Renewal of embryonic and neonatal-derived cardiac-resident macrophages in response to environmental cues abrogated their potential to promote cardiomyocyte proliferation via Jagged-1-Notch1

Cardiac-resident macrophages (CRMs) play important roles in homeostasis, cardiac function, and remodeling. Although CRMs play critical roles in cardiac regeneration of neonatal mice, their roles are yet to be fully elucidated. Therefore, this study aimed to investigate the dynamic changes of CRMs during cardiac ontogeny and analyze the phenotypic and functional properties of CRMs in the promotion of cardiac regeneration. During mouse cardiac ontogeny, four CRM subsets exist successively: CX3CR1+CCR2-Ly6C-MHCII- (MP1), CX3CR1lowCCR2lowLy6C-MHCII- (MP2), CX3CR1-CCR2+Ly6C+MHCII- (MP3), and CX3CR1+CCR2-Ly6C-MHCII+ (MP4). MP1 cluster has different derivations (yolk sac, fetal liver, and bone marrow) and multiple functions population. Embryonic and neonatal-derived-MP1 directly promoted cardiomyocyte proliferation through Jagged-1-Notch1 axis and significantly ameliorated cardiac injury following myocardial infarction. MP2/3 subsets could survive throughout adulthood. MP4, the main population in adult mouse hearts, contributed to inflammation. During ontogeny, MP1 can convert into MP4 triggered by changes in the cellular redox state. These findings delineate the evolutionary dynamics of CRMs under physiological conditions and found direct evidence that embryonic and neonatal-derived CRMs regulate cardiomyocyte proliferation. Our findings also shed light on cardiac repair following injury.

A biomimetic nanoplatform for customized photothermal therapy of HNSCC evaluated on patient-derived xenograft models / 国际口腔科学杂志·英文版

Cancer cell membrane (CCM) derived nanotechnology functionalizes nanoparticles (NPs) to recognize homologous cells, exhibiting translational potential in accurate tumor therapy. However, these nanoplatforms are majorly generated from fixed cell lines and are typically evaluated in cell line-derived subcutaneous-xenografts (CDX), ignoring the tumor heterogeneity and differentiation from inter- and intra- individuals and microenvironments between heterotopic- and orthotopic-tumors, limiting the therapeutic efficiency of such nanoplatforms. Herein, various biomimetic nanoplatforms (CCM-modified gold@Carbon, i.e., Au@C-CCM) were fabricated by coating CCMs of head and neck squamous cell carcinoma (HNSCC) cell lines and patient-derived cells on the surface of Au@C NP. The generated Au@C-CCMs were evaluated on corresponding CDX, tongue orthotopic xenograft (TOX), immune-competent primary and distant tumor models, and patient-derived xenograft (PDX) models. The Au@C-CCM generates a photothermal conversion efficiency up to 44.2% for primary HNSCC therapy and induced immunotherapy to inhibit metastasis via photothermal therapy-induced immunogenic cell death. The homologous CCM endowed the nanoplatforms with optimal targeting properties for the highest therapeutic efficiency, far above those with mismatched CCMs, resulting in distinct tumor ablation and tumor growth inhibition in all four models. This work reinforces the feasibility of biomimetic NPs combining modular designed CMs and functional cores for customized treatment of HNSCC, can be further extended to other malignant tumors therapy.

Clinical features of portal biliopathy / 临床肝胆病杂志

ObjectiveThis article aims to investigate the clinical features of portal biliopathy （PB） patients， in order to improve the understanding of PB. MethodsClinical data were collected from 22 patients who were diagnosed with PB in recent years in The First Hospital of Jilin University， and an analysis was performed for their clinical manifestations， liver function， abdominal color Doppler ultrasound， abdominal CT， and hepatobiliary magnetic resonance imaging. The imaging manifestations of biliary tract abnormalities were described， as well as the type of collateral circulation and the location of thrombosis. ResultsAs for the initial symptom in these 22 patients， three were 11 patients with gastrointestinal bleeding， 5 with abdominal distension， 3 with abdominal pain， 1 with fever， 1 with abdominal discomfort， and 1 with gingival bleeding. There were 3 patients with an increase in aspartate aminotransferase， 4 with an increase in alanine aminotransferase， 4 with an increase in gamma-glutamyl transpeptidase， 7 with an increase in alkaline phosphatase， 8 with a reduction in cholinesterase， 9 with a reduction in albumin， 2 with an increase in globulin， and 5 with an increase in total bilirubin. Among the 22 patients， 20 had cavernous transformation of the portal vein， and 2 had portal vein thrombosis without cavernous transformation. All 22 patients had bile duct abnormalities， among whom 2 had extrahepatic bile duct abnormalities alone， 12 had intrahepatic bile duct dilatation alone， and 8 had dilatation of both intrahepatic and extrahepatic bile ducts. Varices at different sites were observed in 20 patients， among whom 19 had esophageal and gastric varices and 1 had peri-gallbladder varices， and no varices was observed in the superior mesenteric vein or the splenic vein. ConclusionThere are no typical clinical symptoms and changes in liver function parameters in patients with PB， but radiological examination may show dilatation， stenosis， or malformation of the bile ducts at different parts. Therefore， it is necessary to expand the sample size to further explore the diagnosis and treatment of PB.

Clinical study on the treatment of gastrointestinal neurosis with insomnia by combination of "stomach ten acupuncture" and domperidone tablets / 国际中医中药杂志

Objective:To study on the effect of "stomach ten acupuncture" combined with domperidone tablets on clinical symptoms and sleep quality of gastrointestinal neurosis patients with insomnia based on the theory of "stomach harmonious leading to restless".Methods:Randomized controlled trial. From March 2020 to March 2021, 98 patients with gastrointestinal neurosis and insomnia in our hospital who met the inclusion criteria were randomly divided into two groups, with 49 patients in each group. The control group took domperidone tablets orally, and the observation group was treated with "stomach ten acupuncture" on the basis of the control group. Both groups were treated for 8 weeks. Before and after treatment, TCM syndromes were scored, the severity of gastrointestinal symptoms was assessed with Gastrointestinal Symptom Rating Scale (GSRS), anxiety and depression were assessed with Hamilton Anxiety Scale (HAMA) and Hamilton Depression Scale (HAMD), and sleep quality was assessed with Pittsburgh Sleep Quality Index Scale (PSQI).Results:After treatment, the scores and total scores of epigastric pain, belching, abdominal distension, anorexia, noisy acid regurgitation, tiredness and asthenia, constipation and loose stools in the observation group were significantly lower than those in the control group ( t values were 19.61, 19.30, 23.10, 22.05, 20.43, 21.81, 20.51, 16.38, respectively, P<0.01); the scores and total scores of typical symptoms, abdominal pain symptoms, reflux symptoms, diarrhea symptoms, constipation symptoms were significantly lower than those in the control group ( t values were 10.10, 11.14, 11.04, 9.31, 11.24, 5.30, respectively, P<0.01); HAMA and HAMD scores were significantly lower than those in the control group ( t values were 6.96 and 6.85, respectively, P<0.01). The scores of time to fall asleep (1.15 ± 0.56 vs. 2.11 ± 0.75, t=7.18), time to sleep (0.92 ± 0.63 vs. 1.52 ± 1.12, t=3.27), sleep quality (1.02 ± 0.66 vs. 1.96 ± 0.80, t=6.35), sleep efficiency (0.86 ± 0.62 vs. 1.68 ± 0.85, t=5.46), sleep disorders (0.92 ± 0.36 vs. 1.48 ± 0.55, t=5.96), daytime dysfunction (0.96 ± 0.42 vs. 1.97 ± 0.87, t=7.32), hypnotics (0.98 ± 0.45 vs. 1.81 ± 0.62, t=7.58) and total scores (6.85 ± 1.47 vs. 12.73 ± 2.95, t=12.49) were significantly lower than those in the control group ( P<0.01). Conclusion:The "stomach ten acupuncture" combined with domperidone tablets can improve the clinical symptoms and sleep quality of gastrointestinal neurosis patients with insomnia.

Lung Squamous Cell Carcinoma with EML4-ALK Fusion and TP53 Co-mutation Treated with Ensartinib: A Case Report and Literature Review / 中国肺癌杂志

Lung squamous cell carcinoma (LSCC) accounts for approximately 30% of non-small cell lung cancer (NSCLC) cases and is the second most common histological type of lung cancer. Anaplastic lymphoma kinase (ALK)-positive NSCLC accounts for only 2%-5% of all NSCLC cases, and is almost exclusively detected in patients with lung adenocarcinoma. Thus, ALK testing is not routinely performed in the LSCC population, and the efficacy of such treatment for ALK-rearranged LSCC remains unknown. Echinoderm microtubule associated protein like 4 (EML4)-ALK (V1) and TP53 co-mutations were identified by next generation sequencing (NGS) in this patient with advanced LSCC. On December 3, 2020, Ensatinib was taken orally and the efficacy was evaluated as partial response (PR). The progression-free survival (PFS) was 19 months. When the disease progressed, the medication was changed to Loratinib. To our knowledge, Enshatinib created the longest PFS of ALK-mutant LSCC patients treated with targeted therapy since literature review. Herein, we described one case treated by Enshatinib involving a patient with both EML4-ALK and TP53 positive LSCC, and the relevant literatures were reviewed for discussing the treatment of this rare disease.
.

Prognostic Significance of LPCAT1 in Adult Acute Myeloid Leukemia Patients with FAB Subtype M2 / 中国实验血液学杂志

OBJECTIVE@#To study the prognostic value of LPCAT1 in acute myeloid leukemia (AML).@*METHODS@#TaqMan-based reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect relative expression of LPCAT1 in 214 newly diagnosed adult AML patients and 24 normal controls. Survival functions were estimated using the Kaplan-Meier method and were compared by the Log-rank test. A Cox proportional hazard regression model was used to identify prognostic factors.@*RESULTS@#The expression level of LPCAT1 in adult AML was 34.37%(1.83%-392.63%), which was significantly lower than 92.81%(2.60%-325.84%) of normal controls (P<0.001). The prognostic significance of LPCAT1 was evaluated in 171 non-acute promyelocytic leukemia patients with complete clinical information and prognostic data. Survival analysis showed that the expression level of LPCAT1 had no significant effect on the prognosis of the whole cohort. However, in AML patients with FAB subtype M2 (AML-M2), the 2-year relapse-free survival (RFS) rate of patients with low LPCAT1 expression was 35.4%(95%CI: 0.107-0.601), which was significantly lower than 79.2%(95%CI: 0.627-0.957) of patients with high LPCAT1 expression (P=0.012). Multivariate analysis showed that low expression of LPCAT1 was an independent risk factor for RFS of AML-M2 patients (HR=0.355, 95%CI: 0.126-0.966, P=0.049).@*CONCLUSION@#In adult AML patients LPCAT1 shows low expression. Low LPCAT1 expression is an independent risk factor for RFS in M2-AML patients.

Noninvasive Tracking of Every Individual in Unmarked Mouse Groups Using Multi-Camera Fusion and Deep Learning / 神经科学通报·英文版

Accurate and efficient methods for identifying and tracking each animal in a group are needed to study complex behaviors and social interactions. Traditional tracking methods (e.g., marking each animal with dye or surgically implanting microchips) can be invasive and may have an impact on the social behavior being measured. To overcome these shortcomings, video-based methods for tracking unmarked animals, such as fruit flies and zebrafish, have been developed. However, tracking individual mice in a group remains a challenging problem because of their flexible body and complicated interaction patterns. In this study, we report the development of a multi-object tracker for mice that uses the Faster region-based convolutional neural network (R-CNN) deep learning algorithm with geometric transformations in combination with multi-camera/multi-image fusion technology. The system successfully tracked every individual in groups of unmarked mice and was applied to investigate chasing behavior. The proposed system constitutes a step forward in the noninvasive tracking of individual mice engaged in social behavior.

Analysis of Clinical Features and Risk Factors for Oral Ulcers and Bloodstream Infection in Patients with Hematopoietic Stem Cell Transplantation / 中国实验血液学杂志

OBJECTIVE@#To investigate the risk factors of oral ulcers and bloodstream infection in patients with hematopoietic stem cell transplantation.@*METHODS@#The clinical data of 401 hematopoietic stem cell transplant patients in the First Affiliated Hospital of Zhengzhou University from January 2020 to December 2021 were retrospective analyzed, and the risk factors of oral ulcers and bloodstream infection statistical and analyzed.@*RESULTS@#Among the 401 patients, the incidence of oral ulcers was 61.3% (246/401), and the incidence of bloodstream infection was 9.0% (36/401). A total of 40 strains of pathogenic bacteria were isolated from 36 patients, including 26 strains of Gram negative strains (65%), 13 strains of Gram positive strains (32.5%), and 1 strain of fungi (2.5%). Single-factor analysis showed that oral hygiene was associated with the occurrence of bloodstream infection, and the Multi-factor analysis showed that age ≥14 years old, disease diagnosis of leukemia, and allogeneic hematopoietic stem cell transplantation were risk factors for oral ulcers.@*CONCLUSION@#The incidence of oral ulcers in patients with hematopoietic stem cell transplantation is high. The age ≥14 years, disease diagnosis of leukemia, and allogeneic hematopoietic stem cell transplantation were risk factors for oral ulcers in patients, and oral hygiene was associated with the occurrence of bloodstream infection.

Clinical Features and Prognosis of Multiple Myeloma Patients with Secondary Primary Malignancies / 中国实验血液学杂志

OBJECTIVE@#To explore the clinical characteristics and prognosis of multiple myeloma(MM) patients with secondary primary malignancies.@*METHODS@#The clinical data of newly diagnosed MM patients admitted to the First Affiliated Hospital of Zhengzhou University from January 2011 to December 2019 were retrospectively analyzed. The patients with secondary primary malignancies were retrieved, and their clinical features and prognosis were evaluated.@*RESULTS@#A total of 1 935 patients with newly diagnosed MM were admitted in this period, with a median age of 62 (18-94) years old, of which 1 049 cases were hospitalized twice or more. There were eleven cases with secondary primary malignancies (the incidence rate was 1.05%), including three cases of hematological malignancies (2 cases of acute myelomonocytic leukemia and 1 case of acute promyelocytic leukemia) and eight cases of solid tumors (2 cases of lung adenocarcinoma, and 1 case each of endometrial cancer, esophageal squamous cell carcinoma, primary liver cancer, bladder cancer, cervical squamous cell carcinoma, and meningioma). The median age of onset was 57 years old. The median time between diagnosis of secondary primary malignancies and diagnosis of MM was 39.4 months. There were seven cases with primary or secondary plasma cell leukemia, the incidence rate was 0.67%, and the median age of onset was 52 years old. Compared with the randomized control group, the β2-microglobulin level in the secondary primary malignancies group was lower (P=0.028), and more patients were in stage I/II of ISS (P=0.029). Among the 11 patients with secondary primary malignancies, one survived, ten died, and the median survival time was 40 months. The median survival time of MM patients after the secondary primary malignancies was only seven months. All seven patients with primary or secondary plasma cell leukemia died, with a median survival time of 14 months. The median overall survival time of MM patients with secondary primary malignancies was longer than that of the patients with plasma cell leukemia (P=0.027).@*CONCLUSION@#The incidence rate of MM with secondary primary malignancies is 1.05%. MM patients with secondary primary malignancies have poor prognosis and short median survival time, but the median survival time is longer than that of patients with plasma cell leukemia.

Gene Mutation and Overexpression of Newly Diagnosed Multiple Myeloma Patients / 中国实验血液学杂志

OBJECTIVE@#To analyze the characteristics of gene mutation and overexpression in newly diagnosed multiple myeloma (NDMM) patients.@*METHODS@#Bone marrow cells from 208 NDMM patients were collected and analyzed. The gene mutation of 28 genes and overexpression of 6 genes was detected by DNA sequencing. Chromosome structure abnormalities were detected by fluorescence in situ hybridization (FISH).@*RESULTS@#Gene mutations were detected in 61 (29.33%) NDMM patients. Some mutations occurred in 5 or more cases, such as NRAS, PRDM1, FAM46C, MYC, CCND1, LTB, DIS3, KRAS, and CRBN. Overexpression of six genes (CCND1, CCND3, BCL-2, CCND2, FGFR3, and MYC) were detected in 83 (39.9%) patients, and cell cycle regulation gene was the most common. Single nucleotide polymorphisms (SNP) changes were detected in 169 (81.25%) patients, the TP53 P72R gene SNP (70.17%) was the most common. Abnormality in chromosome structure was correlated to gene overexpression. Compared to the patients with normal chromosome structure, patients with 14q32 deletion showed higher proportion of CCND1 overexpression. Similarly, patients with 13q14 deletion showed higher proportion of FGFR3 overexpression, whereas patients with 1q21 amplification showed higher proportion of CCND2, BCL-2 and FGFR3 overexpression.@*CONCLUSION@#There are multiple gene mutations and overexpression in NDMM. However, there is no dominated single mutation or overexpression of genes. The most common gene mutations are those in the RAS/MAPK pathway and the genes of cyclin family CCND are overexpression.

Effect analysis of trajectory screw technique in fragility fracture of pelvic ring / 中国骨伤

OBJECTIVE@#To assess the clinical efficacy of minimally invasive technology with trajectory screw fixation for fragility fractures of pelvic(FFP).@*METHODS@#A retrospective case control study was performed to analyze the clinical data of 35 patients with FFP who were treated and followed up between January 2016 and December 2019. There were 12 males and 23 females, aged from 65 to 99 years with an average of(75.4±7.8) years old. There were 13 cases of type Ⅱb, 7 cases of type Ⅱc, 8 cases of type Ⅲa, 2 cases of type Ⅲb, 2 cases of type Ⅲc, 1 case of type Ⅳb, and 2 cases of type Ⅳc according to Rommens FFP comprehensive classification. All patients received the treatment of minimally invasive technology with trajectory screws fixation. According to the different methods of anterior pelvic ring fixation, FFP patients were divided into two groups:12 cases were fixed with the pedicle screw rod system in the anterior pelvic subcutaneous internal fixator (INFIX) group;23 cases were fixed with hollow screws of the pubic symphysis, superior ramus of pubis or acetabular anterior column in the screw group. The operation time, intraoperative blood loss, intraoperative fluoroscopy times, length of hospital stay, cost of internal fixation, pre- and post-operative visual analogue scale(VAS) were compared between the two groups. The fracture reduction quality was evaluated according to the Matta criteria, and the clinical function was evaluated by the Majeed functional scoring system respectively.@*RESULTS@#All patients were followed up for 12 to 39(16.5±5.4) months after surgery. There was no statistically significant difference in the operation time, intraoperative blood loss, intraoperative fluoroscopy time, and length of hospital stay between the two groups(P>0.05). As for the cost of internal fixation, the cost of internal fixation in the screw group [2 914 (2 914, 4 371) yuan] was significantly lower than that of the INFIX group [6 205 (6 205, 6 205) yuan] (P<0.05). No significant difference was observed in the incidence of postoperative complications between the two groups (P>0.05). There was no significant difference in VAS assessment at admission, 1 week, and 3 months after surgery between the two groups(P>0.05). However, the VAS assessment at 1 week and 3 months after surgery of the two groups were significantly better than those at admission(P<0.05). There was no significant difference in the quality of fracture reduction after the operation and the efficacy evaluation at the last follow-up between the two groups(P>0.05).@*CONCLUSION@#For the treatment of fragility fractures, minimally invasive technology with trajectory screw fixation can achieve good clinical efficacy. It has the advantages of being relatively minimally invasive, less bleeding, relieving the pain. It deserves clinical application.

The influence of application-audit system for doctoral enrollment on scientific research ability and employment development of medical graduate students / 中华医学教育探索杂志

Objective:To investigate and analyze the differences of PhD student scientific research ability, employment and development among types of postgraduate students that admitted by various of doctoral admissions under the perspective of medical students to assess and optimize the existing applications-audit system (AAS).Methods:A self-compiled questionnaire was used to investigate the opinions of medical students at different grades and types on the AAS related issues. Excel and SPSS were used to perform frequency statistics, chi-square test and independent sample t-test. Results:The PhD enrolled from AAS tended to complete the paper-publication at first and second year (38.71%, 12/31; 35.48%, 11/31), while unified enrollment (UE) tended to complete in the second year (33.33%, 10/30) and seven-year degree (SYD) in the third year (40.54%, 15/37) ( P=0.021). In terms of the value of the materials required in the application stage to the doctoral research, 74.19%(23/31) of AAS students and 48.65%(18/37) of SYD students believed that scientific research results were the most helpful to the doctoral research process, while UE believed that English helped the most (26.67%, 8/30), with significant differences among groups ( P=0.002). In terms of fair recognition of enrollment in the application system, 71.53% (304/425) of graduate students believed that AAS for doctoral enrollment was fair. The institution ( P=0.001) and type of master's degree ( P=0.001) significantly affected graduate students' recognition of the fairness of AAS. Conclusion:The degree and speed of dissertation completion of the AAS PhD are prior, reflecting the advantages of AAS in the cultivation of medical doctors' scientific academic ability and achievements. The AAS plays a significant role in enhancing the reserve of high-level scientific researchers in China, and has a high recognition and influence in medical students. In the future, the application examination system will be optimized to create the most suitable way for doctoral enrollment in China.

The effect of "ten needles in the stomach" treatment on sleep perception for the patients with spleen-gastric damp-heat insomnia based on the theory of "stomach upset, sleep restlessness" / 国际中医中药杂志

Objective:To explore the effect of "ten needles in the stomach" on sleep perception of patients with spleen-gastric damp-heat insomnia based on the theory of "stomach discord, then sleep restlessness", to provide references for clinical diagnosis and treatment.Methods:The study subjects were 300 patients with insomnia from the sleep department and outpatient department of Shijiazhuang Traditional Chinese Medicine Hospital. According to the random number method, they were divided into the stomach ten needle group, the diazepam group, and the stomach ten needle plus diazepam group, with 100 in each group. Among them, the stomach ten needles group received "stomach ten needles" acupuncture treatment, the diazepam group was given diazepam therapy, and the stomach ten needles plus diazepam group was given diazepam combined with "stomach ten needles" acupuncture treatment. The Pittsburgh Sleep Quality Index (PSQI) scores, the self-rating disease symptom scale (SCL-90) scores, nighttime polysomnography (PSG) monitoring indicators, and the mean sleep latency (MSL) values were compared before and after treatment in the three groups. The difference in clinical efficacy between the two groups were observed.Results:The total effective rate was 94.0% (94/100) in the combined group, 77.0% (77/100) in the diazepam group, and 85.0% (85/100) in the stomach ten needle group. There were significant differences among the three groups ( χ2=11.56, P<0.01). After treatment, the daytime dysfunction, hypnotic drugs, sleep disturbance, sleep efficiency, sleep time, sleep time, sleep quality score and total score of the combined group were significantly lower than those in the diazepam group and the stomach ten needle group ( F=5.70, 3.65, 5.23, 6.37, 3.66, 6.19, 7.54, 6.40, all Ps<0.01); The scores of SCL-90 and MSL were significantly lower than those in the diazepam group and stomach ten needle group ( F=8.97, 7.53, all Ps<0.01). In the combined group, NWAK [(1.36 ± 0.87) times vs. (2.69 ± 1.15) times, (2.11 ± 1.05) times, F=5.88], SOL [(13.62 ± 5.85) min vs. (25.06 ± 9.42) min, (19.78 ± 7.63) min, F=6.49], N1/TST [(5.69 ± 1.09)% vs. (12.65 ± 2.58)%, (8.49 ± 2.45)%, F=5.13], N2/TST [(51.07 ± 10 2.06)% vs. (58.36 ± 2.18)%, (55.61 ± 2.04)%, F=9.86] were significantly lower than those in the diazepam group and stomach ten needle group ( P<0.01), SE [(90.33 ± 2.89)% vs. (85.39 ± 2.75)%, (87.53 ± 2.69)%, F=8.36], TST [(449.32 ± 23.65) min vs. (421.66 ± 25.33) min, (431.26 ± 25.98) min, F=8.26], REM/TST [(23.87 ± 4.52)% vs. (14.52 ± 3.87)%, (18.36 ± 3.25)%, F=5.34], N3/TST [(18.69 ± 2.02)% vs. (10.31 ± 1.64)%, (14.89 ± 1.74)%, F=7.69] were significantly higher than those in the diazepam group and stomach ten needle group ( P<0.01). Conclusion:Based on the "stomach discord, sleep restlessness" theory, the ten needles on the stomach can treat insomnia and improve psychological state and sleep quality, with the functions of clearing the damp and heat of the middle joker, regulating the lifting and lowering of qi in the middle.

Effect of Toxoplasma gondii Chinese 1 genotype infections on brain iron metabolism in mice / 中国血吸虫病防治杂志

Objective To investigate the effect of Toxoplasma gondii Chinese 1 genotype infections on host brain iron metabolism and brain damages. Methods Twenty C57BL/6 mice, each weighing 15 to 17 g, were randomly divided into the control and infection groups, of 10 mice in each group. Each mouse in the infection group was injected intraperitoneally with 4 000 tachyzoites of the TgCtwh3 isolate with Chinese 1 genotype, while each mouse in the control group was injected with an equal amount of sterile phosphate-buffered saline (PBS). All mice were sacrificed 6 day post-infection and brain tissues were sampled. The iron levels were measured in mouse brain specimens using inductively coupled plasma mass spectrometry (ICP-MS). The differentially expressed genes were determined between the experimental and control groups using RNA chips and Gene Ontology (GO) term enrichment analysis of differentially expressed genes was performed. The mRNA expression of Toxoplasma gondii surface antigen 1 (TgSAG1) gene and some Zrt- and Irt-like protein (ZIP) family member coding genes was detected by quantitative real-time PCR (qPCR) assay. The ultrastructure of the hippocampus dentate gyrus in mouse brain specimens was observed using optical and electronic microscopy. The glutathione peroxidase 4 (GPx4) expression was determined using Western blotting, and malondialdehyde (MDA) level was measured using thiobarbituric acid (TBA) test. In addition, the optical density (OD) of vascular endothelial growth factor (VEGF) protein was measured using immunohistochemistry. Results Optical microscopy showed cell necrosis in the hippocampus dentate gyrus of mouse brain specimens in the infection group, and electronic microscopy cytoplasmic vacuolization, nuclear atrophy and necrosis, disruption of cristae mitochondriales and increased autophagosome levels in the mouse brain hippocampus specimens in the infection group. The iron level was significantly greater in mouse brain specimens in the infection group than in the control group [(32.92 ± 0.90) μg/g vs. (37.72 ± 1.10) μg/g; t = 3.397, P < 0.01]. RNA chips revealed 721 up-regulated genes and 276 down-regulated genes in mouse brain specimens between the infection and control groups, and the differentially expressed genes were significantly enriched in metal ion binding ability (molecular function). Elevated expression of metal element transporter ZIP2 mRNA (t = 8.659, P < 0.05), reduced GPx4 expression [(1.046 ± 0.025) vs. (0.720 ± 0.101); t = 3.129, P < 0.01], increased MDA level [(4.37 ± 0.33) nmol/mgprot vs. (5.93 ± 0.54) nmol/mgprot; t = 2.451, P < 0.05], and up-regulated mean OD of VEGF protein [(0.348 3 ± 0.017 8) vs. (0.490 6 ± 0.010 5); t = 6.641, P < 0.01] were found in mouse brain specimens in the infection group than in the control group. Conclusions Chinese 1 genotype T. gondii infection results in iron accumulation in brain tissues, reduced antioxidant ability and elevated levels of oxidative stress in mice, suggesting that T. gondii infection may cause brain damages through affecting iron metabolism in host brain tissues.

Oxidative Damage to BV2 Cells by Trichloroacetic Acid: Protective Role of Boron via the p53 Pathway / 生物医学与环境科学（英文）

This study aimed to investigate the neurotoxicity induced by trichloroacetic acid (TCA) and the possible protective mechanisms of boron (B). Mouse BV2 cells were treated with TCA (0, 0.39, 0.78, 1.56, 3.12, 6.25, or 12.5 mmol/L) and B (0, 7.8, 15.6, 31.25, 62.5, 125, 500, or 1,000 mmol/L) for 3 h and 24 h, respectively. Then, reactive oxygen species, and supernatant proinflammatory cytokine and protein levels were analyzed after 24 h of combined exposure. Beyond the dose-dependent decrease in the cellular viability, it clearly increased after B supplementation ( P < 0.05). Moreover, B decreased oxidative damage, and significantly down-regulated IL-6 levels and up-regulated TNF-β production ( P < 0.05). B also decreased apoptosis via the p53 pathway. The present findings indicated that TCA may induce oxidative damage, whereas B mitigates these adverse effects by decreasing cell apoptosis.

Effects of shift work on adipokines, inflammatory factors, and insulin sensitivity in non-overweight/obese women / 中华内分泌代谢杂志

Objective:To observe the effect of shift work on the stability of the circadian clock and insulin sensitivity in non-overweight/obese individuals with normal blood glucose, and explore underlying connection.Methods:Female shift working nurses in the Department of Blood Transplantation and non-shift working nurses in the Health Management Center in the First Affiliated Hospital of Zhengzhou University were divided into shift worker group (SW group) and non-shift worker group (NSW group). Serum inflammatory factors [interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α)], adipokines (adiponectin, leptin, chemerin, visfatin), and melatonin levels were measured using enzyme linked immunosorbent assay (ELISA). Realtime fluorescence quantitative PCR was performed to detect peripheral blood circadian clock genes circadian locomotor output cycles protein kaput(Clock) and brain and muscle ARNT-like protein 1(Bmal1). Cortisol and fasting insulin were measured by chemiluminescent microparticle immunoassay, and HbA 1C was measured by capillary electrophoresis. In addition, visceral fat area (VFA) was assessed with bioelectrical impedance analyzer, and mid-sleep time composite phase deviations (CPD) was calculated based on the International Physical Activity Short Questionnaire. Results:SW group had lower serum level of melatonin ( P=0.023) and higher cortisol ( P=0.001) than the NSW group, and altered mRNA expression of Clock and Bmal1 ( P=0.034, P=0.047). Fasting blood glucose and HbA 1C in the SW group, although in the normal range, had been higher than in the NSW group ( P=0.011, P=0.033). Although body mass index was normal in SW group, VFA had been higher than that of the NSW group ( P=0.010). And homeostasis model assessment for insulin resistance (HOMA-IR), IL-6, TNF-α, leptin, chemerin, and visfatin were significantly higher in the SW group than NSW group ( P=0.033, P=0.012, P=0.001, P=0.011, P=0.021, P=0.007). In addition, adjusting for body mass index and activity factors revealed a significant positive correlation between CPD and VFA ( r=0.434, P=0.049), inflammatory factors IL-6 ( r=0.514, P=0.017) and TNF-α ( r=0.700, P<0.001) and pro-inflammatory adipokines leptin ( r=0.473, P=0.030), chemerin ( r=0.439, P=0.047), visfatin ( r=0.521, P=0.015). Conclusion:Shift work can affect circadian clock, with increased visceral adiposity, pro-inflammatory adipokines, inflammatory factors and decreased insulin sensitivity in women without overweight/obese.

Effect of Microelectronic Electromyography Bridge on Motor Function of Extensor Carpi Radialis Longus in Patients with Cervical Spinal Cord Injury / 中国康复理论与实践

Objective:To observe the effect of microelectronic EMG bridge (EMGB) training on the motor function of extensor carpi radialis longus in patients with complete cervical 5 spinal cord injury. Methods:From March, 2016 to March, 2017, 20 patients with complete cervical 5 spinal cord injury were randomly divided into control group (n = 10) and experimental group (n = 10). The control group received routine wrist extensor muscle training, and the experimental group received EMGB training in addition, for 180 days. The motor function of the affected limb was evaluated by sEMG of extensor carpi radialis longus, Manual Muscle Test (MMT), Wolf Motor Function Test (WMFT) and Spinal Cord Lesion Independence Measure (SCIM). Results:After treatment, the peak value and average value of sEMG of extensor carpi longus of both sides increased in both groups (t > 2.510, P < 0.05), the peak value and average value of the left side were higher (t > 2.759, P < 0.05), and the peak value of the right side was higher (t = 2.691, P < 0.05) in the experiment group than in the control group, however, there was no significant difference in average value of the right side between two groups (t = 2.063, P = 0.054). The scores of MMT increased in both groups (t > 2.569, P < 0.05), and were higher in the experimental group than in the control group (t > 2.278, P < 0.05). The scores of WMFT and SCIM increased in both groups (t > 3.839, P < 0.05), however, there was no significant difference between two groups (t < 1.498, P > 0.05). Conclusion:EMGB training could improve the motor function of extensor carpi radialis longus in patients with complete cervical 5 spinal cord injury.

Discussion on the Quality Risk Reminder Mechanism of Drug Sampling and Testing in China / 中国药房

OBJECTIVE：To provide a reference for further improvi ng the quality risk reminder mechanism of the drug sampling and testing （called“the Reminder ”as for short ）in China ，and strengthening the drug quality management. METHODS ： The quality risk management situation of the drug sampling and testing were summarized ，and the legal nature ，main content and working procedures of the Reminder were analyzed. The latest data of the Reminder in 2020 were taken as an example to analyze the role of the Reminder in the investigation of potential drug quality risks ，and made the suggestions for existing problems. RESULTS & CONCLUSIONS ：Based on legal standards ，China’s drug regulatory departments had carried out exploratory research on drugs that may have quality and safety risks due to drug quality control blind spots or deviations of manufacturing enterprises ， and divided them into serious risks and general risks according to the severity of the problems found ，and implemented hierarchical management. The Reminder was an administrative measure for general drug quality risks based on the principle of persuasion first ， and did not have sanctions. Its main content covered all the information required for risk investigation and rectification （basic drug information， suggested risk information ， contact information ， risk discovery methods ， troubleshooting and rectification requirements，and responsibilities of local provincial drug regulatory departments ）. It involved five responsible parties ，ie. the inspection institution ，China Institute for Food and Drug Control ，National Medical Products Administration ，the provincial food and drug administration of the relevant manufacturing enterprises and the relevant manufacturing enterprises. Through the mode of closed-loop management ，the benign interaction between regulatory authorities and manufacturing enterprises could been realized. In 2020，National Medical Products Administration issued 312 reminders to 286 manufacturers，with an accuracy of 87.91％，which was scientific and targeted. The manufacturer had carried out a series of rectification measures for the contents of the Reminder ， including carrying out process verification ，revising internal control standards and strengthening production process control. However， there were also some problems ， such as the rationality of the prompt contents being questioned by the manufacturer and the i nsufficient investigation of the manufacturer. It is suggested that the manufacturers correctly understand the nature and value of the Reminder. The inspection agency should further improve the scientific pertinence of the problems found ，while the drug regulatory department should focus on the troubleshooting of the problems found ，so as to jointly promote the improvement of drug quality.

Effect of CDK1 Interferes with the Regulation of PLK1, Aurora B and TRF1 on the Proliferation of Leukemia Cells / 中国实验血液学杂志

OBJECTIVE@#To investigate the effect of CDK1 interference regulation of PLK1, Aurora B and TRF1 on the proliferation of leukemia cells.@*METHODS@#The human myelogenous leukemia cell line HL-60 was selected as the research object, and the effect of TRF1 expression and its changes on cell proliferation and cycle was investigated by regulating intracellular CDK1 expression. The objects were divided into 5 groups, including control group, shRNA-NC group, CDK1-shRNA group, pcDNA group and pcDNA-CDK1 group. RT-PCR was used to detect the CDK1 expression of cells in each group; colony formation was used to detect the proliferation of the cells. Western blot was used to detect the expression of CDK1, PLK1, Aurora B, TRF1, and cyclin p53, p27, cyclinA.@*RESULTS@#The phosphorylation level of PLK1, Aurora B and the expression of TRF1 in the CDK1-shRNA group were significantly down-regulated as compared with those in the control group (P<0.05). Compared with the control group, the cells in CDK1-shRNA group showed lower clone formation rate, the increasing of cycle-associated proteins p53 and p27 and the decreasing of cyclinA expression (P<0.05). It was shown that interfered CDK1 expression could inhibit the proliferation of HL-60 cells and prolong the time that they enter mitosis, thereby extending the cell cycle. Compared with the control group, the overexpressed CDK1 in the pcDNA-CDK1 group made the phosphorylation level of PLK1, Aurora B, and TRF1 expression increase significantly (P<0.05), also the colony formation rate (P<0.05). The cycle-related proteins p53 and p27 was down-regulated, while cyclinA expression was up-regulate significantly (P<0.05). The results indicted that overexpressed CDK1 could stimulate adverse reactions, thereby promoting the proliferation of HL-60 cells and shortening the cell cycle.@*CONCLUSION@#Knocking out CDK1 can inhibit the phosphorylation of PLK1 and Aurora B and negatively regulate TRF1, thereby inhibiting the proliferation of leukemia cells.

Laparoscopic surgery in colon cancer patients with end-stage renal disease / 中华普通外科杂志

Objective:To explore the efficacy and safety of laparoscopic colon cancer surgery for patients with end-stage renal disease .Methods:Thirty-one end-stage renal disease patients (continuous hemodialysis) underwent laparoscopic colon cancer surgery from Jan 2014 to May 2019 in Tianjin First Central Hospital compared to 35 colon cancer patients with normal renal function.Result:Compared with the control group, the operation time in laparoscopic group was longer[(187±20) min vs. (174±21) min, t=2.381, P=0.020], the intraoperative blood loss was more[90 (80-110) ml vs. 50(40-60) ml, Z=-6.580, P<0.001], the postoperative drainage volume was more[(417±89) ml vs.(208±67) ml, t=10.858, P<0.001], the postoperative hospitalization time was longer[(13.68±2.10) d vs.(9.09±1.65) d, t=9.918. P<0.001], and the total hospitalization costs were higher[9.2 (8.8-9.6) ten thousand yuan vs. 6.1 (5.8-6.5) ten thousand yuan, Z=-6.976, P<0.001]. There was no significant difference in overall morbidity between the two group (23% vs. 9%, P=0.170). Sixty-one patients (92%) were followed up for a median time of 6 months. One case of liver metastasis was found in each group. Conclusion:Laparoscopic colon cancer surgery can be a safe and effective procedure in patients with end-stage renal disease .