Objective To investigate the regulatory role of the programmed cell death protein 1 (PD-1) and its ligand programmed cell death protein ligand 1 (PD-L1) signaling on the subtypes and functions of natural killer (NK) cells at the maternal-fetal interface during the second trimester in mice following Toxoplasma gondii infection during the first trimester. Methods Twelve 6- to 8-week-old female mice of the C57BL/6J strain were divided into a control group and an infection group, of 6 mice in each group. On the 6.5th day of pregnancy (Gd6.5), each pregnant mouse in the infection group was intraperitoneally injected with 150 tachyzoites of the Toxoplasma gondii PRU strain, while mice in the control group were injected with an equal volume of physiological saline. On the 12.5th day of pregnancy (Gd12.5), uterus and placenta tissues were sampled from pregnant mice for pathological observations, and the mRNA expression levels of PD-1, PD-L1, and tumor necrosis factor-α (TNF-α) were quantified in uterus and placenta tissues. The PD-1 and DX5 expression was measured on NK cells at the maternal-fetal interface using flow cytometry. In addition, the in vitro JEG-3 trophoblast cells and NK-92MI cells co-culture system was established as the control group, and the addition of T. gondii tachyzoites in the co-culture system served as the infection group. The PD-1, PD-L1, and DX5 mRNA expression was quantified in cells using real-time fluorescence quantitative reverse transcription PCR (RT-qPCR) assay, and the TNF-α concentration was measured in the cell culture supernatant using enzyme-linked immunosorbent assay (ELISA). Results On Gd12.5, clear and intact cellular structures of placental decidual tissues were seen in pregnant mice in the control group, with no remarkable abnormal changes found in the uterine columnar epithelial cells, and inflammatory cell infiltration and blood stasis at varying degrees were found in uterine and placental tissues from pregnant mice in the infection group. The relative PD-1, PD-L1, and TNF-α mRNA expression was (1.004 ± 0.004), (1.001 ± 0.001), and (1.001 ± 0.001) in uterine tissues from pregnant mice in the control group and (2.480 ± 0.720), (3.355 ± 0.920), and (2.391 ± 0.073) in the infection group, respectively. The relative PD-1, PD-L1, and TNF-α mRNA expression was (1.007 ± 0.010), (1.006 ± 0.006), and (1.001 ± 0.001) in the uterine tissues in the control group and (6.948 ± 1.918), (3.225 ± 1.034), and (1.536 ± 0.150) in the infection group, respectively. The relative PD-1, PD-L1, and TNF-α mRNA expression was higher in both the uterine (t = 3.55, 4.43 and 33.02, all P values < 0.05) and placental tissues (t = 5.36, 3.72 and 6.18, all P values < 0.05) in the infection group than in the control group. Flow cytometry showed that the proportions of PD-1⁺ NK cells, PD-1⁺ DX5⁺ NK cells, and DX5⁺ NK cells were (12.200 ± 1.082)%, (9.373 ± 7.728)%, and (44.000 ± 4.095)% in uterine tissues from pregnant mice in the control group, and (21.733 ± 1.630)%, (18.767 ± 1.242)%, and (73.367 ± 0.611)% in the infection group, respectively. The proportions of PD-1⁺ NK cells, PD-1⁺ DX5⁺ NK cells, and DX5⁺ NK cells were (1.100 ± 0.510)%, (2.277 ± 1.337)%, and (96.167 ± 2.831)% in placental tissues from mice in the control group, and (26.867 ± 9.722)%, (23.433 ± 6.983)%, and (82.467 ± 2.248)% in the infection group, respectively. The proportions of PD-1⁺ NK cells (t = 8.45, P < 0.05) and DX5⁺ NK cells (t = 12.29, P < 0.05) were higher in uterine tissues from pregnant mice in the infection group than in the control group, and no significant difference was seen in the proportion of PD-1⁺ DX5⁺ NK cells (Z = -1.09, P > 0.05). The proportions of PD-1⁺ NK cells (t = 4.58, P < 0.05) and PD-1⁺ DX5⁺ NK cells (t = 5.15, P < 0.05) were higher in placental tissues from pregnant mice in the infection group than in the control group, while the proportion of DX5⁺ NK cells was lower in the infection group than in the control group (t = -6.56, P < 0.05). RT-qPCR assay revealed that the relative PD-1, PD-L1, and DX5 mRNA expression was (1.010 ± 0.005), (1.002 ± 0.003), and (1.001 ± 0.001) in the JEG-3 cells and NK92MI cells co-culture system and (3.638 ± 1.258), (0.397 ± 0.158), and (4.267 ± 1.750) in the control group, and ELISA measured that the TNF-α concentration was higher in the cell culture supernatant in the infection group [(22.056 ± 3.205) pg/mL] than in the control group [(12.441 ± 0.001) pg/mL] (t = 5.20, P < 0.05). The PD-1(t = 3.62, P < 0.05) and DX5 mRNA expression (t = 3.23, P < 0.05) was higher in the infection group than in the control group, and the PD-L1 mRNA expression was lower in the infection group than in the control group (t = -6.63, P < 0.05). Conclusions Following T. gondii infection, both PD-L1 expression and PD-1 expression on DX5⁺ NK cells at the maternal-fetal interface are upregulated in mice during the second trimester; however, the proportion of DX5⁺ NK cells decreases. These findings suggest that PD-1/PD-L1 signaling may suppress NK cell functions by modulating DX5⁺ NK cell subsets.

Objective To investigate the role and related mechanism of the soluble guanylate cyclase(sGC)-cGMP-protein kinase G(PKG)signaling pathway in the amelioration of isoproterenol(ISO)-induced cardiac hypertrophy in mice by aqueous extract of Curcuma kwangsiensis root tubers(GYJS).Methods 72 KM male mice were divided randomly into 6 groups:normal,model,propranolol control(40 mg/kg),and GYJS low-(1 g/kg),medium-(2 g/kg),and high-dose(4 g/kg)groups.Mice in the experimental groups were injected subcutaneously with ISO 10 mg/kg on days 1～3 and ISO 5 mg/kg on days 4～14 to establish a mouse cardiac hypertrophy model.4h after each subcutaneous injection of ISO,the mice in each group were administered the corresponding drugs orally for a dosing cycle of 14 days.The hearts were then removed and whole heart and left ventricle weight were measured.Myocardial tissue pathology was observed using hematoxylin and eosin and Masson staining,and sGC subunit beta-1(GUCY1B3)and transforming growth factor(TGF-β1)were detected by immunohistochemistry.Serum lactate dehydrogenase(LDH),creatine kinase(CK),and Nitric Oxide(NO),and myocardial superoxide dismutase(SOD)activity and malondialdehyde(MDA)content were measured using respective kits.Serum cGMP was detected by enzyme-linked immunosorbent assay and quantitative reverse transcription PCR(RT-qPCR),and atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),GUCY1B3,PKG Ⅰ,and phosphodiesterase(PDE)5A mRNA expression levels were also determined by RT-qPCR.Results Compared with the model group,whole heart and left ventricle weights were significantly reduced in mice treated with propranolol or GYJS(P＜0.001 or P＜0.0001)and myocardial hypertrophy and myocardial fibrosis were significantly reversed.All the treatments significantly elevated myocardial expression of GUCY1B3(P＜0.05 or P＜0.01)and significantly reduced expression of TGF-β1(P＜0.05 or P＜0.01).The myocardial damage markers LDH and CK were significantly reduced(P＜0.05 or P＜0.01)while NO and cGMP were significantly elevated(P＜0.05 or P＜0.01),the myocardial oxidative stress indicator MDA was significantly reduced(P＜0.05 or P＜0.01)and SOD activity was significantly increased(P＜0.05 or P＜0.01).mRNA levels of the myocardial hypertrophy markers ANP,BNP,and PDE5A were significantly reduced(P＜0.05,P＜0.01,or P＜0.001)and the mRNA levels of GUCY1B3 and PKG Ⅰ were significantly increased(P＜0.01 or P＜0.001).Conclusions GYJS may improve cardiac hypertrophy by modulating the sGC-cGMP-PKG signaling pathway.

Objective To investigate the effects of insulin therapy on the mechanical behavior of solids,characteristics of fluid flow,and bone marrow stromal cells(BMSCs)differentiation in the distal femoral cancellous bone of type 2 diabetic rats under normal activity and vigorous exercise conditions.Methods The finite element models of cancellous bones and fluids in the distal femurs of rats in the control,diabetes,treatment,and placebo groups in 4-week and 8-week insulin treatment experiments under normal activity and vigorous exercise conditions were established based on micro-CT scanning images.The mechanical and cell differentiation parameters of the models in each group were analyzed using the fluid-solid interaction numerical simulation method.Correlations between mechanical,cell differentiation,and microstructural morphology parameters were also analyzed.Results Insulin therapy under normal activity and vigorous exercise conditions improved the solid and fluid mechanical parameters and BMSC differentiation parameters in type 2 diabetic rats.In the 4-week experiment,insulin treatment under normal activity and vigorous exercise conditions increased the differentiation areas of bone in type 2 diabetic rats from 64.024%to 69.372%and from 73.225%to 75.336%,respectively;in the 8-week experiment,insulin treatment under normal activity and vigorous exercise conditions increased the differentiation areas of bone in type 2 diabetic rats from 67.239%to 72.910%and from 76.147%to 78.291%,respectively.Morphological parameters BV/TV,Tb.N,Tb.Th,Tb.Sp,and structure model index were significantly correlated with the differentiation areas of the bone and cartilage(P<0.05).Conclusions Under vigorous exercise conditions,BMSCs on the surface of cancellous bone in the 8-week insulin treatment group were more likely to differentiate into bone tissue.This study is of great significance for further understanding the effects of insulin on the bone under normal activity and vigorous exercise conditions,and provides theoretical guidance for the selection of the insulin therapy cycle and exercise mode in the clinical treatment of type 2 diabetes.

Chronic obstructive pulmonary disease(COPD)has become a common chronic disease in the adult in recent years,and more attention has been gradually paid to its prevention and treatment.This paper reviewed the clinical studies about the effect of traditional Chinese medicine(TCM)exercise therapy on COPD,and indicated that TCM exercise therapy can improve the rehabilitation of COPD patients.TCM exercise therapies,such as Tai Chi,Wuqinxi,Baduanjin,and Liuzijue,have been shown to significantly improve lung function,inflammation levels,and exercise capacity in COPD patients in recent studies.Tai Chi significantly improves patient's respiratory problems although lung function indices are not changed.Liuzijue enhances the strength and endurance of respiratory muscles and limbs.Baduanjin helps to improve patient's cognitive and emotional states.Overall,TCM exercise therapy provides an effective rehabilitation option for COPD patients.However,more clinical controlled trials are needed to further confirm their effectiveness and to develop appropriate rehabilitation programs for COPD patients.

OBJECTIVE: To review the research progress of rapid surgery for hip fracture in elderly patients. METHODS: The published studies, expert consensus, and guidelines at home and abroad were systematically summarized from the aspects of the characteristics of aging population, the benefits of rapid surgery, the disadvantages of delayed surgery, and the recommendations of current guidelines, so as to further guide clinical practice. RESULTS: Hip fracture is a common fracture type in the elderly population. As elderly patients generally have poor physique and often have a variety of underlying diseases, such as hypostatic pneumonia, bedsore, lower limb vein thrombosis, and other complications in conservative treatment, its disability rate and mortality are high, so surgical treatment is the first choice. At present, most relevant studies and expert consensus and guidelines at home and abroad support rapid surgery, that is, preoperative examination should be started immediately after admission, and adverse factors such as taking anticoagulant drugs, serious cardiovascular diseases, and severe anemia should be clearly and actively corrected, and surgery should be completed within 48 hours after admission as far as possible. Rapid surgery can not only significantly reduce the mortality of patients, but also reduce the length of hospital stay and the incidence of perioperative cognitive impairment, which is conducive to the recovery of patients with pain during hospitalization and postoperative function, and improve the prognosis of patients. CONCLUSION In order to avoid many problems caused by delayed surgery, the elderly patients with hip fracture should be operated as soon as possible under the condition of actively correcting the adverse factors. Comprehensive evaluation and preparation, the development of an individualized surgical plan, and the formation of a multidisciplinary medical team can reduce surgical risks and improve effectiveness.
Humans ; Aged ; Hip Fractures/epidemiology* ; Hospitalization ; Length of Stay ; Incidence ; Anemia ; Retrospective Studies

Functional hubs with disproportionately extensive connectivities play a crucial role in global information integration in human brain networks. However, most resting-state functional magnetic resonance imaging (R-fMRI) studies have identified functional hubs by examining spontaneous fluctuations of the blood oxygen level-dependent signal within a typical low-frequency band (e.g., 0.01-0.08 Hz or 0.01-0.1 Hz). Little is known about how the spatial distributions of functional hubs depend on frequency bands of interest. Here, we used repeatedly measured R-fMRI data from 53 healthy young adults and a degree centrality analysis to identify voxelwise frequency-resolved functional hubs and further examined their test-retest reliability across two sessions. We showed that a wide-range frequency band (0.01-0.24 Hz) accessible with a typical sampling rate (f_sample = 0.5 Hz) could be classified into three frequency bands with distinct patterns, namely, low-frequency (LF, 0.01-0.06 Hz), middle-frequency (MF, 0.06-0.16 Hz), and high-frequency (HF, 0.16-0.24 Hz) bands. The functional hubs were mainly located in the medial and lateral frontal and parietal cortices in the LF band, and in the medial prefrontal cortex, superior temporal gyrus, parahippocampal gyrus, amygdala, and several cerebellar regions in the MF and HF bands. These hub regions exhibited fair to good test-retest reliability, regardless of the frequency band. The presence of the three frequency bands was well replicated using an independent R-fMRI dataset from 45 healthy young adults. Our findings demonstrate reliable frequency-resolved functional connectivity hubs in three categories, thus providing insights into the frequency-specific connectome organization in healthy and disordered brains.
Brain/diagnostic imaging* ; Connectome/methods* ; Humans ; Magnetic Resonance Imaging/methods* ; Reproducibility of Results ; Rest ; Young Adult

Humans ; COVID-19 ; Quarantine ; Renal Dialysis ; SARS-CoV-2 ; Hospitals

Objective:To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL).Methods:A total of 557 patients from 2000—2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis.Results:The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 ( P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population ( P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy ( P<0.001). Radiotherapy dose was an independent factor affecting LRC( P<0.05). Conclusions:Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.

Objective:To evaluate the prognosis and determine the failure patterns after radiotherapy for low-risk early-stage patients with extranodal NK/T-cell lymphoma, nasal-type (ENKTCL).Methods:A total of 557 patients from 2000—2015 with low-risk early-stage ENKTCL who received radiotherapy (RT) with or without chemotherapy (CT) from China Lymphoma Collaborative Group were retrospectively reviewed. Among them, 427 patients received combined modality therapy, whereas 130 patients received RT alone. Survivals were calculated by Kaplan-Meier method and compared with Log-rank test. Overall survival (OS) was compared with age and sex-matched general Chinese population using expected survival and standardized mortality ratio (SMR). Cox stepwise regression model was used for multivariate analysis.Results:The 5-year OS and progression-free survival (PFS) were 87.2% and 77.2%. The SMR was 3.59 ( P<0.001) at 1 year after treatment, whereas it was 1.50 at 4 years after treatment, without significant difference between ENKTCL group and country-matched general population ( P=0.146). Compared with RT alone, CMT did not result in significantly superior 5-year OS (87.0% vs 87.4%, P=0.961) or PFS (76.1% vs 80.7%, P=0.129). Local failure (11.5%, 64/557) and distant failure (10.8%, 60/557) were the main failure modes, while regional failure was rare (2.9%, 16/557). The 5-year locoregional control rate (LRC) was 87.2% for the whole group, with 89.5% for ≥50 Gy versus 73.7% for <50 Gy ( P<0.001). Radiotherapy dose was an independent factor affecting LRC( P<0.05). Conclusions:Radiotherapy achieves a favorable prognosis in patients with low-risk early-stage ENKTCL. The incidence of either locoregional or distant failure is low. Radiation dose still is an important prognostic factor for LRC.

Objective To have SD rats inhaled with different drugs,and observe their lung pathological change of lungs through light microscopy,in order to evaluate the safety of different drugs inhaled by natural rats. Methods A total of 40 rats were randomly divided into 8 groups,and every group had 5 rats,including blank control groups,9 g/L saline group,Salbutamol group,Dingchuantang group,Shuanghuanglian group,Centamicin group,Danshen group,Silicon dioxide group,twice a day,last 56 days totally. Then,blood and bronchoalveolar lavage fluid were collected and analyzed for cell count,percent of each type of cell,to measure the severity of the inflammation. Additionally,histopathology re-vealed the lungˊs pathological change and the number of dust cell;while immunohistochemistry revealed CD163 respon-ding. Results (1)White blood cell count:blank control group(3. 96 ± 0. 36)×109/L,9 g/L saline group(4. 66 ± 0. 58)×109/L,Salbutamol group(4. 06 ± 0. 86)×109/L,Dingchuantang group(8. 98 ± 1. 08)×109/L,Shuanghuang-lian group(7. 10 ± 0. 88)×109/L,Centamicin group(6. 14 ± 0. 89)×109/L,Danshen group(9. 84 ± 2. 33)×109/L, Silicon dioxide group(8. 99 ± 2. 48)×109/L,and comparative analysis of the 8 groups had significant difference(F＝14. 530,P<0. 05);the differences among blank control group,9 g/L saline group and Salbutamol group were not sig- nificant(all P>0. 05). White cell count in BALF:blank control group(2. 16 ± 1. 04)×109/L,9 g/L saline group (3. 94 ± 0. 67)×109/L,Salbutamol group(4. 36 ± 1. 15)×109/L,Dingchuantang group(14. 58 ± 2. 93)×109/L, Shuanghuanglian group(19. 68 ± 6. 29)×109/L,Gentamicin group(11. 74 ± 1. 03)×109/L,Danshen group(44. 75 ± 10. 8)×109/L,Silicon dioxide group(53. 54 ± 14. 25)×109/L,and comparative analysis of the 8 groups had signifi-cant difference(F＝40. 616,P<0. 05);the differences among blank control group,9 g/L saline group and Salbutamol group were not significant(all P>0. 05). Lymphocyte count in BALF:blank control group(18. 70 ± 9. 00)×108/L, 9 g/L saline group( 36. 01 ± 5. 99 )×108/L,Salbutamol group( 38. 95 ± 11. 69 )×108/L,Dingchuantang group (132. 70 ± 26. 94)×108/L,Shuanghuanglian group(173. 56 ± 57. 6)×108/L,Gentamicin group(106. 60 ± 16. 76)× 108/L,Danshen group(340. 63 ± 70. 97)×108/L,Silicon dioxide group(495. 63 ± 131. 95)×108/L,and comparative analysis of the 8 groups had significant difference(F＝41. 980,P<0. 05);the differences among blank control group, 9 g/L saline group and Salbutamol group were not significant(all P>0. 05).(2)Number of lung dust cell count in 10 sight of high light microscopy:blank control group 12/10 HP,9 g/L saline group 26/10 HP,Salbutamol group 17/10 HP,Dingchuantang group 262/10 HP,Shuanghuanglian group 133/10 HP,Gentamicin group 109/10 HP,Danshen group 96/10 HP,Silicon dioxide group 315/10 HP,and comparative analysis of the 8 groups had significant difference (F＝69. 915,P<0. 05);the differences among blank control group,9 g/L saline group and Salbutamol group were not significant(all P>0. 05).(3)Hematoxylin-eosin staining of lung:blank control group,9 g/L saline group and Sal-butamol group had no pathological change in the lung,but Salbutamol group,Dingchuantang group,Shuanghuanglian group,Gentamicin group,Danshen group and Silicon dioxide group had pathological changes in different degrees.(4) Immunohistochemistry of CD163 responding:blank control group,9 g/L saline group and Salbutamol group had negative expression,Salbutamol group,Dingchuantang group,Shuanghuanglian group,Gentamicin group,Danshen group and Sili-con dioxide group had positive expression in different degrees. Conclusions 9 g/L saline,salbutamol for atomized inhalation does not cause lung tissue damage;Long-term use of non-atomized drugs in atomization can cause lung tissue injury in SD rats,and the severity varies with specific drugs.