OBJECTIVES: To study the molecular mechanisms of LDH-loaded si-NEAT1 for regulating paclitaxel resistance and tumor-associated macrophage (TAM) polarization in breast cancer. METHODS: qRT-PCR and Western blotting were used to detect the expression of lncRNA NEAT1, miR-133b, and PD-L1 in breast cancer SKBR3 cells and paclitaxel-resistant SKBR3 cells (SKBR3-PR). The effects of transfection with si-NEAT1 and miR-133b mimics on MRP, MCRP and PD-L1 expressions and cell proliferation, migration and apoptosis were investigated using qRT-PCR, Western blotting, scratch and Transwell assays, and flow cytometry. Rescue experiments were conducted using si-NEAT1 and miR-133b inhibitor. Human THP-1 macrophages were cultured in the presence of conditioned media (CM) derived from SKBR3 and SKBR3-PR cells with or with si-NEAT1 transfection for comparison of IL-4-induced macrophage polarization by detecting the surface markers. LDH@si-NEAT1 nanocarriers were constructed, and their effects on MRP, MCRP and PD-L1 expressions and cell behaviors of the tumor cells were examined. THP-1 cells were treated with the CM from LDH@si-NEAT1-treated tumor cells, and the changes in their polarization were assessed. RESULTS: SKBR3-PR cells showered significantly upregulated NEAT1 and PD-L1 expressions and lowered miR-133b expression as compared with their parental cells. Transfection with si-NEAT1 and miR-133b mimics inhibited viability, promoted apoptosis and enhanced MRP and BCRP expressions in SKBR3-PR cells. NEAT1 knockdown obvious upregulated miR-133b and downregulated PD-L1, MRP and BCRP expressions. The CM from SKBR3-PR cells obviously promoted M2 polarization of THP-1 macrophages, which was significantly inhibited by CM from si-NEAT1-transfected cells. Treatment with LDH@si-NEAT1 effectively inhibited migration and invasion, promoted apoptosis, and reduced MRP, BCRP and PD-L1 expressions in the tumor cells. The CM from LDH@si-NEAT1-treated SKBR3-PR cells significantly downregulated Arg-1, CD163, IL-10, and PD-L1 and upregulated miR-133b expression in THP-1 macrophages. CONCLUSIONS LDH@si-NEAT1 reduces paclitaxel resistance of breast cancer cells and inhibits TAM polarization by targeting the miR-133b/PD-L1 axis.
Humans ; MicroRNAs/genetics* ; RNA, Long Noncoding/genetics* ; Paclitaxel/pharmacology* ; Breast Neoplasms/metabolism* ; Drug Resistance, Neoplasm ; B7-H1 Antigen/metabolism* ; Cell Line, Tumor ; Female ; Tumor-Associated Macrophages ; Apoptosis ; Cell Proliferation ; Macrophages ; Cell Movement

Objective To investigate the clinical efficacy of the"dynamic and static combination"approach in the treatment of Hepple Ⅰ-Ⅲ type osteochondral lesions of the talus(OLT),utilizing external ankle shaking,pulling,and poking manipulations in conjunction with ankle brace fixation.Methods A total of 82 patients diagnosed with OLT,who sought treatment at four hospitals between June 2022 and December 2023,were included in the study.Both the experimental and control groups received ankle immobilization using braces through-out the treatment period.The control group was administered Voltaren Emulgel topically twice daily(morning and evening),with each treatment course lasting 30 days,for a total of one course.The experimental group received additional therapeutic intervention involving shaking,pulling,and poking manipulations,conducted twice weekly,with the same duration and number of treatment courses as the control group.Follow-up assessments were scheduled at 2 weeks,4 weeks,and 2 months post-treatment.Outcome measures included the pain rating index(PRI),visual analogue scale(VAS)for pain intensity,current pain intensity(PPI),American Orthopaedic Foot & Ankle Society(AOFAS)ankle and hindfoot scores,proprioceptive function,and the size of OLT.Results During the longitudinal assessment conducted at 2-week,4-week,and follow-up intervals,the experimental group exhibited superior clinical outcomes compared to the control group,with statistically significant decreases in PRI,PPI,and AOFAS scores(all P＜0.05).VAS scores showed progressive improvement over time,with significant intergroup differences observed at both the 4-week and follow-up assessments(P＜0.05).Biomechanical analysis performed post-intervention indicated improved kinematic repositioning accuracy in the experimental group,as reflected by significantly reduced active-passive error angles(P＜0.05).Importantly,measurements of OLT area revealed notable therapeutic effects in the experimental group(P＜0.05),whereas no statistically significant changes were observed in the control group throughout the study period(all P＞0.05).Conclusions Under the guidance of the"dynamic and static combination"concept,the integration of shaking,pulling,and poking manipu-lation with conventional Western medicine-based conservative treatment for OLT demonstrates more pronounced advantages in alleviating pain,improving ankle joint function,restoring proprioception,facilitating lesion recovery,and enhancing overall quality of life.

Although percutaneous pulmonary artery denervation (PADN) has demonstrated long-term benefits in combined post- and pre-capillary pulmonary hypertension, its usefulness for isolated post-capillary pulmonary hypertension (IpcPH) remains unclear. This report presents 2 cases of IpcPH due to left heart failure who underwent PADN treatment following an insufficient response to optimized conventional therapy. This case study illustrates how PADN, when combined with heart failure guideline-directed medical therapy, may represent a promising treatment option for IpcPH.

Although percutaneous pulmonary artery denervation (PADN) has demonstrated long-term benefits in combined post- and pre-capillary pulmonary hypertension, its usefulness for isolated post-capillary pulmonary hypertension (IpcPH) remains unclear. This report presents 2 cases of IpcPH due to left heart failure who underwent PADN treatment following an insufficient response to optimized conventional therapy. This case study illustrates how PADN, when combined with heart failure guideline-directed medical therapy, may represent a promising treatment option for IpcPH.

Objective To investigate the clinical efficacy of the"dynamic and static combination"approach in the treatment of Hepple Ⅰ-Ⅲ type osteochondral lesions of the talus(OLT),utilizing external ankle shaking,pulling,and poking manipulations in conjunction with ankle brace fixation.Methods A total of 82 patients diagnosed with OLT,who sought treatment at four hospitals between June 2022 and December 2023,were included in the study.Both the experimental and control groups received ankle immobilization using braces through-out the treatment period.The control group was administered Voltaren Emulgel topically twice daily(morning and evening),with each treatment course lasting 30 days,for a total of one course.The experimental group received additional therapeutic intervention involving shaking,pulling,and poking manipulations,conducted twice weekly,with the same duration and number of treatment courses as the control group.Follow-up assessments were scheduled at 2 weeks,4 weeks,and 2 months post-treatment.Outcome measures included the pain rating index(PRI),visual analogue scale(VAS)for pain intensity,current pain intensity(PPI),American Orthopaedic Foot & Ankle Society(AOFAS)ankle and hindfoot scores,proprioceptive function,and the size of OLT.Results During the longitudinal assessment conducted at 2-week,4-week,and follow-up intervals,the experimental group exhibited superior clinical outcomes compared to the control group,with statistically significant decreases in PRI,PPI,and AOFAS scores(all P＜0.05).VAS scores showed progressive improvement over time,with significant intergroup differences observed at both the 4-week and follow-up assessments(P＜0.05).Biomechanical analysis performed post-intervention indicated improved kinematic repositioning accuracy in the experimental group,as reflected by significantly reduced active-passive error angles(P＜0.05).Importantly,measurements of OLT area revealed notable therapeutic effects in the experimental group(P＜0.05),whereas no statistically significant changes were observed in the control group throughout the study period(all P＞0.05).Conclusions Under the guidance of the"dynamic and static combination"concept,the integration of shaking,pulling,and poking manipu-lation with conventional Western medicine-based conservative treatment for OLT demonstrates more pronounced advantages in alleviating pain,improving ankle joint function,restoring proprioception,facilitating lesion recovery,and enhancing overall quality of life.

Frailty is related to the aging of the elderly, characterized by the decline of multi-system physiological functions and the increase of susceptibility. Both frailty and brain function decline are associated with age increase, and brain health can affect the postoperative outcomes and long-term quality of life in elderly patients. This paper provided a review on the relationship between frailty and brain health, specifically elaborating on the relationships of frailty with olfactory function decline, sleep disorders, and cognitive function, and aimed to remind medical staffs to pay attention to the frailty and brain function status of elderly patients, strengthen early evaluation and intervention, and improve the quality of life of elderly patients.

Dynamic changes in gut dysbiosis and metabolomic dysregulation are associated with immune-complex glomerulonephritis(ICGN).However,an in-depth study on this topic is currently lacking.Herein,we report an ICGN model to address this gap.ICGN was induced via the intravenous injection of cationized bovine serum albumin(c-BSA)into Sprague-Dawley(SD)rats for two weeks,after which mycophenolate mofetil(MMF)and losartan were administered orally.Two and six weeks after ICGN establishment,fecal samples were collected and 16S ribosomal DNA(rDNA)sequencing and untargeted metabolomic were conducted.Fecal microbiota transplantation(FMT)was conducted to determine whether gut normali-zation caused by MMF and losartan contributed to their renal protective effects.A gradual decline in microbial diversity and richness was accompanied by a loss of renal function.Approximately 18 genera were found to have significantly different relative abundances between the early and later stages,and Marvinbryantia and Allobaculum were markedly upregulated in both stages.Untargeted metabolomics indicated that the tryptophan metabolism was enhanced in ICGN,characterized by the overproduction of indole and kynurenic acid,while the serotonin pathway was reduced.Administration of losartan and MMF ameliorated microbial dysbiosis and reduced the accumulation of indoxyl conjugates in feces.FMT using feces from animals administered MMF and losartan improved gut dysbiosis by decreasing the Firmicutes/Bacteroidetes(F/B)ratio but did not improve renal function.These findings indicate that ICGN induces serous gut dysbiosis,wherein an altered tryptophan metabolism may contribute to its pro-gression.MMF and losartan significantly reversed the gut microbial and metabolomic dysbiosis,which partially contributed to their renoprotective effects.

Objective:To study the predictive values of lung ultrasound (LUS) score and Downes score in selecting respiratory support strategies for newborns with dyspnea.Methods:From September 2021 to July 2022, newborns admitted to our hospital with dyspnea were selected and assigned into the non-invasive respiratory support (N) group, invasive respiratory support (I) group and control (C) group based on the respiratory support strategies on admission. LUS scores and Downes scores at 6, 24, and 48 h after birth were recorded. ROC curves were drawn to determine the predictive values of LUS and Downes scores for respiratory support strategies.Results:A total of 263 cases were enrolled, including 105 cases in N group, 56 cases in I group and 102 cases in C group. The differences of LUS and Downes scores between the three groups at the same timepoint were statistically significant with I group had the highest scores, N group second and C group lowest ( P<0.05). LUS and Downes scores within each group at different timepoints were significantly different ( P<0.05).In all three groups, LUS and Downes scores were decreased with longer duration of treatment. LUS score, Downes score and PaO 2/FiO 2 were positively correlated with each other ( P<0.05). The area under the curve (AUC) of LUS score and Downes score predicting non-invasive respiratory support within 6 h after birth were 0.900 (95% CI 0.861-0.940, P<0.05) and 0.889 (95% CI 0.847-0.931, P<0.05), respectively, with the same cutoff of 2.5. The AUC of the combination of LUS and Downes scores predicting non-invasive respiratory support was 0.944 (95% CI 0.915-0.973, P<0.05). The AUC of LUS score and Downes score predicting invasive respiratory support were 0.979 (95% CI 0.963-0.995, P<0.05) and 0.831 (95% CI 0.760-0.902, P<0.05), respectively, with the same cutoff of 5.5. The AUC of the combination of LUS and Downes scores predicting invasive respiratory support was 0.985 (95% CI 0.972-0.998, P<0.05). Conclusions:Both LUS score and Downes score have certain predictive values for respiratory support strategies in newborns with dyspnea.

Evaluating the consistency of herb injectable formulations could improve their product quality and clinical safety, particularly concerning the composition and content levels of trace ingredients. Panax notoginseng Saponins Injection (PNSI), widely used in China for treating acute cardiovascular diseases, contains low-abundance (10%-25%) and trace saponins in addition to its five main constituents (notoginsenoside R₁, ginsenoside Rg₁, ginsenoside Re, ginsenoside Rb₁, and ginsenoside Rd). This study aimed to establish a robust analytical method and assess the variability in trace saponin levels within PNSI from different vendors and formulation types. To achieve this, a liquid chromatography-triple quadrupole mass spectrometry (LC-MS/MS) method employing multiple ions monitoring (MIM) was developed. A "post-column valve switching" strategy was implemented to eliminate highly abundant peaks (NR₁, Rg₁, and Re) at 26 min. A total of 51 saponins in PNSI were quantified or relatively quantified using 18 saponin standards, with digoxin as the internal standard. This study evaluated 119 batches of PNSI from seven vendors, revealing significant variability in trace saponin levels among different vendors and formulation types. These findings highlight the importance of consistent content in low-abundance and trace saponins to ensure product control and clinical safety. Standardization of these ingredients is crucial for maintaining the quality and effectiveness of PNSI in treating acute cardiovascular diseases.
Ginsenosides ; Saponins ; Chemometrics ; Panax notoginseng ; Cardiovascular Diseases ; Chromatography, Liquid ; Tandem Mass Spectrometry

Objective:To investigate the effects of breast milk to total milk intake ratio during hospitalization on the duration of antibiotic therapy in preterm infants less than 34 weeks of gestation.Methods:Clinical data of preterm infants ( n=1 792) less than 34 gestational weeks were retrospectively collected in 16 hospitals of Jiangsu Province Neonatal-Perinatal Cooperation Network from January 1, 2019, to December 31, 2021. The days of therapy (DOT) were used to evaluate the duration of antibiotic administration. The median DOT was 15.0 d (7.0-27.0 d). The patients were divided into four groups based on the quartiles of DOT: Q 1 (DOT≤7.0 d), Q 2 (7.0 d27.0 d) groups. According to the breast milk intake ratio (breast milk intake to total milk intake during hospitalization×100%), they were also divided into four groups: very-low-ratio breastfeeding group (breast milk intake ratio≤25%), low-ratio breastfeeding group (25%75%). Univariate analysis ( Chi-square test and Kruskal-Wallis rank-sum test) was used to analyze the factors influencing DOT. Spearman correlation analysis and trend Chi-square test were used to explore the relationship between breast milk intake ratio and DOT. After using multiple imputations to address missing data, two models were constructed after adjusting for different factors, and multinomial logistic regression model was applied to evaluate the effects of the breast milk intake ratio on DOT. Finally, sensitivity analysis was conducted to assess the stability of the models. Results:(1) Of the 1 792 preterm infants, there were 507 (28.3%) in the Q 1 group, 422 (23.5%) in the Q 2 group, 438 (24.4%) in the Q 3 group and 425 (23.7%) in the Q 4 group. (2) The median values of DOT in the very-low-ratio, low-ratio, medium-ratio and high-ratio breastfeeding groups were 20.0 d (11.0-31.0 d), 20.0 d (11.0-32.0 d), 13.0 d (6.0-25.8 d) and 10.0 d (4.0-21.0 d), respectively. Compared with the very-low-ratio and low-ratio breastfeeding groups, the medium-ratio and high-ratio breastfeeding groups had shorter DOT (all P<0.05). (3) After adjusting for factors with P<0.1 (prenatal glucocorticoid exposure, antimicrobial use within 24 h before delivery, gestational age at delivery, birth weight, Apgar score≤7 at 1 min, neonatal respiratory distress syndrome, infectious pneumonia and early-onset neonatal sepsis) between the DOT quartile groups, it showed that medium-ratio and high-ratio breastfeeding were protective factors in contrast to very-low-ratio breastfeeding in the Q 2, Q 3 and Q 4 groups as compared with the Q 1 group [Q 2 group: OR=0.50 (95% CI: 0.30-0.85) and OR=0.36 (95% CI: 0.26-0.51); Q 3 group: OR=0.31 (95% CI: 0.18-0.55) and OR=0.20 (95% CI: 0.14-0.29); Q 4 group: OR=0.22 (95% CI: 0.12-0.42) and OR=0.17 (95% CI: 0.12-0.26)]. Conclusion:Breast milk intake accounting for over 50% of total milk intake has a positive impact on reducing DOT in premature infants requiring antibiotics, which suggests that breastfeeding should be actively encouraged.