Qualitative and Quantitative Analysis of Chemical Constituents in Liu Junzitang by UPLC-Q-TOF-MS/MS and UPLC / 中国实验方剂学杂志

ObjectiveTo establish a qualitative and quantitative analysis method for chemical constituents in Liu Junzitang（LJZT）， and to clarify its material basis. MethodThe chemical constituents in LJZT were analyzed by ultra performance liquid chromatography-quadrupole-time-of-flight mass spectrometry（UPLC-Q-TOF-MS/MS）， and the resulting compounds were identified by using databases， such as MassBank， PubChem， ChemSpider， Traditional Chinese Medicine Systems Pharmacology Database and Analytical Platform（TCMSP）， and by combining with relevant literature. UPLC was used to establish a quantitative method for analysis of 9 compounds in LJZT， including liquiritin， hesperidin， lobetyolin， liquiritigenin， glycyrrhizic acid， nobiletin， tangeretin， atractylenolide Ⅱ and Ⅰ. ResultBy combining the relevant literature， database and MS information， a total of 79 compounds were identified from LJZT， including 31 flavonoids， 15 terpenoids， 14 nitrogen-containing compounds， 6 phenylpropanoids， 6 organic acids and 7 other compounds. The established quantitative analytical method for the nine representative components showed good linearity within their respective linear ranges， and the precision， stability， reproducibility and recovery were in accordance with the requirements. The quantitative results showed that the contents of liquiritin， hesperidin， lobetyolin， liquiritigenin， glycyrrhizic acid， nobiletin， tangeretin， atractylenolide Ⅱ and Ⅰ in LJZT were 0.376 5， 2.602 1， 0.082 6， 0.128 1， 1.778 6， 0.015 7， 0.006 7， 0.030 4， 0.003 2 mg·g-1， respectively. ConclusionThe established method can quickly， sensitively and accurately analyze the chemical constituents in LJZT， clarify that the material basis of LJZT is mainly flavonoids， terpenoids and nitrogen-containing compounds， and simultaneously determine the contents of the 9 components， which can lay a foundation for the research on quality control， mechanism and clinical application of LJZT.

Quantitative analysis of macular capillaries in diabetic patients using optical coherence tomography angiography / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To quantify early changes of macular capillary parameters in type 2 diabetic patients using optical coherence tomography angiography(OCTA).METHODS: Retrospective case study. A total of 49 healthy subjects, 52 diabetic patients without retinopathy(noDR)patients, and 43 mild nonproliferative diabetic retinopathy(mNPDR)patients were recruited. Capillary perfusion density, vessel length density(VLD), and average vessel diameter(AVD)were calculated from macular OCTA images(3 mm×3 mm)of the superficial capillary plexus after segmenting large vessels and the deep capillary plexus. Parameters were compared among control subjects, noDR, and mNPDR patients. The area under the receiver operating characteristic curve estimated the abilities of these parameters to detect early changes of retinal microvascular networks.RESULTS: Significant differences were found in the VLD and AVD among the three groups(P<0.001). Compared with the control group, the noDR group had significantly higher AVD(P<0.05). VLD of both layers in patients of mNPDR group was significant decreased compared with that of noDR group(all P<0.01). Deep AVD had a higher area under the curve(AUC)of 0.796 than other parameters to discriminate the noDR group from the healthy group. Deep AVD had the highest AUC of 0.920, followed by that of the deep VLD(AUC=0.899)to discriminate the mNPDR group from the healthy group.CONCLUSIONS: NoDR patients had wider AVD than healthy individuals and longer VLD than mNPDR patients in both layers. When compared with healthy individuals, deep AVD had a stronger ability than other parameters to detect early retinal capillary impairments in noDR patients.

Acute cerebral infarction following extracorporeal membrane oxygenation treatment in patients with cardiogenic shock: 2 cases report and review of the literature / 中华危重病急救医学

OBJECTIVE@#To explore the diagnosis and treatment of acute cerebral infarction following extracorporeal membrane oxygenation (ECMO) therapy in patients with cardiogenic shock to review the literature.@*METHODS@#The clinical data of two patients with cardiogenic shock treated with veno-arterial ECMO (VA-ECMO) complicated with acute cerebral infarction admitted to department of intensive care unit (ICU) of Affiliated Hospital of Guizhou Medical University were retrospectively analyzed and the treatment experience was shared.@*RESULTS@#Case 1 was a 46-year-old male patient who was admitted to the hospital on September 16, 2021, due to "repeated chest tightness, shortness of breath, syncope for 2+ years, and worsened for 15 days. Coronary artery angiography showed 3-vessel coronary artery disease lesions. On October 15, 2021, coronary artery bypass grafting (CABG), pericardial fenestration and drainage, thoracic closed drainage, femoral bypass, thoracotomy exploration, and sternal internal fixation were performed under support of extracorporeal circulation. After surgery, the heart rate was 180-200 bpm, the blood pressure could not be maintained, and the improvement was not obvious after active drug treatment. The right femoral artery and femoral vein were intubated, VA-ECMO support treatment was performed, and the patient was transferred to the ICU. Intra-aortic balloon pump (IABP) was treated on the day of transfer because the circulation could not be maintained. Due to acute cerebral infarction in the left hemisphere and right parieto-occipital lobe, subfalcine herniation, tentorial herniation, the patient ultimately died after withdrawing from ECMO. Case 2 was a 43-year-old male patient who was admitted to the hospital on June 29, 2021, with "fever for 8 days and vomiting for 4 days". Bedside ultrasound showed cardiac enlargement and diffuse wall motion reduction in the left and right ventricles. On June 30, 2021, the patient underwent catheterization through the right femoral artery and femoral vein, VA-ECMO support, and was transferred to ICU for treatment. Acute cerebral infarction on both sides of the cerebellum occurred, and after treatment, the patient was discharged with mild impairment of daily living ability.@*CONCLUSIONS@#Strengthen monitoring of anticoagulation; regular neurological examination of patients undergoing ECMO therapy; ECMO under light sedation or awake can be performed if the condition permitsif the condition permits, perform light sedation or awake ECMO, which helpful for the early detection of nervous system injury.

Mangiferin alleviates renal inflammatory injury in spontaneously hypertensive rats by inhibiting MCP-1/CCR2 signaling pathway / 中草药·英文版

OBJECTIVE@#Hypertension is a low-grade inflammation state of the disease and was easily complicated by kidneys' inflammatory response. Mangiferin (MGF), a pharmacologically active compound in various plants including Mangifera indica, has a strong anti-inflammatory activity. However, the effects of MGF on renal inflammatory injury in spontaneously hypertensive rats (SHRs) remain unclear. The purpose of this study was to investigate the protective effects and mechanisms of MGF on renal inflammatory injury in SHRs.@*METHODS@#MGF was used in SHRs at the doses of 10, 20, 40 mg/kg/d for 8 weeks consecutively. The blood and urine were collected for assessment of renal function. Renal tissues were collected for histological, immunohistochemistry, ELISA, Western blot and real time reverse transcription PCR (RT-PCR) analysis.@*RESULTS@#The results showed that the levels of interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and recombinant chemokine C-C-Motif receptor 2 (CCR2) were increased in SHRs, meanwhile, the level of IL-10 was decreased in SHR. Treatment of MGF inhibited the expression of IL-6, TNF-α, MCP-1 and CCR2, and promoted the expression of IL-10. Furthermore, the content of blood urea nitrogen (BUN) and serum uric acid (SUA) was significantly increased in the model group, and treatment of MGF had no obvious effects on these parameters at all dose levels.@*CONCLUSION@#Our study proved that the kidneys of SHRs had significant inflammatory injury, and MGF had the protective effects on renal inflammatory injury in SHRs; The protective mechanism may be mediated partly by the MCP-1/CCR2 signaling pathway. Thus, it is a potential new drug for the treatment of hypertension.

Abscisic acid-mediated cytosolic Ca2+ modulates triterpenoid accumulation of Ganoderma lucidum / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Ganoderma lucidum is a mushroom widely used for its edible and medicinal properties. Primary bioactive constituents of G. lucidum are ganoderic triterpenoids (GTs), which exhibit important pharmacological activity. Abscisic acid (ABA), a plant hormone, is associated with plant growth, development, and stress responses. ABA can also affect the growth, metabolism, and physiological activities of different fungi and participates in the regulation of the tetracyclic triterpenes of some plants. Our findings indicated that ABA treatment promoted GT accumulation by regulating the gene expression levels (squalene synthase (sqs), 3-hydroxy-3-methylglutaryl-CoA reductase (hmgr), and lanosterol synthase (ls)), and also activated cytosolic Ca2+ channels. Furthermore, under ABA mediation, exogenous Ca2+ donors and inhibitors directly affected the cytosolic Ca2+ concentration and related gene expression in Ca2+ signaling. Our study also revealed that ABA-mediated cytosolic Ca2+ played a crucial regulatory role in GT biosynthesis, accompanied by antioxidant defense modulation with increasing superoxide dismutase (SOD) activity and ascorbate peroxidase (APX) activity, and the resistance ability of O2•- and glutathione (GSH) contents.

Lidong needling therapy combined with functional exercise in treatment of upper limb lymphedema after breast cancer surgery: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the clinical efficacy of lidong needling therapy (acupuncture technique combined with therapeutic movement of the body) on upper limb lymphedema after breast cancer surgery in combination with functional exercise.@*METHODS@#A total of 73 patients with postoperative lymphedema of breast cancer in the upper limbs were randomized into an observation group (36 cases) and a control group (37 cases). The routine nursing care and functional exercise were given in the control group, twice a day, for about 10-15 min each time, lasting 8 weeks. On the basis of the treatment as the control group, lidong needling therapy was applied to the acupionts on the affected upper limb, i.e. Jianyu (LI 15), Waiguan (TE 5), Hegu (LI 4) and ashi points (the most obvious swelling sites), as well as to bilateral Yinlingquan (SP 9) and Zusanli (ST 36), etc. The needles were retained for 30 min. While the needles retained, the patients were asked to move the affected shoulder to 90° by the sagittal anteflexion and keep it elevated. Simultaneously, the hand on the affected side was clenched and opened slowly and coordinately. Lidong needling therapy was delivered once every two days, three times weekly for 8 weeks. Before and after treatment, the difference of the circumference between the affected and healthy limbs, the score of visual analogue scale (VAS) for swelling and the score of disability of arm, shoulder and hand (DASH) were compared in the patients of the two groups. The clinical efficacy was evaluated.@*RESULTS@#After 2, 4, 6 and 8 weeks of treatment, except for the circumference of the area 10 cm below the cubitel crease in the control group, the differences in the circumferences of the rest parts between the affected and healthy limbs were reduced in comparison with those before treatment in the two groups (P<0.01, P<0.05). After 6 weeks of treatment, in the observation group, for the circumference at the level of hand between the thumb and the index finger and that of the wrist, the differences between the affected and healthy limbs was smaller compared with those in the control group (P<0.05). After 8 weeks of treatment, except for the areas 5 cm below and above the cubitel crease, the differences of circumferences between the affected and healthy limbs in the observation group were smaller than those in the control group in the rest parts (P<0.01, P<0.05). After 8 weeks of treatment, the swelling VAS scores were reduced when compared with those before treatment in the two groups (P<0.05), and the score in the observation group was lower than that in the control group (P<0.01). After 4 and 8 weeks of treatment, DASH scores were reduced in comparison with those before treatment in the two groups (P<0.01). The total effective rate of the observation group was 83.3% (30/36), which was higher than that of the control group (35.1%, 13/37, P<0.01).@*CONCLUSION@#Lidong needling therapy combined with the functional exercise obtains the satisfactory clinical effect on the upper limb lymphedema after breast cancer surgery. This treatment effectively relieves swelling and improves the upper limb function.

Mediating effect of emotion regulatory self-efficacy in the relationship between musculoskeletal disorders and turnover intention among operating room nurses / 中国职业医学

Objective To explore the mediating effect of emotion regulatory self-efficacy (ERSE) in the relationship between musculoskeletal disorders and turnover intention in operating room nurses. Methods A total of 372 operating room nurses from five hospitals in Shenyang City were selected as the research subjects using covenient sampling method. The Musculoskeletal Disorders Questionnaire, Turnover Intention Scale, and Emotional Self-Regulation Efficacy Scale were used to study the prevalence of work-related musculoskeletal disorders (WMSDs), turnover intention, and ERSE among the study subjects. The Bootstrap method was used for mediation effect analysis of ERSE. Results The prevalence of WMSDs among operating room nurses was 69.9%. The scores for turnover intention and ERSE among operating room nurses were (13.6±6.3) and (34.7±16.2), respectively. ERSE played a partial mediating role in the relationship between WMSDs and turnover intention among operating room nurses, with an effect value of 0.04 and the 95% confidence interval of 0.01 to 0.08, accounting for 8.1% of the total effect. Conclusion WMSDs and ERSE directly influence turnover intention among operating room nurses. WMSDs can indirectly increase turnover intention by reducing ERSE among operating room nurses.

Intravenous Tenecteplase for Acute Ischemic Stroke Within 4.5–24 Hours of Onset (ROSE-TNK): A Phase 2, Randomized, Multicenter Study / 대한뇌졸중학회지

Background@#and Purpose Intravenous tenecteplase (TNK) efficacy has not been well demonstrated in acute ischemic stroke (AIS) beyond 4.5 hours after onset. This study aimed to determine the effect of intravenous TNK for AIS within 4.5 to 24 hours of onset. @*Methods@#In this pilot trial, eligible AIS patients with diffusion-weighted imaging (DWI)-fluid attenuated inversion recovery (FLAIR) mismatch were randomly allocated to intravenous TNK (0.25 mg/kg) or standard care within 4.5–24 hours of onset. The primary endpoint was excellent functional outcome at 90 days (modified Rankin Scale [mRS] score of 0–1). The primary safety endpoint was symptomatic intracranial hemorrhage (sICH). @*Results@#Of the randomly assigned 80 patients, the primary endpoint occurred in 52.5% (21/40) of TNK group and 50.0% (20/40) of control group, with no significant difference (unadjusted odds ratio, 1.11; 95% confidence interval 0.46–2.66; P=0.82). More early neurological improvement occurred in TNK group than in control group (11 vs. 3, P=0.03), but no significant differences were found in other secondary endpoints, such as mRS 0–2 at 90 days, shift analysis of mRS at 90 days, and change in National Institutes of Health Stroke Scale score at 24 hours and 7 days. There were no cases of sICH in this trial; however, asymptomatic intracranial hemorrhage occurred in 3 of the 40 patients (7.5%) in the TNK group. @*Conclusion@#This phase 2, randomized, multicenter study suggests that intravenous TNK within 4.5–24 hours of onset may be safe and feasible in AIS patients with a DWI-FLAIR mismatch.

Research progress in separation surgery combined with stereotactic radiotherapy of spinal metastases / 中国骨伤

With the continuous improvement of cancer treatment, the survival of patients with spinal metastases has been significantly prolonged. Currently, the treatment of spinal metastases presents a trend of multi-mode. Clinical surgical methods include vertebral tumor resecting spinal canal decompression and internal fixation surgery, separation surgery, minimally invasive surgery and percutaneous ablation technology, etc. Radiotherapy techniques include traditional external radiation therapy, stereotactic radiotherapy and brachytherapy, etc. The risk of vertebral tumor resecting spinal canal decompression and internal fixation surgery, and the incidence of intraoperative and postoperative complications is high. The extension of postoperative recovery period may lead to delay of follow-up radiotherapy and other medical treatment, which has a serious impact on patients' survival and treatment confidence. However, the precision of traditional external radiation therapy is not high, and the limitation of tolerance of spinal cord makes it difficult to achieve the goal of controlling insensitive tumor. With the development of radiotherapy and surgical technology, stereotactic radiotherapy with higher accuracy and separation surgery with smaller surgical strike have become the focus of many clinical experts at present. This article reviews the progress of Hybrid treatment of separation surgery combined with stereotactic radiotherapy.

Targeted muscle reinnervation: a surgical technique of human-machine interface for intelligent prosthesis / 中国修复重建外科杂志

OBJECTIVE@#To review targeted muscle reinnervation (TMR) surgery for the construction of intelligent prosthetic human-machine interface, thus providing a new clinical intervention paradigm for the functional reconstruction of residual limbs in amputees.@*METHODS@#Extensively consulted relevant literature domestically and abroad and systematically expounded the surgical requirements of intelligent prosthetics, TMR operation plan, target population, prognosis, as well as the development and future of TMR.@*RESULTS@#TMR facilitates intuitive control of intelligent prostheses in amputees by reconstructing the "brain-spinal cord-peripheral nerve-skeletal muscle" neurotransmission pathway and increasing the surface electromyographic signals required for pattern recognition. TMR surgery for different purposes is suitable for different target populations.@*CONCLUSION@#TMR surgery has been certified abroad as a transformative technology for improving prosthetic manipulation, and is expected to become a new clinical paradigm for 2 million amputees in China.

Study on the relationship between serum cytokines levels after chimeric antigen receptor (CAR)-T cell immunotherapy and the prognosis of bridged allogeneic hematopoietic stem cell transplantation in acute B lymphoblastic leukemia patients / 中华检验医学杂志

Objective:To investigate the relationship between the levels of serum cytokines and chemokines and the prognosis of patients with acute B-ALL after receiving chimeric antigen receptor (CAR)-T cell immunotherapy and acute graft-versus-host disease (aGVHD) in patients after bridging allogeneic hematopoietic stem cell transplantation (allo-HSCT).Methods:According to the case-control principle, Forty-two patients with B-ALL who received CD19-CAR-T cell immunotherapy bridged to allo-HSCT at Heibei Yanda Ludaopei Hospital from September 18, 2019 to May 9, 2022 were enrolled. Mann-Whitney U test was used to compare the changes of aGVHD-related cytokines and chemokine levels between CAR-T cell immunotherapy and bridging transplantation in different patients at the same time. Their plasma levels of cytokines and chemokines related to aGVHD were monitored at the day before CAR-T therapy and after CAR-T treatment at day 4, 7,14,21,28. The receiver operating characteristic curve was drawn to evaluate the predictive value of cytokines and chemokines in predicting the occurrence and the death of aGVHD patients. Kaplan-Meier method and Log-rank tests were used for Overall survival (OS) analysis. Results:Twenty-four of total 42 patients had aGVHD, of which 11 patients died and 31 patients survived. There was no significant difference in cytokines and chemokines between the aGVHD group and the non-aGVHD group on the day before CAR-T cell treatment. According to statistical analysis, the serum Elafin levels of aGVHD group was higher than that of non-aGVHD group at the 21st day [4 482 (2 811, 6 061) ng/L vs 2 466 (1 948, 3 375) ng/L, Z=3.145, P=0.001] and the 28st day [4 391 (2 808, 5594) ng/L vs 2 463 (1 658, 2 830) ng/L, Z=2.038, P=0.048] separately. At the 14th day, serum cytokines and chemokines levels between the two group were as follows,MIP-1 α [21.02 (12.36, 30.35) ng/L vs 5.56 (3.64, 10.79) ng/L], sCD25 [422.47 (257.99, 1 233.78) IU/ml vs 216.11 (133.75,457.39) IU/ml], Elafin [4 101 (2 393, 5 006) ng/L vs 2 155 (1 781, 3 033) ng/L], IL-6 [119.08 (23.97, 183.43) ng/L vs 8.39 (2.91, 17.42) ng/L] and IL-8 [13.56 (12.50, 24.52) ng/L vs 2.83 (1.73,6.87) ng/L] were at higher levels ( Z=2.653, P=0.007; Z=2.176, P=0. 030; Z=2.058, P=0.041; Z=3.329, P<0.001; Z=3.162, P=0.001). The KM survival curve showed that the cumulative survival rates of patients with higher serum levels of MIP-1α, sCD25, Elafin, IL-6 and IL-8 were lower than those with low levels at day 14, and the difference was statistically significant (χ 2=12.353, 4.890, 6.551, 10.563, 20.755, P<0.05). Conclusion:The outcomes of patients treated with CAR-T cell therapy bridged to allo-HSCT was correlated with serum MIP-1α, sCD25, Elafin, IL-6 and IL-8 levels after receiving CAR-T therapy. High concentrations of MIP-1α, sCD25, Elafin, IL-6 and IL-8 suggest poor prognosis and can be used as biomarkers to suggest appropriate clinical selection of therapy.

Influencing factors and effectiveness of community follow-up in patients with cardiac implantable electronic device / 中华全科医师杂志

Objective:To explore the influencing factors and effectiveness of community follow-up in patients with cardiac implantable electronic device (CIED) implantation.Method:A total of 132 patients who received CIED implantation in the Department of Cardiology of Tongren Hospital, Shanghai Jiao Tong University School of Medicine from February 2021 to February 2022 were enrolled in this prospective cohort study. Among them 33 patients were followed up in community health service centers associated with Tongren Hospital (community follow-up group) and 99 matched patients were followed up in the CIED outpatient clinic of the hospital (outpatient follow-up group) with a ratio of 1∶3. The clinical data of the selected patients were collected through a questionnaire survey; the follow-up data were extracted through the CarelinkExpress electronic follow-up platform and the CIED outpatient information system of Tongren Hospital. Adjustment of the treatment protocol or CIED parameters at follow-up, and the referral from the community health service centers were defined as visit with-an-action (VWA). The endpoint of follow-up was the occurrence of major adverse events. The multivariate logistic regression model was used to analyze the factors influencing patient selection for community follow-up.Results:The univariate analysis showed that the frequency of visits to community health service centers and the service contracting rate in community follow-up group were higher than those of outpatient follow-up group ( P<0.05). The multivariate logistic regression analysis showed that the contracted community physician service was an independent influencing factor of patient choosing community follow-up ( OR=2.143, 95% CI: 1.103-4.166, P=0.025). A total of 469 visits of followed up occurred in 132 patients, including 45 community visits and 424 outpatient visits. VWA accounted for 22.2% (10/45) in the community follow-up group, and 17.2% (73/424) in the outpatient follow-up group ( P>0.05). There was no significant difference in the safety and effectiveness indicators (VWA, major adverse events, and unplanned follow-up) between the two groups ( P>0.05). More patients in the community follow-up group walked to the hospital than the outpatient follow-up group ( P<0.05);and the main transportation for the later was by bus or taxi(42(42.4%)or 41(41.4%)). The average waiting time in the community follow-up group was significantly shorter than that in outpatient follow-up group ( P<0.05). The total time required for a single follow-up in the community follow-up group was 50.0 (45.0, 59.5) minutes, which was significantly shorter than that in the routine outpatient follow-up group (107.0 (90.0, 135.0) minutes, P<0.05). Conclusions:The contracting with community physicians is an independent influencing factor for CIED implanted patients to choose community follow-up. The safety and effectiveness of community follow-up are comparable to routine outpatient follow-up, and community follow-up is more convenient.

Regulation of palmitic acid and lipopolysaccharide-induced macrophage polarization by adipokine WNT1-inducible signaling pathway protein 2 / 中华老年医学杂志

Objective:To investigate the regulatory effect of WNT1-inducible signaling pathway protein 2(WISP2)on macrophage polarization in palmitic acid(PA)and lipopolysaccharide(LPS)-induced inflammation.Methods:The macrophage cell line RAW264.7 was treated with different concentrations of WISP2 protein, and cell viability was determined by means of luminescence assay using Cell-Titer Glo to determine the concentration of WISP2.The cells were divided into control group, palmitic acid group, palmitic acid combined with different concentrations of WISP2 group(10 μg/L and 100 μg/L)and lipopolysaccharide group, lipopolysaccharide combined with different concentrations of WISP2 group(10 μg/L and 100 μg/L). mRNA expression of M1 and M2 macrophages phenotype of each group were detected by real-time quantitative polymerase chain reaction.The protein expression of important inflammatory factors, TNF-α and IL-6, were evaluated by ELISA.Results:Compared with the control group, both 10 μg/L and 100 μg/L WISP2 groups had no effect on the activity of RAW264.7 cells, but significantly up-regulated the expression of various inflammatory factors, including Tnfα(1.877±0.039, 2.202±0.034, F=309.7, P<0.001), Il6(1.418±0.056, 1.506±0.059, F=81.39, P<0.001), Mcp1(1.620±0.014, 1.982±0.125, F=71.45, P<0.001), Ccl3(1.892±0.118, 1.942±0.132, F=32.93, P<0.001), and iNos(1.691±0.201, 1.548±0.090, F=13.60, P<0.05). mRNA in macrophages, and significantly down-regulated the expression of anti-inflammatory factors, including Tgfβ(1.376±0.025, 2.152±0.107, F=1.846, P<0.05), CD206(2.123±0.031, 3.139±1.663, F=8.037, P<0.05), Il4(2.098±0.464, 2.494±0.141, F=48.68, P<0.01), and Il10(1.303±0.216, 1.574±0.274, F=5.774, P<0.05)mRNA, causing M1 type macrophage polarization.Compared with the control group, 100 μmol/L palmitic acid could mildly but significantly increase the expression of inflammatory factors such as TNF-α and IL-6 at the transcriptional and protein levels.Compared with palmitic acid stimulation alone, the combination of palmitic acid and WISP2 further promoted the protein expression of macrophage inflammatory factors TNF-α[(589.4±17.0)ng/L, (692.6±83.4)ng/L, F=56.38, P<0.05], IL-6[(15.13±1.14)ng/L, (13.33±1.22)ng/L, F=23.32, P<0.001]and the mRNA expression of chemokines Mcp1(160±9.796, 140±18.91, F=141.1, P<0.0001)and C cl3(17.76±1.92, 14.41±1.27, F=125.2, P<0.0001). Compared with the control group, 100 μg/L lipopolysaccharide strongly stimulated the expression of inflammatory factors such as TNF-α[(3444±423)ng/L, F=71.20, P<0.0001]and IL-6[(497.0±41.2)ng/L, F=63.50, P<0.0001]in macrophages at the protein level.Compared with lipopolysaccharide stimulation alone, the combination of lipopolysaccharide and WISP2 further significantly up-regulated the mRNA expression of chemokines Mcp1(106.8±8.7, 118.7±4.6, F=251.5, P<0.0001)and Ccl3(35.3±12.5, 116.4±4.5, F=160.1, P<0.0001). Conclusions:The adipokine WISP2 can promote M1 macrophage polarization in palmitic acid and lipopolysaccharide-induced inflammation, and it had distinct regulation in macrophage polarization under different inflammatory response conditions.

Effects of adriamycin resistance cell-derived exosomes on the proliferation and migration of osteosarcoma cells through drug resistance transmission / 中华骨科杂志

Objective:To explore the relationship and underlying mechanism between exosomes derived from doxorubicin-resistant osteosarcoma cells and MDR1 and miRNAs. Methods:MG63 and U2OS cell lines were selected to construct doxorubicin-resistant strains, and the 50% inhibitory concentration (half maximal inhibitory concentration, IC 50) of drug-resistant and sensitive strains was detected by MTT, and fluorescence staining was performed at intervals of 15 min between 15 and 120 min to detect the change of fluorescence intensity. RT-PCR and Western Blot were used to detect the expression levels of MDR1 P-gp to verify the drug resistance of osteosarcoma cells. Exosomes were identified by particle size analysis and Western Bolt detection. The endocytosis of PKH26-labeled exosomes from doxorubicin-resistant cells was observed, and the proliferation level and migration of exosomes from doxorubicin-resistant cells co-cultured with osteosarcoma cells were detected by MTT assay and cell scratch assay. The differential expression levels of miRNAs in osteosarcoma-sensitive and drug-resistant cells were verified by sequencing and bioinformatics analysis and RT-PCR assay. Tumor growth, serum exosome identification and mRNA expression level of miR-21-5p in tumor-bearing nude mice between normal osteosarcoma cell group and drug-resistant group, drug-resistant+normal exosome group, drug-resistant+drug-resistant+drug-resistant exosome group were observed. MDR1 expression level in tumor tissue was detected by RT-PCR, Western Blot and immunohistochemistry. Results:The IC 50 of two adriamycin resistant strains were 2.21 vs. 11.81 μg/ml and 0.93 vs. 11.81 μg/ml, respectively, and the fluorescence intensity decreased faster than that of normal strains. The relative mRNA expression levels of MDR1 in two cell lines were normal 1.12±0.16, 1.02±0.11 and drug-resistant 2.15±0.10, 2.127±0.12, respectively. The relative protein expression of P-gp was normal 0.92±0.11, 0.73±0.10 and drug-resistant 0.46±0.03, 0.30±0.04, the differences were statistically significant ( P<0.05). Drug-resistant exosomes can enter osteosarcoma cells through endocytosis and concentrate in the cytoplasm when co-cultured with normal strains. Osteosarcoma cells were co-cultured with drug-resistant exosomes at 2, 4, 6, and 8 μg/ml adriamycin, respectively. Compared with normal group, the proliferation level in drug-resistant group was significantly increased. Compared with the normal cell group 35.95±3.92, 6.72±3.55 and the normal exosome group 51.22±5.55, 19.31±1.93, the drug-resistant cell group 54.20±9.32, 19.24±2.88 and drug-resistant exosome group 76.40±5.41, 30.26±4.87, all had significantly higher cell mobility, the difference was statistically significant ( P<0.05). Exosome sequencing and biogenic analysis of 10 highly upregated miRNAs to validate mRNA expression differences between normal and drug-resistant strains by RT-PCR, showing a significant increase in miR-21-5p expression level of drug-resistant strains (5.89±0.26 vs. 0.99±0.06; 1.05±0.07 vs. 8.80±0.93, P<0.05), the difference was statistically significant ( P<0.05). In MG63 and U2OS, the normal cell group and drug-resistant cell group, and the normal exosome group and drug-resistant exosome group were compared, the tumor volume and the terminal tumor weight of nude mice were increased to varying degrees. MRNA relative expression levels of miR-21-5p in serum exosomes of nude mice after drug intervention were 0.86±0.07 and 0.86±0.05 in normal cell group, respectively. The values were 1.13±0.12, 1.14±0.12 in drug-resistant cell group, 0.71±0.05, 0.75±0.03 in normal exosome group, and 0.90±0.07, 0.93±0.04 in drug-resistant exosome group. Compared with normal and drug-resistant strains, the expression levels of normal and drug-resistant exosome groups were increased, with statistical significance ( P<0.05). Conclusion:The exosomes of drug-resistant cells in osteosarcoma could enhance the proliferation level and migration ability of cells through intercellular transfer of MDR1 and miRNAs. The expression of MDR1 and miR-21-5p in drug-resistant cells and tumor-forming nude mouse serum and tumor tissues were up-regulated which suggested that it might be involved in regulating the drug resistance process of osteosarcoma.

Dose comparison of mammography with two photographic modes / 中华放射医学与防护杂志

Objective:To compare radiation dose between digital breast tomosynthesis (DBT) and full-field digital mammography (FFDM), and explore the correlation of average glandular dose(AGD) with breast density and compression thickness.Methods:The mammographic data of patients with breast diseases who underwent digital breast tomosynthesis (DBT) and the population who underwent full-field digital mammography (FFDM) screening in the First Affiliated Hospital of Kunming Medical University from October 2020 to May 2022 were retrospectively collected. The compression thickness, compression force and AGD were recorded. According to the 2013 ACR BI-RADS MAMMOGRAPHY, the breast gland density was classified into 4 types: a(glandular tissue<25%), b(glandular tissue 25%~50%), c(glandular tissue 50%~75%) and d(glandular tissue >75%), by two senior doctors engaged in breast imaging diagnosis. The relationships between different gland densities, different compression thicknesses and AGD under FFDM and DBT mode were analyzed.Results:In both FFDM and DBT modes, the AGD increased significantly with the increase of breast density( F=861.63, 617.83, 330.33, 451.45, 290.47, P<0.001), and AGD a<AGD b<AGD c<AGD d. For type c and d breasts undergoing FFDM, AGD was lowest when the compression thickness was 31~40 mm. Under the same compression thickness, The AGD DBT was significantly higher than the AGD FFDMin all types (Type a: t=-17.88, -42.19, -29.90, -28.14, -24.95, P<0.001; Type b: t=-49.18, -35.94, -27.25, -28.37, -24.10, P<0.001; Type c: t=-11.78, -32.90, -23.13, -20.51, -18.24, P<0.001; Type d: t=-7.94, -26.24, -17.24, -15.44, -13.81, P<0.001). The difference between two AGDs of Type d with compression thickness of 61~70 mm was the largest, which was 1.07 mGy (95% CI: 0.92~1.22). The AGD was positively correlated with breast density and compression thickness, and the relationship of FFDM was stronger than that of DBT. Conclusions:The AGD is positively correlated with breast density and compression thickness in mammography. Compared with FFDM, DBT can increase AGD, The AGD would increase in DBT than FFDM but be safe. DBT would be beneficial to patients with breast diseases in clinical practice.

Combined HAT score and neutrophil to lymphocyte ratio predict symptomatic intracranial hemorrhage after intravenous thrombolysis in patients with acute ischemic stroke / 国际脑血管病杂志

Objective:To investigate the value of hemorrhage after thrombolytic (HAT) score and neutrophil to lymphocyte ratio (NLR) in combination predicting symptomatic intracerebral hemorrhage (sICH) after intravenous thrombolysis in patients with acute ischemic stroke (AIS).Methods:Consective patients with AIS received intravenous thrombolysis with ateplase in Tianjin TEDA Hospital from January 2016 to December 2021 were retrospectively enrolled. sICH was defined as cerebral CT showing hemorrhage at any part of the brain after intravenous thrombolysis, and the National Institutes of Health Stroke Scale (NIHSS) score was increased by≥4 compared with the baseline, or there was a manifestation indicating clinical aggravation. Univariate analysis was used to compare the baseline data of sICH group and non-sICH group. A binary multivariate logistic regression model was used to determine the independent influencing factors of sICH. The receiver operating characteristic (ROC) curve was used to evaluate the value of HAT score and NLR in combination predicting sICH. Results:A total of 429 patients with AIS were enrolled. Univariate analysis showed that there were significant differences in atrial fibrillation, systolic blood pressure, NLR, HAT score and NIHSS score between the sICH group and the non-sICH group (all P<0.05). Multivariate analysis showed that NLR (odds ratio [ OR] 1.405, 95% confidence interval [ CI] 1.193-2.958), HAT score ( OR 1.512, 95% CI 1.207-3.169) and NIHSS score ( OR 1.221, 95% CI 1.082-2.634) had significant independent correlation with sICH after adjusting for atrial fibrillation and systolic blood pressure. The ROC curve showed that the areas under the curve of HAT score, NLR and their combination predicting sICH were 0.719 (95% CI 0.609-0.832), 0.723 (95% CI 0.618-0.835) and 0.854 (95% CI 0.765-0.931), respectively. The areas under the curve of the two methods in combination were significantly larger than those of the single method ( P=0.029 and 0.032, respectively), and their sensitivity and specificity were 74.1% and 83.5% respectively. Conclusion:Combined HAT score and NLR is of high value in predicting sICH after intravenous thrombolysis in patients with AIS, and has clinical application potential.

Prediction of concentration immediately dangerous to life or health of benzene and its derivatives based on quantitative structure-activity relationship / 环境与职业医学

Background With the increasing exposure to hazardous chemicals in the workplace and frequency of occupational injuries and occupational safety accidents, the acquisition of occupational exposure limits of hazardous chemicals is imminent. Objective To obtain more unknown immediately dangerous to life or health (IDLH) concentrations of hazardous chemicals in the workplace by exploring the application of quantitative structure-activity relationship (QSAR) prediction method to IDLH concentrations, and to provide a theoretical basis and technical support for the assessment and prevention of occupational injuries. Methods QSAR was used to correlate the IDLH values of 50 benzene and its derivatives with the molecular structures of target compounds. Firstly, affinity propagation algorithm was applied to cluster sample sets. Secondly, Dragon 2.1 software was used to calculate and pre-screen 537 molecular descriptors. Thirdly, the genetic algorithm was used to select six characteristic molecular descriptors as dependent variables and to construct a multiple linear regression model (MLR) and two nonlinear models using support vector machine (SVM) and artificial neural network (ANN) respectively. Finally, model performance was evaluated by internal and external validation and Williams diagram was drawn to determine the scopes of selected models. Results The ANN model results showed that \begin{document}$ {R}_{\mathrm{t}\mathrm{r}\mathrm{a}\mathrm{i}\mathrm{n}}

Application of PET-LINAC in Biology-guided Radiotherapy / 中国医疗器械杂志

Biology-guided radiotherapy (BgRT) is a novel technique of external beam radiotherapy, combining positron emission tomography-computed tomography (PET-CT) with a linear accelerator (LINAC). The key innovation is to utilize PET signals from tracers in tumor tissues for real-time tracking and guiding beamlets. Compared with a traditional LINAC system, a BgRT system is more complex in hardware design, software algorithm, system integration and clinical workflow. RefleXion Medical has developed the world's first BgRT system. Nevertheless, its actively advertised function, PET-guided radiotherapy, is still in the research and development phase. In this review study, we presented a number of issues related to BgRT, including its technical advantages and potential challenges.

Determination of misoprostol in workplace air by high performance liquid chromatography / 中华劳动卫生职业病杂志

Objective: To establish a high performance liquid chromatography method for the determination of misoprostol in workplace air. Methods: From February to August 2021, the misoprostol in the workplace air was collected by glass fiber filter membrane, and theeluent was separated by C18 liquid chromatography column, determined by UV detector, and quantified by external standard method. Results: The quantitative lower limit of misoprostol determination method was 0.05 μg/ml, and the lowest quantitative concentration was 1.4 μg/m(3) (calculated by collecting 75 L air sample). The concentration of misoprostol has a good linear relationship between 0.05 to 10.00 μg/ml. The relative coefficient was 0.9998. The regression equation of the standard working curve was y=495759x-45257. The range of average recovery rates were from 95.5% to 102.8%. The intra-assay precision of the method was 1.2%-4.6%, and the inter-assay precision was 2.0%-5.9%. The samples could be stored stably for 7 days at 4 ℃. Conclusion: The high performance liquid chromatography method for the determination of misoprostol has high sensitivity, good specificity and simple procedure of sample pretreatment. It is suitable for the detection of misoprostol in the workplace air.

Analysis of typing conversion and perinatal outcomes in twins with selective intrauterine growth restriction of different subtypes / 中华妇产科杂志

Objective: To retrospectively analyze the clinical data of different types of selective intrauterine growth restriction (sIUGR) pregnant women under expectant management, including the natural evolution, typing conversion and perinatal outcomes. Methods: The clinical data of 153 pregnant women with sIUGR under expected treatment in Women's Hospital, Zhejiang University School of Medicine from January 2014 to December 2018 were collected. Maternal characteristics including maternal age, gravidity, parity, method of conception, pregnancy complication, gestational age at delivery, indication for delivery, birth weight, the rate of intrauterine and neonatal death and neonatal outcomes were recorded. Pregnant women with sIUGR were divided into three types according to end-diastolic umbilical artery flow Doppler ultrasonography, and the differences of typing conversion and perinatal outcomes of sIUGR pregnant women based on the first diagnosis were compared. Results: (1) Clinical characteristics and pregnancy outcomes: among 153 pregnant women with sIUGR, 100 cases (65.3%) were diagnosed with type Ⅰ, 35 cases (22.9%) with type Ⅱ, and 18 cases (11.8%) with type Ⅲ. There were no significant differences in age, conception mode, pregnancy complications, first diagnosis gestational age, characteristics of umbilical cord insertion, delivery indications, fetal intrauterine mortality and neonatal mortality among three types of sIUGR pregnant women (all P>0.05). The average gestational age at delivery of type Ⅰ sIUGR was (33.5±1.9) weeks, which was significantly later than those of type Ⅱ and Ⅲ [(31.3±1.8), (31.2±1.1) weeks, P<0.001]. The percentage disordance in estimated fetal weight (EFW) of type Ⅰ sIUGR was significantly lower than those of type Ⅱ and type Ⅲ (P<0.001). The incidence rate of neonatal intensive care unit (NICU) admission, cerebral leukomalacia and respiratory complications of both fetus and necrotizing enterocolitis of large fetus in type Ⅰ were significantly lower than those in type Ⅱ and type Ⅲ (all P<0.05). (2) Typing conversion: in 100 cases of type Ⅰ sIUGR, 18 cases progressed to type Ⅱ and 10 cases progressed to type Ⅲ. Compared with 72 stable type Ⅰ sIUGR, those with progressed type Ⅰ sIUGR had higher incidence of NICU admission and lung disease in both fetuses, and cerebral leukomalacia and necrotizing enterocolitis in large fetus (all P<0.05). The proportion of inconsistent cord insertion was significantly higher in those type Ⅰ progressed to type Ⅲ (6/10) than in those with stable type Ⅰ (19.4%, 14/72) and type Ⅰ progressed to type Ⅱ sIUGR [0 (0/18), P=0.001]. Four cases of type Ⅱ sIUGR reversed to type Ⅰ and 6 cases reversed to type Ⅲ. Compared with type Ⅱ reversed to type Ⅰ sIUGR, those stable type Ⅱ and type Ⅱ reversed to type Ⅲ sIUGR had a higher incidence of NICU admission in large fetus (P<0.05). Two cases of type Ⅲ sIUGR reversed to type Ⅰ and 6 cases progressed to type Ⅱ. There were no significant differences in fetal serious complications in type Ⅲ sIUGR with or without doppler changes (all P>0.05). Conclusions: The different types of sIUGR could convert to each other. The frequency of ultrasound examinations should be increased for patients with the type Ⅰ sIUGR, especially when the percentage discordance in EFW is substantial or with discordant cord insersion.