OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

177Lu-prostate specific membrane antigen(PSMA)radio-ligand therapy has been approved abroad for advanced prostate cancer and has been in several clinical trials in China.Based on domestic clinical practice and experimental data and referred to international experience and viewpoints,the expert group forms a consensus on the clinical application of 177Lu-PSMA radio-ligand therapy in prostate cancer to guide clinical practice.

Patients with severe trauma require an extremely timely treatment and transfusion plays an irreplaceable role in the emergency treatment of such patients. An increasing number of evidence-based medicinal evidences and clinical practices suggest that patients with severe traumatic bleeding benefit from early transfusion of low-titer group O whole blood or hemostatic resuscitation with red blood cells, plasma and platelet of a balanced ratio. However, the current domestic mode of blood supply cannot fully meet the requirements of timely and effective blood transfusion for emergency treatment of patients with severe trauma in clinical practice. In order to solve the key problems in blood supply and blood transfusion strategies for emergency treatment of severe trauma, Branch of Clinical Transfusion Medicine of Chinese Medical Association, Group for Trauma Emergency Care and Multiple Injuries of Trauma Branch of Chinese Medical Association, Young Scholar Group of Disaster Medicine Branch of Chinese Medical Association organized domestic experts of blood transfusion medicine and trauma treatment to jointly formulate Chinese expert consensus on blood support mode and blood transfusion strategies for emergency treatment of severe trauma patients ( version 2024). Based on the evidence-based medical evidence and Delphi method of expert consultation and voting, 10 recommendations were put forward from two aspects of blood support mode and transfusion strategies, aiming to provide a reference for transfusion resuscitation in the emergency treatment of severe trauma and further improve the success rate of treatment of patients with severe trauma.

Objective: Explore the relationship between tip of the left bundle branch pacing lead and anatomic location of left bundle branch as well as the mechanism of left bundle branch current of injury. To clarify the clinical value of left bundle branch current of injury during operation. Methods: The pacing leads were implanted in the hearts of two living swines. Intraoperative electrophysiological study confirmed that the left bundle branch or only the deep left ventricular septum was captured at low output. Immediately after operation, the gross specimen of swine hearts was stained with iodine to observe the gross distribution of His-purkinje conduction system on the left ventricular endocardium and its relationship with the leads. Subsequently, the swine hearts were fixed with formalin solution, and the pacing leads were removed after the positions were marked. The swine hearts were then sectioned and stained with Masson and Goldner trichrome, and the relationship between the anatomic location of the conduction system and the tip of the lead was observed under a light microscope. Results: After iodine staining of the specimen, the His-purkinje conduction system was observed with the naked eye in a net-like distribution, and the lead tip was screwed deeply and fixed in the left bundle branch area of the left ventricular subendocardium in the ventricular septum. Masson and Goldner trichrome staining showed that left bundle branch pacing lead directly passed through the left bundle branch when there was left bundle branch potential with left bundle branch current of injury, while it was not directly contact the left bundle branch when there was left bundle branch potential without left bundle branch current of injury. Conclusion: The left bundle branch current of injury observed on intracardiac electrocardiogram during His-purkinje conduction system pacing suggests that the pacing lead directly contacted the conduction bundle or its branches, therefore, the captured threshold was relatively low. Left bundle branch current of injury can be used as an important anatomic and electrophysiological evidence of left bundle branch capture.
Animals ; Swine ; Bundle of His/physiology* ; Ventricular Septum ; Cardiac Pacing, Artificial ; Heart Conduction System ; Electrocardiography ; Iodine

Objective To enhance the triage efficiency of patients with acute heart failure(AHF)by improving emergency severity index(ESI)score,and to achieve stratified care for patients with AHF.Additionally,the aim is to improve the combination of stratified scores and nursing care in emergency departments to address the limitations of current studies.Methods A retrospective nested cohort study was conducted on 120 patients with AHF admitted to the Affiliated Hospital of Guizhou Medical University from January 1,2019 to December 30,2021.According to the clinical outcomes of the patients,the patients were divided into subgroup A(71 cases,recovered after treatment,no serious complications during treatment),subgroup B[35 cases,discharged after treatment,multiple organ dysfunction syndrome(MODS),acute respiratory distress syndrome(ARDS),shock and other serious complications occurred during treatment],and subgroup C(14 cases,cardiac death during treatment).A prospective randomized controlled study involving 106 patients with AHF admitted to our hospital from January 1 to December 30,2022,was conducted,and the patients were divided into control group(53 cases)and stratified care group(53 cases)according to the random number table method.The control group received routine nursing care,while patients in the stratified care group received stratified care based on the ESI scoring clinical care pathway.The early warning score model of elderly patients with AHF was constructed with risk threshold as warning signal.The improved ESI scoring criteria were used to score AHF patients,with a total score of 25 points.The higher the score,the higher the risk.0-10 is divided into Ⅰ level risk,>10-20 is divided into Ⅱ level risk,>20 is divided into Ⅲ level risk.Implement nuring at grades Ⅲ,Ⅱ,and Ⅰ,respectively.The changes of modified ESI scores in subgroup A,subgroup B and subgroup C were observed,and Spearman correlation coefficient was used to evaluate the correlation between modified ESI scores and clinical outcomes of different severity of disease.Receiver operator characteristic curve(ROC curve)was drawn to evaluate the effectiveness of the risk threshold classification method of different nursing plan designs in the stratified nursing group and the control group,and to compare the efficiency differences of emergency nursing rescue time,rescue success rate,and stay time in the emergency department,and the incidence of complications such as MODS,ARDS,shock and nursing satisfaction during treatment between the stratified nursing group and the control group.Results The modified ESI score in subgroup C was the highest,significantly higher than that in subgroup B and A(19.6±1.7 vs.17.8±1.5,15.3±1.3,all P<0.05).Spearman correlation analysis showed that the modified ESI score was significantly positively correlated with the occurrence of complications,the occurrence of cardiac death,and the recovery after treatment(r values were 0.623,0.635,0.322,P values were 0.004,0.003,0.012,respectively).Therefore,an improved ESI score has a certain early warning effect on complications and cardiac death of patients.ROC curve analysis showed that the area under the ROC curve(AUC)of routine care for stratified care was 0.710 and 0.620,and the 95％ confidence interval(95％ CI)was 0.620-0.750 and 0.580-0.690,respectively,with Pvalues of 0.023 and 0.034.It shows that the difference between the two nursing methods is significant,and further indicates that the risk threshold classification method designed in this study is effective.With the increase of risk,the rescue time and emergency stay time of the two groups were gradually extended,and the success rate of rescue was gradually decreased,the rescue time and emergency stay time of grade Ⅲ risk were the longest and the success rate of rescue was the lowest,and the rescue time and emergency stay time of the stratified nursing group were significantly shorter than those of the control group(minutes:59.6±6.3 vs.76.5±7.2 and 57.6±5.4 vs.68.2±7.1,both P<0.05),the success rate of rescue was significantly increased[(68.7±6.1)％ vs.(54.6±5.2)％,P<0.05],and the difference of rescue time between grade Ⅰ risk and grade Ⅲ risk was the largest.There were significant differences in the success rate of rescue and the duration of emergency stay in grade Ⅲ risk.The incidence of complications such as MODS,ARDS and shock in stratified care group was significantly lower than that in control group[incidence of MODS:13.2％(7/53)vs.18.9％(10/53),incidence of ARDS:15.1％(8/53)vs.22.6％(12/53),incidence of shock:13.2％(7/53)vs.20.8％(11/53),all P<0.05],satisfaction of patients with service attitude,operation technique,comfort and timeliness were significantly improved compared with the control group[service attitude:28.3％(15/53)vs.18.9％(10/53),operation technology:30.2％(16/53)vs.20.8％(11/53),comfort:32.1％(17/53)vs.24.5％(13/53),timeliness:32.1％(17/53)vs.24.5％(13/53),all P<0.05].Conclusion Based on the modified ESI score,early risk warning thresholds are divided and stratified nursing is conducted,which is beneficial for timely intervention in AHF,effectively ensuring the clinical nursing value of patients during the implementation of medical measures,and has broad application prospects.

italic>α-Conotoxin ArIB[V11L,V16D] is currently the most optimal selective inhibitor of α7 nicotinic acetylcholine receptor (nAChR) known. In order to explore chemical modification methods and enrich its application in targeting nAChR, this study utilized the linker to covalently connect camptothecin and 7-amino-4-methylcoumarin to the [2,4] disulfide bond of ArIB[V11L,V16D]. Therefore, two peptide-drug conjugates (PDCs), ArIB[V11L,V16D]-5 and ArIB[V11L,V16D]-6, and one fluorescent-labeled peptide, ArIB[V11L,V16D]-7 were constructed. Cytotoxicity evaluation showed that the IC₅₀ values against non-small cell lung cancer cell line A549 of the two PDCs were respectively 1.3 and 4.1 times of camptothecin, indicating slight reduction in activity at the cellular level which was related to the linker structure. Fluorescence spectrum scanning revealed that the excitation and emission wavelength of the fluorescent-labeled peptide were 340 nm and 403 nm respectively, and the fluorescence features of 7-amino-4-methylcoumarin as a marker were retained without fluorescence quenching. This modification strategy laid a solid foundation for the further application of α-conotoxin ArIB[V11L,V16D] in PDCs and fluorescent probes.

Objective: Explore the relationship between tip of the left bundle branch pacing lead and anatomic location of left bundle branch as well as the mechanism of left bundle branch current of injury. To clarify the clinical value of left bundle branch current of injury during operation. Methods: The pacing leads were implanted in the hearts of two living swines. Intraoperative electrophysiological study confirmed that the left bundle branch or only the deep left ventricular septum was captured at low output. Immediately after operation, the gross specimen of swine hearts was stained with iodine to observe the gross distribution of His-purkinje conduction system on the left ventricular endocardium and its relationship with the leads. Subsequently, the swine hearts were fixed with formalin solution, and the pacing leads were removed after the positions were marked. The swine hearts were then sectioned and stained with Masson and Goldner trichrome, and the relationship between the anatomic location of the conduction system and the tip of the lead was observed under a light microscope. Results: After iodine staining of the specimen, the His-purkinje conduction system was observed with the naked eye in a net-like distribution, and the lead tip was screwed deeply and fixed in the left bundle branch area of the left ventricular subendocardium in the ventricular septum. Masson and Goldner trichrome staining showed that left bundle branch pacing lead directly passed through the left bundle branch when there was left bundle branch potential with left bundle branch current of injury, while it was not directly contact the left bundle branch when there was left bundle branch potential without left bundle branch current of injury. Conclusion: The left bundle branch current of injury observed on intracardiac electrocardiogram during His-purkinje conduction system pacing suggests that the pacing lead directly contacted the conduction bundle or its branches, therefore, the captured threshold was relatively low. Left bundle branch current of injury can be used as an important anatomic and electrophysiological evidence of left bundle branch capture.
Animals ; Swine ; Bundle of His/physiology* ; Ventricular Septum ; Cardiac Pacing, Artificial ; Heart Conduction System ; Electrocardiography ; Iodine

The development of broad-spectrum antivirals against human coronaviruses (HCoVs) is critical to combat the current coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its variants, as well as future outbreaks of emerging CoVs. We have previously identified a polyethylene glycol-conjugated (PEGylated) lipopeptide, EK1C4, with potent pan-CoV fusion inhibitory activity. However, PEG linkers in peptide or protein drugs may reduce stability or induce anti-PEG antibodies in vivo. Therefore, we herein report the design and synthesis of a series of dePEGylated lipopeptide-based pan-CoV fusion inhibitors featuring the replacement of the PEG linker with amino acids in the heptad repeat 2 C-terminal fragment (HR2-CF) of HCoV-OC43. Among these lipopeptides, EKL1C showed the most potent inhibitory activity against infection by SARS-CoV-2 and its spike (S) mutants, as well as other HCoVs and some bat SARS-related coronaviruses (SARSr-CoVs) tested. The dePEGylated lipopeptide EKL1C exhibited significantly stronger resistance to proteolytic enzymes, better metabolic stability in mouse serum, higher thermostability than the PEGylated lipopeptide EK1C4, suggesting that EKL1C could be further developed as a candidate prophylactic and therapeutic for COVID-19 and other coronavirus diseases.

Objective: To explore the effects of red LEDs on the proliferation and osteogenic differentiation of human stem cells from apical papilla (hSCAPs). Methods: hSCAPs were obtained by isolation, culture and flow cytometry in vitro and irradiated with 1, 3, 5, and 7 J/cm2 red LEDs. The proliferation of hSCAPs was detected using a CCK-8 assay. The osteogenic differentiation of hSCAPs was evaluated using alkaline phosphatase (ALP) staining, ALP activity assay and Alizarin red quantitative detection. The effect of 5 J/cm2 red LEDs on the expression levels of the ALP, Runx2, OCN, OPN and BSP genes and proteins was detected by RT-PCR and western blot, respectively. Results: Red LEDs at 1, 3, 5, and 7 J/cm2 promoted the proliferation of hSCAPs (P < 0.05). The effects of red LEDs with different light energies on the proliferation of hSCAPs were different at different time points (P < 0.05). On the 7th and 14th days after irradiation, red LEDs promoted the osteogenic differentiation of hSCAPs, and the effect of 5 J/cm2 red LEDs was the most obvious under osteogenic induction culture conditions (P<0.05). Red LEDs (5 J/cm2) promoted the expression of the ALP, Runx2, OCN, OPN and BSP genes and proteins (P < 0.05). Conclusion Red LEDs promoted the proliferation and osteogenic differentiation of hSCAPs.

Objective: To investigate the prognostic factors of children with congenital heart disease (CHD) who had undergone cardiopulmonary resuscitation (CPR) in pediatric intensive care unit (PICU) in China. Methods: From November 2017 to October 2018, this retrospective multi-center study was conducted in 11 hospitals in China. It contained data from 281 cases who had undergone CPR and all of the subjects were divided into CHD group and non-CHD group. The general condition, duration of CPR, epinephrine doses during resuscitation, recovery of spontaneous circulation (ROSC), discharge survival rate and pediatric cerebral performance category in viable children at discharge were compared. According to whether malignant arrhythmia is the direct cause of cardiopulmonary arrest or not, children in CHD and non-CHD groups were divided into 2 subgroups: arrhythmia and non-arrhythmia, and the ROSC and survival rate to discharge were compared. Data in both groups were analyzed by t-test, chi-square analysis or ANOVA, and logistic regression were used to analyze the prognostic factors for ROSC and survival to discharge after cardiac arrest (CA). Results: The incidence of CA in PICU was 3.2% (372/11 588), and the implementation rate of CPR was 75.5% (281/372). There were 144 males and 137 females with median age of 32.8 (5.6, 42.7) months in all 281 CPA cases who received CPR. CHD group had 56 cases while non-CHD had 225 cases, with the percentage of 19.9% (56/281) and 80.1% (225/281) respectively. The proportion of female in CHD group was 60.7% (34/56) which was higher than that in non-CHD group (45.8%, 103/225) (χ²=4.00, P=0.045). There were no differences in ROSC and rate of survival to discharge between the two groups (P>0.05). The ROSC rate of children with arthythmid in CHD group was 70.0% (28/40), higher than 6/16 for non-arrhythmic children (χ²=5.06, P=0.024). At discharge, the pediatric cerebral performance category scores (1-3 scores) of CHD and non-CHD child were 50.9% (26/51) and 44.9% (92/205) respectively. Logistic regression analysis indicated that the independent prognostic factors of ROSC and survival to discharge in children with CHD were CPR duration (odds ratio (OR)=0.95, 0.97; 95%CI: 0.92~0.97, 0.95~0.99; both P<0.05) and epinephrine dosage (OR=0.87 and 0.79, 95%CI: 0.76-1.00 and 0.69-0.89, respectively; both P<0.05). Conclusions: There is no difference between CHD and non-CHD children in ROSC and survival rate of survival to discharge was low. The epinephrine dosage and the duration of CPR are related to the ROSC and survival to discharge of children with CHD.
Cardiopulmonary Resuscitation ; Child ; Child, Preschool ; Female ; Heart Arrest/therapy* ; Heart Defects, Congenital/therapy* ; Humans ; Intensive Care Units, Pediatric ; Male ; Retrospective Studies