ObjectiveTo construct and validate a clinical prediction model for Qi deficiency and blood stasis syndrome in chronic heart failure （CHF），aiming to assist clinical diagnosis and provide tools and methods for individualized treatment of CHF. MethodsThe clinical data of patients with chronic heart failure treated at Dongzhimen Hospital of Beijing University of Chinese Medicine from January 2022 to January 2024 were retrospectively collected. The patients were randomly divided into a training group and a validation group with a ratio of 7∶3. First， the least absolute shrinkage and selection operator （LASSO） regression analysis was used to preliminarily screen the predictive factors affecting the diagnosis of Qi deficiency and blood stasis syndrome in CHF. Subsequently， the Logistic regression method was applied to conduct a more in-depth and detailed analysis of these factors. Variables with P<0.05 in the results of the multi-factor Logistic regression were carefully selected and included. Based on the regression coefficients obtained from this analysis， a model was constructed， and a nomogram was accurately drawn. Using R software，the receiver operating characteristic （ROC） curve，calibration curve，and decision curve analysis （DCA） were precisely drawn. These analyses were used to comprehensively evaluate the model from three crucial aspects： discrimination，calibration，and clinical applicability. Additionally， the accuracy，specificity，sensitivity，positive predictive value，and negative predictive value of the model were meticulously calculated to conduct a more all-round and comprehensive assessment. ResultsIn total， 168 cases were successfully obtained in the training group， and 71 cases were included in the validation group. After a thorough comparison， it was found that there were no statistically significant differences in the baseline data between the two groups. After being rigorously screened by the LASSO-multivariate logistic regression method， dark red tongue，smoking history，cardiac troponin I，and N-terminal pro-B-type natriuretic peptide （NT-ProBNP） were identified as the influencing factors for diagnosing patients with the Qi deficiency and blood stasis syndrome in CHF. The constructed model demonstrated an area under the curve （AUC） of 0.812 in the training group and 0.719 in the validation group. The calibration curve showed that the predicted curve of the model was close to the actual observed curve. DCA indicated that the model could provide substantial clinical benefits for patients at the decision thresholds ranging from 0.2 to 0.9. ConclusionThe clinical prediction model for Qi deficiency and blood stasis syndrome in chronic heart failure constructed in this study shows good performance. It has certain application value in clinical practice， which may contribute to the improvement of the diagnosis and treatment of CHF patients with this syndrome.

Skeletal muscle dysfunction is a common extrapulmonary comorbidity of chronic obstructive pulmonary disease (COPD) and is associated with decreased quality-of-life and survival in patients. The autophagy lysosome pathway is one of the proteolytic systems that significantly affect skeletal muscle structure and function. Intriguingly, both promoting and inhibiting autophagy have been observed to improve COPD skeletal muscle dysfunction, yet the mechanism is unclear. This paper first reviewed the effects of macroautophagy and mitophagy on the structure and function of skeletal muscle in COPD, and then explored the mechanism of autophagy mediating the dysfunction of skeletal muscle in COPD. The results showed that macroautophagy- and mitophagy-related proteins were significantly increased in COPD skeletal muscle. Promoting macroautophagy in COPD improves myogenesis and replication capacity of muscle satellite cells, while inhibiting macroautophagy in COPD myotubes increases their diameters. Mitophagy helps to maintain mitochondrial homeostasis by removing impaired mitochondria in COPD. Autophagy is a promising target for improving COPD skeletal muscle dysfunction, and further research should be conducted to elucidate the specific mechanisms by which autophagy mediates COPD skeletal muscle dysfunction, with the aim of enhancing our understanding in this field.
Pulmonary Disease, Chronic Obstructive/physiopathology* ; Autophagy/physiology* ; Humans ; Muscle, Skeletal/pathology* ; Mitophagy ; Animals ; Mitochondria/metabolism* ; Lysosomes

Objective To systematically assess the spatiotemporal distribution,risk factors,and future trends of chronic obstructive pulmonary disease(COPD)among individuals under 50 years of age globally from 1990 to 2021 based on Global Burden of Disease(GBD)data in order to provide support for the formulation of prevention and control strategies of the disease.Methods The GBD data from 1990 to 2021 were analyzed for the incidence,mortality,disability-adjusted life years(DALYs),and estimated annual percentage change(EAPC)of COPD in<50-year-old individuals across 204 countries and regions.The data were stratified by age,sex,region,country,and sociodemographic index(SDI).The COPD trends until 2035 were predicted.Results In 2021,the global incidence of early-onset COPD was estimated at 2.5 million cases(95%uncertainty interval:2.09～2.96 million),representing a 50.55%increase compared to 1990.Significant regional heterogeneity was observed,with low SDI regions experiencing a 134.08%increase,whereas high SDI regions exhibited a rise-then-fall trend.Risk factor analysis identified environmental and occupational exposures(air pollution,ambient ozone pollution,household air pollution from solid fuels,etc.)and smoking as the primary etiological factors.Notably,household solid fuel exposure accounted for 50.90%of COPD-related deaths in low SDI regions,compared to only 0.03%in high SDI regions.Projections indicated that by 2035,the global burden of early-onset COPD will increase to 2.59 million cases.Conclusion The global disease burden of COPD among people under 50 years increased significantly from 1990 to 2021,with pronounced disparities across regions and socioeconomic levels.COPD deaths in low-SDI regions are strongly associated with solid fuel exposure and particulate matter pollution,and these regions are expected to remain the main drivers of global COPD incidence growth through 2035.

Objective To explore the value of combined detection of serum mitogen-activated protein kinase 1(MAPK1)and lysyl oxidase-like protein 2(LOXL2)in early diagnosis of cervical cancer.Methods A total of 218 patients with cervical lesions were selected as study group(103 ca-ses in cervical cancer group,115 cases in benign tumor group).Additionally,100 patients with cer-vical intraepithelial neoplasia grade Ⅱ were selected as precancerous lesion group,and 79 healthy in-dividuals undergoing physical examinations during the same period were selected as control group.Se-rum levels of MAPK1 and LOXL2 were measured in each group.Pearson correlation analysis was used to evaluate the correlations of serum MAPK1 and LOXL2 levels in patients with cervical cancer.Logistic regression analysis was performed to screen influencing factors for the occurrence of cervical cancer.Receiver operating characteristic(ROC)curves were plotted to assess the diagnostic efficacy of serum MAPK1 and LOXL2 for cervical cancer.Results Serum MAPK1 and LOXL2 levels in the study group were higher than those in the precancerous lesion group and the control group,and those in the precancerous lesion group were higher than those in the control group,with statistically signif-icant differences(P＜0.05).The proportion of patients with high-risk human papillomavirus(HPV)infection and serum MAPK1 and LOXL2 levels in the cervical cancer group were higher than those in the benign tumor group,with statistically significant differences(P＜0.05).Serum MAPK1 and LOXL2 levels in patients with stage Ⅲ to Ⅳ cervical cancer were higher than those in patients with stage Ⅰ to Ⅱ cervical cancer,with statistically significant differences(P＜0.05).Pearson correlation analysis showed a positive correlation between serum MAPK1 and LOXL2 levels in patients with cervical cancer(r=0.468,P＜0.001).Logistic regression analysis showed that high-risk HPV infection,MAPK1 and LOXL2 were all influencing factors for the occurrence of cervi-cal cancer(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)for com-bined diagnosis of serum MAPK1 and LOXL2 was 0.911,which was significantly greater than the AUCs for individual diagnoses(0.848 and 0.843,respectively).Conclusion Serum MAPK1 and LOXL2 levels in patients with cervical cancer are significantly upregulated,and the two indicators were positively correlated.High-risk HPV infection,serum MAPK1 and LOXL2 levels were influen-cing factors for the occurrence of cervical cancer.Combined detection of MAPK1 and LOXL2 levels is expected to assist in the diagnosis of cervical cancer.

Objective:Based on the needs of advanced nursing practice development, to establish an indicator system of role function of position of oncology genetic nurses suitable for our national condition, and to provide a basis for position establishing of nocology genetic nurses.Methods:Initial indexes were generated through the literature review and semi-structured interviews. From September to December 2022, two rounds of expert consultations and analytic hierarchy process were conducted to establish the evaluation index for role function of position of oncology genetic nurses.Results:A total of 43 experts were included in the study, the response rates of 2 rounds were 93.62%(44/47) and 97.73%(43/44), and the authority coefficients of the experts were 0.821 and 0.853. The Kendall′s coefficients of concordance for the 2 rounds of consultations were 0.100-0.150 (all P<0.01) and 0.101-0.237 (all P<0.01). Finally, the role function system of position for oncology genetic nurses was formed, which consisted of 5 first-level indexes, 17 second-level indexes and 86 third-level indexes. Conclusions:The system of role function of position for oncology genetic nurses is reasonable, scientific and reliable, professional and specific, which can provide a theoretical reference for the development of advanced nursing practice on hereditary oncology in China.

ObjectiveTo explore the effect and mechanism of Sishenjian on synovial lesions induced by monosodium iodoacetate （MIA） in rats with knee osteoarthritis （KOA）. MethodSixty female Sprague-Dawley （SD） rats were randomly divided into the following six groups： normal group， model group， celecoxib group， and high-， medium-， and low-dose Sishenjian group. The KOA rat model was established by intra-articular injection of MIA. Celecoxib （18 mg·kg^-1） and Sishenjian （14.4， 7.2， 3.6 g·kg^-1） were administered by gavage according to the groups. All rats were euthanized after four weeks of continuous administration. The transverse diameter of the bilateral knee joints of rats was measured， and gross observation of the knee joint was performed. Pathological changes in knee joint synovial tissue were observed by hematoxylin-eosin （HE） staining and picrosirius red staining. Immunohistochemistry （IHC） was used to detect the expression of vascular endothelial growth factor A （VEGFA） in synovial tissue. The levels of inflammatory cytokines in the joint synovial fluid were detected by enzyme-linked immunosorbent assay （ELISA）. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were used to detect the expression of mRNA and proteins related to the transforming growth factor-β₁ （TGF-β₁）/Smad2/3 pathway in knee joint synovium. ResultCompared with the normal group， the transverse diameter of the knee joint in the model group significantly increased （P<0.01）. Compared with the model group， the transverse diameter of the knee joint in rats of each Sishenjian group significantly decreased （P<0.01）. Compared with the normal group， the expression levels of interleukin-1β （IL-1β） and tumor necrosis factor-α （TNF-α） in the knee joint synovial fluid of model group significantly increased （P<0.01）. Compared with the model group， the expression levels of IL-1β and TNF-α in the knee joint synovial fluid of rats in each Sishenjian group significantly decreased （P<0.01）. Compared with the normal group， the expression levels of TGF-β₁， Smad2/3， phosphorylation（p）-Smad2/3， type Ⅰ collagen α1 （ColⅠ_α1）， type Ⅲ collagen α1 （ColⅢ_α1）， VEGFA proteins and TGF-β₁， Smad2/3， ColⅠ_α1， ColⅢ_α1 mRNA in knee joint synovium of model group significantly increased （P<0.01）. Compared with the model group， the expression levels of TGF-β₁， Smad2/3， phosphorylation （p）-Smad2/3， ColⅠ_α1， ColⅢ_α1， VEGFA proteins and TGF-β₁， Smad2/3， ColⅠ_α1， ColⅢ_α1 mRNA in knee joint synovium of rats in each Sishenjian group significantly decreased （P<0.05， P<0.01）. ConclusionSishenjian can inhibit synovial inflammation and angiogenesis， and may become a potential drug for treating synovial lesions in KOA by regulating the TGF-β₁/Smad2/3 pathway.

Background and purpose:The overexpression of carnitine palmitoyl transferase 1A(CPT1A)is related to the poor prognosis of breast cancer,and it can promote the utilization of fatty acids by mitochondria and maximize triphosphate(ATP)production.However,the role of CPT1A in breast cancer metastasis is still unclear.This study aimed to explore the mechanism that mitochondrial dysfunction and CPT1A/extracellular signal-regulated kinase(ERK)signaling pathway in breast cancer jointly regulate the malignant behavior of breast cancer.Methods:The lentivirus system and shRNA tools were used to overexpress or knock down CPT1A in human breast cancer cell lines MDA-MB-231 and MCF7,and the cells were divided into NC group,CPT1A group and shCPT1A group.The invasion ability of cells was detected by transwell assay,and the protein expressions of peroxisome proliferator-activated receptor γ coactivator-1α(PGC-1α),ERK1/2 and CPT1A were analyzed by Western blot.The mitochondrial morphology of MDA-MB-231 and MCF7 cell lines was analyzed using mitochondrial red staining,and mitochondrial respiratory capacity was analyzed by oxygen consumption rate.Results:Compared with cells expressing control vector,overexpression of CPT1A resulted in enhanced invasion abilities of MCF7 cells and MDA-MB-231 cells(P＜0.05),while knockdown of shCPT1A resulted in decreased invasion abilities of cells(P＜0.05).Compared with NC group,the length of mitochondrial branches in MDA-MB-231 and MCF7 cells in CPT1A group was significantly shorter(P＜0.05),and the expressions of ERK1/2 and PGC-1α increased significantly(P＜0.05).In shCPT1A group,the length of mitochondrial branches in MDA-MB-231 and MCF7 cells increased significantly(P＜0.05),and the expressions of ERK1/2 and PGC-1α decreased significantly(P＜0.05).In addition,compared with NC group,the cellular basis,maximum respiratory capacity and ATP production of MDA-MB-231 in CPT1A group increased significantly(P＜0.05),while the cellular basis,maximum respiratory capacity and ATP production of MDA-MB-231 in shCPT1A group decreased significantly(P＜0.05).Conclusion:ERK1/2-PGC-1α activated by CPT1A Signaling pathway plays a key role in mitochondrial division mediated breast cancer cell metastasis.

Objective:Analyze the impact of smoking on the mortality and life expectancy of residents in Tianjin in 2019.Methods:Use mortality case-control study method to collect all cause of death cases of residents in Tianjin in 2019 for analysis. After adjusting for the 5-years-old age group, education level, and marital status, the smoking attributed deaths from different diseases of different genders, smoking attributed deaths in different age groups, and their impact on life expectancy were analyzed.Results:The total number of deaths in 2019 was 75 254, with 42 201 males (56.1%). Among male deaths, 3 215 (9.9%) were attributed to smoking, of which 2 157 (50.2%) lung cancer deaths were attributed to smoking; The risk of lung cancer death among smokers was 3.075 times higher than that of non-smokers (95% CI: 2.812-3.364); Among the 33 053 female deaths (43.9%), 1 396 (5.8%) were caused by smoking, with 744 (29.1%) lung cancer deaths attributed to smoking. The age group with the highest number of deaths attributed to smoking for women was the 75-<80 years old age group, followed by the 70-<75 and 80-<85 years old age groups. The age group with the highest proportion of deaths attributed to smoking for men was the 55-<60 years old age group. In addition, smoking accounts for more than 60% of deaths in the 60-<65, 45-<50, 55-<60, and 65-<70 years old age groups. In 2019, the loss of life expectancy attributed to smoking deaths among all residents in Tianjin was 1.13 years, with a loss of 1.15 years for males and 0.57 years for females. The expected life expectancy excluding deaths caused by smoking was 82.92 years, 80.77 years for males and 84.61 years for females. Conclusions:Smoking remains one of the important risk factors for death among residents. Promoting effective measures to reduce smoking rates is an effective way to increase life expectancy.

Objective To investigate the effect of pelvic floor muscle training based on timing theory in patients undergoing robot-assisted laparoscopic radical prostatectomy.Methods A total of 112 patients undergoing robot-assisted laparoscopic radical resection of prostate cancer in the First Affiliated Hospital of Fujian Medical University were selected as the study subjects from August 2021 to August 2022.57 patients in control group were given routine intervention measures,and 55 patients in experimental group were given pelvic floor muscle intervention based on timing theory on the basis of routine intervention measures.The intervention lasted for 1 year.The intervention effects of urinary control ability,urinary incontinence recovery rate and pelvic floor function rehabilitation were compared between two groups in each period after surgery.Results 24h after catheter removal,3 months and 6 months after the intervention,the experimental group had more advantages in urinary control score,urinary incontinence recovery rate and pelvic floor function recovery score(P＜0.05),but there was no statistical significance in the above aspects between the two groups at 12 months after the operation(P＞0.05).Conclusion The pelvic floor muscle training method based on the timing theory is scientific and feasible to a certain extent,and the intervention starts before surgery and lasts until 1 year after surgery,which significantly improves the postoperative urinary incontinence symptoms of patients with robot-assisted laparoscopic radical prostatectomy within the baseline level,improves the recovery rate of urinary incontinence,and helps the early rehabilitation of patients with postoperative urinary control ability.

P21-activated kinase 5 (PAK5) belongs to the PAK-II subfamily, which is an important regulator of cell survival, adhesion, and motility. However, the functions of PAK5 in endometriosis remain unclear. Here, PAK5 is strikingly upregulated in endometriosis. Furthermore, the knockdown of PAK5 or its inhibitor GNE 2861 blocks the development of endometriosis, which is equally demonstrated in PAK5-knockout mice. In addition, PAK5 promotes glycolysis by enhancing the protein stability of pyruvate kinase 2 (PKM2) in endometriotic cells, which is a key enzyme for glucose metabolism. Moreover, the phosphorylation of PKM2 at Ser519 by PAK5 mediates endometriosis cell proliferation and metastasis. Collectively, PAK5 plays an indispensable role in endometriosis. Our findings demonstrate that PAK5 is an important target for the treatment of endometriosis.
Endometriosis/genetics* ; Female ; Animals ; p21-Activated Kinases/genetics* ; Mice ; Phosphorylation ; Glycolysis ; Humans ; Thyroid Hormone-Binding Proteins ; Membrane Proteins/genetics* ; Carrier Proteins/genetics* ; Cell Proliferation ; Mice, Knockout ; Thyroid Hormones/metabolism* ; Pyruvate Kinase/genetics*