SMAR1 promotes immune escape of Tri-negative Breast Cancer through a mechanism involving T-bet/PD-1 Axis.

This study was aimed at investigating the specific molecular mechanisms involved in the regulation of immune escape of triple-negative breast cancer (TNBC) by SMRI, so as to provide a new clinical treatment target for the disease. Mouse original 4T1 breast cancer cells were inoculated subcutaneously in BALB/C to establish TNBC mouse model. CD8+T cells with immunological effects were selected from mouse thymus glands for primary culture. The CD8+positive T cells were infected with lentivirus interference vectors, and the proliferation of CD8+ T cells were determined by trypan blue staining and flow cytometry. CD8+T cells and 4T1 cells were cultured together so as to determine the cytotoxic effects of SMAR1-downregulated CD8+ T cells on tumor cells and the expression of cytokines (IFN-γ, TNF-α, IL-2, IL-4 and IL-6). The expressions of SMAR1, T-bet and PD-1 were assayed by Western blot. SMAR1-downregulated CD8+T cells were injected into 4T1 tumor-bearing mice through the caudal vein, and the growth of tumor in mice was monitored. Following the infection of CD8+T cells with SMAR1-downregulated lentiviral system, cell apoptosis level was decreased significantly (control vs. sh-SMAR1: 32.23 ± 12.4 % vs. 18.28 ± 8.93 %, p < 0.05). Results from trypan blue staining experiments showed that the proliferation of CD8+ T cells in the SMAR1-downregulated group was significantly increased; SMAR1-downregulated CD8+ T cells promoted the production of IFN-γ, TNF-α, IL-2, IL-4 and IL-6 in 4T1 breast cancer cells (p < 0.05). Western blot showed that SMAR1 down-regulation led to significant upregulation of T-bet, while PD-1 was downregulated, when compared to the control group (p < 0.05). The downregulation of SMAR1 was associated with significant reduction in tumor size in mice (p < 0.05). SMAR1 downregulation enhances the tumor killing effect of CD8+T cells by activating T-bet and down-regulating PD-1.

Loss of HRD functional phenotype impedes immunotherapy and can be reversed by HDAC inhibitor in ovarian cancer.

In recent years, homologous recombination deficiency (HRD) has not achieved the expected substantial promotion of immunotherapeutic efficacy in ovarian cancer. This study aims to explore the role of HRD functional phenotype as a powerful biomarker in identifying HRD patients who may benefit from immunotherapy. HRD functional phenotype, namely HRD-EXCUTE, was defined as the average level of the 15 hub genes upregulated in HRD ovarian cancer. A decision tree was plotted to evaluate the critical role of HRD-EXCUTE in HRD patients. Agents inducing HRD-EXCUTE were identified by CMAP web (Connectivity Map). The mechanisms and immunotherapeutic effect of PARPi and HDACi in promoting HRD-EXCUTE was examined in vitro and in vivo. The decision tree plotted on the basis of HRD and HRD-EXCUTE indicated the HRD patients without the HRD functional phenotype were largely unresponsive to immunotherapy, which was validated by the immunotherapeutic cohorts. Furthermore, loss of HRD-EXCUTE in the HRD patients attenuated immunogenicity and inhibited immune cells in tumor microenvironment. Moreover, Niraparib combined with Entinostat induced HRD-EXCUTE by activating the cGAS-STING pathway and increasing the histone acetylation. The combination therapy could enhance the cytotoxicity of immune cells, and promote pro-immune cells infiltrating into ascites, resulting in inhibited ovarian cancer growth. The HRD functional phenotype HRD-EXCUTE was set up as a potent biomarker to identify whether HRD patients can benefit from immunotherapy. Loss of HRD-EXCUTE in HRD patients were largely insensitive to immunotherapy. The combination of PARPi with HDACi could improve the efficacy of the PARPi-based immunotherapy in ovarian cancer by augmenting the HRD functional phenotype.

Effects of gypenosides on proliferation and apoptosis of human gastric cancer cells and its mechanism / 中国药理学通报

Aim To explore the effect of gypenosides on proliferation and apoptosis of human gastric cancer cells SGC-7901 and AGS and its mechanism. Methods Different concentrations of gypenosides were cultured with human gastric cancer cells SGC-7901 and AGS. Cell viability assay was used to detect cell proliferation activity, and the IC

Application of endoscopic papillary balloon dilatation in the treatment of patients with non-dilated small choledocholithiasis / 中华肝胆外科杂志

Objective:To study the efficacy of endoscopic papillary balloon dilatation (EPBD) in the treatment of non-dilated small choledocholithiasis.Methods:Clinical data of 142 patients with non-dilated small choledocholithiasis admitted to Zhanjiang Central People's Hospital from April 2021 to March 2023 were retrospectively analyzed, including 63 males and 79 females, aged (55.1±15.4) years old. Patients were divided into the EPBD group ( n=63) and endoscopic sphincterotomy (EST) group ( n=79). Blood amylase, liver enzymology, liver metabolism, and blood routine were monitored before and 48 hours after treatment. The occurrences of intraoperative bleeding, perforation, post-ERCP pancreatitis (PEP), and cholangitis were compared between the groups. Patients were followed up and screened for stone recurrence by outpatient review 3 to 12 months from discharge. Results:Compared to preoperative data, the white blood cell count, alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bili-rubin, and direct bilirubin decreased 48 hours after treatment (all P<0.05). The operation time in EPBD group was slightly longer than that in EST group [(43.1±5.9) min vs. (38.5±4.5) min, P=0.064] without statistical significance. There were no case of perforation in both groups. The incidences of intraopera-tive bleeding [3.17%(2/63) vs. 6.33%(5/79)], PEP [17.46%(11/63) vs. 10.53%(8/79)], and postoperative cholangitis [4.76%(3/63) vs. 1.27%(1/79)] were comparable between the groups (all P>0.05). Conclusion:EPBD could be feasible for non-dilated small choledocholithiasis, which does not increase the operation time and incidence of adverse events compared to EST.

Study on Platelet Adhesion and Aggregation Induced by Gradient Shear Stress Using Microfluidic Chip Technology / 中国实验血液学杂志

OBJECTIVE@#To study the effect of gradient shear stress on platelet aggregation by microfluidic chip Technology.@*METHODS@#Microfluidic chip was used to simulate 80% fixed stenotic microchannel, and the hydrodynamic behavior of the stenotic microchannel model was analyzed by the finite element analysis module of sollidwork software. Microfluidic chip was used to analyze the adhesion and aggregation behavior of platelets in patients with different diseases, and flow cytometry was used to detect expression of the platelet activation marker CD62p. Aspirin, Tirofiban and protocatechuic acid were used to treat the blood, and the adhesion and aggregation of platelets were observed by fluorescence microscope.@*RESULTS@#The gradient fluid shear rate produced by the stenosis model of microfluidic chip could induce platelet aggregation, and the degree of platelet adhesion and aggregation increased with the increase of shear rate within a certain range of shear rate. The effect of platelet aggregation in patients with arterial thrombotic diseases were significantly higher than normal group (P<0.05), and the effect of platelet aggregation in patients with myelodysplastic disease was lower than normal group (P<0.05).@*CONCLUSION@#The microfluidic chip analysis technology can accurately analyze and evaluate the platelet adhesion and aggregation effects of various thrombotic diseases unde the environment of the shear rate, and is helpful for auxiliary diagnosis of clinical thrombotic diseases.

Associations between indoor volatile organic compounds and nocturnal heart rate variability of young female adults: A panel study / 北京大学学报(医学版)

OBJECTIVE@#To investigate the association between short-term exposure to indoor total volatile organic compounds (TVOC) and nocturnal heart rate variability (HRV) among young female adults.@*METHODS@#This panel study recruited 50 young females from one university in Beijing, China from December 2021 to April 2022. All the participants underwent two sequential visits. During each visit, real time indoor TVOC concentration was monitored using an indoor air quality detector. The real time levels of indoor temperature, relative humidity, noise, carbon dioxide and fine particulate matter were monitored using a temperature and humidity meter, a noise meter, a carbon dioxide meter and a particulate counter, respectively. HRV parameters were measured using a 12-lead Holter. Mixed-effects models were used to evaluate the association between the TVOC and HRV parameters and establish the exposure-response relationships, and two-pollutant models were applied to examine the robustness of the results.@*RESULTS@#The mean age of the 50 female subjects was (22.5±2.3) years, and the mean body mass index was (20.4±1.9) kg/m2. During this study, the median (interquartile range) of indoor TVOC concentrations was 0.069 (0.046) mg/m3, the median (interquartile range) of indoor temperature, relative humidity, carbon dioxide concentration, noise level and fine particulate matter concentration were 24.3 (2.7) ℃, 38.5% (15.0%), 0.1% (0.1%), 52.7 (5.8) dB(A) and 10.3 (21.5) μg/m3, respectively. Short-term exposure to indoor TVOC was associated with significant changes in time-domain and frequency-domain HRV parameters, and the exposure metric for most HRV parameters with the most significant changes was 1 h-moving average. Along with a 0.01 mg/m3 increment in 1 h-moving average concentration of indoor TVOC, this study observed decreases of 1.89% (95%CI: -2.28%, -1.50%) in standard deviation of all normal to normal intervals (SDNN), 1.92% (95%CI: -2.32%, -1.51%) in standard deviation of average normal to normal intervals (SDANN), 0.64% (95%CI: -1.13%, -0.14%) in percentage of adjacent NN intervals differing by more than 50 ms (pNN50), 3.52% (95%CI: -4.30%, -2.74%) in total power (TP), 5.01% (95%CI: -6.21%, -3.79%) in very low frequency (VLF) power, and 4.36% (95%CI: -5.16%, -3.55%) in low frequency (LF) power. The exposure-response curves showed that indoor TVOC was negatively correlated with SDNN, SDANN, TP, and VLF when the concentration exceeded 0.1 mg/m3. The two-pollutant models indicated that the results were generally robust after controlling indoor noise and fine particulate matter.@*CONCLUSION@#Short-term exposure to indoor TVOC was associated with significant negative changes in nocturnal HRV of young women. This study provides an important scientific basis for relevant prevention and control measures.

Chronic Injury of Mice Bone Marrow Multipotent Hematopoietic Progenitor Cells Induced by Ionizing Radiation / 中国实验血液学杂志

OBJECTIVE@#To explore the chronic injury and its possible mechanism of ionizing radiation on multipotent hematopoietic progenitor cells (MPPs) by determining the related indicators of MPPs in bone marrow of mice post-radiation.@*METHODS@#Sixteen C57BL/6 adult mice were randomly divided into normal control and irradiation groups, 8 mice in each group. The mice in irradiation group were exposed to 6 Gy X-ray. The proportion of bone marrow MPPs, their apoptosis and proliferation 2 months after irradiation were detected by flow cytometry. Mitochondrial activity and levels of reactive oxygen species (ROS) in each MPPs population were detected by Mitotracker Red and DCFDA probes, and the senescent state of MPPs in the bone marrow was analyzed.@*RESULTS@#Ionizing radiation could reduce the proportion of MPPs in mouse bone marrow. The proportions and numbers of MPP1, MPP3 and MPP4 in the bone marrow were significantly decreased after whole-body irradiation with 6 Gy X-ray (P<0.05). In addition, radiation significantly reduced the colony-forming capacity of MPPs in bone marrow (P<0.05), the proportions of apoptotic cells in the MPP1 and MPP4 cell populations increased significantly in the bone marrow (P<0.05). The activity of mitochondria was significantly reduced in the bone marrow MPP2, MPP3 and MPP4 cell populations compared with that of the control group (P<0.05). It was also found that the radiation could significantly increase the ROS levels of MPPs in bone marrow, and the content of ROS in the MPP2, MPP3 and MPP4 cell population of the bone marrow was significantly increased(P<0.05). The senescent cells ratios of MPP1, MPP3 and MPP4 cells in the bone marrow after irradiation were significantly higher than those in the control group (P<0.05).@*CONCLUSION@#Ionizing radiation can cause chronic MPPs damage in mice, which is closely associated with persistent oxidative stress, cells apoptosis, and cellular senescence.

Chronic injury of hematopoietic stem and progenitor cells induced by different doses of radiation / 环境与职业医学

Background The chronic injury of the hematopoietic system caused by ionizing radiation (IR) is often ignored. The essential cause of this injury is the damage of hematopoietic stem and progenitor cells (HSPCs). Objective To explore the long-term effects of IR at different radiation doses and at different radiation fractions of the same radiation dose on HSPCs in the bone marrow of mice, and to provide a scientific basis for reducing the chronic damage to the hematopoietic system caused by IR. Methods A total of 16 male C57BL/6 mice aged 8-10 weeks were randomly divided into four groups that received different doses or fractions of total body X-ray irradiation, including 1.5 Gy×4 irradiation group (n=5), 3 Gy irradiation group (n=4), 6 Gy irradiation group (n=4), and non-irradiation group (n=3). Two months after irradiation, bone marrow cells from each mouse were collected and counted. The clone forming ability of bone marrow cells was analyzed by cobblestone area-forming cell (CAFC) assay. The proportion of HSPCs was measured by flow cytometry. The cell cycle of HSPCs was assessed by antigen identified by monoclonal antibody Ki 67 (Ki-67) and 7-amino-actinomycin D (7-AAD) double staining. The reactive oxygen species (ROS) levels of HSPCs were estimated with a 2,7-dichlorodihydrofluorescein diacetate (DCFDA) probe. The cellular senescence of HSPCs was evaluated with a 5-dodecanoylaminofluorescein di-β-D-galactopyranoside (C12FDG) probe. The expression of senescence related genes such as P16, P19, P21, and P27 was measured by real-time fluorescence quantitative PCR. Results There was no significant change in the numbers of bone marrow cells 2 months after different doses and fractions of radiation (P>0.05). The clone forming ability of bone marrow cells was significantly decreased after 3 Gy and 6 Gy irradiation when compared to non-irradiated mice (P<0.01). HSPCs responded inconsistently to different doses and fractions of irradiation. Overall, there was no significant change in long-term hematopoietic stem cells (LT-HSCs) proportion after irradiation (P>0.05), the proportions of hematopoietic progenitor cells (HPCs), hematopoietic stem cells (HSCs), short-term hematopoietic stem cells (ST-HSCs), and multipotent progenitors 2 (MPP2) increased after irradiation (P<0.05), and the proportions of LSK, MPP1, MPP3, and MPP4 cells decreased after irradiation (P<0.05); except for HPCs and MPP2, the proportion of HSPCs in G0 phase was decreased (P<0.05). The ROS production in HSPCs was increased significantly after 6 Gy irradiation (P<0.05), while the ROS levels after 3 Gy and 1.5 Gy×4 irradiation were similar to that of the non-radiation group (P>0.05). The cellular senescent proportion of HPCs, LSK, and HSCs increased after irradiation (P<0.05). The expression levels of senescence related genes P16, P19, and P21 in HSCs were significantly increased (P<0.05). Conclusion The responses of HSPCs in bone marrow to IR vary depending on doses and fractions of irradiation. Increased ROS production and cellular senescence may be involved in the damage process of HSPCs under radiation settings.

Association of ambient fine particulate air pollution with hospitalization costs and stays for depression in China: a multicity analysis / 中华预防医学杂志

Objective: To explore the effect of fine particulate matter (PM2.5) pollution on depression hospitalization cost and length of stay in 57 cities of China. Methods: A total of 84 207 patients with depression in 57 cities of China from January 2013 to December 2017 were selected as the subjects. The demographic characteristics and hospitalization status of the patients were obtained from the database of basic medical insurance for urban workers and urban residents in China. The environmental exposure data of the same period were obtained from the national air quality real-time release platform of China Environmental Monitoring Station. A generalized additive model based on quasi-Poisson distribution was used to analyze PM2.5 exposure effect in each city, and the nonlinear mixing of moving average temperature, relative humidity and date was controlled by natural smooth spline function. Results: Among the included cities, southern cities accounted for 50.88% (29), and the number of female inpatients, hospitalization costs and hospitalization days accounted for 62.65%, 63.50% and 60.85% (42 735 cases, 567.78 million yuan and 1.14 million days, respectively). The proportion of hospitalized cases, hospitalization cost and length of stay in the age group of 40 to 64 years old were 59.15% (40 346 cases), 53.92% (482.15 million yuan) and 52.07% (0.98 million days), respectively. PM2.5 level was positively correlated with the number of hospitalized cases with depression, hospitalization cost and length of stay. When the 3-day moving average of PM2.5 exposure level increased by 10 μg/m3, the number of hospitalization cases increased by 0.64%. The attributed percentage (95%CI) of hospitalized cases, hospitalization costs and length of stay were 3.35% (0.57%-6.04%), 3.04% (0.52%-5.48%) and 3.07% (0.49%-5.56%), respectively. Subgroup analysis showed that the attributed percentage of hospitalization cases, hospitalization cost and length of stay to PM2.5 exposure ranged from 3.97% to 4.68%, 4.04% to 4.33% and 4.13% to 4.30% in northern China, male and cold season, respectively. Conclusion: PM2.5 exposure is associated with the increase of hospitalization cost and length of stay among Chinese urban population with depression.

Agreement between ultrasound-detected inflammation and clinical signs in ankles and feet joints in patients with rheumatoid arthritis / 北京大学学报(医学版)

OBJECTIVE@#To investigate the agreement between clinical signs (tenderness and/or swelling) in ankles and feet joints and ultrasound findings in patients with rheumatoid arthritis (RA).@*METHODS@#RA patients with at least 1 tender and/or swollen joint in bilateral ankles and metatarsophalangeal (MTP) joints detected by physical examination were enrolled and underwent ultrasound examination by greyscale (GS) and power Doppler (PD) mode. The agreement between clinical signs and ultrasound-detected inflammation (joint effusion, synovitis, or tenosynovitis) was analyzed.@*RESULTS@#In the study, 113 consecutive RA patients were included, with mean age of (52.5±12.6) years, median duration of 60 (13, 129) months, mean disease activity score in 28 joints based on erythrocyte sedimentation rate [DAS28 (ESR)] of 5.1±1.7, mean disease activity score in 28 joints based on C reactive protein[DAS28 (CRP)]of 4.6±1.5. The tenderness and swelling was most commonly detected in ankles (52.7% and 31.9%, respectively), while GS (+) synovitis was most frequently detectable in MTP2 (34.1%), followed by ankles (32.7%) and MTP1 (27.9%), and PD (+) synovitis was most frequently detectable in MTP1 (14.2%), followed by ankles (12.4%) and MTP2 (10.6%). The prevalence of tenosynovitis was 41.1%, which mostly located in tibialis posterior tendon (22.1% of GS positive and 17.6% of PD positive). The highest prevalence of joint effusion was detected in ankles (9.7%), while that of bone erosion in MTP5 (19%). The overall concordance rate between positive clinical signs and ultrasound-determined joint inflammation was poor in the above joints (κ < 0.2, P < 0.05), in which swelling had the highest κ coefficient with ultrasound-determined joint inflammation in ankles (κ=0.225, P < 0.05). Moreover, swelling had the highest κ coefficient with synovitis in ankles (κ=0.231, P < 0.05).The concordance between tenosynovitis and signs in ankles was also poor (κ < 0.20, P < 0.05). There was no significant agreement between joint effusion and clinical signs (P > 0.05).@*CONCLUSION@#The overall concordance between clinical signs and inflammation on ultrasound was poor in ankles and feet joints. Tenderness and swelling was more common in ankles, while more lesions were detected by ultrasound at MTP joints. Ultrasound is useful in assessing the lesions besides physical examination in patients with RA.

The effectiveness and safety of multimodal endovascular treatment for acute ischemic stroke in elderly patients / 中华老年医学杂志

Objective:To evaluate the efficacy and safety of multimodal endovascular therapy for acute ischemic stroke in elderly patients.Methods:A total of 263 elderly patients with acute ischemic stroke were enrolled as research subjects from January 2017 to December 2018.Patients were divided into two groups: the intravenous thrombolytic therapy group and the endovascular therapy group.Treatment outcomes were compared by using the National Institutes of Health Stroke Scale(NIHSS)and the modified Rankin Scale(mRS).Results:Of 263 patients, 125 were in the intravenous thrombolytic therapy group and 138 were in the intravascular therapy group.The rate of good/excellent outcomes was higher in the endovascular treatment group than in the intravenous thrombolytic therapy group(97.8% vs.91.2%, χ2=5.713, P<0.05). The NIHSS score and mRS score were lower in the endovascular treatment group than the in intravenous thrombolytic therapy group[(2.3±0.3) vs.(6.0±1.8), (1.1±0.1) vs.(2.3±0.3), t=9.067 and 16.970, P<0.05]. There was no significant difference in the incidence of adverse reactions between the two groups(8.6% vs.8.0%, χ2=0.041, P>0.05). Conclusions:Multimodal mechanical thrombus retrieval is a safe and effective treatment for intracranial large vessel occlusion in acute ischemic stroke patients and should be recommended and promoted.

[Analysis of capabilities of microscopic examinations of Plasmodium in Dongxihu District, Wuhan City].

OBJECTIVE: To investigate and analyze the capabilities of Plasmodium microscopic examinations in medical and health organizations in Dongxihu District, Wuhan City, so as to provide evidences for achieving the standard of malaria elimination and malaria control in the future. METHODS: The basic information of the laboratorians and the hardware facilities in 15 microscopic examination stations of Plasmodium were collected and analyzed from 2010 to 2015. Meanwhile, the quality of making, dyeing, cleanliness of all the negatives blood smears were evaluated, and all the positive smears were re-checked in the district during the period above mentioned. RESULTS: Totally, there were 28 laboratorians and 9 qualified microscopes in 15 microscopy stations in Dongxihu District. The age of the laboratorians in the first-level and third-level organizations was mainly from 40 to 50 years old, but the age of those in the second-level organizations was from 20 to 30 years old. The years for microscopic examination working of most of the laboratorians in the first-level and third-level organizations were more than 15 years, while the working years of those in the second-level organizations were mainly less than 10 years. The education level of the laboratorians in the first-level organization was mainly (50.00%) junior college, while the education levels of those in the second and third organizations were mainly bachelor. From 2010 to 2015, 8 561 blood smears were produced and 539 of them were reviewed, the coincidence rates of review were all 100%, and the average qualified rates of making, dyeing, and cleanliness of the negative blood smears were 82.08%, 79.92% and 83.33%, respectively. All the rates mentioned above in 2015 were higher than those in 2010 (χ2 = 26.45, 16.85, 13.93, all P ＜ 0.01). CONCLUSIONS: The capability of microscopic examinations of Plasmodium has improved obviously in Dongxihu District, but the human resources construction and hardware input in this district should be improved, meanwhile, the check on the quality control of microscopic examinations of Plasmodium should be continued, so as to guarantee the sustainable and healthy development of malaria control work in this district.

Risk factors associated with osteoporosis and fracture in psoriatic arthritis / 中华医学杂志(英文版)

BACKGROUND@#Although there are few studies mentioned there may be some relationship between psoriatic arthritis (PsA) and osteoporosis, clinical data in real world still need to be clarified in China. The aim of this study was to assess the areal and volumetric bone mineral density (BMD), frequency of fracture, and risk factors in patients with PsA.@*METHODS@#A total of one hundred PsA patients who visited Peking University First Hospital and one hundred age- and sex-matched healthy controls with DXA data were enrolled in the study. Patients with clinical fractures confirmed by X-ray during follow-up were also recorded. Clinical characteristics of the patients were recorded and compared between the abnormal BMD group and the normal BMD group, as well as between the fracture and non-fracture groups. Risk factors for fracture and low BMD were analyzed.@*RESULTS@#Mean BMD at the total hip and femoral neck was significantly lower in PsA patients than that in healthy controls (0.809 ± 0.193 vs. 0.901 ± 0.152 g/cm2, P  = 0.041; 0.780 ± 0.146 vs. 0.865 ± 0.166 g/cm2, P  = 0.037, respectively). Moreover, lumbar spine BMD was negatively correlated with psoriasis duration, swollen joint count and DAS28-CRP (r = -0.503, -0.580, -0.438; P < 0.05). Total hip BMD and femoral neck BMD were negatively correlated with HAQ (r = -0.521, -0.335; P < 0.05). Fractures occurred in 29 patients during the follow-up period. Logistic regression analysis showed that older age (OR 1.132 [95%CI: 1.026-1.248), P < 0.05], higher HAQ score (OR 1.493, 95%CI: 1.214-1.836, P < 0.01), higher disease activity index for psoriatic arthritis (OR 1.033, 95% CI: 1.002-1.679, P < 0.05) and hip joint involvement (OR 6.401, 95% CI: 4.012-44.180, P < 0.05) were risk factors for fracture in the multivariate model.@*CONCLUSIONS@#Increased risks of osteoporosis and fracture were found in PsA patients compared to healthy controls. Besides age, high disease activity and hip joint involvement were risk factors for decreased BMD and fracture.

Benefit of ultrasound in the phenotype recognition of psoriatic arthritis / 北京大学学报(医学版)

OBJECTIVE@#To explore the difference in phenotype recognition of PsA patients in two clinical scenarios, physical examination with and without ultrasound assessment.@*METHODS@#PsA patients who visited the rheumatology and clinical immunology department of Peking University First Hospital between January 2010 and October 2020, with complete data of clinical and ultrasound assessment were enrolled. The phenotypes were first identified based on physical examination only, and then combined with enthesitis and dactylitis shown on power doppler and gray-scale ultrasound. The phenotype groupings without and with ultrasound assessment were presented with Wayne diagram. The distributions of different clinical phenotypes were compared by using χ2 test or Fisher's exact test. The differences of clinical phenotypes with and without ultrasound assessment were compared by using Wilcoxon signed rank test.@*RESULTS@#A total of 227 patients with PsA were enrolled with one or more clinical domains. Physical examination revealed that psoriasis was in 209 (92.1%, 209/227) patients, nail involvement in 98 (43.2%, 98/227) patients, peripheral arthritis in 219 (96.5%, 219/227) patients, axial involvement in 25 (11.0%, 25/227) patients, dactylitis in 80 (35.2%, 80/227) patients, and enthesitis in 18 (7.9%, 18/227) patients. Besides 18 patients with clinical enthesitis, ultrasound scan revealed acute enthesitis in 80 patients, with hypoechogenicity (55 cases), tendon thickening (62 cases), and presence of Doppler signals (48 cases). Similarly, dactylitis on ultrasound was found in 18 patients besides those patients with clinical dactylitis. Compared with the phenotypes recognized based on physical examination only, the additional ultrasound assessment revealed that the most common phenotypes, peripheral arthritis was significantly less frequently recognized (49.8% vs. 27.8%, P < 0.001), however on the other hand, the proportion of the patients with peripheral arthritis and enthesitis was significantly increased (4.4% vs. 18.1%, P < 0.001). The phenotype of peripheral arthritis combined with enthesitis, and dactylitis was also dramatically increased (1.8% vs. 17.6%, P < 0.001).@*CONCLUSION@#Ultrasound is a useful tool to identify enthesitis and dactylitis. With the aid of ultrasound assessment, rheumatologists can better identify the lesions of PsA, accurately identify the phenotypes, and further guide the subsequent treatment.

Identification of Chinese medicine sea snake based on cytochrome B (Cytb) / 中国中药杂志

The identification of species primordium has been one of the hot issues in the identification of traditional Chinese medicine. Sea snake is one of the most valuable Chinese medicinal materials in China. In order to understand the origin and varieties of sea snake in the market, we studied the molecular identification of 46 sea snakes by cytochrome B(Cytb). After comparison and manual correction, the sequence length was 582 bp, and the content of A+T(58.9%) was higher than that of G+C(41.1%). There exist 197 variable sites and 179 parsimony-informative sites of the sequence. There are 44 kinds of sequence alignment with consistency equal to 100%, and 2 kinds equal to 96%. A total of 408 Cytb effective sequences were downloaded from GenBank database, with a total of 68 species. Phylogenetic tree of a total of 454 sea snake sequences with the samples in this study were constructed by neighbor-joining trees and Bayesian inference method, respectively, which can identify 42 samples of medicinal materials, while 4 samples can not be identified because of their low node support. The results showed that the species of the sea snake medicine were at least from 2 genera and 5 species, namely, Aipysurus eydouxii, Hydrophis curtus, H. caerulescen, H. curtus, H. ornatus and H. spiralis. This study suggested that the original species of commercial sea snake are very complex and can provide insight into the identification of sea snakes.

Biomechanical affect of percutaneous transforaminal endoscopic discectomy on adjacent segments with different degrees of degeneration:a finite element analysis / 中国骨伤

OBJECTIVE@#To investigate the biomechanical affect of percutaneous transforaminal endoscopic discectomy(PTED) on adjacent segments with different degrees of degeneration and related risk of adjacent segment diseases (ASD) caused by this operation.@*METHODS@#A healthy male adult volunteer was selected, and the lumbosacral vertebra image data was obtained by CT scan, and the external contour of the bone structure was reconstructed. On this basis, the external contour of the bone structure was fitted by using the smooth curve in 3D-CAD software, and the complete three-dimensional finite element modelof the non degenerate L@*RESULTS@#In the finite element model without adjacent segmental disc degeneration, the annulus fibrosus von Mises stress and intradiscal pressure of the PTED model showed only a slight increase under most stress conditions, and a slight decrease in a few conditions, and there was no significant change trend before and after surgery. In the original degenerated adjacent segment disc model, the biomechanical indicators related to disc degeneration in the pre- and post-PTED model showed significant deterioration, leading to an increased risk of potential adjacent spondylopathy.@*CONCLUSION@#PTED surgery will not lead to the significant deterioration of postoperative biomechanical environment of non-degeneration adjacent intervertebral discs, and the original degeneration of adjacent intervertebral discs is a important risk factor for ASD.

Therapeutic options and risk factors of mortality in patients with carbapenem-resistant Acinetobacter baumannii bloodstream infections / 中华传染病杂志

Objective:To analyze the clinical characteristics, therapeutic options and risk factors of mortality in patients with carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infection, and to provide evidence for clinical treatment option and prognosis evaluation of CRAB bloodstream infections. Methods:A retrospective study was carried out in 224 patients with confirmed diagnosis of CRAB bloodstream infection during the period from January 2012 to December 2017 in West China Hospital, Sichuan University. The patients were divided into the death group and the survival group according to the survival status 28 days after collecting blood samples. The clinical features and therapeutic options of antibacterial drugs were reviewed. Student′s t test was used for analyzing normally distributed data and Mann-Whitney U test for non-normal data.Chi-square test was used for categorical variables. Univariate and multivariate logistic analysis were used to analyze the risk factors of mortality associated with CRAB bloodstream infection. Results:Among 224 cases of CRAB bloodstream infection, 121 cases died (54.02%). These patients were mainly in intensive care unit (ICU) and hematology department. The common underlying diseases were severe acute pancreatitis and severe cardiovascular events. The interleukin (IL)-6 level (median (interquartile range)) in the death group (480.40 ng/L (1 432.95 ng/L)) was higher than that of the survival group (107.05 ng/L (263.08 ng/L)), the difference was statistically significant ( Z=4.526, P<0.01). The procalcitionin (PCT) levels in the death group and the survival group were 3.81 μg/L (17.26 μg/L) and 2.12 μg/L (12.74 μg/L), respectively, with no difference between the two groups ( P>0.05). The death rate of empirical treatment with a single or more non-active antimicrobial agents was 57.14% (64/112), that of monotherapy with active agent was 45.68% (37/81), and that of combination therapy with at least one active drug was 64.52% (20/31). The differences had no statistical significance ( P=0.130). The logistic regression analysis showed that the risk factors of mortality associated with CRAB bloodstream infection were renal dysfunction (odds ratio ( OR)=2.181, P=0.024) and multiple organ dysfunction syndrome (MODS; OR=20.376, P<0.01). Conclusions:The fatality rate of patients with CRAB bloodstream infection is high. These patients with renal dysfunction or MODS have poor prognosis. In addition to early effective antibacterial therapy, individual comprehensive treatment should be implemented in order to improve the curative effect.

Silencing long non-coding RNA HIF1A-AS2 inhibits proliferation, invasion and migration of cervical cancer cells / 南方医科大学学报

OBJECTIVE@#To explore the inhibitory effects of silencing long non-coding RNA (LncRNA) HIF1A-AS2 on epithelialmesenchymal transition (EMT) and tumor stem cell-like phenotype in cervical cancer cells.@*METHODS@#We designed 3 shRNA constructs for silencing HIF1A-AS2 in CaSki cells, and the shRNA with the strongest interference effect was selected for subsequent experiment. CaSki cells were transfected with shRNA-NC or Sh-HIF1A-AS2, and the changes in cell viability, invasion ability, EMT, expressions of EMT-related proteins, formation of cell spheres and expressions of stem cell markers were detected.@*RESULTS@#Transfection with shRNA-NC and Sh-HIF1A-AS2 did not significantly affected the viability of CaSki cells (@*CONCLUSIONS@#Silencing HIF1A-AS2 can inhibit proliferation, invasion and migration of cervical cancer cells

Monitoring metrics for short-term exposure to ambient ozone and pulmonary function and airway inflammation in healthy young adults / 北京大学学报(医学版)

OBJECTIVE@#To assess the associations of different monitoring metrics for short-term exposure to ambient ozone (O3) with pulmonary function and airway inflammation in healthy young adults.@*METHODS@#A total of 97 healthy young college students were recruited and followed in a panel study conducted from December 2017 to June 2018. Each participant underwent 3 follow-up visits, and lung function and fractional exhaled nitric oxide (FeNO) were measured at each visit. Ambient air pollutant concentrations were obtained from the environment monitoring station of Beijing closest to the participant residences, and meteorological data were collected from China Meteorological Data Service Center. Linear mixed-effect models were applied to assess the associations between different monitoring metrics for ambient O3 short-term exposure with pulmonary function or airway inflammation in the healthy young adults.@*RESULTS@#During the study period, the P50 (P25, P75) values for ambient O3 concentration expressed as daily 1-hour maximum (O3-1 h max), daily maximum 8-hour average (O3-8 h max) and 24-hour average (O3-24 h avg) were 102.5 (76.8, 163.0) μg/m3, 91.1 (68.3, 154.3) μg/m3 and 61.6 (36.9, 81.7) μg/m3, respectively. The different monitoring metrics for short-term exposure to ambient O3 were significantly associated with reduced forced expiratory volume in the first second (FEV1) and increased FeNO. An interquartile range (IQR) increase in 6-d moving average of O3-1 h max (IQR=71.5 μg/m3) was associated with a 6.2% (95%CI: －11.8%, －0.5%) decrease in FEV1 and a 63.3% (95%CI: 13.8%, 134.3%) increase in FeNO. An IQR increase in 7-d moving average of O3-8 h max (IQR=62.0 μg/m3) was associated with a 6.2% (95%CI: －11.6%, －0.7%) decrease in FEV1and a 75.5% (95%CI: 19.3%, 158.0%) increase in FeNO. An IQR increase in 5-d moving average of O3-24 h avg (IQR=32.9 μg/m3) was associated with a 3.7% (95%CI: －7.1%, －0.2%) decrease in FEV1and a 25.3% (95%CI: 3.6%, 51.6%) increase in FeNO. There was no significant association between the three monitoring metrics for O3 exposure and peak expiratory flow (PEF).@*CONCLUSION@#Short-term exposure to ambient O3 was associated with decreased lung function and increased airway inflammation among the healthy young adults, and daily 1-hour maximum was more sensitively to the respiratory effects of O3.

Depression and anxiety in patients with psoriatic arthritis: Prevalence and associated factors / 北京大学学报(医学版)

OBJECTIVE@#To determine the prevalence of depression and anxiety in patients with psoriatic arthritis (PsA), to investigate whether there is a difference in the prevalence of depression and anxiety between PsA and rheumatoid arthritis (RA) patients and to identify associated risk factors for depression and anxiety in PsA patients.@*METHODS@#PsA and RA patients who visited Department of Rheumatology and Clinical Immunology in Peking University First Hospital from May 2018 to Sep 2019 were recruited. Self-rating anxiety scale and self-rating depression scale were surveyed and compared between PsA and RA patients. Demographics and clinical features including age, gender, disease duration, disease activity score, psoriasis area and severity index (PASI), and medical application were collected. Power Doppler and grey-scale ultrasound of joints, tenosynovitis and enthesis were performed. Multivariate Logistic regression was used to identify the factors associated with mood disorders and the odds ratio of depression and anxiety between the PsA and RA patients.@*RESULTS@#Among the 114 enrolled PsA patients, 37 (32.5%) had mood disorders, in which 36 (31.6%) with depression and 15 (13.2%) with anxiety. Compared with 201 RA patients, PsA patients showed greater odds for depression [adjusted OR (95%CI): 2.7 (1.1-6.4)]. Depression was more often observed in the PsA than in the RA patients (31.6% vs. 18.9%, P=0.011). The similar trend for anxiety was also observed, although the difference was insignificant (13.2% vs. 8.5%, P=0.185). Age (OR=0.95, P=0.008), psoriasis duration (OR=0.94, P=0.018), pain visual analogue scale (OR=1.47, P=0.011), PASI score (OR=1.07, P=0.007) and presence of ultrasound enthesitis (OR=4.13, P=0.009) were identified as factors associated with depression in the PsA patients. PASI score (OR=1.07, P=0.001) was identified as associated factor for anxiety in the PsA patients.@*CONCLUSION@#The prevalence of depression and anxiety is elevated in PsA patients. Depression is significantly more prevalent in PsA patients than in RA patients. Younger age, shorter psoriasis duration, worse pain and presence of ultrasound enthesitis are associated with depression, while severe psoriasis rash is associated with both depression and anxiety in PsA patients.