Literature analysis of compatible stability of commonly used intravenous drugs in ICU / 中国药房

OBJECTIVE To analyze the compatible stability of commonly used intravenous drugs in the intensive care units （ICU）， and to provide a reference for improving medication safety in clinic. METHODS The commonly used intravenous drugs in the ICU of Hebei General Hospital were investigated and confirmed in April 1-30， 2022， and used as keywords to retrieve the relevant literature about compatible stability from PubMed， CNKI， Wanfang Data and other databases， and manually filtered with Micromedex database at the same time. Then， the compatible stability results of the included literature were analyzed descriptively. RESULTS Totally 32 commonly used intravenous drugs and 39 mixed infusion combinations were collected from ICU of this hospital. A total of 40 studies were included， only 2 studies followed all quality requirements； 18 studies validated their methods to guarantee correct reproducibility； 33 studies evaluated physical stability， including precipitate formation and pH changes； 32 studies evaluated chemical compatibility， mainly content/concentration changes. A total of 666 possible two-drug combinations were obtained from the included literature， of which 254 combinations of stability data were available， including 176 were stable， 68 were unstable， and 10 were contradictory. Totally 412 combinations had no stability results. Among two-drug combinations in ICU of this hospital， 42 combinations were stable， 14 combinations were unstable， and 2 combinations were contradictory. CONCLUSIONS The pH， solvent， excipients and preparation concentration are the factors that affect the stability. There are drug combinations with unstable compatibility of commonly used intravenous drugs in ICU of this hospital. The stability study methods are limited， and the stability data cannot meet the actual clinical needs.

Prevalence and influencing factors of work-related musculoskeletal disorders among workers in chemical pharmaceutical industry / 环境与职业医学

Background Work-related musculoskeletal disorders (WMSDs) are one of the major occupational health problems in the world. Pharmaceutical industry is an important part of China's national economy. At present, there are few related studies reported at home and abroad. Objective To investigate the status and influencing factors of WMSDs in chemical pharmaceutical industry. Methods A cross-sectional epidemiological survey was conducted among all workers from three chemical pharmaceutical enterprises in Guangzhou. The Musculoskeletal Disorders Questionnaire was used to collect information on demographic characteristics, symptoms of musculoskeletal disorders, types of work, work organization, and and work postures. Multiple logistic regression method was used to analyze the risk factors of WMSDs in chemical pharmaceutical workers. Results In this study, 563 workers were selected as subjects. The total prevalence rate of WMSDs symptoms in the chemical pharmaceutical workers was 43.9% (247/563), and the leading body part-specific prevalence rate from high to low was 34.3% in the lower back, 24.3% in the upper back, 24.0% in the shoulders, and 23.8% in the neck. The prevalence rate of WMSDs symptoms in multiple body parts (30.0%) was 2.16 times higher than that in single body part (13.9%), and the prevalence rate of WMSDs symptoms in four body parts was the highest (11.4%). The results of multiple logistic regression analysis showed that age ≥50 years (reference age <30 years) (OR=2.140, 95%CI: 1.054-4.345), often or very often (reference never/rarely) long-time head rotating (OR=2.695, 95%CI: 1.753-4.142) and long-time keeping arms above shoulders (OR=1.902, 95%CI: 1.108-3.265) increased the risk of reporting WMSDs symptoms (P<0.05). Regarding education level, workers with high school and technical secondary school (OR=0.333, 95%CI: 0.175-0.636) or college and above (OR=0.413, 95%CI: 0.216-0.790) education had a lower risk of reporting WMSDs symptoms than those with middle school or below (P<0.05). Conclusion The prevalence rate of reporting WMSDs symptoms in chemical pharmaceutical industry is high, the involving body parts are lower back, upper back, shoulders, and neck, and reporting simultaneous occurrence of WMSDs symptoms in multiple body parts is common. The chemical pharmaceutical manufacturers can reduce the risk of WMSDs by strengthening the training on workers' ergonomics knowledge, paying attention to the less educated personnel, protecting the elderly workers, and avoiding awkward work postures, like rotating head for a long time and raising arms over shoulders.

Work-related musculoskeletal disorders and their influencing factors among workers in a furniture factory / 环境与职业医学

Background Furniture manufacturing is one of the typical labor-intensive industries, and workers in this industry face a high risk of work-related musculoskeletal disorders (WMSDs), which seriously affect the physical and mental health of workers. Objective To explore the prevalence and potential risk factors of WMSDs among workers in a large-scale furniture manufacturing factory. Methods A cross-sectional study of 3431 workers in a furniture factory in Guangdong Province was conducted from September to December 2019. Information including reported WMSDs in various body parts in the past year, demographic characteristics, work organization factors, job characteristics, and work postures was collected by an electronic version of Musculoskeletal Disorders Questionnaire. Pearson χ2 test and binary logistic regression were used to analyze the risk factors leading to WMSDs. Results The overall prevalence rate of WMSDs was 32.12% (1102/3431). The most common WMSDs symptoms occurred in the neck (16.85%), followed by the feet (15.27%), shoulders (14.81%), and hands (14.25%). The prevalence rates of WMSDs in the neck, shoulders, elbows, hands, legs, and feet were significantly different among different types of work (P<0.05). The results of multiple logistic regression analysis showed that individual factors, work organization factors, job characteristics, and awkward work postures were associated with the frequency of reporting WMSDs in specific parts of workers. Comparatively poor physical health (including moderate, poor, and very poor) was positively correlated with neck, shoulder, hand, and foot WMSDs (OR=1.479-4.077); working with an uncomfortable posture (OR=1.983) and doing the same task almost every day (OR=1.783) were positively correlated with neck pain; doing the same task almost every day (OR=2.408) and neck twisting for a long time (OR=1.830) were positively correlated with shoulder pain; bending wrists up and down frequently (OR=1.948) and bending wrists for a long time (OR=2.081) were positively correlated with hand pain; prolonged standing (OR=1.953) and often working overtime (OR=1.627) were positively correlated with feet pain; sufficient rest time was negatively correlated with WMSDs in the neck, shoulders, hands, and foot (OR=0.544-0.717). Conclusion The prevalence rate of WMSDs in furniture manufacturing workers is relatively high, and neck, feet, shoulders, and hands are the most involved body parts. The frequency of reporting WMSDs is related to individual factors, work organization factors, job characteristics, and awkward work postures.

Relationship between occupational stress, job burnout, and depressive symptoms among workers in an automobile manufacturing enterprise in Guangzhou / 环境与职业医学

Background The operation mode of automobile manufacturing industry (AMI) makes workers have different degrees of occupational stress and burnout, which may lead to negative emotions and depressive symptoms. Objective To study the relationship between occupational stress, job burnout, and depressive symptoms in AMI workers. Methods In this study, 1300 workers from a Guangzhou AMI company were selected as subjects by cluster random sampling method. Occupational stress, job burnout, and depressive symptoms of the workers were assessed by using the Effort-Reward Imbalance (ERI) questionnaire, the Maslach Burnout Inventory general survey questionnaire, and the Patient Health Questionnaire-9, respectively. Hierarchical regression was used to analyze the effects of occupational stress and job burnout on depressive symptoms in AMI workers. Mediating effect model was used to analyze the mediating effect of job burnout on the relationship between occupational stress and depressive symptoms. Results There were 1300 questionnaires distributed, 1228 valid questionnaires collected, with a 94.5% recovery rate. The ERI ratio of 1228 AMI workers was 1.06±0.72, and the positive rate of occupational stress was 37.3% (458/1228). The score of job burnout was 2.18±1.37, and the positive rate of job burnout was 62.6% (769/1228). The score of depressive symptoms was 10.27±6.42, and the positive rate of depressive symptoms was 47.1% (578/1228). The dimensional scores of effort and over-commitment in occupational stress as well as emotional exhaustion and depersonalization in job burnout of AMI workers were positively correlated with the depressive symptom scores (rs=0.415, 0.571, 0.573, 0.593, P＜0.05). The dimensional scores of reward and personal achievement were negatively correlated (rs=−0.454, −0.339, P＜0.05). The percentages of variance in depressive symptoms score explained by occupational stress and job burnout were 26.7% and 16.6%, respectively. Job burnout had a partial mediating effect between the three dimensions of occupational stress and depressive symptoms, and the mediating effect values were −0.2832 (95%CI: −0.3250– −0.2434), 0.3553 (95%CI: 0.3071–0.4041), and 0.4193 (95%CI: 0.3681–0.4725), respectively. Conclusion AMI workers' occupational stress affects job burnout, but also indirectly affects depressive symptoms. Job burnout partially mediates the association between occupational stress and depressive symptoms. Reducing occupational stress and burnout levels of AMI workers may alleviate depressive symptoms.

Investigation of medication adherence for superficial mycoses among students in a college based on Morisky Medication Adherence Scale / 药学实践杂志

Objective To investigate the medication adherence of military academy students with superficial mycoses. Methods A 8-item Morisky medication adherence scale (MMAS) was modified into 7-item scale to evaluate the compliance of antifungal drugs in the sick students. The reliability and validity of the scale were analyzed. Results A total of 243 questionnaires were collected, of which 242 were valid questionnaires. 90.08% of the students took topical medication and 8.68% were treated both with topical and systematic combination. High, medium and low medication adherence rates as assessed by the modified MMAS were 9.09%, 23.97% and 66.94%, respectively. The reliability analysis showed that the internal consistency coefficient (Cronbach’s α ) was 0.781，and the adjusted Cronbach’s α was 0.790, indicating the high reliability of the scale. The KMO value was 0.798, and the Bartlett’s spherical test value was 440.866, P=0.000. One factor was extracted by exploratory factor analysis. The factor loadings of the items were all above 0.5. Therefore, the high convergent validity was good. Conclusion The modified MMAS has good reliability and validity and is applicable for the evaluation of medication compliance for superficial mycoses. In this study, the military students have a low level of medication adherence for superficial mycoses. Effective measures should be taken to help students strengthen their daily medication management and improve compliance.

Effect of Main Component of Realgar Arsenic Disulfide （As2S2） on DNA Methylation of SKM-1 Cells with Myelodysplastic Syndrome / 中国实验方剂学杂志

ObjectiveTo explore the effects of the main component of Realgar arsenic disulfide （As2S2） on DNA methylation of SKM-1 cells with myelodysplastic syndrome. MethodCell Counting Kit-8 （CCK-8） was used to detect the inhibitory effect of As2S2（0， 1， 2， 4， 8， 16 μmol·L-1）on SKM-1 cells. Propidium iodide （PI） staining was applied to detect the effect of As2S2（0， 1， 2， 4 μmol·L-1）on the SKM-1 cell cycle. The effect of As2S2 （0， 4 μmol·L-1） on the methylation of SKM-1 cells on a genome-wide scale was observed by using Human Methylation 850K BeadChip， followed by Kyoto Encyclopedia of Genes and Genomes （KEGG） and gene ontology （GO） analyses. According to the microarray data， the antioncogene TUSC3 was selected， and real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were adopted to investigate the effect of As2S2 （0， 1， 2， 4 μmol·L-1） on the mRNA and protein expression of TUSC3， respectively. ResultCompared with the conditions in the blank group， As2S2 inhibited SKM-1 cells， increased the proportion of cells in the G0/G1 phase， and decreased the proportion of cells in the S phase（P<0.05）. The 850K microarray showed that 4 μmol·L-1 As2S2 could significantly induce DNA methylation in SKM-1 cells， with 12 710 differentially methylated genes involved （50% hypermethylated and 50% hypomethylated genes）. KEGG and GO analyses showed that differentially methylated genes were involved in many important biological functions and signaling pathways， including purine metabolism， natural killer cell-mediated cytotoxicity， endocytosis， chemokine signaling pathway， and nuclear ubiquitin ligase complex. In terms of downstream gene expression， Real-time PCR and Western blot showed that As2S2 increased the expression of TUSC3， as compared with the conditions in the blank group （P<0.05）. ConclusionAs2S2， the main component of Realgar， has a significant regulatory effect on the methylation of SKM-1 cells， which is presumedly achieved by increasing the expression of TUSC3.

mRNA cancer vaccines: Advances, trends and challenges

Patients exhibit good tolerance to messenger ribonucleic acid (mRNA) vaccines, and the choice of encoded molecules is flexible and diverse. These vaccines can be engineered to express full-length antigens containing multiple epitopes without major histocompatibility complex (MHC) restriction, are relatively easy to control and can be rapidly mass produced. In 2021, the U.S. Food and Drug Administration (FDA) approved the first mRNA-based coronavirus disease 2019 (COVID-19) vaccine produced by Pfizer and BioNTech, which has generated enthusiasm for mRNA vaccine research and development. Based on the above characteristics and the development of mRNA vaccines, mRNA cancer vaccines have become a research hotspot and have undergone rapid development, especially in the last five years. This review analyzes the advances in mRNA cancer vaccines from various perspectives, including the selection and expression of antigens/targets, the application of vectors and adjuvants, different administration routes, and preclinical evaluation, to reflect the trends and challenges associated with these vaccines.

Difficult and complicated oral ulceration: an expert consensus guideline for diagnosis / 国际口腔科学杂志·英文版

The complexity of oral ulcerations poses considerable diagnostic and therapeutic challenges to oral specialists. The expert consensus was conducted to summarize the diagnostic work-up for difficult and complicated oral ulcers, based on factors such as detailed clinical medical history inquiry, histopathological examination, and ulceration-related systemic diseases screening. Not only it can provide a standardized procedure of oral ulceration, but also it can improve the diagnostic efficiency, in order to avoid misdiagnosis and missed diagnosis.

Construction and application of intelligent outpatient pre-admission medical history collection system / 中华医院管理杂志

Digital and intelligent technology is an important driving force to promote the transformation and innovation of medical service mode and improve service quality. In February 2020, Peking Union Medical College Hospital established an intelligent outpatient pre-admission medical history collection system in order to improve the intelligent level of clinical application business system and the medical experience of outpatients.The system consisted of artificial intelligence capability layer, application service layer, capability resource layer and user application layer and hardware technology architecture. By docking with the hospital information system and using mobile terminal App, patients could submit pre-admission medical history information by themselves, and generate structured patient history for the visiting doctors to call. By November 2021, the pre-admission medical history collection system had covered 80% of the departments of the hospital, serving 1.68 million people in total, and the patient filling rate had reached 60%. The duration of patient′s medical history collection and the duration of doctor′s outpatient electronic medical record writing had been continuously shortened, greatly improving the efficiency of outpatient medical services.

Consistency between multifrequency bioelectrical impedance analysis and dual-energy x-ray absorptiometry for muscle mass assessment in elderly patients with advanced chronic kidney disease / 中华老年医学杂志

Objective:To compare the consistency between bioelectrical impedance analysis(BIA)and dual-energy X-ray absorptiometry(DXA)in skeletal muscle mass assessment in elderly patients with advanced chronic kidney disease(CKD), and to provide a basis for accurate clinical diagnosis of sarcopenia.Methods:Elderly patients with advanced CKD at the Department of Nephrology of Shanghai Sixth People's Hospital were included.Parameters for physical performance included handgrip strength and gait speed, and body muscle mass was measured by DXA and multifrequency BIA.The consistency between the two methods was assessed by the intraclass correlation coefficient, Bland-Altman analysis and kappa coefficient test.Results:This study included 67 elderly patients with advanced CKD with a mean age of(70.7±6.1)years and an average BMI of(24.6±3.5)kg/m 2.The proportion of enrolled male patients was 61.2% and the mean estimated glomerular filtration rate was(27.7±12.7)ml·min -1·1.73m -2.The intraclass correlation coefficients of muscle mass and appendicular skeletal-muscle mass index(ASMI)measured by BIA and DXA ranged from 0.81 to 0.90.Bland-Altman analysis showed that BIA overestimated muscle mass against DXA, and the mean difference in ASMI was(0.44±0.13)kg/m 2.In addition, there was a moderate agreement between the two measurement methods for determining muscle loss(Kappa=0.47). Conclusions:BIA and DXA offer a fair level of consistency in the assessment of muscle mass in elderly patients with advanced CKD.However, compared with DXA, BIA overestimates muscle mass in elderly patients with CKD.

The clinical value analysis of MRN on diagnosis and treatment of lumbosacral nerve injury associated with sacral fractures / 中华骨科杂志

Objective:To discuss the clinical value of magnetic resonance neurography (MRN) on diagnosis and treatment of lumbosacral nerve injury associated with sacral fractures and analyze the characters of nerve injury which was caused by sacral fractures.Methods:The clinical data of 40 patients who had lumbosacral nerve injury associated with sacral fractures and accepted treatment in Tianjin hospital from August 2018 to December 2020 were collected based on inclusion and exclusion criteria. Twenty-four patients had unilateral sacral fractures (Tile C1) which included 16 Denis II type fractures and 8 Denis III type fractures. Sixteen patients had bilateral sacral fractures which were all Tile C3, U shaped and Denis II type sacral fractures. All patients had symptoms or signs of lumbosacral nerve injury, and accepted contrast-enhanced three-dimensional magnetic resonance neurography (CE-3D MRN) to diagnose the injury part and severity degree. The L 5-S 4 nerves were separated to three parts based on injured side and intraspinal type (IS), intraforaminal type (IF) and extraforaminal type (EF) location, and were judged the mild, medium or severe degree of nerve injury severity. Overall and pairwise Chi-square test was performed on the number of nerve injuries. Eleven patients accepted the operation of nerve dissection and exploration. The nerve injury part and severity were recorded under direct vision, and were statistically analyzed with CE-3D MRN outcome. Results:The outcome of 239 lumbosacral nerve injuries which had different part and severity were found by MRN, and all combined with sacral fractures of the same side. The nerves which ranked from largest to fewest according to injured numbers were L 5, S 1, S 2, S 3 and S 4. The statistical analysis showed that there were significant differences of injured nerve numbers except between S 1 and S 2, S 3 and S 4, and there were no significant difference of nerve injury part and severity degree between the direct visual judgement intraoperatively and preoperative CE-3D MRN examination. Conclusion:MRN can reveal the part and severity degree of lumbosacral nerve injury associated with sacral fracture clearly and accurately, which has important clinical value and should become the preferred examination of such injuries. The lumbosacral nerve injury has the most frequent features of S 1 and S 2, followed by L 5, and the least in S 3 and S 4.

The imaging evaluation and clinical significance of sacral vestibule / 中华骨科杂志

Objective:To measure the anatomical parameters of three-dimensional available space of S 1 and S 2 vestibules on Chinese adults by imaging methods, and discuss their clinical values. Methods:Data of 200 cases of pelvic CT with complete posterior ring were collected from January 2015 to January 2021, included 110 males and 90 females. The ages ranged from 21 to 63 years (average, 40.72±10.70 years). Then the parameters of both the left vestibule and the right vestibule of S 1 and S 2 such as vestibular width, vestibular height and vestibular area were measured by the three-dimensional CT reconstructions. Statistical analyses were performed among the groups which were classified according to the gender, side of vestibule to compare the difference of vestibular morphological characteristics among different groups. Results:The average vestibular area of S 1 was 425.71± 45.07 mm 2 (range, 296.3-604.4 mm 2), which was 449.80±28.62 mm 2 (range, 338.3-604.4 mm 2) in males and 388.25±34.01 mm 2 (range, 296.3-498.4 mm 2) in females. The average vestibular width was 28.52±4.34 mm (range, 17.1-36.3 mm), 31.77±2.33 mm (range, 22.46-36.30 mm) in males and 24.55±2.55 mm (range, 17.1-26.1 mm) in females. The mean vestibular height was 21.05±2.29 mm (range, 17.5-32.0 mm), with 21.34±2.37 mm (range, 18.5-32.0 mm) of men and 20.69±1.60 mm (range, 17.5-25.6 mm) of women. The mean S 2 vestibular area was 230.19±35.57 mm 2 (range, 142.5-297.3 mm 2), which was 258.91±28.04 mm 2 (range, 218.3-297.3 mm 2) in males and 205.61±24.12 mm 2 (range, 142.5-258.6 mm 2) in females. The average vestibular width was 15.94±1.72 mm (range, 12.4-20.3 mm), 16.51±1.59 mm (range, 14.4-20.3 mm) in male and 15.25±1.63 mm (range, 12.4-18.1 mm) in female. The mean vestibular height was 14.30±1.20 mm (range, 12.9-17.8 mm), 15.49±1.46 mm (range, 13.6-17.8 mm) in males and 13.73±0.93 mm (range, 12.9-16.1 mm) in females. There were significant differences in vestibular width, height and area between S 1 and S 2 (vestibular width t=3.934, P< 0.001; vestibular height t=3.692, P< 0.001; vestibular area t=4.816, P< 0.001). There were significant differences in S 1 vestibular width, S 1 vestibular height, S 1 and S 2 vestibular area between male groups and female groups (S 1 vestibular width: t=2.969, P=0.003; S 1 vestibular height: t=0.316, P=0.049; S 1 vestibular area: t=1.975, P=0.049; S 2 vestibular area: t=2.023, P=0.044). While there was no significant difference in S 2 vestibular width and height between the two gender groups. There were significant differences in S 1 and S 2 vestibular width, height and area between male and female groups ( P < 0.001). There were no significant difference in parameters between the left and right values of the same vestibular site. Conclusion:The parameters of S 1 sacral vestibule are larger than that of S 2. It implies that S 1 was more feasible to insert iliosacral screws than S 2; lesser diameter iliosacral screws should be selected to insert into S 2. The female S 1 vestibule is smaller than the male, so the iliosacral screws placement has more stringent requirements on the selection of the insertion point and the direction of the screw. And the surgeon can utilize the intact contralateral sacral vestibule as the damaged side to proceed the iliosacral screw inserted simulation.

A chain mediating model of rumination and depression between non-suicidal self-injury and suicidal ideation in adolescents with depressive disorder / 中华行为医学与脑科学杂志

Objective:To explore the effects of non-suicidal self-injury on suicidal ideation in adolescents with depressive disorder, and the mediating role of rumination and depression between them.Methods:A sample of 397 depressive disorder adolescents were recruited to complete the adolescent non-suicidal self-injury behaviour questionnaire, ruminative responses scale (RRS), self-rating depression scale (SDS), and Beck scale for suicide ideation-Chinese version(BSI-CV). All data processing and analysis were performed using SPSS 23.0.The mediating effect was tested by correlation analysis and Bootstrap analysis.Results:The non-suicidal self-injury score was (29.192±11.281), the rumination score was (65.036±12.284), the depression score was (75.770±11.278), and the suicidal ideation score was (40.681±11.626). Non-suicidal self-injury was significantly and positively correlated with suicidal ideation( r=0.403, P<0.01), rumination and depression( r=0.332, 0.470, both P<0.01). Rumination was significantly and positively correlated with depression and suicidal ideation( r=0.549, 0.181, both P<0.05). Depression was significantly and positively correlated with suicidal ideation( r=0.313, P<0.01). The direct effect value of non-suicidal self-injury on suicidal ideation was 0.341(95% CI=0.238-0.444), the indirect effect of non-suicidal self-injury on suicidal ideation through two pathways, the separate mediating effect value of depression was 0.057(95% CI=0.077-0.114), and the chain mediating effect value of rumination and depression was 0.026(95% CI=0.004-0.057). Conclusion:Non-suicidal self-injury can directly affect suicidal ideation of depressive disorder adolescents and indirectly through rumination and depression.

Comparison of the characteristics of NK cells after two different methods of expansion and observation of the clinical efficacy in patients who relapsed post allogeneic hematopoietic stem cell transplantation / 中华血液学杂志

Objective: To explore the differences in the biological effects of different expansion systems on natural killer (NK) cells, as well as the safety and preliminary clinical efficacy in the treatment of patients with recurrence after allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: Peripheral blood cells from healthy donors were stimulated with either CD3 combined with CD52 or K562 feeder cells loaded with IL-21/4-1BB to induce NK cell expansion. Changes in the NK cell phenotype, cytokine secretion, and cytotoxicity before and after expansion were detected. We also evaluated the safety and clinical efficacy of two different expansion strategies for patients received NK infusion. Results: Compared with the CD3/CD52 monoclonal antibody amplification system, the feeder cell expansion group had a higher purity of NK cells and higher expression ratios of NK cell surface activation receptors such as DNAM-1 and NKp30, while inhibitory receptor CTLA-4 expression was low and NKG2D/CD25/CD69/ Trail/PD-1/TIM-3/TIGIT had no statistically significant differences between the groups. Further functional results showed that the expression level of KI67 in NK cells after expansion in the two groups increased significantly, especially in the feeder cell expansion group. Simultaneously, the perforin and granzyme B levels of NK cells in the feeder cell expansion group were significantly higher than in the CD3/CD52 expansion group. A retrospective analysis of eight patients who received monoclonal antibody-expanded NK cell reinfusion and nine patients with trophoblast cell-expanded NK cell reinfusion was done. The disease characteristics of the two groups were comparable, NK cell reinfusion was safe, and there were no obvious adverse reactions. Clinical prognostic results showed that in the CD3/CD52 monoclonal antibody amplification group, the MRD conversion rate was 50% (2/4) , and the feeder cell expansion group was 50% (3/6) . After 5 years of follow-up from allo-HSCT, three patients in the monoclonal antibody expansion group had long-term survival without leukemia, and the remaining five patients had died; two patients died in the feeder cell expansion group, and the other six patients had long-term survival. Six cases had GVHD before NK cell reinfusion, and GVHD did not aggravate or even relieved after NK cell reinfusion. Conclusions: Preliminary results show that the biological characteristics of NK cells with diverse expansion strategies are significantly different, which may affect the clinical prognosis of patients with recurrence or persistent minimal residual disease after HSCT. The two groups of patients treated with NK cells from different expansion strategies had no obvious adverse reactions after NK cell infusion, but efficacy still needs to be further confirmed.

Construction and mechanism of dry eye model in mice with ocular surface iron overload / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To establish a dry eye mouse model of iron overload by intraperitoneal injection of iron dextran and preliminarily explore its possible mechanism.METHODS: A total of 40 male C57BL/6 mice(taking the right eye as the experimental eye)were divided into 4 groups by random number table method: There were 10 mice in the control group, each time by intraperitoneal injection of 0.2mL of normal saline; Low-dose group, middle-dose group and high-dose iron group with 10 mice in each group were the model group. Each time, 0.2mL of iron dextran solution with concentrations of 12.5, 25, and 50 mg/mL was injected intraperitoneally. One injection 3d for a total of 28d. We observed the ocular surface inflammation index, corneal fluorescein staining, tear break-up time(BUT)and Schimer I test(SIt)on the 7, 14 and 28d after injection and evaluated the degree of dry eye and ocular surface inflammation. After 28d, the mice were sacrificed for cornea, conjunctiva and lacrimal glands tissue for HE staining, Prussian blue staining and tissue iron detection, to evaluate the inflammatory reaction and iron overload. The expression of inflammatory factors interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α)and matrix metallo proteinase-9(MMP-9)were detected by enzyme-linked immunosorbent assay(ELISA).RESULTS: Compared with the control group, the mice in the model group showed a series of dry eye symptoms, the inflammation index of ocular surface in mice were increased, the score of corneal fluorescein staining increased, the BUT shortened and the amount of tear secretion decreased(all P&#x003C;0.05). The cornea, conjunctiva and lacrimal gland tissues of the mice were damaged to varying degrees, the iron deposition on the eye surface of the model group was more serious than that of the control group, and the iron content of the tissue was significantly increased than the control group(all P&#x003C;0.01). The contents of inflammatory factors(IL-1β, TNF-α, MMP-9)in the cornea, conjunctiva and lacrimal gland tissue of the mice in the model group were significantly higher than those of the control group(all P&#x003C;0.01). With the increase of injection time and concentration of iron dextran, the degree of dry eye and ocular surface inflammation in mice gradually increased. CONCLUSION: The mouse iron overload dry eye model was successfully established by intraperitoneal injection of iron dextran, the mechanism may be related to the ocular surface inflammation aggravated by iron overload.

Efferocytosis impacts ocular surface inflammation in high-iron environment by regulating macrophage polarization / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To explore whether efferocytosis impacts ocular surface inflammation in high-iron environment by regulating macrophage polarization. METHODS: A total of 50 healthy C57BL/6 male mice aged 6-8wk were randomly divided into normal control group, iron group, inhibitor group, enhancer group and solvent control group, with 10 mice in each group. The normal control group was injected intraperitoneally with 0.2mL of normal saline, and the other groups were injected intraperitoneally with 50mg/mL iron dextran of 0.2mL, once every 3d. From the 14d, the inhibitor group, the enhancer group and the solvent control group were injected intraperitoneally with the same volume(0.2mL)50mg/kg XMD8-92, 10mg/kg simvastatin and 50% DMSO solvent once a day, respectively. The anterior segment of the eyes was observed under slit lamp microscope on the 7, 14, 28d after intraperitoneal injection, and the ocular surface inflammation index and corneal fluorescein staining score were evaluated. The cornea, conjunctiva and lacrimal gland tissues were taken at 28d for the HE staining and immunofluorescence staining, and RT-PCR were used to detect the expression of macrophage polarization related indexes(CD86, CD206, iNOS, Arg-1); Western blot were used to detect the expression of efferocytosis related signal factors(Gas6, MerTK); ELISA was used to detect the expression of inflammatory factors(IL-1β, TNF-α, MMP-9).RESULTS: After injection for 28d, compared with the normal control group, the ocular surface inflammatory index and corneal fluorescein staining score were increased in the iron group and the solvent control group. HE staining showed incomplete corneal epithelium, reduced conjunctival goblet cells, unclear lacrimal gland structure and relatively disordered arrangement of cells. In all tissues, the expressions of polarization related indexes of M1 macrophages such as CD86 and iNOS were up-regulated, while those of M2 macrophages such as CD206 and Arg-1 were down-regulated, and the expressions of inflammatory factors such as IL-1β, TNF-α and MMP-9 were up-regulated(all P&#x003C;0.05). Compared with the iron group and the solvent control group, the ocular surface inflammation index and corneal fluorescein staining score of the inhibitor group were further increased. HE staining showed obvious exfoliation of corneal epithelium, further decrease or even disappearance of conjunctival goblet cells, disorder of lacrimal gland structure and irregular arrangement of cells. In all tissues, the expression of signal factors related to efferocytosis such as Gas6 and MerTK was down-regulated(all P&#x003C;0.05), the expression of polarization related indexes of M1 macrophages such as CD86 and iNOS and the expression of inflammatory factors such as IL-1β, TNF-α and MMP-9 were further up-regulated(all P&#x003C;0.05). But the ocular surface inflammation index and corneal fluorescein staining score decreased in the enhancer group. HE staining showed the integrity of corneal epithelial, the increase of conjunctival goblet cells and the improvement of lacrimal gland structure and morphology. In all tissues, the expression of signal factors related to efferocytosis such as Gas6 and MerTK was up-regulated(all P&#x003C;0.05), and the expression of polarization related indexes of M2 macrophages such as CD206 and Arg-1 was up-regulated, while the expression of inflammatory factors such as IL-1β, TNF-α and MMP-9 was down-regulated(all P&#x003C;0.05). CONCLUSION: High-iron environment induces macrophages polarize to M1, which aggravates ocular surface inflammation and tissue damage. Efferocytosis by regulating the polarization of macrophages impact the occurrence of ocular surface inflammation in high-iron environment.

A comprehensive profile of TCF1+ progenitor and TCF1- terminally exhausted PD-1+CD8+ T cells in head and neck squamous cell carcinoma: implications for prognosis and immunotherapy / 国际口腔科学杂志·英文版

The heterogeneity of exhausted T cells (Tex) is a critical determinant of immune checkpoint blockade therapy efficacy. However, few studies have explored exhausted T cell subpopulations in human cancers. In the present study, we examined samples from two cohorts of 175 patients with head and neck squamous cell cancer (HNSCC) by multiplex immunohistochemistry (mIHC) to investigate two subsets of Tex, CD8+PD1+TCF1+ progenitor exhausted T cells (TCF1+Texprog) and CD8+PD1+TCF1- terminally exhausted T cells (TCF1-Texterm). Moreover, fresh tumor samples from 34 patients with HNSCC were examined by flow cytometry and immunohistochemistry to further investigate their properties and cytotoxic capabilities and their correlation with regulatory T cells (Tregs) in the tumor immune microenvironment (TIME). mIHC and flow cytometry analysis showed that TCF1-Texterm represented a greater proportion of CD8+PD1+Tex than TCF1+Texprog in most patients. TCF1+Texprog produced abundant TNFα, while TCF1-Texterm expressed higher levels of CD103, TIM-3, CTLA-4, and TIGIT. TCF1-Texterm exhibited a polyfunctional TNFα+GZMB+IFNγ+ phenotype; and were associated with better overall survival and recurrence-free survival. The results also indicated that larger proportions of TCF1-Texterm were accompanied by an increase in the proportion of Tregs. Therefore, it was concluded that TCF1-Texterm was the major CD8+PD1+Tex subset in the HNSCC TIME and that these cells favor patient survival. A high proportion of TCF1-Texterm was associated with greater Treg abundance.

Efficient gene editing in a medaka (Oryzias latipes) cell line and embryos by SpCas9/tRNA-gRNA / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Generation of mutants with clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) is commonly carried out in fish species by co-injecting a mixture of Cas9 messenger RNA (mRNA) or protein and transcribed guide RNA (gRNA). However, the appropriate expression system to produce functional gRNAs in fish embryos and cells is rarely present. In this study, we employed a poly-transfer RNA (tRNA)-gRNA (PTG) system driven by cytomegalovirus (CMV) promoter to target the medaka (Oryzias latipes) endogenous gene tyrosinase(tyr) or paired box 6.1 (pax6.1) and illustrated its function in a medaka cell line and embryos. The PTG system was combined with the CRISPR/Cas9 system under high levels of promoter to successfully induce gene editing in medaka. This is a valuable step forward in potential application of the CRISPR/Cas9 system in medaka and other teleosts.

Recent advances in isolation, identification, and culture of mammalian spermatogonial stem cells / 亚洲男科学杂志(英文版)

Continuous spermatogenesis depends on the self-renewal and differentiation of spermatogonial stem cells (SSCs). SSCs, the only male reproductive stem cells that transmit genetic material to subsequent generations, possess an inherent self-renewal ability, which allows the maintenance of a steady stem cell pool. SSCs eventually differentiate to produce sperm. However, in an in vitro culture system, SSCs can be induced to differentiate into various types of germ cells. Rodent SSCs are well defined, and a culture system has been successfully established for them. In contrast, available information on the biomolecular markers and a culture system for livestock SSCs is limited. This review summarizes the existing knowledge and research progress regarding mammalian SSCs to determine the mammalian spermatogenic process, the biology and niche of SSCs, the isolation and culture systems of SSCs, and the biomolecular markers and identification of SSCs. This information can be used for the effective utilization of SSCs in reproductive technologies for large livestock animals, enhancement of human male fertility, reproductive medicine, and protection of endangered species.

The identification of bZIP gene family in Cannabis sativa L. and its preliminary research of the function in regulation of lipid metabolism / 药学学报

The bZIP (basic leucine zipper) gene family is one of the largest transcription factor families in eukaryotes, and its members play important roles in stress response, secondary metabolism, plant growth, seed development and other aspects. To investigate the biological functions of the bZIP (CsbZIP) gene in Cannabis sativa L., we systematically investigated the CsbZIP gene family using bioinformatics methods based on the whole-genome and transcriptome data. The results showed that 55 CsbZIP gene family members (CsbZIP1-CsbZIP55) were identified and distributed on 10 chromosomes, belonging to 12 subfamilies. The gene structure and protein motif distribution of the same subfamily members were similar. Segment repeats were the main reasons for the expansion of CsbZIP gene family. Cis-elements analysis showed that the promoter regions of 73 lipid synthesis genes contained G-box or A-box element. qRT-PCR showed that the relative expression levels of 7 CsbZIP genes and 7 lipid synthesis genes were relatively high in hemp seed. 7 CsbZIP genes had a significant positive correlation with 7 lipid synthesis genes. This study revealed the structural features, evolutionary patterns and expression patterns of CsbZIP, providing important clues for further study on the regulation of CsbZIP on oil metabolism of hemp seed.