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.

Objective To observe the therapeutic effect and mechanism of allicin on uremic-induced myocardial injury in rats.Methods Twenty-four rats were randomly divided into sham-operated group,model group,and low-,and high-dose allicin groups,with six rats in each group.Except for the sham-operated group,the uremic-induced myocardial injury model was constructed using the 5/6 nephrectomy method in all other groups of rats.After successful modeling,corresponding interventions were carried outed.At the end of the intervention,the renal function of rats was observed,the cardiac mass index was calculated,the levels of serum high-sensitive cardiac troponinⅠ(hs-cTnI)and creatine kinase isoenzyme(CK-MB)were detected by enzyme-linked immunosorbent assay(ELISA),the pathological changes of rat cardiac tissues were observed by hematoxylin-eosin(HE)staining,the changes of autophagosomes and autolysosomes were observed by transmission electron microscopy,and the protein expressions of PTEN-induced putative kinase 1(PINK1)and E3 ubiquitin protein ligase(Parkin)in myocardial tissues were detected by Western Blot.Results Compared with the sham-operated group,the serum creatinine(SCr),blood urine nitrogen(BUN),cardiac mass index,CK-MB and hs-cTnI in rats in the model group were elevated(P<0.05),the pathological damage of cardiac tissues were obvious,and the autophagosomes and autolysosomes were decreased,and PINK1 and Parkin protein expressions in myocardial tissues were decreased(P<0.05);compared with the model group,SCr,BUN,cardiac mass index,CK-MB and hs-cTnI in allicin low-and hogh-dose groups were decreased,the changes of pathological damage of cardiac tissues were relieved,the autophagosomes and autolysosomes were increased,and PINK1 and Parkin protein expressions in myocardial tissues were increased(P<0.05).Conclusion Allicin can reduce myocardial injury in uremic rats,and its mechanism may be related to the up-regulation of PINK1/Parkin-mediated mitochondrial autophagy.

Myocardial injury is the leading cause of death in uremic patients.PINK 1/Parkin-mediated mitochondrial autophagy is involved in the progression of myocardial injury.In recent years,pathogenic turbidity has been gradually accepted as a representative of a new type of toxic pathogens by the researchers of traditional Chinese medicine(TCM).This paper sorts out literature about pathogenic turbidity,analyzes the etiological and pathogenic characteristics of pathogenic turbidity,and suggests that the pathogenesis of uremia-induced myocardial injury can be more comprehensively clarified from the perspective of healthy-qi deficiency resulting in latent pathogenic turbidity.In the patients with uremia,the down-regulation of PINK1/Parkin causes the weakening of mitochondrial autophagy,which leads to the elevation of levels of reactive oxygen species(ROS)and inflammatory factors,and eventually causes the injury of myocardial cell.The above pathogenic mechanism is similar to the process of traditional Chinese medicine(TCM)in which the deficiency of the healthy-qi(in particular kidney deficiency)results in the production of the pathogenic turbidity(showing as dampness,blood stasis,phlegm,toxin and so on)and then causes the pathogenic turbidity hide in vessels and collaterals and gradually injure the heart vessels,and eventually results in the deficiency of heart vessels.The mitochondrial autophagy mechanism mediated by the PINK1/Parkin pathway is suitalbe for explaining the TCM pathogenesis of uremia-induced myocardial injury,characterized by healthy-qi deficiency resulting in latent pathogenic turbidity,and also is suitable for interpretating the principle of supporting healthy-qi to eliminate pathogenic turbidity for treating uremia-induced myocardial injury.Under the guidance of the theory of health y-qi deficiency and turbid pathogens in TCM,the development of specific PINK 1/Parkin agonists may expand the approach for the treatment of uremia-induced myocardial injury.

Objective To analyze the clinical efficacy of low temperature plasma radiofrequency ablation(RFA)combined with nasal irrigation in the treatment of allergic rhinitis(AR)with nasal septal deviation.Methods A total of 120 AR patients with nasal septal deviation who were diagnosed and treated in Taikang Xianlin Drum Tower Hospital from August 2018 to December 2022 were selected as research objects.They were assigned to observation group or control group according to random number table method,with 60 cases in each group.The control group received nasal irrigation,and the observation group received low temperature plasma RFA and nasal irrigation.The efficacy,immunity,inflammation,quality of life,safety and prognosis were compared between the two groups.Results The observation group had better curative effect than the control group(P<0.05).The natural killer(NK)cells were increased,and the levels of immunoglobulin G(IgE),thymic stromal lymphopoietin(TSLP),hypoxia-inducible factor-1(HIF-1)and fractional exhaled nitric oxide(FeNO)were decreased in both groups after treatment.The level of NK cells in the observation group was higher than that in the control group after treatment,and the levels of IgE,TSLP,HIF-1,and FeNO in the observation group were lower than those in the control group(P<0.05).After treatment,the rhinoconjunctivitis quality of life questionnaire(RQLQ)scores decreased in both groups,and the scores in the observation group were lower than those in the control group(P<0.05).There was no significant difference in safety between the two groups(P>0.05).The control group had higher recurrence rate than the observation group(P<0.05).Conclusion Low temperature plasma RFA combined with nasal irrigation can effectively improve the immune function and inflammation of AR patients with nasal septal deviation,thereby improving the efficacy and quality of life,and reducing the recurrence rate,with high safety.

Objective:To investigate the feasibility of ductus arteriosus (DA) stent placement through femoral artery approach without guiding catheter.Methods:In this retrospective case study, the birth weight, intervention age, preoperative echocardiography, intraoperative angiography and other clinical data, as well as the follow-up status (Nakata index and final circulatory status, etc.) of 15 patients with congenital heart disease who are dependent on the DA for pulmonary circulation at Women and Children′s Hospital, Qingdao University between January 2018 to June 2023 were collected. All pediatric patients underwent placement of a DA stent without a guiding catheter, the efficacy and safety of this approach were analyzed.Results:Among all 15 cases, there were 9 males and 6 females, with the birth weight of (3.3±0.3) kg and the intervention age of (15.0±0.1) d. Of which, there were 9 cases of pulmonary atresia with intact ventricular septum (PA-IVS), and 6 cases of critical pulmonary stenosis (CPS) with intact ventricular septum. The tricuspid annulus diameter before intervention was (8.8±0.8) mm, and the tricuspid annulus Z-score was -0.7±0.9. There were 3 cases of mild right ventricular dysplasia, 9 cases of moderate dysplasia, and 3 cases of severe dysplasia. All patients successfully completed the intervention without major complications. The narrowest diameter of the DA was (2.2±0.1) mm, the diameter of the DA stent was (3.9±0.3) mm, the preoperative percutaneous oxygen saturation (SpO 2) was 0.83±0.03, and the postoperative SpO 2 was 0.96±0.02. The follow-up time was (7.0±0.5) months. The Nakata index was (163±30) mm 2/m 2 before intervention, and was (173±34) mm 2/m 2 at the last follow-up. Biventricular circulation was successfully achieved in 14 patients, and the other one patient currently under close observation. Conclusion:The placement of a ductus arteriosus stent through femoral artery retrogradely without guiding catheter could serve as an effective and safe plan for neonates with PA-IVS or CPS accompanied by hypoplastic right heart syndrome.

Objective To review clinical trial registration status of TCM treatment for coronary microvascular disease;To analyze the effectiveness and safety of TCM in treating coronary microvascular disease.Methods The clinical trials of TCM in the treatment of coronary artery microvascular disease included in the Chinese Clinical Trials Registry and the US Clinical Trials Registry from the establishment of the database to January 31,2024 were retrieved,and the general characteristics(time,region,funding source),design type,intervention regimen and outcome indicators of the included clinical trials were extracted and analyzed using Excel 2019 software.Results A total of 17 clinical trials were included,including 16 pre-registrations.The registered units were distributed in 5 provinces across the country,involving 17 registration institutions.The two regions with the most distribution were Shanghai(6 studies,35.29%)and Beijing(5 studies,29.41%).The types of studies were mainly interventional studies,and most of the study designs were randomized parallel controlled studies(16 studies,94.12%).A total of 8 interventions were reported,including Chinese patent medicine,TCM decoction,TCM intravenous preparation,and acupuncture and moxibustion.A total of 143 outcome indicators were designed,including 10 first-level indicators,including coronary artery microcirculation,clinical efficacy,symptoms and signs,TCM syndromes,quality of life,exercise tolerance,cardiac function,physical and chemical testing,safety,and pharmacoeconomic evaluation.Conclusion The registration of clinical trials by TCM in the treatment of coronary microvascular diseases has been gradually receiving attention from researchers,but the overall number is still small.At present,the study needs to be optimized in terms of study design and index selection.

AIM:This study aims to investigate the effects of Feixin decoction(FXD)on pyroptosis of pulmo-nary artery smooth muscle cells(PASMCs)by modulating nuclear factor κB(NF-κB)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway,and to explore how FXD attenuates hypoxic pulmonary hypertension(HPH)in mice.METHODS:A mouse model of HPH was established using the Sugen 5416 combined hypoxia(SuHx)method.Sixty C57BL/6 mice were randomly divided into 6 groups:control group,SuHx group,sildenafil group,and low-,medium-and high-dose FXD groups,with 10 mice in each group.Five weeks after treatment,echocardiographic pa-rameters,including pulmonary artery acceleration time(PAT),pulmonary artery ejection time(PET),right ventricular anterior wall thickness at diastole(RVAWd)and tricuspid annular plane systolic excursion(TAPSE),were measured.Right ventricular systolic pressure(RVSP)was assessed via right heart catheterization.Right ventricular hypertrophy in-dex(RVHI)was determined by weighing the hearts.Histological examination using HE staining was conducted to observe pathological changes in small pulmonary arteries and the right ventricle,while Masson staining was used to assess fibrosis in the right ventricular wall.Immunofluorescence staining was used to detect co-localized expression of α-smooth muscle actin(α-SMA)with NLRP3,N-terminal fragment of gasdermin D(N-GSDMD)and caspase-1 in the pulmonary arteries.Western blot analysis was conducted to measure the protein levels of NF-κB,p-NF-κB,NLRP3,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),N-GSDMD,interleukin(IL)-1β,IL-18 and cleaved caspase-1 in lung tissues.Transmission electron microscopy was employed to observe the ultrastructure of PASMCs.RE-SULTS:Compared with control group,the mice in SuHx group exhibited elevated RVSP and RVHI(P＜0.01),de-creased right heart function(P＜0.01),increased right ventricular wall fibrosis,and pulmonary vascular remodeling(P＜0.01).There was also increased co-localized expression of α-SMA with NLRP3,N-GSDMD and caspase-1 in small pul-monary arteries(P＜0.01),as well as elevated levels of p-NF-κB,NLRP3,ASC,N-GSDMD,IL-1β,IL-18 and cleaved caspase-1 in lung tissues(P＜0.01),indicating induced pyroptosis of PASMCs.Compared with SuHx group,FXD treat-ment significantly reduced RVSP and RVHI,improved right ventricular function,and attenuated right ventricular wall fi-brosis and pulmonary vascular remodeling(P＜0.05 or P＜0.01).Treatment with FXD also decreased the co-localized ex-pression of α-SMA with NLRP3,N-GSDMD and caspase-1 in small pulmonary arteries(P＜0.05 or P＜0.01),and down-regulated the protein expression of p-NF-κB,NLRP3,ASC,N-GSDMD,IL-1β,IL-18 and cleaved caspase-1 in lung tis-sues(P＜0.05 or P＜0.01),thereby attenuating the pyroptosis of PASMCs.CONCLUSION:FXD attenuates pulmonary vascular remodeling and right ventricular dysfunction in a mouse model of HPH.This effect may be attributed to its inhibi-tion of NF-κB/NLRP3 pathway,which subsequently reduces the pyroptosis of PASMCs.

Objective To review clinical trial registration status of TCM treatment for coronary microvascular disease;To analyze the effectiveness and safety of TCM in treating coronary microvascular disease.Methods The clinical trials of TCM in the treatment of coronary artery microvascular disease included in the Chinese Clinical Trials Registry and the US Clinical Trials Registry from the establishment of the database to January 31,2024 were retrieved,and the general characteristics(time,region,funding source),design type,intervention regimen and outcome indicators of the included clinical trials were extracted and analyzed using Excel 2019 software.Results A total of 17 clinical trials were included,including 16 pre-registrations.The registered units were distributed in 5 provinces across the country,involving 17 registration institutions.The two regions with the most distribution were Shanghai(6 studies,35.29%)and Beijing(5 studies,29.41%).The types of studies were mainly interventional studies,and most of the study designs were randomized parallel controlled studies(16 studies,94.12%).A total of 8 interventions were reported,including Chinese patent medicine,TCM decoction,TCM intravenous preparation,and acupuncture and moxibustion.A total of 143 outcome indicators were designed,including 10 first-level indicators,including coronary artery microcirculation,clinical efficacy,symptoms and signs,TCM syndromes,quality of life,exercise tolerance,cardiac function,physical and chemical testing,safety,and pharmacoeconomic evaluation.Conclusion The registration of clinical trials by TCM in the treatment of coronary microvascular diseases has been gradually receiving attention from researchers,but the overall number is still small.At present,the study needs to be optimized in terms of study design and index selection.

AIM:This study aims to investigate the effects of Feixin decoction(FXD)on pyroptosis of pulmo-nary artery smooth muscle cells(PASMCs)by modulating nuclear factor κB(NF-κB)/nucleotide-binding oligomerization domain-like receptor protein 3(NLRP3)pathway,and to explore how FXD attenuates hypoxic pulmonary hypertension(HPH)in mice.METHODS:A mouse model of HPH was established using the Sugen 5416 combined hypoxia(SuHx)method.Sixty C57BL/6 mice were randomly divided into 6 groups:control group,SuHx group,sildenafil group,and low-,medium-and high-dose FXD groups,with 10 mice in each group.Five weeks after treatment,echocardiographic pa-rameters,including pulmonary artery acceleration time(PAT),pulmonary artery ejection time(PET),right ventricular anterior wall thickness at diastole(RVAWd)and tricuspid annular plane systolic excursion(TAPSE),were measured.Right ventricular systolic pressure(RVSP)was assessed via right heart catheterization.Right ventricular hypertrophy in-dex(RVHI)was determined by weighing the hearts.Histological examination using HE staining was conducted to observe pathological changes in small pulmonary arteries and the right ventricle,while Masson staining was used to assess fibrosis in the right ventricular wall.Immunofluorescence staining was used to detect co-localized expression of α-smooth muscle actin(α-SMA)with NLRP3,N-terminal fragment of gasdermin D(N-GSDMD)and caspase-1 in the pulmonary arteries.Western blot analysis was conducted to measure the protein levels of NF-κB,p-NF-κB,NLRP3,apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),N-GSDMD,interleukin(IL)-1β,IL-18 and cleaved caspase-1 in lung tissues.Transmission electron microscopy was employed to observe the ultrastructure of PASMCs.RE-SULTS:Compared with control group,the mice in SuHx group exhibited elevated RVSP and RVHI(P＜0.01),de-creased right heart function(P＜0.01),increased right ventricular wall fibrosis,and pulmonary vascular remodeling(P＜0.01).There was also increased co-localized expression of α-SMA with NLRP3,N-GSDMD and caspase-1 in small pul-monary arteries(P＜0.01),as well as elevated levels of p-NF-κB,NLRP3,ASC,N-GSDMD,IL-1β,IL-18 and cleaved caspase-1 in lung tissues(P＜0.01),indicating induced pyroptosis of PASMCs.Compared with SuHx group,FXD treat-ment significantly reduced RVSP and RVHI,improved right ventricular function,and attenuated right ventricular wall fi-brosis and pulmonary vascular remodeling(P＜0.05 or P＜0.01).Treatment with FXD also decreased the co-localized ex-pression of α-SMA with NLRP3,N-GSDMD and caspase-1 in small pulmonary arteries(P＜0.05 or P＜0.01),and down-regulated the protein expression of p-NF-κB,NLRP3,ASC,N-GSDMD,IL-1β,IL-18 and cleaved caspase-1 in lung tis-sues(P＜0.05 or P＜0.01),thereby attenuating the pyroptosis of PASMCs.CONCLUSION:FXD attenuates pulmonary vascular remodeling and right ventricular dysfunction in a mouse model of HPH.This effect may be attributed to its inhibi-tion of NF-κB/NLRP3 pathway,which subsequently reduces the pyroptosis of PASMCs.

Objective:To investigate the feasibility of ductus arteriosus (DA) stent placement through femoral artery approach without guiding catheter.Methods:In this retrospective case study, the birth weight, intervention age, preoperative echocardiography, intraoperative angiography and other clinical data, as well as the follow-up status (Nakata index and final circulatory status, etc.) of 15 patients with congenital heart disease who are dependent on the DA for pulmonary circulation at Women and Children′s Hospital, Qingdao University between January 2018 to June 2023 were collected. All pediatric patients underwent placement of a DA stent without a guiding catheter, the efficacy and safety of this approach were analyzed.Results:Among all 15 cases, there were 9 males and 6 females, with the birth weight of (3.3±0.3) kg and the intervention age of (15.0±0.1) d. Of which, there were 9 cases of pulmonary atresia with intact ventricular septum (PA-IVS), and 6 cases of critical pulmonary stenosis (CPS) with intact ventricular septum. The tricuspid annulus diameter before intervention was (8.8±0.8) mm, and the tricuspid annulus Z-score was -0.7±0.9. There were 3 cases of mild right ventricular dysplasia, 9 cases of moderate dysplasia, and 3 cases of severe dysplasia. All patients successfully completed the intervention without major complications. The narrowest diameter of the DA was (2.2±0.1) mm, the diameter of the DA stent was (3.9±0.3) mm, the preoperative percutaneous oxygen saturation (SpO 2) was 0.83±0.03, and the postoperative SpO 2 was 0.96±0.02. The follow-up time was (7.0±0.5) months. The Nakata index was (163±30) mm 2/m 2 before intervention, and was (173±34) mm 2/m 2 at the last follow-up. Biventricular circulation was successfully achieved in 14 patients, and the other one patient currently under close observation. Conclusion:The placement of a ductus arteriosus stent through femoral artery retrogradely without guiding catheter could serve as an effective and safe plan for neonates with PA-IVS or CPS accompanied by hypoplastic right heart syndrome.