BACKGROUND: The atherogenic index of plasma (AIP) has been shown to be positively correlated with cardiovascular disease in previous studies. However, it is unclear whether elderly people with long-term high AIP levels are more likely to develop coronary heart disease (CHD). Therefore, the aim of this study was to investigate the relationship between AIP trajectory and CHD incidence in elderly people. METHODS: 19,194 participants aged ≥ 60 years who had three AIP measurements between 2018 and 2020 were included in this study. AIP was defined as log₁₀ (triglyceride/high-density lipoprotein cholesterol). The group-based trajectory model was used to identify different trajectory patterns of AIP from 2018 to 2020. Cox proportional hazards models were used to estimate the hazard ratio (HR) with 95% CI of CHD events between different trajectory groups from 2020 to 2023. RESULTS: Three different trajectory patterns were identified through group-based trajectory model: the low-level group (n = 7410, mean AIP: -0.25 to -0.17), the medium-level group (n = 9981, mean AIP: 0.02-0.08), and the high-level group (n = 1803, mean AIP: 0.38-0.42). During a mean follow-up of 2.65 years, a total of 1391 participants developed CHD. After adjusting for potential confounders, compared with the participants in the low-level group, the HR with 95% CI of the medium-level group and the high-level group were estimated to be 1.24 (1.10-1.40) and 1.43 (1.19-1.73), respectively. These findings remained consistent in subgroup analyses and sensitivity analyses. CONCLUSIONS There was a significant correlation between persistent high AIP level and increased CHD risk in the elderly. This suggests that monitoring the long-term changes in AIP is helpful to identify individuals at high CHD risk in elderly people.

OBJECTIVE: To examine the effectiveness of Chinese medicine (CM) Lianhua Qingwen Granule (LHQW) and Jingyin Gubiao Prescription (JYGB) in asymptomatic or mild patients with Omicron infection in the shelter hospital. METHODS: This single-center retrospective cohort study was conducted in the largest shelter hospital in Shanghai, China, from April 10, 2022 to May 30, 2022. A total of 56,244 asymptomatic and mild Omicron cases were included and divided into 4 groups, i.e., non-administration group (23,702 cases), LHQW group (11,576 cases), JYGB group (12,112 cases), and dual combination of LHQW and JYGB group (8,854 cases). The length of stay (LOS) in the hospital was used to assess the effectiveness of LHQW and JYGB treatment on Omicron infection. RESULTS: Patients aged 41-60 years, with nadir threshold cycle (C_T) value of N gene <25, or those fully vaccinated preferred to receive CM therapy. Before or after propensity score matching (PSM), the multiple linear regression showed that LHQW and JYGB treatment were independent influence factors of LOS (both P<0.001). After PSM, there were significant differences in LOS between the LHQW/JYGB combination and the other groups (P<0.01). The results of factorial design ANOVA proved that the LHQW/JYGB combination therapy synergistically shortened LOS (P=0.032). CONCLUSIONS Patients with a nadir C_T value <25 were more likely to accept CM. The LHQW/JYGB combination therapy could shorten the LOS of Omicron-infected individuals in an isolated environment.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Male ; Female ; Middle Aged ; Adult ; China/epidemiology* ; Hospitalization ; COVID-19 Drug Treatment ; COVID-19/epidemiology* ; SARS-CoV-2 ; Retrospective Studies ; Treatment Outcome ; Length of Stay ; Young Adult ; Aged

OBJECTIVE: To investigate the effect of zedoarondiol on neovascularization of atherosclerotic (AS) plaque by exosomes experiment. METHODS: ApoE^-/- mice were fed with high-fat diet to establish AS model and treated with high- and low-dose (10, 5 mg/kg daily) of zedoarondiol, respectively. After 14 weeks, the expressions of anti-angiogenic protein thrombospondin 1 (THBS-1) and its receptor CD36 in plaques, as well as platelet activation rate and exosome-derived miR-let-7a were detected. Then, zedoarondiol was used to intervene in platelets in vitro, and miR-let-7a was detected in platelet-derived exosomes (Pexo). Finally, human umbilical vein endothelial cells (HUVECs) were transfected with miR-let-7a mimics and treated with Pexo to observe the effect of miR-let-7a in Pexo on tube formation. RESULTS: Animal experiments showed that after treating with zedoarondiol, the neovascularization density in plaques of AS mice was significantly reduced, THBS-1 and CD36 increased, the platelet activation rate was markedly reduced, and the miR-let-7a level in Pexo was reduced (P<0.01). In vitro experiments, the platelet activation rate and miR-let-7a levels in Pexo were significantly reduced after zedoarondiol's intervention. Cell experiments showed that after Pexo's intervention, the tube length increased, and the transfection of miR-let-7a minics further increased the tube length of cells, while reducing the expressions of THBS-1 and CD36. CONCLUSION Zedoarondiol has the effect of inhibiting neovascularization within plaque in AS mice, and its mechanism may be potentially related to inhibiting platelet activation and reducing the Pexo-derived miRNA-let-7a level.
Animals ; MicroRNAs/genetics* ; Exosomes/drug effects* ; Plaque, Atherosclerotic/genetics* ; Neovascularization, Pathologic/genetics* ; Human Umbilical Vein Endothelial Cells/metabolism* ; Humans ; Blood Platelets/drug effects* ; Apolipoproteins E/deficiency* ; Thrombospondin 1/metabolism* ; CD36 Antigens/metabolism* ; Platelet Activation/drug effects* ; Male ; Mice ; Mice, Inbred C57BL

ObjectiveProtein arginine methyltransferases (PRMTs) play pivotal roles in numerous cellular biological processes. However, the precise regulatory effects of PRMTs on the fate determination of mesenchymal stromal/stem cells (MSCs) remain elusive. Our previous studies have shed light on the regulatory role and molecular mechanism of PRMT5 in MSC osteogenic differentiation. This study aims to clarify the role and corresponding regulatory mechanism of PRMT7 during the adipogenic differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Methods(1) Human bone marrow-derived mesenchymal stem cells (hBMSCs) were cultured in a medium that induces adipogenesis. We used qRT-PCR and Western blot to monitor changes in PRMT7 expression during adipogenic differentiation. (2) We created a cell line with PRMT7 knocked down and assessed changes in PRMT7 expression and adipogenic capacity using Oil Red O staining, qRT-PCR and Western blot. (3) We implanted hBMSCs cell lines mixed with a collagen membrane subcutaneously into nude mice and performed Oil Red O staining to observe ectopic lipogenesis in vivo. (4) A cell line overexpressing PRMT7 was generated, and we examined changes in PRMT7 expression using qRT-PCR and Western blot. We also performed Oil Red O staining and quantitative analysis after inducing the cells in lipogenic medium. Additionally, we assessed changes in PPARγ expression. (5) We investigated changes in insulin-like growth factor 1 (IGF-1) expression in both PRMT7 knockdown and overexpressing cell lines using qRT-PCR and Western blot, to understand PRMT7’s regulatory effect on IGF-1 expression. siIGF-1 was transfected into the PRMT7 knockdown cell line to inhibit IGF-1 expression, and knockdown efficiency was confirmed. Then, we induced cells from the control and knockdown groups transfected with siIGF-1 in lipogenic medium and performed Oil Red O staining and quantitative analysis. Finally, we assessed PPARγ expression to explore IGF-1’s involvement in PRMT7’s regulation of adipogenic differentiation in hBMSCs. Results(1) During the adipogenesis process of hBMSCs, the expression level of PRMT7 was significantly reduced (P<0.01). (2) The adipogenic differentiation ability of PRMT7 knockdown group was significantly stronger than that of control group (P<0.001). (3) The ectopic adipogenic differentiation ability of PRMT7 knockdown group was significantly stronger than that of control group. (4) The adipogenic differentiation ability of the PRMT7 overexpression group was significantly weaker than that of the control group (P<0.01). (5) The expression level of IGF-1 increased after PRMT7 knockdown (P<0.000 1). The expression level of IGF-1 decreased after PRMT7 overexpression (P<0.000 1), indicating that PRMT7 regulates the expression of IGF-1. After siIGF-1 transfection, the expression level of IGF-1 in all cell lines decreased significantly (P<0.001). The ability of adipogenic differentiation of knockdown group transfected with siIGF-1 was significantly reduced (P<0.01), indicating that IGF-1 affects the regulation of PRMT7 on adipogenic differentiation of hBMSCs. ConclusionIn this investigation, our findings elucidate the inhibitory role of PRMT7 in the adipogenic differentiation of hBMSCs, as demonstrated through both in vitro cell-level experiments and in vivo subcutaneous transplantation experiments conducted in nude mice. Mechanistic exploration revealed that PRMT7’s regulatory effect on the adipogenic differentiation of hBMSCs operates via modulation of IGF-1 signaling pathway. These collective findings underscore PRMT7 as a potential therapeutic target for fatty metabolic disorders, thereby offering a novel avenue for leveraging PRMT7 and hBMSCs in the therapeutic landscape of relevant diseases.

Objective:To compare the effects of high-power and conventional power atrial fibrillation ablation on intraoperative acute pulmonary vein isolation, postoperative troponin levels, and atrial fibrillation recurrence.Methods:A retrospective selection was conducted on 105 patients with paroxysmal atrial fibrillation admitted to the Baoding NO.1 Central Hospital from January 2017 to December 2020. According to different treatment methods, they were divided into a high-power ablation group of 52 cases and a conventional power ablation group of 53 cases. The intraoperative rate of single circle acute pulmonary vein isolation, the recovery of electrical conduction after acute pulmonary vein isolation, and the location and number of points that need to be added were compared between the two groups; At the same time, two groups were compared in terms of surgical time, ablation time, surgical radiation exposure time and radiation dose, intraoperative complications postoperative cardiac troponin levels at 12 hours, and recurrence of atrial fibrillation within 1 year after ablation.Results:The intraoperative single loop pulmonary vein isolation rate and postoperative troponin levels in the high-power atrial fibrillation ablation group were higher than those in the conventional atrial fibrillation ablation group (all P<0.05). The surgical time, ablation time, and the number of sites and points that need to be added during surgery were less than those in the conventional atrial fibrillation ablation group (all P<0.05). There was no statistically significant difference in the incidence of intraoperative complications and postoperative atrial fibrillation recurrence between the two groups (all P>0.05). Conclusions:High power atrial fibrillation ablation has a higher single loop acute pulmonary vein isolation rate, fewer patch sites and points, shorter surgical time, and greater ablation damage compared to conventional ablation, and the clinical efficacy of the two groups is similar after surgery.

For the past 30 years,percutaneous balloon mitral valve dilatation has been performed under the guidance of X-rays and bedside ultrasound.However,there are still some cases of mitral valve stenosis in the large atrium where balloon dilation failed.Intraperitoneal ultrasound-guided percutaneous balloon mitral valve plasty is accurate and feasible,which can reduce the occurrence of complications and improve the success rate of such elderly complex cases.Two patients with severe mitral stenosis underwent percutaneous balloon mitral valve plasty guided by intracardiac ultrasound.The operations were successful without any complications,which can provide reference for clinical treatment of mitral stenosis.

The canonical transient receptor potential channel(TRPC)proteins form Ca2+-permeable cation channels that are involved in various heart diseases.However,the roles of specific TRPC proteins in myocardial ischemia/reperfusion(I/R)injury remain poorly understood.We observed that TRPC1 and TRPC6 were highly expressed in the area at risk(AAR)in a coronary artery ligation induced I/R model.Trpc1-/-mice exhibited improved cardiac function,lower serum Troponin T and serum creatine kinase level,smaller infarct volume,less fibrotic scars,and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6-/-mice.Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury.Furthermore,Trpc1 deficiency protected adult mouse ventricular myocytes(AMVMs)and HL-1 cells from death during hypoxia/reoxygenation(H/R)injury.RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species(ROS)generation in Trpc1-/-cardiomyocytes.Among these genes,oxoglutarate dehydrogenase-like(Ogdhl)was markedly downregulated.Moreover,Trpc1 deficiency impaired the calcineurin(CaN)/nuclear factor-kappa B(NF-κB)signaling pathway in AMVMs.Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions.Chromatin immunoprecipitation assays confirmed NF-κB binding to the Ogdhl promoter.The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-κB and Ogdhl in cardiomyocytes.In conclusion,our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R,leading to increased Ca2+influx into associated cardiomyocytes.Subsequently,this upregulates Ogdhl expression through the CaN/NF-κB signaling pathway,ultimately exacerbating ROS production and aggravating myocardial I/R injury.

ObjectiveTo observe the effects of fire-needle of Lingnan on the vitiligo model after hydroquinone-induced oxidative stress based on the Hippo-YAP signaling pathway. MethodsC57BL/6 mice were randomly divided into normal group （Control）， model group （HQ）， HQ+fire-needle group （FA）， and positive control group （Halometasone）， with 8 mice in each group. The vitiligo model was prepared by hydroquinone （HQ）. The skin pathological changes were observed by depigmentation score， HE staining and Masson-Fontana. Elisa was used to detect the levels of tyrosinase （TYR）， malondialdehyde （MDA） and monoamine oxidase （MAO）.Western-blot and PCR were used to detect the expression of Yap1 and Tp73 among the groups. ResultsCompared with the control group， the epidermis and dermis were significantly thicker. The number of melanocyte hair follicles， basal melanocytes， epidermal cells containing melanin granules were significantly decreased， and the depigmentation score was significantly reduced（P＜0.01）. The level of TYR decreased， and the levels of MDA and MAO increased after modeling（P＜0.01）. The expression of Yap1 and Tp73 were significantly reduced （P<0.01）. The dermis became thinner in the halometasone and FA group after treatment of 4 weeks. The number of melanocyte hair follicles， basal melanocytes， epidermal cells containing melanin granules increased （P<0.05）. Compared with that of the HQ group， the level of TYR in the halometasone group and FA group was significantly increased （P<0.01）. The levels of MDA and MAO in the FA group were decreased （P<0.05）. The expressions of Yap1 and Tp73 in the FA group were significantly increased （P<0.01）， and their effects were better than those in the Halometasone group （P<0.05）. ConclusionsFire-needle of Lingnan protects melanocytes from oxidative stress by activating the Hippo-YAP pathway. It enhances the synthesis and function of melanocytes and promotes repigmentation by reducing the content and activity of oxidative stress products.

Objective: To investigate the impact of obstructive sleep apnea syndrome (OSAS) on pregnancy outcomes, especially the relationship between OSAS and hypertensive disorders in pregnancy (HDP). Methods: A total of 228 pregnant women with high risk of OSAS who underwent sleep monitoring during pregnancy in Peking University People's Hospital from January 2021 to April 2022 were collected by reviewing their medical records for retrospective analysis. According to the diagnosis of OSAS, the pregnant women were divided into OSAS group (105 cases) and non-OSAS group (123 cases). The non-parametric Mann-Whitney U test, χ² test or Fisher's exact test were used to compare the general data and maternal and fetal outcomes between the two groups, and the occurrence of each type of HDP was further compared. Results: (1) Compared with the non-OSAS group, the median pre-pregnancy body mass index (23.6 vs 27.6 kg/m²) and the proportion of snoring [28.9% (33/114) vs 59.2% (61/103)] in the OSAS group were higher, and the differences were both statistically significant (both P<0.001). (2) The incidence of HDP [67.6% (71/105) vs 39.0% (48/123)] and gestational diabetes mellitus [GDM; 40.0% (42/105) vs 26.8% (33/123)] of pregnant women in the OSAS group were higher than those in the non-OSAS group, and the median delivery week was shorter than that in the non-OSAS group (38.4 vs 39.0 weeks). The differences were all statistically significant (all P<0.05). Between-group differences for the delivery way, postpartum hemorrhage, the rate of intensive care unit admission, preterm birth, small for gestational age infants, neonatal asphyxia, the rate of neonatal intensive care unit admission, newborn birth weight and the proportion of umbilical artery blood pH<7.00 were not statistically significant (all P>0.05). (3) Compared with the non-OSAS group, the incidence of chronic hypertension [11.4% (14/123) vs 22.9% (24/105)] and chronic hypertension with superimposed pre-eclampsia [11.4% (14/123) vs 30.5% (32/105)] were higher in the OSAS group, and the differences were both statistically significant (both P<0.01). Conclusion: OSAS is related to HDP (especially chronic hypertension and chronic hypertension with superimposed pre-eclampsia) and GDM, which could provide a practical basis for the screening, diagnosis and treatment of OSAS in pregnant women at high risk.
Infant, Newborn ; Pregnancy ; Infant ; Humans ; Female ; Pre-Eclampsia/epidemiology* ; Hypertension, Pregnancy-Induced/epidemiology* ; Retrospective Studies ; Premature Birth ; Sleep Apnea, Obstructive/epidemiology* ; Diabetes, Gestational/epidemiology*

Based on the idea of modification of sugar drugs, or transforming other active substances with sugar molecules, sixteen D-glucosamine-fluoroquinolone (FQ) derivatives were designed by combining D-glucosamine with FQs and synthesized by a multi-step reaction with shared intermediates. The assay results of anti-human pathogenic bacteria and anti-citrus canker showed that the inhibitory activities of two target molecules TM2b and TM2d against Staphylococcus aureus ATCC14125 were stronger than those of all tested positive control drugs, and the inhibitory rates of target molecules TM2m and TM2n against citrus canker were higher than that of the positive control streptomycin at the concentrations of 0.5 and 0.2 µg·mL^-1, respectively, which all were worthy of further study. In this study, a series of novel molecules composed of D-glucosamine and FQs were synthesized for the first time, and super antibacterial molecules were found, which expanded the types and biological activities of D-glucosamine derivatives.