Azvudine and nirmatrelvir/ritonavir (Paxlovid) are recommended for COVID-19 treatment in China, but their safety and efficacy in the elderly population are not fully known. In this multicenter, retrospective, cohort study, we identified 5131 elderly hospitalized COVID-19 patients from 32,864 COVID-19 patients admitted to nine hospitals in Henan Province, China, from December 5, 2022, to January 31, 2023. The primary outcome was all-cause death, and the secondary outcome was composite disease progression. Propensity score matching (PSM) was performed to control for confounding factors, including demographics, vaccination status, comorbidities, and laboratory tests. After 2:1 PSM, 1786 elderly patients receiving azvudine and 893 elderly patients receiving Paxlovid were included. Kaplan-Meier and Cox regression analyses revealed that compared with Paxlovid group, azvudine could significantly reduce the risk of all-cause death (log-rank P = 0.002; HR: 0.71, 95% CI: 0.573-0.883, P = 0.002), but there was no difference in composite disease progression (log-rank P = 0.52; HR: 1.05, 95% CI: 0.877-1.260, P = 0.588). Four sensitivity analyses verified the robustness of above results. Subgroup analysis suggested that a greater benefit of azvudine over Paxlovid was observed in elderly patients with primary malignant tumors (P for interaction = 0.005, HR: 0.32, 95% CI: 0.18-0.57) compared to patients without primary malignant tumors. Safety analysis revealed that azvudine treatment had a lower incidence of adverse events and higher lymphocyte levels than Paxlovid treatment. In conclusion, azvudine treatment is not inferior to Paxlovid treatment in terms of all-cause death, composite disease progression and adverse events in elderly hospitalized COVID-19 patients.

This study was designed to explore the correlation between alterations in NLRP3 levels and Th17/Treg imbalance in asthmatic mice undergoing epithelial-mesenchymal transition(EMT).A murine model of asthma was established by intraperitoneal injection combined with nebulization of ovalbumin(OVA).Mice were randomly grouped into asthma model group and normal control group.The airway reactivity was detected with non-invasive lung function instrument.Hematoxylin and Eosin(HE)and Masson's trichrome staining were applied to evaluate the histopathological injury of lung tissue and the extent of lung fibrosis;RT-qPCR was applied to detect EMT-related biomarkers(Snail,E-Cadherin,N-Cadherin),the specific transcription factors of T cell subsets(RoRγt,Foxp3)and NLRP3 in lung tissue of mice;Western blot was used to detect the protein expression of E-cadherin,N-Cadherin and NLRP3 in lung tissue of mice.The Th17 and Treg cell populations in the spleen were enumerated via flow cytometry.Furthermore,the expression levels of NLRP3,IL-17 and IL-10 in bronchoalveolar lavage fluid(BALF)were analyzed by Giemsa staining.Compared with the control group,the asthma model group showed higher level of airway resistance,coupled with an obviously decrease in pulmonary ventilation compliance.Pathological alterations in lung tissue were evident,characterized by thickening of the airway epithelium,airway stenosis,infiltration of inflammatory cells,higher expression levels of N-Cadherin and NLRP3 proteins(P<0.05),lower expression level of E-Cadherin(P<0.001)and higher levels of marker genes(Snail and N-Cadherin)in lung tissue.Furthermore,model mice demonstrated higher level of NLRP3 in BALF(P<0.05),higher level of Th17 in spleen,and higher levels of retinoic acid orphan receptor(ROR)-γt mRNA(P<0.05)and Th17-related cytokines(IL-17)(P<0.01).Concurrently,model mice also showed an obviously decrease in the prevalence of Treg cells,Forkhead box Foxp3 mRNA(P<0.001),and Treg-related cytokine IL-10(P<0.05).The results of the Pearson correlation analysis indicated that the level of NLRP3 mRNA was positively correlated the ratio of RoR γt mRNA,but negatively correlated with Foxp3 mRNA in the lung tissue of asthmatic mice.Additionally,NLRP3 in BALF demonstrated a positive correlation with IL-17 and a negative correlation with IL-10.In conclusion,These findings suggest that NLRP3 may trigger bronchial EMT by exacerbating the immune imbalance of Th17/Treg cells.

Objectives:To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy.Methods:Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS).Results:Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% ( P＜0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P＜0.001), resection status ( HR, 3.00, 95% CI, 1.64-5.52, P＜0.001), and adjuvant chemotherapy ( HR, 3.25, 95% CI, 2.01-5.27, P＜0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not ( P＜0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions:The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

Objectives:To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy.Methods:Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (＜8), intermediate (8-16), and high (＞16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS).Results:Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% ( P＜0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, P＜0.001), resection status ( HR, 3.00, 95% CI, 1.64-5.52, P＜0.001), and adjuvant chemotherapy ( HR, 3.25, 95% CI, 2.01-5.27, P＜0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not ( P＜0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions:The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.

Objective To monitor heart-related parameters of hypoxic pulmonary hypertension(PH)mouse models induced by hypoxia alone and hypoxia combined with vascular endothelial growth factor receptor inhibitor SU5416 using echocardiography,and to construct the prediction equation of right ventricular systolic pressure(RVSP).Twenty-four C57BL/6J male mice were randomly divided into simple hypoxia group(group A),hypoxia combined with SU5416 group(group B),control group(group C),each group 8 mice.Hypoxic PH models were constructed with hypoxia alone and hypoxia combined with SU5416 in group A and group B,respectively.Echocardiography was performed before and during modeling(2,3,4 weeks after interventions),and the relevant parameters were obtained.RVSP was measured using right heart catheterization after the last echocardiography.The changes of ultrasonic parameters were observed,the correlations of ultrasonic parameters 4 weeks after intervention with RVSP were observed,and linear equations for predicting RVSP were established.Results With time going,during modeling,pulmonary artery diameter(PAD),PAD/aorta diameter(AOD)and right ventricle anterior wall thickness(RVAWT)increased,while heart rate,pulmonary artery acceleration time(PAAT),PAAT/pulmonary artery ejection time(PAET)and tricuspid annular plane systolic excursion(TAPSE)decreased in group A and B(all P＜0.05).Three and 4 weeks after interventions,PAET,PAAT/PAET and TAPSE in group B decreased compared with those in group A(all P＜0.05).Four weeks after interventions,RVSP in group A and B were highly correlated with PAD/AOD,RVAWT,PAAT,PAAT/PAET and TAPSE(all P＜0.05).The linear regression equations of PAAT/PAET and TAPSE for predicting RVSP in simple hypoxic PH mice models included RVSP=-161.7 ×(PAAT/PAET)+63.85,as well as RVSP=-36.53 ×TAPSE+71.55,while of predicting RVSP in hypoxia combined with VEGFR-2 inhibitor PH mouse models were as follows:RVSP=-266.4 ×(PAAT/PAET)+91.59,RVSP=-69.14 × TAPSE+116.5.Conclusion Four weeks after inerventions,the phenotypes of hypoxic PH mouse models induced by hypoxia alone and hypoxia combined with SU5416 became obvious.Prediction equations of RVSP established based on PAAT/PAET and TAPSE obtained with echocardiography could provide references for relevant research.

Objective:To analyze the clinical features and outcomes of paroxysmal supraventricular tachycardia (PSVT) in neonates without structural heart disease.Methods:A retrospective study was conducted on PSVT neonates without structural heart disease who were treated and followed up at the Women and Children's Hospital, Qingdao University, from January 2019 to June 2022. Clinical data, including the prenatal history of PSVT, the time at first onset of PSVT after birth, anti-arrhythmic treatment, and follow-up outcomes, were collected and analyzed. These patients were divided into two groups based on the presence and absence of fetal PSVT history. Differences in the clinical data between the two groups were compared, including the time at first onset of PSVT, the proportion of patients with persistent tachycardia at initial diagnosis, and hospitalization frequency. Statistical analysis was performed using t-test, Mann-Whitney U test, or Pearson's Chi-square test. Results:A total of 72 neonates with PSVT were included, with an average gestational age at delivery of (38.8±1.8) weeks and an average birth weight of (3 260±330) g. There were 26 (36.1%) cases with a prenatal history of PSVT, while 46 (63.9%) cases without. The median time at the first onset of PSVT after birth was 2.1 (0.3-13.7) d. Anti-arrhythmic drugs used for the patients included propafenone (44 cases, 61.1%), amiodarone (28 cases, 38.9%), and cedilanid (14 cases, 19.4%). There were 44 cases (61.1%) received single drug therapy, 26 (36.1%) receiving dual therapy, and only two (2.8%) receiving triple therapy. Prophylactic drugs were administered to 38 patients (52.8%) for six months, and 20 (27.8%) for 12 months. Fourteen cases (19.4%) still exhibited tachycardia during follow-up and continued their drug therapy. No major illnesses or deaths occurred in the 72 patients during a 12-month follow-up. Compared with the patients without a history of fetal PSVT, those with a history of fetal PSVT had an earlier onset of PSVT after birth [0.2 d (0.0-0.7 d) vs. 12.0 d (2.2-15.0 d), Z=－4.83, P<0.001], a high rate of persistent tachycardia at first diagnosis [76.9% (20/26) vs. 39.1% (18/46), χ2=4.76, P=0.029], more hospitalizations [4.0 times(3.0-7.0 times) vs. 1.0 times (1.0-1.0 times), Z=－3.52, P<0.001], and longer duration of preventive anti-arrhythmic treatment [12.0 months (10.5-21.0 months) vs. 6.0 months (3.0-6.0 months), Z=－4.17, P<0.001]. Conclusion:Attention should be given to PSVT screening in neonates without structural heart disease, particularly for those with a history of fetal PSVT, who tend to have an early onset of PSVT after birth, persistent tachycardia at first diagnosis with high rates of recurrence and require longer preventive anti-arrhythmic treatment.

Objective:To analyze the diagnostic and prognostic value of routine bone marrow examination in patients with extranodal NK/T-cell lymphoma (ENKTCL) based on PET-CT staging.Methods:Clinical data of 186 patients who received bone marrow biopsy and bone marrow aspiration in Fujian Medical University Union Hospital from 2013 to 2021 were retrospectively analyzed. All patients were divided into bone marrow biopsy + bone marrow aspiration group ( n=186) and PET-CT + bone marrow biopsy group ( n=139). The sensitivity, specificity, positive and negative predictive values were compared between two groups. The data were analyzed and plotted. Survival analysis was performed using Kaplan-Meier method and log-rank test. Results:In the whole cohort, 45 patients were positive for bone marrow biopsy, and 30 of them were positive for bone marrow aspiration. A total of 141 patients who were negative for bone marrow biopsy also achieved negative results for bone marrow aspiration. A total of 139 patients completed PET-CT staging and bone marrow biopsy. And 30 patients were diagnosed with positive bone marrow by PET-CT, in which 22 of them were confirmed positive by bone marrow biopsy. Among 109 patients diagnosed with negative bone marrow by PET-CT, 5 of them were confirmed positive by bone marrow biopsy. All these cases were classified as stage Ⅳ due to distant metastases. PET-CT had a diagnostic sensitivity of 81.5%, a specificity of 92.9%, a positive predictive value of 73.3%, and a negative predictive value of 95.4%. Among early stage (Ⅰ-Ⅱ stage) patients diagnosed with PET-CT, all of them were negative for bone marrow biopsy (the negative predictive value was 100%). In stage Ⅳ patients ( n=55), the 1-year overall survival of patients with bone marrow involvement by bone marrow biopsy or PET-CT ( n=35) compared with their counterparts with the involvement of other organs ( n=20) was 28.7% vs.42.0% ( P=0.13), and 1-year progression free survival rates was 23.2% vs. 23.3% in ( P=0.94). Conclusions:Routine bone marrow biopsy does not change the original staging of patients with early stage ENKTCL based on PET-CT staging. Advanced stage patients with positive bone marrow biopsy tend to obtain worse prognosis, indicating that bone marrow biopsy still has certain value.

Objective:To construct and validate a predictive model of fecal/urinary incontinence among older adults in China.Methods:Data was obtained from the Seventh Chinese Longitudinal Healthy Longevity Survey in 2018.In the questionnaire, "Are you able to control your bowel and urine" , was regarded as the main effect indicator.Receiver operating curves(ROC)were used to find the best cut-off values of calf circumference for predicting fecal/urinary incontinence, and univariate Logistic model method was used to explore the potential factors associated with fecal/urinary incontinence among community-living older adults in China.A random sampling method was used to extract 70% of the survey data as the training set, and the remaining 30% of the survey data as the test set.A multivariate Logistic regression analysis was conducted in the training set to build a prediction model that encompassed all predictors, and a nomogram was plotted.Results:Logistic regression analysis showed that age, small calf circumference(male <28.5 cm, female <26.5 cm), inability to walk 1 km continuously, inability to lift 5 kg items, inability to do three consecutive squats, limited daily activities, and a history of urinary system disorders, nervous system disorders, and cerebrovascular disorders were all risk factors for fecal/urinary incontinence for older adults in China.Female, better socioeconomic status, and normal body mass index were protective factors for fecal/urinary incontinence.The Logistic regression model for predicting fecal/urinary incontinence among Chinese older adults was constructed using the above twelve factors.The consistency index(C-index)value of the model was 0.907, indicating that the model had good predictive ability.The area under the ROC curve(AUC)of the overall sample, training set and test set were 0.906(95% CI: 0.896-0.917), 0.907(95 % CI: 0.894-0.921)and 0.910(95% CI: 0.892-0.928), respectively, indicating that the model had high prediction ability and good discrimination. Conclusions:Age, sex, calf circumference, ability to walk 1 km continuously, ability to lift 5 kg items, ability to do three consecutive squats, daily activities, history of urinary system disorders, nervous system disorders and cerebrovascular disorders, socioeconomic status, and body mass index were independent predictors for fecal/urinary incontinence among older adults in China.The nomogram based on the above indicators has a good predictive effect on fecal/urinary incontinence for older adults.

Objective:To compare the outcomes of watch&wait (W&W) strategy in patients with locally advanced rectal cancer who achieved complete clinical response (cCR) after neoadjuvant therapy, with those who obtained pathological complete response (pCR) after total mesorectal excision (TME).Methods:This is a retrospective cohort analysis study. Patients histologically proven with locally advanced rectal adenocarcinoma (stage Ⅱ-Ⅲ) who had received neoadjuvant chemotherapy were eligible between January 2014 and December 2019. In whom we included patients who had cCR offered management with W&W strategy after completing neoadjuvant therapy and follow-up ≥1 year (W&W group), and patients who did not have cCR but pCR after TME (pCR group). The primary endpoints were 3-year and 5-year overall survival (OS), colostomy-free survival (CFS), disease-free survival (DFS), non-local regrowth disease-free survival (NR-DFS), and organ preservation rate. Kaplan-Meier analysis was used for survival analysis and log-rank test was performed. For comparative analysis, we also derived one-to-one paired cohorts of W&W versus pCR using propensity-score matching (PSM).Results:A total of 118 patients were enrolled, 49 of whom had cCR and managed by W&W, 69 had pCR, with a median follow-up period of 49.5 months (12.1-79.9 months). No difference was observed in the 3-year OS (97.1% vs. 96.7%) and 5-year OS (93.8% vs. 90.9%, P=0.696) between the W&W and pCR groups. Patients managed by W&W had significantly better 3-year and 5-year CFS (89.1% vs. 43.5%, P<0.001), better 3-year DFS (83.6% vs. 97.0%) and 5-year DFS (83.6% vs. 91.2%, P=0.047) compared with those achieving pCR. The 3-year NR-DFS (95.9% vs. 97.0%) and 5-year NR-DFS (92.8% vs. 97.0%, P=0.407) did not significantly differ between the W&W and pCR groups. Local regeneration occurred in six cases, and 87.7% of patients had successful rectum preservation in the W&W group. In the PSM analysis (34 patients in each group), absolutely better CFS (90.1% vs. 26.5%, P<0.001) was noted in the W&W group. A median interval of 17.5 weeks was observed for achieving cCR, while only 23.9% of patients achieved cCR within 5 to 12 weeks from radiation completion. Patients with short-course sequential chemoradiotherapy achieved cCR significantly later when compared with those with long-course concurrent chemoradiotherapy (19.0 vs. 9.8 weeks, P<0.001). Conclusions:The oncological outcomes of W&W strategy in patients with locally advanced rectal cancer are safe and effective, significantly improving the quality of life. Longer interval for cCR evaluation may improve rectal organ preservation rate.

OBJECTIVES: The purpose of the study was to evaluate the effect of hydroxyapatite (HA)-based desensiti-zing agents and determine their influence on the bonding performance of mild universal adhesives. METHODS: Mid-coronal dentin samples were sectioned from human third molars and prepared for a dentin-sensitive model. According to desensitizing applications, they were randomly divided into four groups for the following treatments: no desensitizing treatment (control), Biorepair toothpaste (HA-based desensitizing toothpaste) treatment, Dontodent toothpaste (HA-based desensitizing toothpaste) treatment, and HA paste treatment. Dentin tubular occlusion and occluded area ratios were evaluated by scanning electron microscopy (SEM). Furthermore, All-Bond Universal, Single Bond Universal, and Clearfil Universal Bond were applied to the desensitized dentin in self-etch mode. The wettability and surface free energy (SFE) of desensitized dentin were evaluated by contact angle measurements. Bonded specimens were sectioned into beams and tested for micro-tensile bond strength to analyze the effect of desensitizing treatment on the bond strength to dentin of universal adhesives. RESULTS: SEM revealed that the dentin tubule was occluded by HA-based desensitizing agents, and the area ratios for the occluded dentin tubules were in the following order: HA group>Biorepair group>Dontodent group (P<0.05). Contact angle analysis demonstrated that HA-based desensitizing agents had no statistically significant influence on the wettability of the universal adhesives (P>0.05). The SFE of dentin significantly increased after treatment by HA-based desensitizing agents (P<0.05). The micro-tensile bond strength test showed that HA-based desensitizing toothpastes always decreased the μTBS values (P<0.05), whereas the HA paste group presented similar bond strength to the control group (P>0.05), irrespective of universal adhesive types. CONCLUSIONS HA-based desensitizing agents can occlude the exposed dentinal tubules on sensitive dentin. When mild and ultra-mild universal adhesives were used for subsequent resin restoration, the bond strength was reduced by HA-based desensitizing toothpastes, whereas the pure HA paste had no adverse effect on bond strength.
Humans ; Dental Cements/analysis* ; Dentin/chemistry* ; Durapatite/pharmacology* ; Tensile Strength ; Toothpastes