The rapid emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that evade immunity elicited by vaccination has posed a global challenge to the control of the coronavirus disease 2019 (COVID-19) pandemic. Therefore, developing countermeasures that broadly protect against SARS-CoV-2 and related sarbecoviruses is essential. Herein, we have developed a lipid nanoparticle (LNP)-encapsulated mRNA (mRNA-LNP) encoding the full-length Spike (S) glycoprotein of SARS-CoV-2 (termed RG001), which confers complete protection in a non-human primate model. Intramuscular immunization of two doses of RG001 in Rhesus monkey elicited robust neutralizing antibodies and cellular response against SARS-CoV-2 variants, resulting in significantly protected SARS-CoV-2-infected animals from acute lung lesions and complete inhibition of viral replication in all animals immunized with low or high doses of RG001. More importantly, the third dose of RG001 vaccination elicited effective neutralizing antibodies against current epidemic XBB and JN.1 strains and similar cellular response against SARS-CoV-2 Omicron variants (BA.1, XBB.1.16, and JN.1) were observed in immunized mice. All these results together strongly support the great potential of RG001 in preventing the infection of SARS-CoV-2 variants of concern (VOCs).

Tumor cell-intrinsic programmed death-ligand 1 (PD-L1) signals mediate tumor initiation, progression and metastasis, but their effects in ameloblastoma (AM) have not been reported. In this comprehensive study, we observed marked upregulation of PD-L1 in AM tissues and revealed the robust correlation between elevated PD-L1 expression and increased tumor growth and recurrence rates. Notably, we found that PD-L1 overexpression markedly increased self-renewal capacity and promoted tumorigenic processes and invasion in hTERT⁺-AM cells, whereas genetic ablation of PD-L1 exerted opposing inhibitory effects. By performing high-resolution single-cell profiling and thorough immunohistochemical analyses in AM patients, we delineated the intricate cellular landscape and elucidated the mechanisms underlying the aggressive phenotype and unfavorable prognosis of these tumors. Our findings revealed that hTERT⁺-AM cells with upregulated PD-L1 expression exhibit increased proliferative potential and stem-like attributes and undergo partial epithelial‒mesenchymal transition. This phenotypic shift is induced by the activation of the PI3K-AKT-mTOR signaling axis; thus, this study revealed a crucial regulatory mechanism that fuels tumor growth and recurrence. Importantly, targeted inhibition of the PD-L1-PI3K-AKT-mTOR signaling axis significantly suppressed the growth of AM patient-derived tumor organoids, highlighting the potential of PD-L1 blockade as a promising therapeutic approach for AM.
Ameloblastoma/metabolism* ; Humans ; B7-H1 Antigen/metabolism* ; Neoplasm Recurrence, Local/pathology* ; Signal Transduction ; Cell Proliferation ; Up-Regulation ; TOR Serine-Threonine Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Telomerase/metabolism* ; Jaw Neoplasms/metabolism* ; Epithelial-Mesenchymal Transition ; Animals ; Cell Line, Tumor ; Female ; Male

OBJECTIVE: To investigate the efficacy and safety of autologous blood transfusion during weaning from venous-arterial extracorporeal membrane oxygenation (VA-ECMO) under controlled rotational speed. METHODS: A retrospective study was conducted, selecting patients who underwent extracorporeal membrane oxygenation (ECMO) and successfully weaned at the emergency and critical care medicine center of Henan Provincial Third People's Hospital from January 2023 to May 2024. General data including gender, age, body mass index (BMI), European system for cardiac operative risk evaluation (EuroScore), and disease types were collected. Vital signs at weaning [heart rate, systolic blood pressure (SBP), diastolic blood pressure (DBP), and peripheral oxygen saturation], parameters before and after weaning [B-type natriuretic peptide (BNP), hemoglobin (Hb), partial pressure of arterial oxygen (PaO₂), partial pressure of arterial carbon dioxide (PaCO₂), arterial lactate, central venous pressure (CVP), inferior vena cava collapsibility index, left ventricular ejection fraction (LVEF), and right heart load], post-weaning inflammatory markers at 1-day and 3-day [body temperature, white blood cell count (WBC), neutrophil percentage (NEU%), C-reactive protein (CRP), procalcitonin (PCT), interleukin-10 (IL-10)], as well as complications (infection, thrombosis, renal failure, gastrointestinal bleeding) and post-weaning blood return status were recorded. Patients were divided into an observation group (with post-weaning blood return) and a control group (without post-weaning blood return) based on the presence of blood return after weaning. The changes in the aforementioned parameters were compared between the two groups. RESULTS: A total of 62 patients were included, with 31 cases in each group. No statistically significant differences were observed between the two groups in baseline characteristics including gender, age, BMI, and EuroScore. At weaning, the observation group exhibited relatively stable vital signs, with no significant differences in heart rate, SBP, DBP, or peripheral oxygen saturation compared to the control group. After weaning, the observation group showed significantly lower levels of BNP, PaCO₂, arterial lactate, CVP, and right heart load compared to pre-weaning values [BNP (ng/L): 2 325.96±78.51 vs. 4 878.48±185.47, PaCO₂ (mmHg, 1 mmHg≈0.133 kPa): 35.23±3.25 vs. 40.75±4.41, arterial lactate (mmol/L): 2.43±0.61 vs. 6.19±1.31, CVP (cmH₂O, 1 cmH₂O≈0.098 kPa): 8.32±0.97 vs. 15.34±1.74, right heart load: 13.24±0.97 vs. 15.69±1.31, all P < 0.05], while Hb, PaO₂, inferior vena cava collapsibility index, and LVEF were significantly higher than pre-weaning values [Hb (g/L): 104.42±9.78 vs. 96.74±6.39, PaO₂ (mmHg): 94.12±7.78 vs. 75.51±4.39, inferior vena cava collapsibility (%): 28±7 vs. 17±3, LVEF (%): 62.41±6.49 vs. 45.30±4.51, all P < 0.05]. No statistically significant differences were found between the observation group and control group in these parameters. At 3 days post-weaning, the observation group demonstrated significantly lower levels of body temperature, WBC, NEU%, CRP, PCT, and IL-10 compared to 1 day post-weaning [body temperature (centigrade): 36.83±1.15 vs. 37.94±1.41, WBC (×10⁹/L): 7.82±0.96 vs. 14.34±2.15, NEU%: 0.71±0.05 vs. 0.80±0.07; CRP (mg/L): 4.34±0.78 vs. 8.94±1.21, PCT (μg/L): 0.11±0.02 vs. 0.26±0.05, IL-10 (ng/L): 8.93±1.52 vs. 13.51±2.17, all P < 0.05], with no significant differences compared to the control group. No statistically significant differences were observed between the two groups in the incidence of complications including infection, thrombosis, renal failure, and gastrointestinal bleeding. CONCLUSION Autologous blood reinfusion during VA-ECMO weaning under controlled rotational speed is safe and effective, without increasing risks of infection or thrombosis.
Humans ; Retrospective Studies ; Extracorporeal Membrane Oxygenation/methods* ; Blood Transfusion, Autologous ; Male ; Female ; Adult ; Middle Aged ; Natriuretic Peptide, Brain/blood*

Background::Evidence indicates that low muscle strength is associated with an increased cardiovascular diseases (CVDs) risk. However, the association between muscle strength changes based on repeated measurements and CVD incidence remains unclear.Methods::The study used data from the China Health and Retirement Longitudinal Study in 2011 (Wave 1), 2013 (Wave 2), 2015 (Wave 3), and 2018 (Wave 4). Low muscle strength was defined as handgrip strength <28 kg for men or <18 kg for women, or chair-rising time ≥12 s. Based on changes in muscle strength from Waves 1 to 2, participants were categorized into four groups of Normal-Normal, Low-Normal, Normal-Low, and Low-Low. CVD events, including heart disease and stroke, were recorded using a self-reported questionnaire during Waves 3 and 4 visits. Cox proportional hazards models were used to investigate the association between muscle strength changes and CVD incidence after multivariable adjustments. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated with the Normal-Normal group as the reference.Results::A total of 1164 CVD cases were identified among 6608 participants. Compared to participants with sustained normal muscle strength, the CVD risks increased progressively across groups of the Low-Normal (HR = 1.20, 95% CI: 1.01-1.43), the Normal-Low (HR = 1.35, 95% CI: 1.14-1.60), and the Low-Low (HR = 1.76, 95% CI: 1.49-2.07). Similar patterns were observed for the significant associations between muscle strength status and the incidence risks of heart disease and stroke. Subgroup analyses showed that the significant associations between CVD and muscle strength changes were consistent across age, sex, and body mass index (BMI) categories.Conclusions::The study found that muscle strength changes were associated with CVD risk. This suggests that continuous tracking of muscle status may be helpful in screening cardiovascular risk.

Objective:To analyze the concentration of formic acid,propionic acid and butyric acid in gingival crevicular fluid(GCF)of patients with stages Ⅲ and Ⅳ periodontitis,and their relationship with periodontitis.Methods:The study enrolled 37 systemically healthy patients with periodontitis and 19 healthy controls who visited Department of Periodontology,Peking University School and Hospital of Sto-matology from February 2008 to May 2011.Their GCFs were collected from the mesial-buccal site of one molar or incisor in each quadrant.Periodontal clinical parameters,including plaque index(PLI),probing depth(PD),bleeding index(BI),and attachment loss(AL).Concentrations of formic acid,propionic acid and butyric acid in the supernatant of the GCFs were analyzed by high-performance capil-lary electrophoresis(HPCE).The prediction ability of formic acid,propionic acid and butyric acid with the risk of periodontitis and the differences between grade B and grade C periodontitis were analyzed.Results:In this study,32 patients with stage Ⅲ and 5 patients with stage Ⅳ were enrolled,including 9 patients with grade B and 28 patients with grade C.Clinical periodontal variables in the patients with pe-riodontitis were significantly higher than those in the control group(P＜0.001).Formic acid was signifi-cantly lower in periodontitis than that in the control group[5.37(3.39,8.49)mmol/L vs.12.29(8.35,16.57)mmol/L,P＜0.001].Propionic acid and butyric acid in periodontitis were significantly higher than those in the control group:Propionic acid,10.23(4.28,14.90)mmol/L vs.2.71(0.00,4.25)mmol/L,P＜0.001;butyric acid,2.63(0.47,3.81)mmol/L vs.0.00(0.00,0.24)mmol/L,P＜0.001.There was no significant difference in formic acid,propionic acid and butyric acid concentrations between grade B and grade C periodontitis(P＞0.05).Propionic acid and butyric acid in the deep pocket were significantly higher than in the shallow pocket,while the concentration of formic acid decreased with the increase of PD.Propionic acid(OR=1.51,95％CI:1.29-1.75)and butyric acid(OR=3.72,95％CI:1.93-7.17)were risk factors for periodontitis,while formic acid(OR=0.87,95％CI:0.81-0.93)might be a protective factor for periodontitis.Propionic acid(AUC=0.852,95％CI:0.805-0.900),butyric acid(AUC=0.889,95％CI:0.841-0.937),f(formic acid,AUC=0.844,95％CI:0.793-0.895)demonstrated a good predictive capacity for the risk of periodontitis.Conclusion:The concentration of formic acid decrease in the GCF of periodontitis patients,which is a protective factor for periodontitis,its reciprocal have good predictive capacity.However,propionic acid and butyric acid increase,which are risk factors for periodontitis and have good predictive capacity.The concentration of formic acid,propionic acid,and butyric acid vary with probing depth,but there is no significant difference between grade B and grade C periodontitis.

Objective:To analyze the efficacy and safety of nalbuphine for analgesia in patients with non-mechanical ventilation in intensive care unit (ICU).Methods:From December 2018 to August 2021, a multicenter randomized controlled clinical study was conducted to select non-mechanical ventilation patients with analgesic needs admitted to ICU of four hospitals in Henan Province and Guizhou Province. Patients were randomly assigned to nalbuphine group and fentanyl group. The nalbuphine group was given continuous infusion of nalbuphine [0.05~0.20 mg/(kg·h)], and the fentanyl group was given continuous infusion of fentanyl [0.5~2.0 μg/(kg·h)]. The analgesic target was critical-care pain observation tool (CPOT) score<2. The observation time was 48 hours. The primary endpoint was CPOT score, the secondary endpoints were Richmond agitation-sedation score (RASS), ICU length of stay, adverse events, and proportion of mechanical ventilation. The quantitative data of the two groups were compared by t test or Mann-Whitney U test. The enumeration data were compared by chi square test or Fisher exact probability method. The data at different time points between groups were compared by repeated measures analysis of variance. Results:A total of 210 patients were enrolled, including 105 patients in the nalbuphine group and 105 patients in the fentanyl group. There was no significant difference in baseline data between the two groups (all P>0.05). There was no significant difference in CPOT score between nalbuphine group and fentanyl group at each time point after medication ( P>0.05), the CPOT score of both groups at each time point after medication was significantly lower than that before medication, and the analgesic target could be achieved and maintained 2 hours after medication. There was no significant difference in RASS between the two groups at each time point after medication ( P>0.05), which was significantly lower than that before medication, and the target sedative effect was achieved 2 hours after medication. There was no significant difference in ICU length of stay between nalbuphine group and fentanyl group [5.0(4.0,7.5) d vs. 5.0(4.0,8.0) d, P=0.504]. The incidence of delirium, nausea and vomiting, abdominal distension, pruritus, vertigo and other adverse events in the nalbuphine group was lower than that in the fentanyl group (all P<0.05). There was no significant difference in the incidence of other adverse events such as deep sedation, hypotension and bradycardia between the two groups (all P>0.05). The incidence of respiratory depression in nalbuphine group was not significantly different from that in fentanyl group ( P>0.05), but the proportion of mechanical ventilation was significantly lower than that in the fentanyl group [1.9% (2/105) vs. 8.6%(9/105), P=0.030]. Conclusions:Nalbuphine could be used for analgesia in ICU patients with non-mechanical ventilation. The target analgesic effect could be achieved within 2 hours, and it had a certain sedative effect with a low incidence of adverse reactions.

Objective To compare the safety and efficacy of direct thrombectomy versus bridging thrombectomy in the treatment of acute anterior circulation large vessel occlusion stroke under different collateral circulation statuses.Methods Totally 93 patients with acute anterior circulation ischemic stroke admitted to the First Affiliated Hospital of Xinxiang Medical University from September 2020 to March 2023 were selected as the research subjects.Patients were divided into direct throm-bectomy group(n=47)and bridging thrombectomy group(n=46)based on the type of thrombectomy.Patients in the direct thrombectomy group received direct intravascular thrombectomy,while patients in the bridging thrombectomy group received intravenous thrombolysis with alteplase combined with mechanical thrombectomy.According computed tomography angiography,the collateral circulation Tan classification was applied to divide the patients into good collateral circulation sub-group and poor collateral circulation sub-group.The modified thrombolysis in cerebral infarction grading(mTICI)was used to evaluate vessel recanalization.Head computed tomography plain scan was performed at 24-48 hours postoperatively to assess if there was hemorrhagic transformation,and modified Rankin Scale score was performed at 90 days postoperatively.Information such as imaging examination time,femoral artery puncture time,vessel recanalization time after thrombectomy,prognosis and spontaneous non-traumatic symptomatic intracerebral hemorrhage(SICH)were collected.Results The age,gender,baseline Alberta stroke program early computed tomography score,baseline national institutes of health stroke scale score,proportions of hypertension,diabetes and atrial fibrillation,baseline systolic pressure,creatinine,baseline blood glucose,platelet count,occlusion site,stroke etiologies and collateral circulation status of patients in the two groups were not statistically significantly different(P＞0.05).There were no significant differences in the post-admission imaging examination time,femoral artery puncture time,vessel recanalization time after thrombectomy,successful vascular reperfusion rate,good prognosis rate,mortality rate,and SICH incidence between the two groups(P＞0.05).The hemorrhagic transformation rate of patients in the direct thrombectomy group was significantly lower than that in the bridging thrombectomy group(P＜0.05).There were no significant differences in the post-admission imaging examination time,femoral artery puncture time,vessel recanalization time after thrombectomy,successful vascular reperfusion rate,good prognosis rate,mortality rate,and SICH incidence between patients with good collateral circulation and patients with poor collateral circulation in the two groups(P＞0.05).The hemorrhagic transformation rate of patients with good and poor collateral circulation in the direct thrombectomy group was significantly lower than that in the bridging thrombectomy group(P＜0.05).Conclusion Under different collateral circulation conditions,the safety and efficacy of direct thrombectomy and bridging thrombectomy in the treatment of acute anterior circulation large vessel occlusion stroke are similar,but bridging thrombectomy is more likely to result in cerebral hemorrhage transformation compared with direct thrombectomy.

Objective To explore and verify the protective and therapeutic effects and possible mechanisms of Zukamu granules on hypoxia alone and hypoxia+Su5416-induced hypoxic pulmonary hypertension(HPH)in mice.Methods Multiple databases and related literature were used to collect the active ingredients data in Zukamu granules and the HPH-related targets were predicted and obtained.The network construction and enrichment analysis were performed.The HPH mouse models were es-tablished by two-week hypoxia and four-week hypoxia+Su5416 induction,and the relevant indicators and the main pharmacodyna-mic indexes such as right ventricular pressure were tested.Masson staining was used to observe the pathological changes in lung tissues,and Western blotting was used to detect the expression levels of bax,bcl-2,PI3K,p-PI3K,eNOS,and HIF-1α in lung tis-sues.Results A total of 167 active ingredients of Zukamu granules were screened,with 179 intersecting targets with HPH,in-cluding targets like PIK3CA and HIF-1.The validation experimental results showed that Zukamu granules could significantly re-duce right ventricular systolic pressure and right ventricular hypertrophy in HPH mice,and down-regulate the expression of bcl-2 and HIF-1α and up-regulate the expression of bax,PI3K,p-PI3K and eNOS in mice lung tissues.Conclusion Zukamu gran-ules may act against HPH by modulating bax/bcl and PI3K-eNOS/HIF-1α signaling pathways.

Objective:To establish a predictive model for the progression of acute kidney injury (AKI) to stage 3 AKI (renal failure) in the intensive care unit (ICU), so as to assist physicians to make early and timely decisions on whether to intervene in advance.Methods:A retrospective analysis was conducted. Thirty-eight patients with AKI admitted to the intensive care medicine of the Third People's Hospital of Henan Province from January 2018 to May 2023 were enrolled. Patient data including acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) upon admission, serum creatinine (SCr), blood urea nitrogen (BUN), daily urine output during hospitalization, and the timing of continuous renal replacement therapy (CRRT) intervention were recorded. Based on clinically collected pathological data, standardized creatinine value ratio mean polynomial fitting models were established as the first criterion for judging the progression to stage 3 AKI after data cleansing, screening, and normalization. Additionally, standardized creatinine value ratio index fitting models were established as the second criterion for predicting progression to stage 3 AKI.Results:A total of 38 AKI patients were included, including 25 males and 13 females. The average age was (58.45±12.94) years old. The APACHEⅡ score was 24.13±4.17 at admission. The intervention node was (4.42±0.95) days. Using a dual regression model approach, statistical modeling was performed with a relatively small sample size of statistical data samples, yielding a scatter index non-linear regression model for standardized creatinine value ratio data relative to day " n", with y = 1.246?2 x1.164?9 and an R2 of 0.860?1, indicating reasonable statistical fitting. Additionally, a quadratic non-linear regression model was obtained for the mean standardized creatinine value ratio relative to day " n", with y = -0.260?6 x2+3.010?7 x-1.612 and an R2 of 0.998?9, indicating an excellent statistical fit. For example, using a baseline SCr value of 66 μmol/L for a healthy individual, the dual regression model predicted that the patient would progress to stage 3 AKI within 3-5 days. This prediction was consistent when applied to other early intervention renal injury patients. Conclusion:The established model effectively predicts the time interval of the progression of AKI to stage 3 AKI (renal failure), which assist intensive care physicians to intervene AKI as early as possible to prevent disease progression.

Objective To observe the value of ultrasound-guided percutaneous ethanol injection(PEI)combined with microwave ablation(MWA)for treating thyroid benign partially cystic masses.Methods A total of 100 patients with single benign partially cystic mass who would undergo ultrasound-guided ablation treatment were prospectively enrolled.The patients were randomly assigned into PEI group(received PEI combined with MWA sequential ablation)or control group(received simple MWA),each n=50.Data before and after treatments were compared within groups,the therapeutic efficacy were compared between groups after treatments,and the value of sequential ablation was analyzed.Results Ultrasound-guided ablation was successfully performed for all 100 masses.During follow-up,5 cases in PEI group and 3 cases in control group were lost.The operation time of MWA,total MWA energy and patients'pain level during treatments in PEI group were all lower than those in control group(all P＜0.05).Significant difference of thyroid mass volumes were found before and 3,6 and 12 months after treatments in both groups(all P＜0.05).The volume reduction rate(VRR)in PEI group before and 1,3,6 and 12 months after treatments were all higher than that in control group(all P＜0.05).The success rate was 95.56％(43/45)in PEI group and 89.36％(42/47)in control group 12 months after treatments,respectively,without significant difference(P=0.451).There were significant differences of neck aesthetics scores and symptom scores before and 3,6 and 12 months after treatments in both groups(all P＜0.05).The incidence of complications in PEI group was 6.67％(3/45),while in control group was 14.89％(7/47),the former was lower than the latter(P＜0.05).Conclusion Ultrasound-guided PEI combined with MWA sequential ablation had better effect for treating thyroid benign partially cystic masses than single MWA.