This study aimed to compare the ameliorative effects of Lycii Fructus and Chrysanthemi Flos at different ratios on retinal damage in mice and to elucidate the underlying mechanisms. A retinal injury model was established by intraperitoneal injection of sodium iodate(NaIO_3) solution. The mice were divided into the following groups: blank group, model group, positive drug(AREDS 2) group, low-and high-dose groups of Lycii Fructus and Chrysanthemi Flos at 1∶1, low-and high-dose groups at 3∶1, and low-and high-dose groups at 1∶3. Administration was carried out 15 days after modeling. The visual acuity of the mice was assessed using the black-and-white box test. The fundus was observed using an optical coherence tomography device, and retinal thickness was measured. HE staining was used to observe the morphology and pathological changes of the retina. The levels of oxidative factors in serum and ocular tissues were measured using assay kits. The levels of inflammatory factors in serum and ocular tissues were detected by enzyme-linked immunosorbent assay(ELISA), and the expression of Nrf2, HO-1, and NF-κB proteins in ocular tissues was analyzed by Western blot. The results showed that after administration of Lycii Fructus and Chrysanthemi Flos at different ratios, the model group showed improved retinal thinning and disordered arrangement of retinal layers, elevated content of SOD and GSH in the serum and ocular tissues, and reduced levels of MDA, TNF-α, IL-1β, and IL-6. Lycii Fructus and Chrysanthemi Flos at 1∶1 and 1∶3 showed better improvement effects. The combination significantly upregulated the expression levels of Nrf2 and HO-1 and downregulated the expression of NF-κB p65. These results indicate that Lycii Fructus and Chrysanthemi Flos at different ratios can improve retinal damage, reduce oxidative stress, and alleviate inflammation in both the body and ocular tissues of mice. The mechanism may be related to the regulation of the Nrf2/HO-1 and NF-κB signaling pathways in ocular tissues. These findings provide a theoretical basis for the clinical application of Lycii Fructus and Chrysanthemi Flos in the treatment of dry age-related macular degeneration.
Animals ; Mice ; Retina/injuries* ; Male ; Lycium/chemistry* ; Drugs, Chinese Herbal/administration & dosage* ; Chrysanthemum/chemistry* ; NF-kappa B/genetics* ; Humans ; Retinal Diseases/metabolism* ; NF-E2-Related Factor 2/metabolism* ; Oxidative Stress/drug effects* ; Flowers/chemistry* ; Heme Oxygenase-1/genetics*

BACKGROUND: The association of systemic inflammatory response index (SIRI) with prognosis of coronary artery disease (CAD) patients has never been investigated in a large sample with long-term follow-up. This study aimed to explore the association of SIRI with all-cause and cause-specific mortality in a nationally representative sample of CAD patients from United States. METHODS: A total of 3386 participants with CAD from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 were included in this study. Cox proportional hazards model, restricted cubic spline (RCS), and receiver operating characteristic curve (ROC) were performed to investigate the association of SIRI with all-cause and cause-specific mortality. Piece-wise linear regression and sensitivity analyses were also performed. RESULTS: During a median follow-up of 7.7 years, 1454 all-cause mortality occurred. After adjusting for confounding factors, higher lnSIRI was significantly associated with higher risk of all-cause (HR = 1.16, 95% CI: 1.09-1.23) and CVD mortality (HR = 1.17, 95% CI: 1.05-1.30) but not cancer mortality (HR = 1.17, 95% CI: 0.99-1.38). The associations of SIRI with all-cause and CVD mortality were detected as J-shaped with threshold values of 1.05935 and 1.122946 for SIRI, respectively. ROC curves showed that lnSIRI had robust predictive effect both in short and long terms. CONCLUSIONS SIRI was independently associated with all-cause and CVD mortality, and the dose-response relationship was J-shaped. SIRI might serve as a valid predictor for all-cause and CVD mortality both in the short and long terms.

Accurate timing of myelination is crucial for the proper functioning of the central nervous system. Here, we identified a de novo heterozygous mutation in TMEM63A (c.1894G>A; p. Ala632Thr) in a 7-year-old boy exhibiting hypomyelination. A Ca²⁺ influx assay suggested that this is a loss-of-function mutation. To explore how TMEM63A deficiency causes hypomyelination, we generated Tmem63a knockout mice. Genetic deletion of TMEM63A resulted in hypomyelination at postnatal day 14 (P14) arising from impaired differentiation of oligodendrocyte precursor cells (OPCs). Notably, the myelin dysplasia was transient, returning to normal levels by P28. Primary cultures of Tmem63a^-/- OPCs presented delayed differentiation. Lentivirus-based expression of TMEM63A but not TMEM63A_A632T rescued the differentiation of Tmem63a^-/- OPCs in vitro and myelination in Tmem63a^-/- mice. These data thus support the conclusion that the mutation in TMEM63A is the pathogenesis of the hypomyelination in the patient. Our study further demonstrated that TMEM63A-mediated Ca²⁺ influx plays critical roles in the early development of myelin and oligodendrocyte differentiation.
Animals ; Cell Differentiation/physiology* ; Oligodendroglia/metabolism* ; Mice, Knockout ; Mice ; Male ; Myelin Sheath/metabolism* ; Humans ; Child ; Cells, Cultured ; Oligodendrocyte Precursor Cells/metabolism*

Objective:To evaluate the preservation efficacy of 7 non-inactivating virus preservation solutions.Methods:Equal amounts of H1N1 virus were added to 7 commercially available non-inactivating virus preservation solutions, and the samples were stored at -20 ℃, 4 ℃, 25 ℃ and 37 ℃ for 1 hour, 6 hours, 1 day, 3 days, and 5 days. The viral nucleic acid in each simulated sample under different storage conditions was measured using real-time quantitative PCR. The hemagglutination (HA) titer was determined through viral isolation culture and hemagglutination assay, comparing the differences in viral growth activity across different storage solutions and conditions.Results:Except for solution E, the other solutions effectively protected viral nucleic acid at the 4 storage temperatures. In terms of viral activity, solutions A, B, C, and D effectively maintained viral viability. A and B showing the best performance, E and F showed poorer performance, and G performed the worst.Conclusions:Most non-inactivating virus preservation solutions effectively protect viral nucleic acid, but there are significant differences in their ability to maintain viral viability. To ensure optimal virus preservation, it is recommended that medical institutions evaluate the effectiveness of preservation solutions before use.

Objective:To assess the clinical utility of vector flow mapping（VFM）for evaluating left ventricular wall shear stress（WSS）in individuals with non-obstructive hypertrophic cardiomyopathy（nHCM）.Methods:Forty patients with non-obstructive HCM（nHCM）and 46 healthy volunteers in Tangdu Hospital of Air Force Medical University from May 2020 to September 2023 were enrolled prospectively in this study. The left ventricular WSS of each of 18 segments was measured and analyzed by VFM during rapid filling phase（T1），slow filling phase（T2），isovolumetric contraction phase（T3）and rapid ejection phase（T4）.Results:① WSS decreased gradually from basal to apical segments in control group，while there was no such change pattern in nHCM group. ② Diastolic phase：When compared to the control group，the nHCM group demonstrated significantly increased WSS across all segments of the inferoseptal regions，the basal anteroseptal segment，and the middle and apical inferior segments during the T1 stage. Additionally，at the T2 stage，the WSS was significantly higher in the nHCM group across all segments of the inferoseptal and anteroseptal regions，the basal anterolateral segment，and the apical inferolateral and anterior segments（all P<0.05）. Conversely，during the T1 stage，the basal anterolateral segment，basal inferolateral segment，and the middle and apical anteroseptal segments，as well as during the T2 stage，the basal and middle inferior segments，exhibited lower WSS values compared to the control group，with these differences being statistically significant（all P<0.05）. ③Systolic Phase：During the T3 stage，the WSS values in all segments of the anteroseptal and anterolateral regions，as well as the apical inferior and anterior segments，were significantly elevated in the nHCM group compared to the control group（all P<0.05）.At the T4 stage，WSS in each segment of the inferolateral and inferior regions，as well as the basal and middle anterior segments，was significantly elevated in the nHCM group compared to the control group（all P<0.01）. Conversely，during the same stage，the WSS values in the basal inferolateral segment，the basal and middle anterolateral segments，and the basal and middle anteroseptal segments were significantly lower in the nHCM group than in the control group，with all differences reaching statistical significance（all P<0.01）.Regarding global WSS，the left ventricular global WSS in the nHCM group was significantly higher than that in the control group at both the T2 and T3 stages（all P<0.001）. Furthermore，the global WSS at the T3 stage was negatively correlated with left ventricular end-systolic volume，end-diastolic volume，and left ventricular stroke volume（ r=-0.226， P=0.036； r=-0.345， P=0.001； r=-0.303， P=0.005）. Conclusions:Significant differences in WSS are observed between patients with nHCM and control groups at various phases. WSS may serve as an early indicator of changes in cardiac function in nHCM patients.

Objective:To investigate the incidence and high-risk pathogenic factors of cardiovascular disease（CVD）in patients with rheumatic and autoimmune diseases，and to construct and validate a predictive model for the risk of CVD occurrence in these patients.Methods:A retrospective analysis was conducted on 239 patients with rheumatic and autoimmune diseases who underwent treatment and echocardiography at the Affiliated Hospital of Inner Mongolia Medical University between June 2020 and June 2023. General patient data，laboratory test results，and echocardiographic findings were collected. Follow-up was performed via electronic medical records or telephone surveys until December 2024 to determine the incidence of CVD，starting from the date of the first echocardiographic examination. Predictive factors were screened using univariate analysis and Lasso regression，and a Logistic regression model was constructed. Internal validation was performed using the Bootstrap method. The model's accuracy and clinical utility were assessed using the Hosmer-Lemeshow test，calibration curve，and decision curve analysis.Results:Among the 239 patients，111 developed CVD. Logistic regression analysis identified age，diastolic blood pressure，use of immunosuppressants，lymphocyte count（LYM），α-hydroxybutyrate dehydrogenase（α-HBDH）level，serum cystatin C（CysC），and right ventricular fractional area change（RVFAC）as independent predictive factors for CVD in these patients（all P<0.05）. The area under the ROC curve（AUC）for the prediction model was 0.895（95% CI = 0.856 - 0.935），and after Bootstrap validation，it was 0.894（95% CI = 0.861-0.925）. The Hosmer-Lemeshow test，calibration curve，and decision curve analysis all indicated that the model had good accuracy and clinical utility. Conclusions:Age，diastolic blood pressure，use of immunosuppressants，LYM，α-HBDH，CysC，and RVFAC may serve as independent risk factors for CVD in patients with rheumatic and autoimmune diseases. The prediction model based on echocardiography combined with laboratory indicators can，to some extent，predict the risk of CVD occurrence in these patients.

Objective To investigate the incidence of placental abruption in the third trimester of pregnancy in Hebei Province,identify its associated risk factors,and develop a corresponding nomogram prediction model.Methods Data from pregnant women at 22 monitored hospitals in Hebei Province,collected between 2013 and 2023,were analyzed to assess the incidence,trends,and associated risk factors of placental abruption.A prediction model was developed and visualized using R programming to generate the receiver operating characteristic(ROC)curve.The model's predictive performance was evaluated using the area under the curve(AUC)and calibration curve parameters.Results A total of 480 690 pregnant women were included in this study over the specified period.The incidence of placental abruption was 0.29%(1 395 out of 480 690),with an average annual percentage change of 2.73%,indicating a stable trend(P=0.34).Multivariate logistic regression analysis revealed that pregnancy-related anemia,preeclampsia,placenta previa,vaginal bleeding before 28 weeks'gestation,and between 28 and 31+6 weeks'gestation were significant risk factors for placental abruption(all P<0.05).In contrast,regular prenatal examinations(7～11 visits)and multiple pregnancies were identified as protective factors against placental abruption(both P<0.05).The area under the curve(AUC)for the nomogram model constructed based on independent risk factors for placental abruption was 0.79,and the calibration curve demonstrated that the predicted values closely aligned with the observed values.Conclusions Prenatal examinations should be prioritized,especially for women with preeclampsia,placenta previa,or a history of vaginal bleeding before 28 weeks of gesta-tion.Management of pregnancies between 28 and 31+6 weeks is also crucial to reduce the incidence of placental abruption and mitigate adverse maternal and neonatal outcomes.The nomogram model constructed based on these factors exhibits excellent predictive performance,providing a solid theoretical foundation for the prevention and clinical management of placental abruption.

Objective To evaluate the efficacy of stellate ganglion block(SGB)on postoperative sleep quality in the patients undergoing general anesthesia operation.Methods The randomized controlled trials(RCT)of the effect of SGB on postoperative sleep quality in the patients undergoing general anesthesia were searched from PubMed,Cochrane Library,Embase,CNKI,CBM,VIP and Wang Fang Data.The retrieval limi-tation was from the database establishment to July 21,2023.The screened literatures were evaluated by using the Cochrane 5.1.0 bias risk assessment tool,and then the meta analysis was performed by using Rev Man 5.4 software.Results A total of eight literatures were screened and included.The results of meta analysis showed that the incidence rate of sleep disorders in the first night after surgery in the SGB group was lower than that in the control group(OR=0.26,95％CI:0.15-0.45,P＜0.001),and the postoperative total sleep duration in the SGB group was higher than that in the control group(MD=69.06,95％CI:53.69-84.44,P＜0.001),the sleep efficiency of the SGB group was higher than that of the control group(MD=13.59,95％CI:10.70-16.49,P＜0.001);the postoperative Assens Insomnia Scale(AIS)scores(MD=-1.73,95％CI:-2.43 to-1.03,P＜0.001)and Pittsburgh Sleep Quality Index Scale(PSQI)scores(MD=-3.26,95％CI:-5.40 to-1.12,P＜0.003)in the SGB group were lower than those in the control group.Conclusion SGB could reduce the incidence rate of sleep disturbances at the postoperative first night,extend the postoperative total sleep time,increase the postoperative sleep efficiency,reduce the postoperative sleep quality score,and improve the postoperative sleep quality,which is a non-pharmacological method with good effect and high safety,has good clinical application prospect and is worth promoting.

Background and aims:Hepatocellular carcinoma(HCC)is a malignant tumor with a high mortality rate,but there are still no effective treatments.The aim of this study was to investigate the anticancer po-tential of the combined use of brefeldin A(BFA)and tunicamycin(TM)in HepG2 cells,as well as the underlying mechanisms.Methods:HepG2 cells were treated with different concentrations of BFA(0.1-2.5 mg/L)and TM(1-5 mg/L)for 24 h.DMSO(0.1％,v/v)was used as a vehicle control.Cell viability and cell migration were measured using MTT assay and scratch wound assay,respectively.Apoptosis was detected using flow cytometry and acridine orange(AO)staining.The protein and mRNA levels of various factors involved in apoptosis(poly(ADP-ribose)polymerase-1(PARP-1),caspase-12,caspase-3,and stearoyl-CoA desaturase 1)and endoplasmic reticulum(ER)stress(binding immunoglobulin protein(BiP),protein kinase R-like endoplasmic reticulum kinase(PERK),p-PERK,phosphorylation of eukaryotic translation initiation factor 2alpha(p-eIF2α),activating transcription factor(ATF)4,and C/EBP homologous protein(CHOP))were measured using Western blotting and qRT-PCR,respectively.Results:Both BFA and TM alone significantly reduced the viability of HepG2 cells in a dose-dependent way.The co-incubation with TM(1 mg/L)further significantly reduced the viability of HepG2 cells treated with BFA(0.25 mg/L)alone(P＜0.05).BFA significantly increased the protein and mRNA levels of caspase-3 and PARP-1(P＜0.05)compared to control and DMSO-treated cells,indicating that BFA induced apoptosis in HepG2 cells by increasing the expression of caspase-3 and PARP-1.The induction of apoptosis by BFA could be further significantly enhanced by co-incubation with TM.In addition,BFA significantly increased the mRNA levels of BiP,PERK and ATF4(P＜0.05)compared to control and DMSO-treated cells.After co-incubation of BFA and TM,the protein levels of BiP,p-PERK,p-eIF2α and CHOP were significantly increased,indicating that TM could enhance BFA-induced ER stress in HepG2 cells through the PERK-eIF2α-ATF4-CHOP pathway.Conclusions:BFA could induce apoptosis and ER stress,and TM could enhance the ability of BFA to induce apoptosis and ER stress in HepG2 cells through the PERK-eIF2α-ATF4-CHOP pathway.The findings highlight the therapeutic potential of the combined use of BFA and TM in treating HCC.

Objective To observe the clinical efficacy and safety of filiform-heated needle combined with Qingbu Huacuo Decoction in the treatment of acne of damp-heat due to spleen deficiency syndrome.Methods Seventy patients with acne of damp-heat due to spleen deficiency syndrome admitted to the seventh clinical Medical School of Guangzhou University of Chinese Medicine from May 2023 to March 2024 were randomly divided into the observation group and the control group according to random number table method,with 35 patients in each group.Health education was given to the patients in both groups.The control group was given oral administration of Doxycycline Hyclate Tablets combined with filiform-heated needle for treatment,and the observation group was treated with filiform-heated needle combined with Qingbu Huacuo Decoction orally,the course of treatment for the two groups covered six weeks.After six weeks of treatment,the clinical efficacy of the two groups was evaluated,and the changes in Global Acne Grading System(GAGS)score and Quality of Life-Acne(Qol-Acne)score,as well as the traditional Chinese medicine(TCM)syndrome scores before and after treatment were observed.The changes of skin barrier function indicators such as trans epidermal water loss(TEWL)content,skin moisture content,and sebum content before and after treatment were compared between the two groups of patients.Moreover,the safety of the two groups and the occurrence of adverse reactions were evaluated.Results(1)After treatment,the GAGS scores of patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,with a statistically significant difference(P<0.05).(2)After treatment,the Qol-Acne scores of the patients in the two groups were significantly improved(P<0.05),and the observation group was significantly superior to the control group in improving the three aspects of self-perception,emotional functioning,and self-assessment,with a statistically significant difference(P<0.05),and the observation group was slightly superior to the control group in improving social functioning,but the difference being not statistically significant(P>0.05).(3)After treatment,the content of TEWL,skin moisture,and sebum of patients in the two groups were significantly improved(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(4)After treatment,the TCM syndrome scores of the two groups of patients were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,with a statistically significant difference(P<0.05).(5)The total effective rate was 94.29%(33/35)in the observation group and 74.29%(26/35)in the control group.The clinical efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(6)Comparison of the incidence of adverse reactions between the two groups,the difference being not statistically significant(P>0.05).Conclusion Filiform-heated needle combined with Qingbu Huacuo Decoction in the treatment of acne of damp-heat due to spleen deficiency syndrome can significantly improve the clinical symptoms of patients,thus improving their quality of life,with good safety.