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 construct a nursing quality evaluation indicator system for pulse indicator continuous cardiac output (PiCCO) monitoring and provide a basis for evaluating the nursing quality of PiCCO monitoring.Methods:Using Donabedian′s "structure-process-result" three-dimensional quality evaluation model as the theoretical framework, the nursing quality evaluation indicator system for PiCCO was established through literature search, Delphi expert correspondence, and hierarchical analysis during the period May to August 2023.Results:Of the 22 experts, 6 were male and 16 were female, aged (46.59 ± 4.34) years. The return rates of the questionnaires of the 2 rounds of expert correspondence were both 100%, the coefficients of expert authority were both 0.945, and the Kendall coordination coefficients were 0.045-0.186 ( χ2 values were 2.00-221.46, all P<0.05) and 0.045-0.132 ( χ2 values were 2.00-82.16, all P<0.05), respectively. The finalized nursing quality evaluation indicator system for PiCCO included 3 primary indicators, 7 secondary indicators, and 36 tertiary indicators. Conclusions:The nursing quality evaluation indicator system for PiCCO is practical and scientific, which can provide reference for PiCCO monitoring nursing quality evaluation.

Objective:To construct a nursing quality evaluation indicator system for pulse indicator continuous cardiac output (PiCCO) monitoring and provide a basis for evaluating the nursing quality of PiCCO monitoring.Methods:Using Donabedian′s "structure-process-result" three-dimensional quality evaluation model as the theoretical framework, the nursing quality evaluation indicator system for PiCCO was established through literature search, Delphi expert correspondence, and hierarchical analysis during the period May to August 2023.Results:Of the 22 experts, 6 were male and 16 were female, aged (46.59 ± 4.34) years. The return rates of the questionnaires of the 2 rounds of expert correspondence were both 100%, the coefficients of expert authority were both 0.945, and the Kendall coordination coefficients were 0.045-0.186 ( χ2 values were 2.00-221.46, all P<0.05) and 0.045-0.132 ( χ2 values were 2.00-82.16, all P<0.05), respectively. The finalized nursing quality evaluation indicator system for PiCCO included 3 primary indicators, 7 secondary indicators, and 36 tertiary indicators. Conclusions:The nursing quality evaluation indicator system for PiCCO is practical and scientific, which can provide reference for PiCCO monitoring nursing quality evaluation.

Objective:To analyze the regional differences and equity of the high-quality health resource allocation in primary healthcare institutions,and provide decision-making references for improving the equity of high-quality health resource allocation in primary healthcare institutions among provinces in China.Methods:The entropy weight method is used to determine the weights of indicators.Breakpoint method,Gini coefficient and grey correlation method are applied to conduct the classification,equity analysis and influencing factor analysis on the allocation levels of 31 provinces.Results:The Gini coefficients of the supply-demand ratio index in 2011,2016 and 2021 were 0.34,0.33 and 0.34,respectively.Population density,education level,education investment level,public service level,per capita GDP,regional income level and average altitude were the key influencing factors.Conclusion:There are significant differences in the high-quality health resource allocation among community-level medical and health care institutions in different provinces of China,and there are certain issues with equity.It is necessary to comprehensively consider multiple influencing factors to promote the balanced development of high-quality health resource allocation in community-level medical and health care institutions in China.

Skeletal muscle dysfunction is a common extra-pulmonary complication in patients with chronic ob-structive pulmonary disease(COPD),significantly impacting exercise capacity and quality of life,leading to a poorer prognosis and increased mortality.Oxidative stress closely associates with the development and progression of skeletal muscle dysfunction in COPD.Exercise,a core component of pulmonary rehabilitation,stands as the primary non-pharma-cological treatment for skeletal muscle dysfunction in COPD patients and exerts a positive modulating effect on oxidative stress.This paper reviews the effects of oxidative stress on skeletal muscle dysfunction in COPD and discusses the mecha-nisms by which exercise improves skeletal muscle dysfunction in COPD from an anti-oxidative stress perspective.It has been found that oxidative stress affects the structure and function of muscles in COPD patients by upregulating the protein hydrolysis system,disrupting mitochondrial function,and impairing calcium homeostasis.Mechanisms by which exercise modulates oxidative stress to improve skeletal muscle dysfunction include the activation of antioxidant genes such as silent mating type information regulation 2 homolog 1 and nuclear factor erythroid 2 related factor to enhance the body's antioxi-dant capacity,inhibiting muscle atrophy.Exercise also regulates mitochondrial reactive oxygen species metabolism,im-proving mitochondrial function,and reduces oxidase activity to protect sarcoplasmic reticulum calcium regulation.In con-clusion,the regulation of skeletal muscle oxidative stress by exercise is a crucial target for improving skeletal muscle dys-function in COPD.

Objective:To analyze the regional differences and equity of the high-quality health resource allocation in primary healthcare institutions,and provide decision-making references for improving the equity of high-quality health resource allocation in primary healthcare institutions among provinces in China.Methods:The entropy weight method is used to determine the weights of indicators.Breakpoint method,Gini coefficient and grey correlation method are applied to conduct the classification,equity analysis and influencing factor analysis on the allocation levels of 31 provinces.Results:The Gini coefficients of the supply-demand ratio index in 2011,2016 and 2021 were 0.34,0.33 and 0.34,respectively.Population density,education level,education investment level,public service level,per capita GDP,regional income level and average altitude were the key influencing factors.Conclusion:There are significant differences in the high-quality health resource allocation among community-level medical and health care institutions in different provinces of China,and there are certain issues with equity.It is necessary to comprehensively consider multiple influencing factors to promote the balanced development of high-quality health resource allocation in community-level medical and health care institutions in China.

Skeletal muscle dysfunction is a common extra-pulmonary complication in patients with chronic ob-structive pulmonary disease(COPD),significantly impacting exercise capacity and quality of life,leading to a poorer prognosis and increased mortality.Oxidative stress closely associates with the development and progression of skeletal muscle dysfunction in COPD.Exercise,a core component of pulmonary rehabilitation,stands as the primary non-pharma-cological treatment for skeletal muscle dysfunction in COPD patients and exerts a positive modulating effect on oxidative stress.This paper reviews the effects of oxidative stress on skeletal muscle dysfunction in COPD and discusses the mecha-nisms by which exercise improves skeletal muscle dysfunction in COPD from an anti-oxidative stress perspective.It has been found that oxidative stress affects the structure and function of muscles in COPD patients by upregulating the protein hydrolysis system,disrupting mitochondrial function,and impairing calcium homeostasis.Mechanisms by which exercise modulates oxidative stress to improve skeletal muscle dysfunction include the activation of antioxidant genes such as silent mating type information regulation 2 homolog 1 and nuclear factor erythroid 2 related factor to enhance the body's antioxi-dant capacity,inhibiting muscle atrophy.Exercise also regulates mitochondrial reactive oxygen species metabolism,im-proving mitochondrial function,and reduces oxidase activity to protect sarcoplasmic reticulum calcium regulation.In con-clusion,the regulation of skeletal muscle oxidative stress by exercise is a crucial target for improving skeletal muscle dys-function in COPD.

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.

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.

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.