Objective:To investigate the early right heart function management strategy and prognosis after left ventricular assist device(LVAD) implantation in patients with preoperative right ventricular dysfunction.Methods:A retrospective study was conducted. From March 2022 to April 2024, a total of 28 patients with end-stage heart failure underwent LVAD implantation at Nanjing First Hospital and were admitted to the intensive care unit(ICU) after surgery. Among them, patients with preoperative right ventricular dysfunction were enrolled. All patients were implanted with Corheart 6 implantable left ventricular assist device. The clinical data, occurrence of postoperative right heart failure and postoperative survival situations of enrolled patients were collected and analyzed.Results:A total of 12 patients were included in this study, including 11 males and 1 female, the mean age was(58.4±7.6) years old. Upon postoperative admission to ICU, the most commonly used positive inotropic agent was epinephrine(9 cases), followed by dobutamine(8 cases). By the second day after surgery, the most frequently utilized vasoactive medications were epinephrine and phosphodiesterase type Ⅲ inhibitors, both with 9 cases of usage. None of the enrolled patients utilized temporary mechanical circulatory assist devices. The LVAD pump speed of the patients enrolled in the study was set at approximately 2 700 revolutions per minute, and the pump flow was approximately 3 liters per minute. During the first two days after the operation, the fluid balance of the enrolled patients ranged from(-523.4±775.6)ml to(-1 248.0±1 023.9)ml. At 48 h following the operation, the mean pulmonary artery pressure(MPAP)[(26.2±4.8) mmHg vs.(32.1±6.5) mmHg(1 mmHg=0.133 kPa), P=0.042] and the pulmonary artery wedge pressure(PAWP)[(15.6±5.5)mmHg vs.(24.9±5.9) mmHg, P=0.003) ] of the enrolled patients were significantly decreased compared to preoperative levels, while the cardiac index(CI) was significantly improved[(2.7±0.2)L·min -1·m -2 vs.(2.1±0.5)L·min -1·m -2,P=0.024]. Echocardiography showed that the left atrial diameter(LAD)[(51.5±7.6)mm vs.(57.2±9.0)mm, P=0.005] and left ventricular end diastolic diameter(LVDd)[(73.5±11.5)mm vs.(78.3 ± 12.3)mm, P=0.012) ] were significantly reduced post LVAD implantation as compared to before LVAD implantation, while there was no significant difference in tricuspid annular plane systolic excusion(TAPSE). Postoperative total bilirubin(TBIL) decreased significantly compared to preoperative levels[(15.5±5.0)μmol/L vs.(27.5±17.0)μmol/L, P=0.038]. Three patients experienced right heart failure after the LVAD implantation, with an incidence rate of 25%. Nevertheless, the right heart failure was rectified during the ICU treatment period. The mean ICU treatment time for all enrolled patients was(8.6±2.9) days, the average postoperative hospital stay was(24.3±4.8) days. All enrolled patients survived at 3 months after LVAD implantation. Conclusion:Despite the presence of right ventricular dysfunction in patients before LVAD implantation, with strict fluid management, reasonable LVAD parameters, and appropriate vasoactive drugs, they are able to smoothly pass through the perioperative period, achieve the goals of left ventricular decompression, increase cardiac output, improve perfusion of the end organs, and obtain favorable short-term therapeutic effects.

Objective:To investigate the early right heart function management strategy and prognosis after left ventricular assist device(LVAD) implantation in patients with preoperative right ventricular dysfunction.Methods:A retrospective study was conducted. From March 2022 to April 2024, a total of 28 patients with end-stage heart failure underwent LVAD implantation at Nanjing First Hospital and were admitted to the intensive care unit(ICU) after surgery. Among them, patients with preoperative right ventricular dysfunction were enrolled. All patients were implanted with Corheart 6 implantable left ventricular assist device. The clinical data, occurrence of postoperative right heart failure and postoperative survival situations of enrolled patients were collected and analyzed.Results:A total of 12 patients were included in this study, including 11 males and 1 female, the mean age was(58.4±7.6) years old. Upon postoperative admission to ICU, the most commonly used positive inotropic agent was epinephrine(9 cases), followed by dobutamine(8 cases). By the second day after surgery, the most frequently utilized vasoactive medications were epinephrine and phosphodiesterase type Ⅲ inhibitors, both with 9 cases of usage. None of the enrolled patients utilized temporary mechanical circulatory assist devices. The LVAD pump speed of the patients enrolled in the study was set at approximately 2 700 revolutions per minute, and the pump flow was approximately 3 liters per minute. During the first two days after the operation, the fluid balance of the enrolled patients ranged from(-523.4±775.6)ml to(-1 248.0±1 023.9)ml. At 48 h following the operation, the mean pulmonary artery pressure(MPAP)[(26.2±4.8) mmHg vs.(32.1±6.5) mmHg(1 mmHg=0.133 kPa), P=0.042] and the pulmonary artery wedge pressure(PAWP)[(15.6±5.5)mmHg vs.(24.9±5.9) mmHg, P=0.003) ] of the enrolled patients were significantly decreased compared to preoperative levels, while the cardiac index(CI) was significantly improved[(2.7±0.2)L·min -1·m -2 vs.(2.1±0.5)L·min -1·m -2,P=0.024]. Echocardiography showed that the left atrial diameter(LAD)[(51.5±7.6)mm vs.(57.2±9.0)mm, P=0.005] and left ventricular end diastolic diameter(LVDd)[(73.5±11.5)mm vs.(78.3 ± 12.3)mm, P=0.012) ] were significantly reduced post LVAD implantation as compared to before LVAD implantation, while there was no significant difference in tricuspid annular plane systolic excusion(TAPSE). Postoperative total bilirubin(TBIL) decreased significantly compared to preoperative levels[(15.5±5.0)μmol/L vs.(27.5±17.0)μmol/L, P=0.038]. Three patients experienced right heart failure after the LVAD implantation, with an incidence rate of 25%. Nevertheless, the right heart failure was rectified during the ICU treatment period. The mean ICU treatment time for all enrolled patients was(8.6±2.9) days, the average postoperative hospital stay was(24.3±4.8) days. All enrolled patients survived at 3 months after LVAD implantation. Conclusion:Despite the presence of right ventricular dysfunction in patients before LVAD implantation, with strict fluid management, reasonable LVAD parameters, and appropriate vasoactive drugs, they are able to smoothly pass through the perioperative period, achieve the goals of left ventricular decompression, increase cardiac output, improve perfusion of the end organs, and obtain favorable short-term therapeutic effects.

Objective To investigate the relationship between nuclear factor(NF)-κB signaling pathway and gender differences in alcoholic liver fibrosis. Methods C57BL/6 N mice at 7-8 weeks of age were randomly divided into: male normal group, male model group, female normal group and female model group of 20 mice each. The normal group was fed with control liquid diet for 8 weeks, and the model group was fed with alcoholic liquid diet for 8 weeks combined with 31.5% ethanol gavage (5g/kg twice a week) to establish an alcoholic liver fibrosis model. The mice were executed at the end of 8 weekends, and the alanine aminotransferase (ALT), aspartate aminotransferase (AST) activity, estradiol (E

Objective To describe the epidemiological characteristics of falls among hospitalized elderly patients in Shanghai,to explore the external and self-factors that affect falls in the elderly,and to provide evidence for the elderly to prevent falls.Methods All the injury cases collected from the hospital information system of a general hospital in Shanghai during 2020 and 2022 based on Haddon Model were taken as the research objects.The epidemiological characteristics were analyzed using constituent ratio,chi-square test and Logistic regression analysis.Results Falls occured in 11 152 cases(11.63%)within 95 880 hospitalized elderly patients aged 65 years old and over.The ratio of males to females was 0.49∶1.Falls were more likely to occur in females and those who lived with children,and the place was mainly home/residential institutions.The time distribution showed the fewest occurrence in February.The mainly injured part was the trunk and limbs with the nature of fracture.Multiple regression analysis showed that compared to males,65-75 years old,spring,married status and living with spouses,the risk factors of falls in elderly patients were female,older age,winter,not in marriage and living with children.Conclusion The elderly have a high risk of falls,which is influenced by a combination of factors such as personal health,the natural environment,and social support.Comprehensive measures should be taken to identify and address the risk of falls in the elderly,including personal health promotion,home environment optimization,harmonious family atmosphere,professional medical support,and social collaboration,in order to achieve effective prevention and management.

Objective:To analyze the status of respiratory pathogen detection and the clinical features in children with Mycoplasma pneumoniae pneumonia (MPP). Methods:A prospective, multicenter study was conducted to collect clinical data, including medical history, laboratory examinations and multiplex PCR tests of children diagnosed with MPP from 4 hospitals in China between November 15 th and December 20 th, 2023. The multiplex PCR results and clinical characteristics of MPP children in different regions were analyzed. The children were divided into severe and mild groups according to the severity of the disease. Patients in the severe group were further divided into Mycoplasma pneumoniae (MP) alone and Multi-pathogen co-detection groups based on whether other pathogens were detected besides MP, to analyze the influence of respiratory pathogen co-detection rate on the severity of the disease. Mann-Whitney rank sum test and Chi-square test were used to compare data between independent groups. Results:A total of 298 children, 136 males and 162 females, were enrolled in this study, including 204 children in the severe group with an onset age of 7.0 (6.0, 8.0) years, and 94 children in the mild group with an onset age of 6.5 (4.0, 7.8) years. The level of C-reactive protein, D-dimer, lactic dehydrogenase (LDH) were significantly higher (10.0 (5.0, 18.0) vs. 5.0 (5.0, 7.5) mg/L, 0.6 (0.4, 1.1) vs. 0.5 (0.3, 0.6) mg/L, 337 (286, 431) vs. 314 (271, 393) U/L, Z=2.02, 2.50, 3.05, all P<0.05), and the length of hospitalization was significantly longer in the severe group compared with those in mild group (6.0 (6.0, 7.0) vs. 5.0 (4.0, 6.0) d, Z=4.37, P<0.05). The time from onset to admission in severe MPP children was significantly shorter than that in mild MPP children (6.0 (5.0, 9.5) vs. 9.0 (7.0, 13.0) d, Z=2.23, P=0.026). All patients completed the multiplex PCR test, with 142 cases (47.7%) MPP children detected with 21 pathogens including adenovirus 25 cases (8.4%), human coronavirus 23 cases (7.7%), rhinovirus 21 cases (7.0%), Streptococcus pneumoniae 21 cases (7.0%), influenza A virus 18 cases (6.0%). The pathogens with the highest detection rates in Tianjin, Shanghai, Wenzhou and Chengdu were Staphylococcus aureus at 10.7% (8/75), adenovirus at 13.0% (10/77), adenovirus at 15.3% (9/59), and both rhinovirus and Haemophilus influenzae at 11.5% (10/87) each. The multi-pathogen co-detection rate in severe MPP children was significantly higher than that in mild MPP group (52.9% (108/204) vs. 36.2% (34/94), χ2=10.62, P=0.005). Among severe MPP children, there are 89 cases in the multi-pathogen co-detection group and 73 cases in the simple MPP group. The levels of LDH, D-dimer and neutrophil counts in the multi-pathogen co-detection group were significantly higher than those in the simple MPP group (348 (284, 422) vs. 307 (270, 358) U/L, 0.8 (0.5, 1.5) vs. 0.6 (0.4, 1.0) mg/L, 4.99 (3.66, 6.89)×10 9vs. 4.06 (2.91, 5.65)×10 9/L, Z=5.17, 4.99, 6.11, all P<0.05). Conclusions:The co-detection rate of respiratory pathogens, LDH and D-dimer in children with severe MPP were higher than those with mild MPP. Among severe MPP children the stress response of children in co-detection group was more serious than that of children with simple MPP.

Objective To investigate the application effect of external treatment method of Xingqi Huoxue Zhitong Paste in the treatment of phlebitis. Methods Using mannitol as an inflammatory agent, a phlebitis model was established by infusion into the ear marginal vein of rabbits. Successfully modeled rabbits were randomly divided into four subgroups for intervention, while the blank control group was routinely raised without any intervention. After the intervention, the improvement effect of Xingqi Huoxue Zhitong Paste on mannitol-induced transfusion-induced phlebitis in rabbits was explored by observing the manifestations of phlebitis, serum interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and vascular endothelial growth factor A (VEGF-A) levels. Results The success rate was up to 90.0%. On the first day of treatment, there were 8 ineffective cases and 1 effective case in the saline group; 6 ineffective cases and 3 effective cases in the hirudoid group; 7 ineffective cases and 2 effective cases in the magnesium sulfate group; 7 ineffective cases and 2 effective cases in the Xingqi Huoxue Zhitong Paste group. There was no significant difference in the curative effect among the four groups (P=0.431). On the fourth day of treatment, there were 5 ineffective cases, 2 effective cases, and 2 markedly effective cases in the saline group; 1 effective case, 5 markedly effective cases, and 3 cured cases in the hirudoid group; 2 effective cases, 5 markedly effective cases, and 2 cured cases in the magnesium sulfate group; 2 effective cases, 4 markedly effective cases, and 3 cured cases in the Xingqi Huoxue Zhitong Paste group. On the fourth day of treatment, compared with the saline group, the curative effects of the hirudoid group (P=0.001), the magnesium sulfate group (P=0.020), and the Xingqi Huoxue Zhitong Paste group (P=0.003) were statistically significant. There was no significant difference in curative effect in the magnesium sulfate group and the Xingqi Huoxue Zhitong Paste group when compared with the hirudoid group (P>0.05); there was no significant difference in curative effect in the Hirudoid group and the Xingqi Huoxue Zhitong Paste group when compared with the magnesium sulfate group (P>0.05); there was no significant difference in curative effect in the hirudoid group and the magnesium sulfate group when compared with the Xingqi Huoxue Zhitong Paste group (P>0.05). The effective rate of the saline group was 11.1%, and the cure rate was 0%. The effective rate of the hirudoid group was 100.0%, and the cure rate was 33.3%. The effective rate of the magnesium sulfate group was 77.7%, and the cure rate was 44.4%. The effective rate of the Xingqi Huoxue Zhitong Paste group was 66.7%, and the cure rate was 22.2%. The drug effectiveness of the Xingqi Huoxue Zhitong Paste group, the hirudoid group, and the magnesium sulfate group was higher than that of the saline group (P < 0.05). After the intervention, the levels of serum inflammatory factors IL-6, TNF-α, and VEGF-A in the four model subgroups were statistically significant compared with the blank control group (P < 0.05). The levels of serum inflammatory factors IL-6, TNF-α, and VEGF-A in the saline group showed significant difference from those in the hirudoid group, the magnesium sulfate group, and the Xingqi Huoxue Zhitong Paste group (P < 0.05). Compared with the hirudoid group, the differences in serum inflammatory factors IL-6, TNF-α, and VEGF-A contents in the magnesium sulfate group and the Xingqi Huoxue Zhitong Paste group were statistically significant (P < 0.05). The inflammatory factor levels in the blank control group were the lowest, while those in the normal saline group were the highest. Conclusion Xingqi Huoxue Zhitong Paste group has an improving effect on mannitol-induced infusion phlebitis in rabbits, but its efficacy is inferior to that of the commonly used hirudoid ointment. Therefore, appropriate adjustments and improvements can be made to the drug formula to enhance its effectiveness.

Nuclear transporter importin-β1 is emerging as an attractive target by virtue of its prevalence in many cancers. However, the lack of druggable inhibitors restricts its therapeutic proof of concept. In the present work, we optimized a natural importin-β1 inhibitor DD1 to afford an improved analog DD1-Br with better tolerability (>25 folds) and oral bioavailability. DD1-Br inhibited the survival of castration-resistant prostate cancer (CRPC) cells with sub-nanomolar potency and completely prevented tumor growth in resistant CRPC models both in monotherapy (0.5 mg/kg) and in enzalutamide-combination therapy. Mechanistic study revealed that by targeting importin-β1, DD1-Br markedly inhibited the nuclear accumulation of multiple CRPC drivers, particularly AR-V7, a main contributor to enzalutamide resistance, leading to the integral suppression of downstream oncogenic signaling. This study provides a promising lead for CRPC and demonstrates the potential of overcoming drug resistance in advanced CRPC via targeting importin-β1.

OBJECTIVE: To observe the impacts of acupuncture on depressive mood and sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia, and explore its effect mechanism. METHODS: A total of 60 patients with comorbid mild-to-moderate depressive disorder and insomnia were randomly divided into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 2 cases dropped off). In the observation group, acupuncture and low frequency repeated transcranial magnetic stimulation (rTMS) were combined for the intervention. Acupuncture was applied to Baihui (GV 20), Yintang (GV 24⁺), Neiguan (PC 6) and Yanglingquan (GB 34), etc., the needles were retained for 30 min; and the intradermal needles were embedded at Xinshu (BL 15) and Danshu (BL 19) for 2 days. After acupuncture, the rTMS was delivered at the right dorsolateral prefrontal cortex (R-DLPFC), with 1 Hz and 80% of movement threshold, lasting 30 min in each treatment. In the control group, the sham-acupuncture was adopted, combined with low frequency rTMS. The acupoint selection and manipulation were the same as the observation group. In the two groups, acupuncture was given once every two days, 3 times weekly; while, rTMS was operated once daily, for consecutive 5 days a week. The duration of treatment consisted of 4 weeks. Hamilton depression scale-17 (HAMD-17) and Pittsburgh sleep quality index (PSQI) scores were observed before and after treatment, as well as 1 month after the treatment completion (follow-up period) separately. Besides, the levels of nerve growth factor (BDNF) and γ-aminobutyric acid (GABA) in the serum were detected before and after treatment in the two groups. RESULTS: After treatment and in follow-up, the HAMD-17 scores were lower than those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than the control group (P<0.05). After treatment, the total scores and the scores of each factor of PSQI were reduced in the two groups in comparison with those before treatment except for the score of sleep efficiency in the control group (P<0.05); the total PSQI score and the scores for sleep quality, sleep latency, sleep efficiency and daytime dysfunction in the observation group were all lower than those in the control group (P<0.05). In the follow-up, except for the scores of sleep duration and sleep efficiency in the control group, the total PSQI score and the scores of all the other factors were reduced compared with those before treatment in the two groups (P<0.05); the total PSQI score and the scores of sleep quality, sleep latency, sleep duration, sleep efficiency and daytime dysfunction in the observation group were lower than the control group (P<0.05). After treatment, the levels of serum BDNF and GABA were increased in comparison with those before treatment in the observation group (P<0.05), and the level of serum BDNF was higher than that in the control group (P<0.05). CONCLUSION Acupuncture relieves depressive mood and improves sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia. The effect mechanism may be related to the regulation of BDNF and GABA levels and the promotion of brain neurological function recovery.
Humans ; Sleep Initiation and Maintenance Disorders/therapy* ; Transcranial Magnetic Stimulation ; Brain-Derived Neurotrophic Factor ; Treatment Outcome ; Acupuncture Therapy ; Acupuncture Points ; gamma-Aminobutyric Acid ; Depressive Disorder

BACKGROUND: Although intensively studied in patients with cardiovascular diseases (CVDs), the prognostic value of diastolic blood pressure (DBP) has little been elucidated in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD). This study aimed to reveal the prognostic value of DBP in AECOPD patients. METHODS: Inpatients with AECOPD were prospectively enrolled from 10 medical centers in China between September 2017 and July 2021. DBP was measured on admission. The primary outcome was all-cause in-hospital mortality; invasive mechanical ventilation and intensive care unit (ICU) admission were secondary outcomes. Least absolute shrinkage and selection operator (LASSO) and multivariable Cox regressions were used to identify independent prognostic factors and calculate the hazard ratio (HR) and 95% confidence interval (CI) for adverse outcomes. RESULTS: Among 13,633 included patients with AECOPD, 197 (1.45%) died during their hospital stay. Multivariable Cox regression analysis showed that low DBP on admission (<70 mmHg) was associated with increased risk of in-hospital mortality (HR = 2.16, 95% CI: 1.53-3.05, Z = 4.37, P <0.01), invasive mechanical ventilation (HR = 1.65, 95% CI: 1.32-2.05, Z = 19.67, P <0.01), and ICU admission (HR = 1.45, 95% CI: 1.24-1.69, Z = 22.08, P <0.01) in the overall cohort. Similar findings were observed in subgroups with or without CVDs, except for invasive mechanical ventilation in the subgroup with CVDs. When DBP was further categorized in 5-mmHg increments from <50 mmHg to ≥100 mmHg, and 75 to <80 mmHg was taken as reference, HRs for in-hospital mortality increased almost linearly with decreased DBP in the overall cohort and subgroups of patients with CVDs; higher DBP was not associated with the risk of in-hospital mortality. CONCLUSION: Low on-admission DBP, particularly <70 mmHg, was associated with an increased risk of adverse outcomes among inpatients with AECOPD, with or without CVDs, which may serve as a convenient predictor of poor prognosis in these patients. CLINICAL TRIAL REGISTRATION Chinese Clinical Trail Registry, No. ChiCTR2100044625.
Humans ; Blood Pressure ; Pulmonary Disease, Chronic Obstructive/therapy* ; Cohort Studies ; Respiration, Artificial ; Inpatients ; Hospital Mortality

Male diabetic individuals present a marked impairment in fertility; however, knowledge regarding the pathogenic mechanisms and therapeutic strategies is unsatisfactory. The new hypoglycemic drug dapagliflozin has shown certain benefits, such as decreasing the risk of cardiovascular and renal events in patients with diabetes. Even so, until now, the effects and underlying mechanisms of dapagliflozin on diabetic male infertility have awaited clarification. Here, we found that dapagliflozin lowered blood glucose levels, alleviated seminiferous tubule destruction, and increased sperm concentrations and motility in leptin receptor-deficient diabetic db/db mice. Moreover, the glucagon-like peptide-1 receptor (GLP-1R) antagonist exendin (9-39) had no effect on glucose levels but reversed the protective effects of dapagliflozin on testicular structure and sperm quality in db/db mice. We also found that dapagliflozin inhibited the testicular apoptotic process by upregulating the expression of the antiapoptotic protein B-cell lymphoma 2 (BCL2) and X-linked inhibitor of apoptosis protein (XIAP) and inhibiting oxidative stress by enhancing the antioxidant status, including total antioxidant capacity, total superoxide dismutase (SOD) activity, and glutathione peroxidase (GPx) activity, as well as decreasing the level of 4-hydroxynonenal (4-HNE). Exendin (9-39) administration partially reversed these effects. Furthermore, dapagliflozin upregulated the glucagon-like peptide-1 (GLP-1) level in plasma and GLP-1R expression by promoting AKT8 virus oncogene cellular homolog (Akt) phosphorylation in testicular tissue. Exendin (9-39) partially inhibited Akt phosphorylation. These results suggest that dapagliflozin protects against diabetes-induced spermatogenic dysfunction via activation of the GLP-1R/phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Our results indicate the potential effects of dapagliflozin against diabetes-induced spermatogenic dysfunction.
Mice ; Animals ; Male ; Proto-Oncogene Proteins c-akt/metabolism* ; Antioxidants ; Phosphatidylinositol 3-Kinases/metabolism* ; Semen/metabolism* ; Diabetes Mellitus