dental pulp tissues and DPSCs from inflammatory teeth was significantly lower when compared to the control group (P<0. 05). Interfer⁃ ence and over⁃expression of miR⁃31 expressions in DPSCs were specifically divided into three groups: the NC group, the miR⁃31 agomir (over⁃expressed) group and the miR⁃31 antagomir (inhibitor) group. RTq⁃PCR results showed that the transfection was successful (P<0. 001). The results of CCK⁃8, wound⁃ healing, and Transwell migration experiments showed that overexpression of miR⁃31 successfully improved the proliferation and migration abilities of DPSCs compared with the control group (P<0. 05). Further⁃ more, Western blotting analysis revealed that miR⁃31 overexpression increased the expression of important migratory proteins, including CXC chemokine receptor type 4 (CXCR4) and matrix metalloproteinase2 (MMP2), as well as key proliferation proteins Ki67 and proliferating cell nuclear antigen (PCNA) (P< 0. 05). This study demonstrates that miR⁃31 can effectively boost the proliferation and migratory ability of DPSCs, providing strong theoretical support for the increased use of DPSCs in regenerative medicine.

Role and research progress of circular RNA in Alzheimer’s disease / 解剖学报

[Abstract] The circular RNA (circRNA) is a class of endogenous expressed non-coding RNA that are formed by covalently closed cyclization through reverse splicing. In recent years, a variety of highly conserved and cell-type specific circRNA have been identified in eukaryotes. Alzheimer’ s disease (AD) is a common neurodegenerative disease and the most common cause of dementia in the elderly. Recent studies had shown that circRNA was involved in the pathogenesis and development of AD, such as amyloid β-protein (Aβ) metabolic, neuroinflammation, oxidative stress, autophagy and synaptic plasticity. The role and application value of circRNA in AD pathology are reviewed to provide a theoretical basis for the application of circRNA in the treatment and diagnosis of AD.

Clinical characteristics and related factors analysis of adrenal crisis occurred in children with primary nephrotic syndrome / 中华儿科杂志

Objective: To investigate the clinical characteristics and related factors of corticosteroid induced adrenal crisis (AC) in children with primary nephrotic syndrome (NS). Methods: Case control study. The case group included 7 children aged 1 to 18 years with NS combined with AC hospitalized in Peking University First Hospital from January 2016 to May 2021 (AC group). According to the ratio of case group: control group 1: 4, 28 children aged 1 to 18 years who were diagnosed with NS without AC during the same period were matched as controls (non-AC group). Clinical data were collected. The clinical characteristics of AC were described. The clinical parameters were compared between the 2 groups by t test, Mann-Whitney U test or Fisher's test. Receiver operating characteristic (ROC) curve was used to analyze the cutoff values of clinical parameters for prediction of AC. Results: The AC group included 4 boys and 3 girls aged 6.9 (4.6, 10.8) years. The non-AC group included 20 boys and 8 girls aged 5.2 (3.3, 8.4) years. All AC events occurred during the relapse of NS with infection. Seven children had gastrointestinal symptoms such as nausea, vomiting and abdominal pain. Six children had poor mental state or impaired consciousness. No significant differences in NS course, corticosteroid treatment course, corticosteroid type, steroid dosage, steroid medication interval, the proportion of gastroenteritis and fever existed between the two groups (all P>0.05). Compared with the non-AC group, the duration from the onset of the relapse of NS until hospitalization in the AC group was significantly shorter (0.2 (0.1, 0.6) vs. 1.0 (0.4, 5.0) month,U=25.50, P=0.005). The 24 h urinary total protein (UTP) level was significantly higher in the AC group (193 (135, 429) vs. 81 (17, 200) mg/kg, U=27.00,P=0.036) than the non-AC group. The serum albumin level in the AC group was significantly lower((13.1±2.1) vs. (24.5±8.7) g/L,t=-6.22,P<0.001) than the non-AC group. There were significantly higher total white blood cell counts ((26±9)×109 vs. (11±5)×109/L,t=4.26,P=0.004), percentage of neutrophils (0.71±0.08 vs. 0.60±0.19,t=2.56,P=0.017) and the proportion of children with C reactive protein level≥8 mg/L (3/7 vs. 0,P=0.005) in the AC group than in the non-AC group. ROC curve analysis showed that the cutoff value of 24 h UTP was 122 mg/(kg·d) with a sensitivity of 100.0% and specificity of 70.4%. The cutoff value of serum albumin was 17.0 g/L with a sensitivity of 100.0% and specificity of 82.1%. Conclusions: Gastrointestinal symptoms and poor mental state were prominent manifestations of AC in children with NS. High 24 h UTP level, low serum albumin level, high peripheral white blood cell counts, high neutrophils percentage, and high C-reactive protein level during the early stage of NS relapse may be related to the occurrence of AC in children with NS.

Clinical significance of Epstein-Barr Virus detection in the cerebrospinal fluid of patients who underwent hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To analyze the detection rate, clinical significance, and prognosis of Epstein-Barr virus (EBV) in the cerebrospinal fluid (CSF) of patients following allogeneic hematopoietic stem cell transplantation. Methods: A retrospective analysis was performed on 1100 patients who underwent the CSF virus test after allogeneic hematopoietic stem cell transplantation in Peking University People's Hospital between January 2017 and June 2022. Among them, 19 patients were screened positive for EBV in their CSF, and their clinical characteristics, treatment, and prognosis were analyzed. Results: Among 19 patients with EBV-positive cerebrospinal fluid, 12 were male and 7 were female, with 5 patients aged <18 years and 12 aged ≥18 years, with a median age of 27 (5-58) years old. There were 7 cases of acute myeloid leukemia, 8 of acute lymphocytic leukemia, 2 of aplastic anemia, 1 of Hodgkin's lymphoma, and 1 of hemophagocytic syndrome. All 19 patients underwent haploid hematopoietic stem cell transplantation, including 1 secondary transplant. Nineteen patients had neurological symptoms (headache, dizziness, convulsions, or seizures), of which 13 had fever. Ten cases showed no abnormalities in cranial imaging examination. Among the 19 patients, 6 were diagnosed with EB virus-related central nervous system diseases, with a median diagnosis time of 50 (22-363) days after transplantation. In 9 (47.3%) patients, EBV was detected in their peripheral blood, and they were treated with intravenous infusion of rituximab (including two patients who underwent lumbar puncture and intrathecal injection of rituximab). After treatment, EBV was not detected in seven patients. Among the 19 patients, 2 died from EBV infection and 2 from other causes. Conclusion: In patients who exhibited central nervous system symptoms after allogeneic hematopoietic stem cell transplantation, EBV should be screened as a potential pathogen. EBV detected in the CSF may indicate an infection; however, it does not confirm the diagnosis.

Treatment Outcomes in COVID-19 Patients with Brucellosis: Case Series in Heilongjiang and Systematic Review of Literature / 生物医学与环境科学（英文）

OBJECTIVE@#Clinical characteristics and outcome in COVID-19 with brucellosis patients has not been well demonstrated, we tried to analyze clinical outcome in local and literature COVID-19 cases with brucellosis before and after recovery.@*METHODS@#We retrospectively collected hospitalization data of comorbid patients and prospectively followed up after discharge in Heilongjiang Infectious Disease Hospital from January 15, 2020 to April 29, 2022. Demographics, epidemiological, clinical symptoms, radiological and laboratory data, treatment medicines and outcomes, and follow up were analyzed, and findings of a systematic review were demonstrated.@*RESULTS@#A total of four COVID-19 with brucellosis patients were included. One patient had active brucellosis before covid and 3 patients had nonactive brucellosis before brucellosis. The median age was 54.5 years, and all were males (100.0%). Two cases (50.0%) were moderate, and one was mild and asymptomatic, respectively. Three cases (75.0%) had at least one comorbidity (brucellosis excluded). All 4 patients were found in COVID-19 nucleic acid screening. Case C and D had only headache and fever on admission, respectively. Four cases were treated with Traditional Chinese medicine, western medicines for three cases, no adverse reaction occurred during hospitalization. All patients were cured and discharged. Moreover, one case (25.0%) had still active brucellosis without re-positive COVID-19, and other three cases (75.0%) have no symptoms of discomfort except one case fell fatigue and anxious during the follow-up period after recovery. Conducting the literature review, two similar cases have been reported in two case reports, and were both recovered, whereas, no data of follow up after recovery.@*CONCLUSION@#These cases indicate that COVID-19 patients with brucellosis had favorable outcome before and after recovery. More clinical studies should be conducted to confirm our findings.

Aurora A Kinase Plays a Key Role in Mitosis Skip during Senescence Induced by Ionizing Radiation / 生物医学与环境科学（英文）

OBJECTIVE@#To investigate the fate and underlying mechanisms of G2 phase arrest in cancer cells elicited by ionizing radiation (IR).@*METHODS@#Human melanoma A375 and 92-1 cells were treated with X-rays radiation or Aurora A inhibitor MLN8237 (MLN) and/or p21 depletion by small interfering RNA (siRNA). Cell cycle distribution was determined using flow cytometry and a fluorescent ubiquitin-based cell cycle indicator (FUCCI) system combined with histone H3 phosphorylation at Ser10 (pS10 H3) detection. Senescence was assessed using senescence-associated-β-galactosidase (SA-β-Gal), Ki67, and γH2AX staining. Protein expression levels were determined using western blotting.@*RESULTS@#Tumor cells suffered severe DNA damage and underwent G2 arrest after IR treatment. The damaged cells did not successfully enter M phase nor were they stably blocked at G2 phase but underwent mitotic skipping and entered G1 phase as tetraploid cells, ultimately leading to senescence in G1. During this process, the p53/p21 pathway is hyperactivated. Accompanying p21 accumulation, Aurora A kinase levels declined sharply. MLN treatment confirmed that Aurora A kinase activity is essential for mitosis skipping and senescence induction.@*CONCLUSION@#Persistent p21 activation during IR-induced G2 phase blockade drives Aurora A kinase degradation, leading to senescence via mitotic skipping.

Reasons, safety and efficacy analysis for conversion of HAART to TAF/FTC/BIC among HIV-infected patients / 中华医学杂志(英文版)

BACKGROUND@#This study aimed to determine the reasons for conversion and elucidate the safety and efficacy of transition to tenofovir alafenamide/emtricitabine/bictegravir sodium (TAF/FTC/BIC) in highly active antiretroviral therapy (HAART)-experienced HIV-infected patients in real-world settings.@*METHODS@#We conducted a retrospective cohort study. The treatment conversion rationales, safety, and effectiveness in 1684 HIV-infected patients with previous HAART experience who switched to TAF/FTC/BIC were evaluated at Beijing Ditan Hospital from September 2021 to Auguest 2022.@*RESULTS@#Regimen simplification (990/1684, 58.79%) was the most common reason for switching, followed by osteoporosis or osteopenia (375/1684, 22.27%), liver dysfunction (231/1684, 13.72%), decline in tenofovir alafenamide/emtricitabine/elvitegravir/cobicistat (TAF/FTC/EVG/c) with food restriction (215/1684, 12.77%), virological failure (116/1684, 6.89%), and renal dysfunction (90/1684, 5.34%). In patients receiving non-nucleotide reverse transcriptase inhibitors (NNRTI)-containing regimens, lipid panel changes 1 year after switching indicated a difference of 3.27 ± 1.10 mmol/L vs . 3.40 ± 1.59 mmol/L in triglyceride ( P  = 0.014), 4.82 ± 0.74 mmol/L vs . 4.88 ± 0.72 mmol/L in total cholesterol ( P  = 0.038), 3.09 ± 0.70 mmol/L vs . 3.18 ± 0.66 mmol/L in low-density lipoprotein ( P  <0.001), and 0.99 ± 0.11 mmol/L vs . 0.95 ± 0.10 mmol/L in high-density lipoprotein ( P  <0.001). Conversely, among patients receiving booster-containing regimens, including TAF/FTC/EVG/c and lopinavir/ritonavir (LPV/r), lipid panel changes presented decreased trends. We also observed an improved trend in viral load suppression, and alanine transaminase (ALT), aspartate transaminase (AST), estimated glomerular filtration rate (eGFR), and serum creatinine levels after the transition ( P  <0.001).@*CONCLUSION@#The transition to TAF/FTC/BIC demonstrated good treatment potency. Furthermore, this study elucidates the motivations behind the adoption of TAF/FTC/BIC in real-world scenarios, providing clinical evidence supporting the stable conversion to TAF/FTC/BIC for HAART-experienced patients.

Advances in methods for detecting plastics biodegradation / 生物工程学报

The pollution caused by improper handling of plastics has become a global challenge. In addition to recycling plastics and using biodegradable plastics, an alternative solution is to seek efficient methods for degrading plastics. Among them, the methods of using biodegradable enzymes or microorganisms to treat plastics have attracted increasing attention because of its advantages of mild conditions and no secondary environmental pollution. Developing highly efficient depolymerizing microorganisms/enzymes is the core for plastics biodegradation. However, the current analysis and detection methods cannot meet the requirements for screening efficient plastics biodegraders. It is thus of great significance to develop rapid and accurate analysis methods for screening biodegraders and evaluating biodegradation efficiency. This review summarizes the recent application of various commonly used analytical techniques in plastics biodegradation, including high performance liquid chromatography, infrared spectroscopy, gel permeation chromatography, and determination of zone of clearance, with fluorescence analysis techniques highlighted. This review may facilitate standardizing the characterization and analysis of plastics biodegradation process and developing more efficient methods for screening plastics biodegraders.

Effects of polyphyllin Ⅵ on the proliferation and apoptosis of glioma cells and potential mechanism / 中国药房

OBJECTIVE To investigate the effects of polyphyllin Ⅵ（PPⅥ） on the proliferation and apoptosis of glioma cells and potential mechanism. METHODS Using human glioma LN229 cells as objects， MTT assay was used to detect the survival rate after treated with different concentrations of PPⅥ [0 （control group）， 1， 2， 4， 8， 16， 32， 64 μmol/L] for different time （24， 48， 72 h）. The clone formation experiments were adopted to detect the number of cell clones and clone formation rate after being treated with different concentrations of PPⅥ [0 （control group）， 2， 4， 8 μmol/L] for 14 days. The flow cytometry and Western blot assay were used to detect the apoptotic rate of cells， the expressions of apoptosis-related protein [B cell lymphoma-2 （Bcl-2）， Bcl-2 associated X protein （Bax）， cleaved caspase-3]， and the expressions of related proteins of Fas/Fas ligand （FasL） death receptor pathway and protein kinase B （Akt）/glycogen synthesis kinase-3β （GSK-3β） pathway after being treated with different concentrations of PPⅥ [0（control group）， 4， 8 μmol/L] for 24 h. RESULTS Compared with the control group， the survival rate of cells， the number of clones and clone formation rate， the protein expression of Bcl-2， and the phosphorylation levels of Akt and GSK-3β protein were decreased significantly in different concentration groups of PPⅥ （P＜0.05 or P＜0.01）. The apoptotic rate， the protein expressions of Bax， cleaved caspase-3， Fas， FasL and cleaved caspase-8 were increased significantly （P＜0.05 or P＜ 0.01）. CONCLUSIONS PPⅥ can inhibit the proliferation and induce the apoptosis of human glioma LN229 cells， which may be related to the activation of the Fas/FasL death receptor pathway and the inhibition of the Akt/GSK-3β pathway.

Measurement of thyroid 131I activity in 162 iodine treatment workers in Hubei Province, China / 中国辐射卫生

Objective To determine the current status of occupational internal exposure to 131I in the thyroid of nuclear medicine workers, to explore the influencing factors for internal exposure, and to provide a basis for the radiation safety management of nuclear medicine. Methods The cluster sampling method was used to select 162 workers practicing 131I treatment in 24 hospitals in Hubei Province, China. Thyroid 131I activity levels were measured in vitro using a portable γ-spectrometer, and the committed effective dose was estimated. Results The thyroid 131I activity detected in 13 (54.17%) hospitals was above the lower limit of detection of the instrument. Two hospitals had the highest detection rates, 62.50% and 61.90%; the difference was significant compared with the remaining 11 hospitals (P < 0.0001). Thyroid 131I was detected in 34 workers in total, with a detection rate of 20.99% and a mean activity of 179.09 ± 138.71 (6.02-589.74) Bq. The highest detection rates were found in cleaners and nurses, which were 35.71% and 33.33%, respectively, with no significant difference in detection rate between positions (least P > 0.08). The mean value of the committed effective dose was 0.68 ± 0.52 (0.02-2.22) mSv/a in the 34 workers. Conclusion The 131I consumption and workplace ventilation may be important factors affecting the level of internal exposure. It is important to strengthen the training of nuclear medicine workers on radioprotection and workflow management, as well as the regular monitoring of occupational internal exposure for 131I treatment-related workers.

Qualitative Analysis of Metabolites of Aristolochiae Fructus Aqueous Extract in Rats / 中国实验方剂学杂志

ObjectiveBased on ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MSE） technique， we identified qualitatively the metabolites of aristolochic acid（AAs） in rat in order to analyze the metabolic differences between water extract of Aristolochiae fructus（AFE） and Aristolochic acid Ⅰ（AAⅠ）. MethodSD rats were selected and administered AFE（110 g·kg-1·d-1） or AAⅠ（5 mg·kg-1·d-1） by oral for 5 days， respectively. Serum， urine and feces were collected after administration. Through sample pretreatment， ACQUITY UPLC BEH C18 column（2.1 mm×100 mm， 1.7 μm） was used with the mobile phase of 0.01% formic acid methanol（A）-0.01% formic acid water（B， containing 5 mmol·L-1 ammonium acetate） for gradient elution（0-1 min， 10%B； 1-7 min， 10%-75%B； 7-7.2 min， 75%-95%B； 7.2-10.2 min， 95%B； 10.2-10.3 min， 95%-10%B； 10.3-12 min， 10%B） at a flow rate of 0.3 mL·min-1. Positive ion mode of electrospray ionization（ESI+） was performed in the scanning range of m/z 100-1 200. In combination with UNIFI 1.9.4.053 system， the Pathway-MSE was used to qualitatively analyze and identify the AAs prototype and related metabolites in biological samples（serum， urine and feces）， and to compare the similarities and differences of metabolites in rats in the subacute toxicity test between AFE group and AAⅠ group. ResultCompared with AAⅠ group， 6， 10， 13 common metabolites and 14， 20， 30 unique metabolites were identified in biological samples（serum， urine and feces） of AFE group， respectively. Moreover， the main AAs components always followed the metabolic processes of demethylation， nitrate reduction and conjugation. Compared with common metabolites in AAⅠ group， prototype components of AAⅠ in serum and most metabolic derivatives of AAⅠ［AAⅠa， aristolochic lactam Ⅰ（ALⅠ）a， 7-OHALⅠ and its conjugated derivatives］ in biological samples were significantly increased in AFE group（P<0.05， P<0.01）， except that the metabolic amount of ALⅠ in feces of AFE group was remarkably lowed than that of AAⅠ group（P<0.01）. In addition， a variety of special ALⅠ efflux derivatives were also identified in the urine and feces of the AFE group. ConclusionAlthough major AAs components in AFE all show similar metabolic rules as AAⅠ components in vivo， the coexistence of multiple AAs components in Aristolochiae Fructus may affect the metabolism of AAⅠ， and achieve the attenuating effect by increasing the metabolic effection of AAⅠ and ALⅠ.

Design of variable stiffness insole based on diabetics plantar pressure during gait period / 中国康复理论与实践

ObjectiveTo analyze the characteristics of plantar pressure of diabetic patients during gait cycle, and to design a offloading insole with variable stiffness. MethodsThe plantar pressure experiment was carried out and a database including 157 subjects was established. The differences of plantar pressure distribution were analyzed among diabetic patients with and without peripheral neuropathy, and healthy people. The insole pressure area was divided, and porous units were filled in different insole areas according to the pressure gradient. The fed-calf-insole finite element model of diabetic patients was constructed. The simulation analysis of different insole schemes was carried out under the conditions of push-off, footheel-strike and dynamic neutrality posture, and to explore the most reasonable insole stiffness design. ResultsCompared with the healthy group, the percentage of peak pressure and high pressure in the left and right heel areas of diabetic neuropathy patients showed a decreasing trend, in which the left peak pressure was significantly reduced by 11% (P = 0.026) and the percentage of high pressure was significantly reduced by 9.8% (P = 0.02). When the porous elements of 2.5 MPa and 1.9 MPa were used in the high pressure area of the insole metatarsal and high pressure area of the heel, the peak plantar pressure of footheel-strike, dynamic neutral and push-off was reduced by 42.4%, 27.4% and 26.4%, and the peak stress of the soft tissue was reduced by 49.8%, 43.6% and 25.1%, respectively. ConclusionThere is a higher risk of ulcer in the metatarsal region than in the heel region for diabetic patients. The variable stiffness insoles based on the optimization of plantar pressure and internal stress under multi-posture can effectively reduce the peak pressure of plantar and peak stress of soft tissue during walking, which provides a reference for the design of variable stiffness insoles.

Risk Factors of Multiple Myeloma Complicated with Venous Thromboembolism / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical characteristics of venous thromboembolism (VTE) in patients with multiple myeloma (MM) and to identify the risk factors of VTE in MM patients.@*METHODS@#179 newly diagnosed MM (NDMM) patients admitted to The Second Hospital of Shanxi Medical University from January 2014 to December 2020 who were followed up for more than 6 months were collected, and they were divided into VTE group and control group according to whether combined with VTE. The clinical and laboratory data were compared between the two groups. Mann-whitney U test was used for inter-group comparison of measurement data, Chi-square test or Fisher's exact test was used for inter-group comparison of count data, and multivariate logistic regression analysis was performed to explore the risk factors of VTE in MM patients.@*RESULTS@#Compared with control group, the serum albumin (ALB) level in VTE group was significantly lower (P =0.033), the fibrinogen (FIB) level was significantly higher (P =0.016), and the proportion of patients with D-dimer≥2 000 ng/ml was significantly higher than that in the control group (26.3% vs 4.4%, P =0.002). There was a significant difference in M-component type between the two groups (P =0.028), and the proportion of IgG type in VTE group was higher. There were no statistically significant differences between two groups in age, sex, body mass index (BMI), the proportions of patients with hypertension, diabetes, coronary heart disease and cerebral infarction, white blood cell (WBC) count, platelet (PLT) count, liver and kidney function, plasma cells ratio in bone marrow, serum globulin (GLO), lactate dehydrogenase (LDH), β2-microglobulin (β2-MG) level, C-reactive protein (CRP) level, erythrocyte sedimentation rate (ESR), prothrombin time (PT), activated partial thromboplastin time (APTT), disease stage, thrombosis prevention and the use of immunomodulators (P >0.05). Multivariate logistic regression analysis showed that FIB level (OR=1.578, 95%CI:1.035-2.407, P =0.034), D-dimer≥2 000 ng/ml (OR=5.467, 95%CI:1.265-23.621, P =0.023) and IgG type (OR=4.780, 95%CI: 1.221-18.712, P =0.025) were independent risk factors for VTE in MM patients.@*CONCLUSION@#MM patients are prone to VTE, and FIB level, D-dimer≥2 000 ng/ ml and IgG type are independent risk factors for VTE in MM patients.