Objective To analyze the related factors of prognosis in patients with primary Sjogren’s syndrome (SS) complicated with renal damage, and to provide reference for clinical development of personalized prevention and treatment measures. Methods A total of 508 patients with primary SS complicated with renal damage in the First Affiliated Hospital of Xinjiang Medical University from February 2020 to February 2022 were enrolled as study subjects. According to the prognosis status within 3 years, the enrolled patients were divided into good prognosis group (n=426) and poor prognosis group (n=82). Univariate and logistic multivariate regression analyses were adopted to analyze the influencing factors of poor prognosis. Results There were significant differences in hypertension, anemia, renal interstitial chronicity grading, and levels of globulin (GLO), immunoglobulin G (IgG) and hemoglobin between the two groups (P<0.05). Logistic multivariate analysis showed that concurrent hypertension, anemia, increased grade of renal interstitial chronicity, and elevated GLO and IgG levels were risk factors of poor prognosis in patients with primary SS complicated with renal damage, while hemoglobin level was a protective factor (OR: 1.962, 95%CI: 1.056-3.645; OR: 2.467, 95%CI: 1.153-5.278; OR: 17.796, 95%CI: 5.157-61.419; OR: 3.655, 95%CI: 1.812-7.372; OR: 5.732, 95%CI: 2.632-12.480; OR: 0.325, 95%CI: 0.165-0.640, P<0.05). Conclusion Patients with primary SS complicated with renal damage have a higher risk of poor prognosis, which is affected by factors such as hypertension, anemia, and GLO, IgG and hemoglobin levels. Clinically, it is necessary to take active prevention and treatment measures to improve the prognosis of patients.

Height， as one of the crucial indicators for assessing children’s growth and development， has consistently been a global focus. With economic development and improvements in social living standards， the clinical management needs for children with short stature have been increasingly growing. While growth hormone brings hope to children with short stature， it also triggers ethical challenges such as medical standardization， expansion of indications， equitable accessibility， and informed consent. To avoid the ethical issues related to the use of pediatric growth hormone， multidimensional and comprehensive clinical management should be implemented for children with short stature， including strictly adhering to medical standards and ethical guidelines， enhancing public awareness， and promoting the standardized development of recombinant human growth hormone （rhGH） therapy and ethics.

Hypoxic-ischemic (HI) brain damage poses a high risk of death or lifelong disability, yet effective treatments remain elusive. Here, we demonstrated that miR-100-5p levels in the lesioned cortex increased after HI insult in neonatal mice. Knockdown of miR-100-5p expression in the brain attenuated brain injury and promoted functional recovery, through inhibiting the cleaved-caspase-3 level, microglia activation, and the release of proinflammation cytokines following HI injury. Engineered extracellular vesicles (EVs) containing neuron-targeting rabies virus glycoprotein (RVG) and miR-100-5p antagonists (RVG-EVs-Antagomir) selectively targeted brain lesions and reduced miR-100-5p levels after intranasal delivery. Both pre- and post-HI administration showed therapeutic benefits. Mechanistically, we identified protein phosphatase 3 catalytic subunit alpha (Ppp3ca) as a novel candidate target gene of miR-100-5p, inhibiting c-Fos expression and neuronal apoptosis following HI insult. In conclusion, our non-invasive method using engineered EVs to deliver miR-100-5p antagomirs to the brain significantly improves functional recovery after HI injury by targeting Ppp3ca to suppress neuronal apoptosis.
Animals ; MicroRNAs/metabolism* ; Extracellular Vesicles/metabolism* ; Mice ; Recovery of Function/physiology* ; Hypoxia-Ischemia, Brain/therapy* ; Mice, Inbred C57BL ; Antagomirs/administration & dosage* ; Male ; Animals, Newborn ; Apoptosis/drug effects* ; Brain Injuries/metabolism* ; Glycoproteins ; Peptide Fragments ; Viral Proteins

Objective:To determine the erythromycin resistance of Bordetella pertussis isolates and their ptxP1 and ptxP3 phenotypic composition and compare clinical manifestations of children with pertussis caused by the two types of strains. Methods:This was a cross-sectional study, the pertussis cases diagnosed using bacterial culture from January 2019 to December 2022 in Beijing Children′s Hospital and the First People′s Hospital of Wuhu were collected.Any suspected Bordetella pertussis colonies were identified by the slide agglutination test.The susceptibility of isolates to erythromycin was detected by the E-test and K-B test.The ptxP gene was amplified by polymerase chain reaction and sequenced to determine its genotype. t-test, Mann-Whitney U-test, Chi-square test and Fisher′s exact test were use to statistical analysis. Results:A total of 192 strains of Bordetella pertussis were identified, including 188 (97.9%) erythromycin-resistant strains.Among the 188 strains, 30.3%(57/188) belonged to the ptxP1 genotype and 69.7%(131/188) belonged to the ptxP3 genotype.In children aged below 1 year old, the incidence of paroxysmal cough caused by infection with the ptxP3 strain was higher than that with the ptxP1 strain (57.1% vs.29.4%, P<0.05), and children infected with the ptxP3 strain were more likely to develop apnea or asphyxia (23.8% vs.17.6%), post-tussive vomiting (44.4% vs.32.4%), whooping cough (72.0% vs.50.0%) and pneumonia or bronchitis (85.7% vs.73.5%) compared to those infected with the ptxP1 strain, but the differences were not statistically significant(all P>0.05). In children aged 1 year old and above, the white blood cell count of children infected with the ptxP1 strain was higher than that of infections with the ptxP3 strain [13.5(9.9, 24.5)×10 9/L, 10.3 (7.0, 16.4)×10 9/L, P<0.05], and children infected with the ptxP1 strain were more likely to contract other pathogen infections than those infected with the ptxP3 strain (17.4% vs.4.4%, P>0.05). Conclusions:ptxP3 erythromycin-resistant Bordetella pertussis has become the main pathogen of pertussis.Infants with pertussis caused by the ptxP3 erythromycin-resistant strain show more significant manifestations and a higher possibility of severe symptoms than those infected with the ptxP1 erythromycin-resistant strain.

Objective:This study evaluates the performance of chemiluminescence assay, which is designed to detect Hepatitis D Virus (HDV) Immunoglobulin G (IgG) antibodies.Methods:A comparative analysis was conducted among chemiluminescence anti-HDV IgG reagent, the magnetic particle-based domestic reagent A and domestic reagent B, and the Robo Gene HDV RNA kit, using 1909 HBsAg-positive plasma samples. This comparison aimed to delineate clinical specificity and detection accuracy. The anti-HDV IgG reagent precision was assessed at three different concentration levels following the Clinical Laboratory Standards Institute EP5-A2 guidelines. The specificity of the assay was validated using 200 HAV IgM positive, 545 HBsAg-positive but anti-HDV IgG-negative, 350 anti HCV positive plasma samples and 200 healthy human blood samples. Additionally, a concordance study was conducted with 545 HBsAg-positive and 37 anti-HDV IgG-positive plasma samples, comparing the anti-HDV IgG reagent against reagent A.Results:1 909 HBsAg-positive plasma samples were tested using 3 anti HDV IgG reagent and 1 HDV RNA reagent, 19 samples were identified as anti-HDV IgG-positive. The anti-HDV IgG demonstrated superior accuracy and specificity. The assay exhibited excellent precision, with intra-assay coefficient of variation (CV) values ranging from 1.57% to 4.30%, and inter-assay CV values between 1.71% and 4.67% for detecting samples at high, medium, and low concentration levels. Concordance with Reagent A showed consistent results in both positive and negative detections.Conclusion:In this study, the anti-HDV IgG reagent (chemiluminescence method) displayed outstanding specificity in detecting clinical samples and exhibited a high conformity rate with commercialized reagents, making it potentially suitable for screening anti-HDV IgG in HBsAg-positive samples.

Objective:This study aims to evaluate the quality and explore the preliminary clinical applications of a domestically developed hepatitis D virus nucleic acid quantification reagent (abbreviated as"domestic HDV RNA reagent").Methods:The sensitivity and accuracy of the reagent were evaluated in accordance with the WHO HDV RNA international standard, employing the Bio-Rad CFX Opus 96 real-time fluorescence quantitative PCR analysis system. Serial dilutions of pseudo-viruses or cell culture-derived virus were used to determine the linear range of the domestic HDV RNA reagent. Specificity was assessed using positive samples of HAV, HBV, HCV infection, and HEV national reference materials. Precision was evaluated with samples at both high and low concentrations. In a comparative analysis, 30 HDV IgG positive samples were tested using both the domestic HDV RNA reagent and the RoboGene HDV RNA kit based on the ABI 7500 FAST DX system. The Pearson correlation coefficient (r) was used to examine the correlation between the two reagents.Results:The domestic HDV RNA reagent demonstrated a high sensitivity of up to 6 IU/ml, consistent with that of the comparator reagent. The calibration curve for WHO HDV RNA standards had a slope of -3.286, with an amplification efficiency of 101.6%. The linear detection range spanned from 10 to 10 8 IU/ml for eight HDV genotypes. The domestic HDV RNA reagent exhibited exceptional specificity, without cross-reactivity observed with HAV, HBV, HCV, or HEV. Accuracy assessments at five concentration levels met the required standards, with intra-assay precision coefficient of variation ( CV) ranging from 1.20% to 4.20%, and inter-assay precision CV from 1.20% to 7.90%. The detection results for HDV IgG positive samples were highly correlated with the comparator reagent ( r=0.984, P<0.001), achieving a diagnostic accuracy of 100% compared to sequencing results. Conclusion:In this study, the domestic HDV RNA reagent possesses excellent specificity, accuracy, precision, and a broad linear range, attaining a sensitivity level on par with international reagents of the same type.

ObjectiveTo explore the potential mechanism of different processed products of Baiyaojian and its compound Xiangmei pills in rats with ulcerative colitis（UC） by comparing the pharmacodynamic and metabolomic differences. MethodEighty SD rats were acclimatized and kept for 3 d， and randomly divided into 8 groups［blank group， model group， mesalazine group（0.4 g·kg^-1）， Baiyaojian group（1.89 g·kg^-1）， stir-fried Baiyaojian group（1.89 g·kg^-1）， carbonized Baiyaojian group（1.89 g·kg^-1）， and Xiangmei pills low and high dose groups（1.89， 5.67 g·kg^-1）］， with 10 rats in each group. Rats in the blank group were administered physiological saline by gavage， and rats in the remaining 7 groups were orally administered 5% dextran sodium sulfate（DSS） solution daily for 8 consecutive days to induce UC model. After successful modeling， each dosing group was given the corresponding dose of drug solution by gavage， and the blank and model groups were given equal amounts of saline by gavage， and the drug was administered continuously for 8 d. Then serum levels of tumor necrosis factor-α（TNF-α）， interleukin（IL）-6， IL-10 and IL-1β were measured by enzyme-linked immunosorbent assay（ELISA）， hematoxylin-eosin（HE） staining was used to observe the histopathological changes of colon tissue， the proportion of T helper 17 cells（Th17） and regulatory T cells（Treg） in the peripheral blood of rats in each group was detected by flow cytometry. The endogenous metabolites in serum of rats were detected by ultra performance liquid chromatography-quadrupole/electrostatic field orbitrap high-resolution mass spectrometry（UPLC-Q-Exactive Orbitrap MS）， and the differential metabolites were characterized by combining principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）， and were analyzed according to the variable importance in the projection（VIP） value>1.0 and P<0.05， and potential metabolic pathways were analyzed according to Human Metabolome Database（HMDB）. ResultCompared with the blank group， the colon tissue of the model group was congested and the mucosa was ulcerated， the colon length was significantly reduced（P<0.01） and the quality was significantly increased（P<0.05）， the proportion of Th17/Treg in the peripheral blood and the serum levels of TNF-α， IL-6 and IL-1β were significantly increased， while the IL-10 expression wassignificantly reduced（P<0.05， P<0.01）. Compared with the model group， the colon tissue of UC rats in each treatment group was improved with scattered ulcers， reduced inflammatory cell infiltration， significantly increased colon length， and significantly decreased mass（P<0.05）， the proportion of Th17/Treg in the peripheral blood decreased， the expression of TNF-α，IL-6 and IL-1β was significantly reduced（P<0.05， P<0.01）， while the IL-10 expression was significantly increased（P<0.01）. The therapeutic effect of different administration groups on UC was in the order of high dose group of Xiangmei pills>low dose group of Xiangmei pills>carbonized Baiyaojian group>stir-fried Baiyaojian group>Baiyaojian group. And a total of 26 differential metabolites were screened in the metabolomics results. Compared with the blank group， 14 differential metabolites were up-regulated and 5 metabolites were down-regulated in the model group， and 14， 9， 14， 12 and 17 metabolites could be recalled in the Baiyaojian group， stir-fried Baiyaojian group， carbonized Baiyaojian group， Xiangmei pills low and high dose groups. The main metabolic pathways involved were citrate cycle pathway， pantothenic acid and coenzyme A biosynthesis pathway， aromatic hydrocarbon receptor（AhR） signaling pathway， glycolysis/gluconeogenesis pathway. ConclusionThe therapeutic effect of Baiyaojian on UC is significantly improved after charcoal stir-frying， and the efficacy is more prominent when combined with Angelicae Dahuricae Radix and Mume Fructus Carbonisata， which can provide a basis for the development of Baiyaojian compound preparations.

Objective:To explore the predictive value of early serum tumor markers (STM) , neutrophil to lymphocyte ratio (NLR) , platelet to lymphocyte ratio (PLR) combination score on the efficacy of gastric cancer immunotherapy.Methods:A total of 76 patients with gastric cancer who received immunotherapy at Second Affiliated Hospital of Shandong First Medical University from January 1, 2020 to June 30, 2022 were selected. Patients' leading STM, NLR, PLR were collected. Optimal cut-off value of NLR and PLR were determined by the receiver operating characteristic (ROC) curve. The clinical efficacy and prognosis of different leading STM, NLR, PLR and combined scores in gastric cancer patients received immunotherapy were analyzed. ROC curve was used to evaluate the predictive efficiency of each index and the combined score. Cox regression model was used to analyze the factors affecting patients' survival.Results:The best truncation value for NLR was 2.75, and the best truncation value for PLR was 175.9. All patients completed at least 2 cycles of immunotherapy, the objective response rate (ORR) was 23.7% (18/76) , and the disease control rate (DCR) was 88.2% (67/76) . There were no significant differences in ORR [ (20.9% (9/43) vs. 27.3% (9/33) ], DCR [83.7% (36/43) vs. 93.9% (31/33) ] between the high NLR group ( n=43) and low NLR group ( n=33) ( χ2=0.42, P=0.519; χ2=1.02, P=0.313) . There were no significant differences in ORR [27.3% (12/44) vs. 18.8% (6/32) ], DCR [81.8% (36/44) vs. 96.9% (31/32) ] between the high PLR group ( n=44) and low PLR group ( n=32) ( χ2=0.75, P=0.388; χ2=2.71, P=0.555) . The ORR for the high combined score group ( n=39) and low combined score group ( n=37) was 17.9% (7/39) and 29.7% (11/37) , respectively, with no statistically significant difference ( χ2=1.46, P=0.230) ; the DCR was 79.5% (31/39) and 97.3% (36/37) , respectively, with a statistically significant difference ( χ2=4.19, P=0.041) . The median progression free survival (PFS) and overall survival (OS) of 76 patients were 8.0 and 12.0 months. The median PFS in the high NLR group and low NLR group was 7.0 and 10.0 months, respectively, with a statistically significant difference ( χ2=7.95, P=0.005) ; the median OS was 12.0 and 14.0 months, respectively, with no statistically significant difference ( χ2=1.04, P=0.307) . The median PFS in the high PLR group and low PLR group was 8.0 and 10.0 months, respectively, with a statistically significant difference ( χ2=3.90, P=0.048) ; the median OS was 13.0 and 13.0 months, respectively, with no significant difference ( χ2=0.02, P=0.896) . The median PFS in the high combined score group and low combined score group was 7.0 and 10.0 months, respectively, with a statistically significant difference ( χ2=13.52, P<0.001) ; the median OS was 12.0 and 14.0 months, respectively, with a statistically significant difference ( χ2=5.02, P=0.025) . ROC curve analysis showed that the area under curve (AUC) of leading STM, NLR, PLR and combined score to predict the efficacy of gastric cancer immunotherapy was 0.662, 0.697, 0.601 and 0.773. Univariate analysis showed that, surgery ( HR=0.59, 95% CI: 0.36-0.95, P=0.031) , leading STM ( HR=0.57, 95% CI: 0.34-0.93, P=0.026) , NLR ( HR=0.54, 95% CI: 0.34-0.87, P=0.011) , combined score ( HR=0.42, 95% CI: 0.26-0.68, P<0.001) were all influencing factors for PFS in gastric cancer patients received immunotherapy; tumor stage ( HR=0.30, 95% CI: 0.12-0.75, P=0.011) , leading STM ( HR=0.28, 95% CI: 0.15-0.50, P<0.001) , combined score ( HR=0.55, 95% CI: 0.31-0.96, P=0.036) were all influencing factors for OS in gastric cancer patients received immunotherapy. Multivariate analysis showed that, leading STM ( HR=0.56, 95% CI: 0.33-0.98, P=0.041) was an independent influencing factor for PFS in gastric cancer patients received immunotherapy; tumor stage ( HR=0.29, 95% CI: 0.11-0.76, P=0.012) , leading STM ( HR=0.32, 95% CI: 0.17-0.58, P<0.001) , combined score ( HR=0.46, 95% CI: 0.25-0.82, P=0.009) were all independent influencing factors for OS in gastric cancer patients received immunotherapy. Conclusion:The combined score of leading STM, NLR and PLR is an independent factor influencing OS in patients receiving immunotherapy for gastric cancer, and can predict the efficacy of immunotherapy for gastric cancer.

Objective·To investigate the effect of ceria nanoparticles-polyethylene glycol(CeNP-PEG)on scavenging reactive oxygen species(ROS)and alleviating disease activity in dextran sulphate sodium(DSS)-induced colitis mice.Methods·CeNP was synthesized with the hydrates of cerium acetate,oleamine,and xylene,which was modified with polyethylene glycol-stearyl phosphatidylethanolamine(mPEG-DPSE)to obtain CeNP-PEG.Then CeNP-PEG was purified.The particle size and zeta potential of CeNP-PEG were measured by using transmission electron microscopy(TEM)and dynamic light scattering(DLS).Mouse macrophages(Raw264.7)were cultured in vitro and induced to a pro-inflammatory phenotype(M1 phenotype).M1 macrophages were treated with 0.5 μg/mL and 1.0 μg/mL CeNP-PEG,respectively,and then Western blotting was used to detect the expression changes of the proteins related with nuclear factor-κB(NF-κB)signaling pathway.DSS-induced colitis mice models were constructed,and CeNP-PEG(1.0 mg/mL)was intravenously administrated for 3 times via tail vein during the modeling period.Meanwhile,the body weight,fecal characteristics,and frequency of rectal bleeding in mice were monitored in the normal control group(Normal group),the model group(DSS group),and the CeNP-PEG treatment group.The disease activity index(DAI)was calculated to evaluate the intestinal inflammation.The level of ROS in mouse intestinal tissues was detected by dihydroethidine(DHE)staining and the mRNA expression levels of inflammatory cytokines interferon-γ(Ifn-γ),interleukin-6(Il-6),Il-1β and tumor necrosis factor-α(Tnf-α)were detected by real-time quantitative PCR(RT-qPCR).Results·The hydrated particle size of synthesized CeNP-PEG was(6.96±0.27)nm,and the average zeta potential was(-6.02±1.31)mV.Western blotting results showed that the expression of p-P65 increased in the pro-inflammatory macrophages compared with the control group.The expression of NF-κB inhibitor-α(IκB-α)decreased,and their expressions tended to recover after the intervention of different concentrations of CeNP-PEG.In the DSS-induced colitis models,mice in the CeNP-PEG treatment group lost less weight than those in the DSS group(P= 0.000)and had lower DAI scores(P=0.000).The RT-qPCR results of intestinal tissues showed that the mRNA levels of Ifn-γ,Il-1β,Il-6 and Tnf-α in the DSS group were significantly up-regulated compared with those in the Normal group(P=0.000),and all of them significantly decreased in the CeNP-PEG treatment group.The results of DHE staining showed that the fluorescence intensity of intestinal tissues in the DSS group was significantly enhanced than that in the Normal group,and the fluorescence intensity decreased in the CeNP-PEG treatment group.Conclusion·CeNP-PEG can inhibit the expression of intestinal inflammatory factors and the activation of NF-κB-related inflammatory pathway of pro-inflammatory macrophages,eliminate intestinal ROS,improve the intestinal inflammatory microenvironment,and alleviate the disease activity of DSS-induced colitis in mice.

Objective:Preliminary explore the safety and efficacy of using only vitamin K antagonists without antiplatelet therapy after left ventricular assist devices (LVAD) implantation.Methods:This is a cohort study. Patients who underwent HeartCon LVAD implantation in TEDA International Cardiovascular Hospital from September 2020 to September 2022 were included. Oral warfarin sodium was given on postoperative days 1 to 2, with the target international standardized ratio (INR) of 2.0 to 2.5. Follow-up until September 2022, survival, INR level and occurrence of bleeding and thrombosis were recorded. Survival analysis was performed by the Kaplan-Meier method (censored for heart transplantation).Results:A total of 22 patients, including 16 male patients (72.7%), aged (51.0±13.3) years, were included. The duration of HeartCon LVAD support was (458±166) days and the INR during support was 2.28±0.26. One patient underwent the heart transplant at 307 d after implantation. One patient (4.5%) occured cardiac tamponade, two patients (9.1%) occured hemorrhagic stroke, five patients (22.7%) occured gastrointestinal bleeding, four patients (18.2%) occured gingival hemorrhage, two patients (9.1%) occured epistaxis, one patient (4.5%) occurred ischemic stroke, one patient (4.5%) occured pump thrombosis, and one patient (4.5%) occured aortic valve thrombosis. The survival rates were 100%, 95%, 95%, and 95% at 3 months, 6 months, 1 year, 2 years after implantation respectively.Conclusion:The single antithrombotic strategy using warfarin (target INR 2.0-2.5) without antiplatelet for patients with implantations of HeartCon type LVAD may be safe and effective.