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

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.

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.

Objective To analyze the clinical effect of ultrasound-guided quadratus lumborum block(QLB)and erector spinae plane block(ESPB)in elderly patients with laparoscopic colorectal cancer surgery.Methods A total of 75 elderly patients who underwent elective laparoscopic radical resection of colorectal cancer in wenzhou central hospital,from August 2021 to March 2022 were selected and divided into quadratus lumborum group(group Q,n=25),erector spinae muscle group(group E,n=25)and group C(n=25).Group Q received QLB combined with general anesthesia,group E received ESPB combined with general anesthesia,the group C was given tracheal intubation with total intravenous general anesthesia.The perioperative anesthesia and analgesic dosage,postoperative recovery quality,resting and cough visual analogue scale(VAS)scores were compared among the groups.Results In contrast to the group C,the number of effective PCIA compressions,the dose of sufentanil,and the analgesic rescue rate were significantly decreased in groups Q and E(P<0.05);In contrast to the the group C,the spontaneous breathing,eye opening and tracheal extubation time of patients in group Q and group E were apparently shortened(P<0.05),and patients in group Q and group E recovered indoor nausea and vomiting,lethargy,restlessness and respiratory depression The number of cases was apparently reduced(P<0.05);at each time point from 2 to 48 hours after operation,compared with the group C,the VAS scores at rest and cough in groups Q and E were apparently decreased(P<0.05).However,there was no significant difference in the above indicators between the group Q and the group E(all P>0.05).Conclusion Ultrasound-guided QLB and ESPB for laparoscopic colorectal cancer surgery can both improve the quality of recovery and achieve satisfactory analgesia in elderly patients.

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.

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 evaluate the safety and efficacy of irreversible electroporation (IRE) combined with neoadjuvant chemotherapy in patients with locally advanced pancreatic cancer. Methods We searched PubMed, Embase, Cochrane Library, Web of Science, China Biomedical Literature Database, CNKI, Wanfang, and VIP databases for articles dated from the establishment of each database to March 2022. Meta-analysis was performed using RevMan5.4 software. Results A total of 3970 patients with locally advanced pancreatic cancer were enrolled in eight studies, including one randomized controlled trial, four retrospective studies, and three prospective studies. The patients were divided into the combined therapy group with 344 patients and the chemotherapy-only group with 3626 patients. Meta-analysis showed that the overall survival of patients in the combined therapy group was significantly higher than that in the chemotherapy-only group (OR=4.52; 95%CI: 2.63-7.77; P < 0.00001). However, no significant difference existed in the disease control rate between the combined therapy group and the chemotherapy-only group (OR=0.58; 95%CI: 0.02-18.74; P=0.76). Moreover, no significant difference existed in the disease progression between the two groups (OR=0.49; 95%CI: 0.23-1.02; P=0.06). The combination of neoadjuvant chemotherapy and IRE had no significant effect on the incidence of adverse reactions of gastrointestinal reaction (OR=0.37; 95%CI: 0.10-1.34; P=0.13) and bone marrow suppression (OR=0.61; 95%CI: 0.26-1.40; P=0.24). Conclusion IRE combined with neoadjuvant chemotherapy can remarkably improve the prognosis of patients with locally advanced pancreatic cancer, and significantly prolong the overall survival.

During the traumatic brain injury (TBI), improved expression of circulatory miR-21 serves as a diagnostic feature. Low levels of exosome-miR-21 in the brain can effectively improve neuroinflammation and blood-brain barrier (BBB) permeability, reduce nerve apoptosis, restore neural function and ameliorate TBI. We evaluated the role of macrophage derived exosomes-miR-21 (M-Exos-miR-21) in disrupting BBB, deteriorating TBI, and Rg1 interventions. IL-1

Objective: To investigate the prevalence and related factors of obesity and central obesity among 35-75 year-old population in Jiangsu Province. Methods: During 2015-2017,83 530 eligible subjects aged 35-75 years from six study sites of Jiangsu Province were interviewed and examined. The data of demography,lifestyles,disease history,height,weight and waistline were collected. Logistic regression analysis was conducted for the influencing factors for obesity and central obesity. Results: A total of 83 393 residents completed the study,with a response rate of 99.84%. The prevalence of overweight,obesity and central obesity was 43.35%（standardized rate：35.90%）,20.02%（19.48%）and 59.93%（57.03%）. The results of multivariate logistic regression analysis showed that females（OR=0.822,95%CI：0.786-0.859;OR=0.900,95%CI：0.851-0.952;OR=1.130,95%CI：1.083-1.179）,45-75 years old（OR：1.120-1.731,95%CI：1.102-1.881）,graduating from high school or above（OR：0.767-0.902,95%CI：0.721-0.943）,living in urban areas（OR：1.530-2.077,95%CI：1.284-3.007）,smoking（OR：0.724-0.855,95%CI：0.678-0.898）,drinking （OR：1.125-1.179,95%CI：1.076-1.235）,hypertension（OR：1.884-3.461,95%CI：1.821-3.613）,diabetes（OR：1.363-1.758,95%CI：1.305-1.851）, dyslipidemia（OR：1.478-1.870,95%CI：1.429-1.851）were associated with overweight,obesity and central obesity. Conclusion The standardized prevalence rates of overweight,obesity and central obesity among 35-75 year-old population in Jiangsu Province are 35.90%,19.48% and 57.03%,respectively. Gender,age,education,residence,smoking,drinking,hypertension,diabetes and dyslipidemia are related factors.