Association of HDL and LDL levels with osteoporosis in rheumatoid arthritis: a retrospective cohort study.

OBJECTIVES: A correlation exists between lipids and osteoporosis (OP), as well as between lipids and rheumatoid arthritis (RA). However, lipids, the relationship between RA and OP is still unclear. This study mainly investigates the relationship between lipid levels and OP risk in RA patients. METHODS: Retrospective collection of RA patient data from July 2017 to May 2022, encompassing baseline demographics, treatment regimens, laboratory results, and bone mineral density (BMD) measurements. Analyses, stratified by BMD subgroups, were conducted using propensity score matching (PSM) based on age, sex, and baseline duration, and binary logistic regression to examine the interplay between lipoprotein levels and other risk factors. The relationship between continuous variables and OP risk was assessed using restricted cubic spline (RCS), followed by a reanalysis of the correlation between varying lipoprotein levels and different factors, segmented according to RCS-determined cutoffs. RESULTS: The study included 2673 RA patients. Binary logistic regression revealed significant associations between high-density lipoprotein (HDL), low-density lipoprotein (LDL), and RA-OP (p < 0.01). Specifically, HDL emerged as a protective factor against OP (OR = 0.40, 95% CI 0.250-0.629; p < 0.001), whereas LDL was identified as a risk factor (OR = 1.56, 95% CI 1.290-1.890; p < 0.001). Furthermore, HDL (RCS cutoff point 1.28 mmol/L) showed a negative, linear correlation with RA-related OP, while LDL (RCS cutoff point 2.63 mmol/L) demonstrated a positive, linear correlation. CONCLUSIONS: The levels of HDL and LDL may be indicators of OP occurrence in RA patients.

Plastic bronchitis associated with human bocavirus 1 infection in children.

BACKGROUND: Plastic bronchitis (PB) is a clinical-pathological syndrome characterized by the abnormal accumulation of endogenous substances in the bronchial airways, causing partial or complete obstruction and resulting in impaired lung ventilation. METHODS: In this retrospective analysis, we aim to summarize the clinical manifestations, imaging characteristics, diagnostic methods, and treatment approaches to enhance clinicians' ability to detect children who are infected with human bocavirus 1 (hBoV 1) and develop PB. RESULTS: In the period from January 2021 to January 2024, a total of six hBoV 1 infection children were diagnosed with PB through bronchoscopy. The onset of the condition was mainly concentrated between June and December. The detection methods used included metagenomic next-generation sequencing for pathogen identification (three cases) and respiratory pathogen nucleic acid 13-plex detection (oropharyngeal swab) (three cases), both of which confirmed the presence of hBoV 1. Out of the six children with PB, two were girls and four were boys. Their ages ranged from 10 months to 4 years old. Common symptoms reported by all patients included fever, cough, and wheezing. Chest high-resolution computed tomography scans revealed atelectasis in six cases, in addition to pneumonia. After the removal of the plastic bronchi via bronchoscopy, the airway obstruction symptoms in the children were relieved, and no recurrence was observed during the follow-up period. Pathological findings indicated cellulose exudation and inflammatory cell infiltration, consistent with nonlymphatic PB. CONCLUSION: When children infected with hBoV 1 exhibit persistent or worsening symptoms such as cough, fever, and wheezing despite treatment, clinicians should remain highly vigilant for the potential occurrence of PB. Bronchoscopy plays a crucial role not only in diagnosing the presence of a plastic bronchus but also in effectively treating PB.

Study of genetic profiles and haematological phenotypes of δ-thalassemia in Guangdong population / 中华检验医学杂志

Objective:To investigate genetic variation profiles of δ-globin (HBD gene) and hematological phenotypes in Guangdong population.Methods:Retrospective case analysis was performed in this study. Blood samples of 11 616 couples who participated in free thalassemia screening in Guangzhou from July 2020 to December 2022 were collected which underwent blood routine tests and hemoglobin (Hb) capillary electrophoresis. According to the results, 154 samples were enrolled in this study: (1)group of 35 cases with HbA 2 <2.0% but no HbF band; (2)group of 64 cases with HbA 2 < 2.0% and HbF band; (3)group of 25 cases with HbA 2 <2.0% and suspected HbA 2 variants; (4) group of 25 cases with HbA 2 ≥2.0% and <3.5% and HbF band, as well as abnormal blood routine report [mean corpuscular volume (MCV) <82 fl and/or mean corpuscular hemoglobin (MCH) <27 pg]; (5)group of 5 cases with HbA 2 ≥2.0% and <3.0% accompanied with β thalassemia gene carriers Sanger sequencing was used to detect single nucleotide variants of δ-globin. Results:(1) A total of 22 genetic variations were detected, including 6 de novo variations, and the top 3 genetic variations were respectively c.-127T>C (57.02%, 65/114), c.-80T>C (9.65%, 11/114), c.349C>T (7.89%, 9/114). (2) In group of patients with HbA 2 <2.0% but no HbF band, 22 cases (62.85%, 22/35) had HBD gene variation, including 7 cases with MCV and MCH lower than reference values, 4 cases with α thalassemia; 13 cases had no HBD gene variation, including 12 cases with lower MCV and MCH. Among 19 cases with abnormal blood routine test results, levels of HbA 2 in patients (7 cases) with HBD gene variation were lower compared with those without HBD gene variation (12 cases) ( P<0.01%). (3)In group of patients with HbA 2<2.0% with HbF band, 59 cases (92.18%, 59/64) had HBD gene variations whose mutations all occurred in promoter region, and the HbF were all lower than 5.0%; 5 cases with HbF >5.0% had no HBD gene variation. (4) In group of patients with HbA 2 <2.0% and suspected HbA 2 variants, the detection rate was 100% (25/25) and δ-globin variants <1.0%. (5) In group of patients with HbA 2 ≥2.0% and <3.5% and HbF band accompanied with abnormal blood routine results, no HBD gene variation was found. (6) In group of 5 patients with HbA 2 ≥2.0% and <3.0% with β thalassemia gene carriers, HBD gene variation were found in all cases, and the level of HbA 2 was (2.62±0.17)% and HbF was (3.62±2.22)%. Conclusions:There are various genotypes of HBD gene variation, among which HBD: c.-127T>C is the most common in Guangdong population in China. Mutations in the promoter region may cause decrease in HbA 2 and increase in HbF which is mostly less than 5% but exceeds 5.0% when combined with β thalassemia. Our study enriched the gene mutation profiles of HBD gene in Guangdong population.

PI3K/AKT/mTOR in synovial fluid extends the proinflammatory response of macrophage polarization in knee osteoarthritis / 安徽医科大学学报

Objective @#Given that the PI3K/AKT/mTOR signaling pathway is associated with the progression of knee osteoarthritis (KOA) , this study aims to investigate whether the polarization induction of synovial macrophages mediated by the PI3K/AKT/mTOR signaling axis is the cause of KOA progression . @*Methods @#The synovial fluid of KOA KL-Ⅱ and KL-Ⅲ patients and normal individuals was collected , and the percentage of M1 macrophages (CD80 , CD86) and M2 macrophages (CD163 , CD206) in the synovial fluid (M1 /M2 ratio) was measured to e- valuate the polarization of macrophage cytokines such as IL-1 , IL-6 , IL-10 , and tumor necrosis factor (TNF) -α, transforming growth factor ( TGF)-βExpression in KOA synovial fluid , and detect and analyze of key molecules PI3K/AKT/mTOR signaling axis PI3K , AKT3 , mTORC1 , and inducible nitric oxide synthase ( iONS) in KOA synovial fluid . @*Results @#Compared with the synovial fluid of normal individuals , the percentage of M1 macrophages (CD80 , CD86) in KOA patients increased (P < 0. 01) , and the M1 /M2 ratio increased ( P < 0. 001) ; The ex- pression of IL-1 , IL-6 , and TNF-αin the synovial fluid of the KOA group was also higher than that of the control group (P < 0. 01) , while the expression of IL-10 and TGF-βin the KOA group was significantly reduced ( P < 0. 01) ; The key proteins PI3K , AKT3 , mTORC1 , and downstream inflammatory factor iONS in the PI3K/AKT/ mTOR signaling pathway in the synovial fluid of the KOA group were higher than those in the control group (P < 0. 01) . @*Conclusion @#In KOA synovial fluid , M1 macrophage polarization plays a dominant role , and the inflam- matory response mediated by M1 macrophage polarization may be the cause of synovitis . At the same time , the PI3K/AKT/mTOR signaling pathway may mediate the polarization of M1 macrophages involved in KOA inflammato- ry response .

Research progress and maturity assessment of continuous manufacturing of traditional Chinese medicine / 中国中药杂志

The pharmaceutical manufacturing model is gradually changing from intermittent manufacturing to continuous manufacturing and intelligent manufacturing. This paper briefly reviewed the supervision and research progress in continuous pharmaceutical manufacturing in China and abroad and described the definition and advantages of continuous pharmaceutical manufacturing. The continuous manufacturing of traditional Chinese medicine(TCM) at the current stage was summarized in the following three terms: the enhancement of the continuity of intermittent manufacturing operations, the integration of continuous equipment to improve physical continuity between units, and the application of advanced process control strategies to improve process continuity. To achieve continuous manufacturing of TCM, the corresponding key technologies, such as material property characterization, process modeling and simulation, process analysis technology, and system integration, were analyzed from the process and equipment, respectively. It was proposed that the continuous manufacturing equipment system should have the characteristics of high speed, high response, and high reliability, "three high(H~3)" for short. Considering the characteristics and current situation of TCM manufacturing, based on the two dimensions of product quality control and production efficiency, a maturity assessment model for continuous manufacturing of TCM, consisting of operation continuity, equipment continuity, process continuity, and quality control continuity, was proposed to provide references for the application of continuous manufacturing technology for TCM. The implementation of continuous manufacturing or the application of key continuous manufacturing technologies in TCM can help to systematically integrate advanced pharmaceutical technology elements and promote the uniformity of TCM quality and the improvement of production efficiency.

Manufacturing classification system for oral solid dosage forms of traditional Chinese medicines (Ⅱ): classification of tablets disintegration behavior / 中国中药杂志

In this paper, 50 batches of representative traditional Chinese medicine tablets were selected and the disintegration time was examined with the method in Chinese Pharmacopoeia. The disintegration time and disintegration phenomenon were recorded, and the dissolution behaviors of water-soluble and ultraviolet-absorbent components during the disintegration process of tablets were characterized by self-control method. The results revealed that coating type and raw material type influenced the disintegration time of tablets. It was found that only 4% of traditional Chinese medicine tablets had obvious fragmentation during the disintegration process, while 96% of traditional Chinese medicine tablets showed gradual dissolution or dispersion. Furthermore, according to the disintegration speed, disintegration phenomenon, and whether the cumulative dissolution of measured components was > 90% at complete disintegration, a disintegration behavior classification system(DBCS) was created for the regular-release traditional Chinese medicine tablets. As a result, the disintegration behaviors of 50 batches of traditional Chinese medicine tablets were classified into four categories, i.e. ⅠA_2, ⅠB_1, ⅡB_1, and ⅡB_2. traditional Chinese medicine tablets(Class I) with disintegration time ≤ 30 min were defined to be rapid in disintegration, which can be the objective of optimization or improvement of Chinese herbal extract(semi extract) tablets. Different drug release models were used to fit the dissolution curve of traditional Chinese medicine tablets with gradual dissolution or dispersion phenomenon(i.e. Type B tablets). The results showed that the dissolution curves of water-soluble components in the disintegration process conformed to the zero order kinetics and the Ritger-Peppas model. It could be inferred that the disintegration mechanisms of type B tablets were a combination of dissolution controlled and swelling controlled mechanisms. This study contributes to understanding the disintegration behavior of traditional Chinese medicine tablets, and provides a reference for the design and improvement of disintegration performance of traditional Chinese medicine tablets.

Patent application of intelligent quality control technology in traditional Chinese medicine production process: a review / 中国中药杂志

In the new stage for intelligent manufacturing of traditional Chinese medicine(TCM) from pilot demonstration to in-depth application and comprehensive promotion, how to raise the degree of intelligence for the process quality control system has become the bottleneck of the development of TCM production process control technology. This article has sorted out 226 TCM intelligent manufacturing projects that have been approved by the national and provincial governments since the implementation of the "Made in China 2025" plan and 145 related pharmaceutical enterprises. Then, the patents applied by these pharmaceutical enterprises were thoroughly retrieved, and 135 patents in terms of intelligent quality control technology in the production process were found. The technical details about intelligent quality control at both the unit levels such as cultivation, processing of crude herbs, preparation pretreatment, pharmaceutical preparations, and the production workshop level were reviewed from three aspects, i.e., intelligent quality sensing, intelligent process cognition, and intelligent process control. The results showed that intelligent quality control technologies have been preliminarily applied to the whole process of TCM production. The intelligence control of the extraction and concentration processes and the intelligent sensing of critical quality attributes are currently the focus of pharmaceutical enterprises. However, there is a lack of process cognitive patent technology for the TCM manufacturing process, which fails to meet the requirements of closed-loop integration of intelligent sensing and intelligent control technologies. It is suggested that in the future, with the help of artificial intelligence and machine learning methods, the process cognitive bottleneck of TCM production can be overcome, and the holistic quality formation mechanisms of TCM products can be elucidated. Moreover, key technologies for system integration and intelligent equipment are expected to be innovated and accelerated to enhance the quality uniformity and manufacturing reliability of TCM.

Effect of family management intervention on disease management ability of parents and family function with coronary artery lesions in Kawasaki disease / 中国实用护理杂志

Objective:To investigate the intervention effects and influencing factors of family management intervention on parents' disease management ability, family function of children with coronary artery lesions in Kawasaki disease.Methods:This was a quasi experimental study. Conveniently, 88 parents of children with Kawasaki disease coronary artery lesions from the Children's Hospital of Chongqing Medical University from March 2020 to June 2021 were selected for the study, and they were divided into the control group and the intervention group according to the order of the first consultation with 44 cases in each group. In the control group, conventional care and health education were used, while in the intervention group, a 6-month family management intervention was implemented on the basis of the control group. Family Management Measure (FaMM), Family Assessment Device (FAD) were used to assess the parents' disease management ability, family function before and after the intervention, respectively.Results:A total of 88 study subjects completed the pre-intervention survey in this study, and a total of 79 study subjects were surveyed when they returned to the hospital for review at the end of 6 months of intervention, including 40 in the intervention group and 39 in the control group, with a missed rate of 10.23% (9/88). There was no significant difference in the score of FAD, FaMM, Kawasaki disease knowledge questionnaire before the intervention between the two groups ( P>0.05). The scores of FAD in the intervention group was (21.58 ± 4.60) points, which was lower than that in the control group (24.62 ± 5.28) points, and the difference was statistically significant ( t=2.73, P <0.05). The scores of FaMM in the intervention group was (46.83 ± 6.02) points, which was higher than that in the control group (42.72 ± 6.09) points, and the differences was statistically significant ( t=-3.01, P <0.05). The age of the child, and whether the child was an only child were the influencing factors of the difference in disease management ability, and the difference in the family function of the parents of the child, respectively (all P<0.05). Conclusions:Family management intervention can improve the disease management ability of the parents of children with coronary artery lesion, improve family function. In the future, targeted interventions can be conducted according to different ages of children, and different family members' composition in order to obtain better intervention effects.

Progress of human-computer interaction devices applied in chronic disease management for the elderly / 医疗卫生装备

The current research status of human-computer interaction(HCI)devices applied in disease warning,disease surveillance and medication monitoring for the elderly was introduced,the problems of HCI devices during the application were analyzed in high cost,portability,privacy and high technical requirements,and its future development directions were pointed out.

Analysis of 90 Cases of Serious Adverse Reactions Induced by Nedaplatin for Injection / 医药导报

Objective In order to discuss the rationality of clinical use of medication and the strategies of serious adverse reactions(SADR),the reports of SADRs caused by nedaplatin for injection were summarized and analyzed.Methods Methods Serious adverse reactions to all medicines reported to the National Adverse Reaction Monitoring Centre(NARMC)in Tongji Hospital Affiliated to Tongji Medical College,Huazhong University of Science and Technology from January 2012 to December 2021 were collected,and a retrospective analysis of 90 patients among those cases with SADR after nedaplatin injection was carried out.Results The occurrence of SADRs was not related to the gender.In monotherapy with nedaplatin,the rate of serious adverse effects was high with the first use of nedaplatin(74.3%).The incidence of adverse reactions was highest within 30 minutes and 2-14 days,including severe allergic reaction(34.4%)and grade Ⅱ-Ⅳ myelosuppression(51.2%),respectively.Drug withdrawal and symptomatic treatment were often the preferred treatment methods in clinical practice.Conclusion While using nedaplatin as a chemotherapy regimen,especially for the first time,patients should be closely monitored for the occurrence of severe anaphylaxis within 30 minutes and severe bone marrow suppression within 2 weeks.A rescue emergency plan for resuscitation and regular checking of the hemogram should be made to prevent the occurrence of serious adverse reactions.

Discrete element simulation study of mixing process of Guizhi Fuling Capsules: parameter calibration / 中国中药杂志

The mixing process is a critical link in the formation of oral solid preparations of traditional Chinese medicine. This paper took the extract powder of Guizhi Fuling Capsules and Paeonol powder as research objects. The angle of repose, loose packing density, and particle size of the two powders were measured to calibrate discrete element simulation parameters for the mixing process. The discrete element method was used to calibrate the simulated solid density of Paeonol powder and extract powder of Guizhi Fuling Capsules based on the Hertz-Mindlin with JKR V2 contact model and particle scaling. The Plackett-Burman experimental design was used to screen out the critical contact parameters that had a significant effect on the simulation of the angle of repose. The regression model between the critical contact parameters and the simulated angle of repose was established by the Box-Behnken experimental design, and the critical contact parameters of each powder were optimized based on the regression model. The best combination of critical contact parameters of the extract powder of Guizhi Fuling Capsules was found to be 0.51 for particle-particle static friction coefficient, 0.31 for particle-particle rolling friction coefficient, and 0.64 for particle-stainless steel static friction coefficient. For Paeonol powder, the best combination of critical contact parameters was 0.4 for particle-particle static friction coefficient and 0.19 for particle-particle rolling friction coefficient. The best combination of contact parameters between Paeonol powder and extract powder of Guizhi Fuling Capsules was 0.27 for collision recovery coefficient, 0.49 for static friction coefficient, and 0.38 for rolling friction coefficient. The verification results show that the relative error between the simulated value and the measured value of the angle of repose of the two single powders is less than 1%, while the relative error between the simulated value and the measured value of the angle of repose of the mixed powder with a mass ratio of 1∶1 is less than 4%. These research results provide reliable physical property simulation data for the mixed simulation experiment of extract powder of Guizhi Fuling Capsules and Paeonol powder.

Discordance analysis for apolipoprotein and lipid measures for predicting myocardial infarction in statin-treated patients with coronary artery disease: a cohort study / 老年心脏病学杂志（英文版）

BACKGROUND@#The optimal apolipoprotein or lipid measures for identifying statin-treated patients with coronary artery disease (CAD) at residual cardiovascular risk remain controversial. This study aimed to compare the predictive powers of apolipoprotein B (apoB), non-high-density lipoprotein cholesterol (non-HDL-C), low-density lipoprotein cholesterol (LDL-C), apoB/apolipoprotein A-1 (apoA-1) and non-HDL-C/HDL-C for myocardial infarction (MI) in CAD patients treated with statins in the setting of secondary prevention.@*METHODS@#The study included 9191 statin-treated CAD patients with a five-year median follow-up. All measures were analyzed as continuous variables and concordance/discordance groups by medians. The hazard ratio (HR) with 95% CI was estimated by Cox proportional hazards regression. Patients were classified by the clinical presentation of CAD for further analysis.@*RESULTS@#The high-apoB-low-LDL-C and the high-non-HDL-C-low-LDL-C categories yielded HR of 1.40 (95% CI: 1.04-1.88) and 1.51 (95% CI: 1.07-2.13) for MI, respectively, whereas discordant high LDL-C with low apoB or non-HDL-C was not associated with the risk of MI. No association of MI with discordant apoB versus non-HDL-C, apoB/apoA-1 versus apoB, non-HDL-C/HDL-C versus non-HDL-C, or apoB/apoA-1 versus non-HDL-C/HDL-C was observed. Similar patterns were found in patients with acute coronary syndrome. In contrast, no association was observed between any concordance/discordance category and the risk of MI in patients with chronic coronary syndrome.@*CONCLUSIONS@#ApoB and non-HDL-C better predict MI in statin-treated CAD patients than LDL-C, especially in patients with acute coronary syndrome. ApoB/apoA-1 and non-HDL-C/HDL-C show no superiority to apoB and non-HDL-C for predicting MI.

The emerging role of blood lipoprotein levels in osteoporosis of postmenopausal women with rheumatoid arthritis / 中华风湿病学杂志

Objective:To retrospectively analyze the correlation between blood lipoprotein levels and the risk of osteoporosis (OP) development in postmenopausal patients with RA and its influencing factors.Methods:Patients hospitalized with a definite diagnosis of RA from July 2017 to May 2020 were retrospectively collected and analyzed by bone mineral density (BMD) in subgroups, using correlation analysis, di-chotomous Logistic regression to quantify independent associations between laboratory test results and out-comes, and restrictive cubic spline (RCS) to fit the relationship of OP risk occurrence.Results:Six hundred and sixty-six eligible RA patients were included according to inclusion criteria, including 253 RA-OP and 413 RA-non-OP patients. After exclusion of relevant influencing factors by comparing demographic characteristics, a significant correlation was found between blood HDL-C ( r=-0.11, P=0.006) LDL-C ( r=0.12, P=0.003) levels and RA-OP( P<0.05), and dichotomous Logistic regression showed that as BMI ( OR(95% CI)=0.81(0.77, 0.86), P<0.001], calcium [ OR(95% CI)=0.24(0.10, 0.63), P<0.001], HDL-C[ OR(95% CI)=0.38(0.22, 0.66), P<0.001] increased, the risk of developing OP in RA patients decreased. In contrast, the risk of developing OP increased with increasing age [ OR(95% CI)=1.10(1.07, 1.21), P<0.001), disease duration [ OR(95% CI)=1.00(1.00, 1.00), P=0.020], and LDL-C[ OR(95% CI)=1.71(1.38, 2.12), P<0.001]. Conclusion:Blood HDL-C and LDL-C levels are significantly correlated with the development of RA-OP, and can be used as predictors of OP development and good indicators for disease monitoring in RA patients.

Anethole ameliorates inflammation induced by monosodium urate in an acute gouty arthritis model via inhibiting TLRs/MyD88 pathway

Objective To assess the effects of anethole on monosodium urate (MSU)-induced inflammatory response, investigate its role in acute gouty arthritis (AGA), and verify its molecular mechanism. Methods Hematoxylin and eosin staining assay and time-dependent detection of degree of ankle swelling were performed to assess the effects of anethole on joint injury in MSU-induced AGA mice. Enzyme-linked-immunosorbent serologic assay was performed to demonstrate the production levels of inflammatory factors (interleukin 1β [IL-1β], interleukin 6 [IL-6], interleukin 8 [IL-8], tumor necrosis factor α [TNF-α], and monocyte chemo-attractant protein-1 [MCP-1]) in MSU-induced AGA mice. Western blot assays were used to confirm the effects of anethole on oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activity and the activation of toll-like receptors (TLRs)–myeloid differentiation factor 88 (MyD88) pathway in MSU-induced AGA mice. Results We observed that a significant joint injury occurred in MSU-induced AGA mice. Anethole could alleviate the pathological injury of the synovium in MSU-induced AGA mice and suppressed ankle swelling. In addition, we observed that anethole could inhibit MSU-induced inflammatory response and inflammasome activation in MSU-induced AGA mice. Moreover, we discovered that anethole enabled to inhibit the activation of TLRs/MyD88 pathway in MSU-induced AGA mice. Our findings further confirmed that anethole contributed to the inhibitory effects on progression in MSU-induced AGA mice. Conclusion It confirmed that anethole ameliorated the MSU-induced inflammatory response in AGA mice in vivo via inhibiting TLRs–MyD88 pathway (AU)

Safety and immunogenicity of a broad-spectrum mosaic vaccine as a booster dose against SARS-CoV-2 Omicron and other circulating variants

BACKGROUNDThe rising breakthrough infections caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, especially Omicron and its sub-lineages, have raised an urgent need to develop broad-spectrum vaccines against coronavirus disease 2019 (COVID-19). We have developed a mosaic-type recombinant vaccine candidate, named NVSI-06-09, having immune potentials against a broad range of SARS-CoV-2 variants. METHODSAn ongoing randomized, double-blind, controlled phase 2 trial was conducted to evaluate the safety and immunogenicity of NVSI-06-09 as a booster dose in subjects aged 18 years and older from the United Arab Emirates (UAE), who had completed two or three doses of BBIBP-CorV vaccinations at least 6 months prior to the enrollment. The participants were randomly assigned with 1:1 to receive a booster dose of NVSI-06-09 or BBIBP-CorV. The primary outcomes were immunogenicity and safety against SARS-CoV-2 Omicron variant, and the exploratory outcome was cross-immunogenicity against other circulating strains. RESULTSA total of 516 participants received booster vaccination. Interim results showed a similar safety profile between NVSI-06-09 and BBIBP-CorV booster groups, with low incidence of adverse reactions of grade 1 or 2. For immunogenicity, by day 14 after the booster vaccination, the fold rises in neutralizing antibody geometric mean titers (GMTs) from baseline level elicited by NVSI-06-09 were remarkably higher than those by BBIBP-CorV against the prototype strain (19.67 vs 4.47-fold), Omicron BA.1.1 (42.35 vs 3.78-fold), BA.2 (25.09 vs 2.91-fold), BA.4 (22.42 vs 2.69-fold), and BA.5 variants (27.06 vs 4.73-fold). Similarly, the neutralizing GMTs boosted by NVSI-06-09 against Beta and Delta variants were also 6.60-fold and 7.17-fold higher than those boosted by BBIBP-CorV. CONCLUSIONSA booster dose of NVSI-06-09 was well-tolerated and elicited broad-spectrum neutralizing responses against SARS-CoV-2 prototype strain and immune-evasive variants, including Omicron and its sub-lineages. The immunogenicity of NVSI-06-09 as a booster vaccine was superior to that of BBIBP-CorV. (Funded by LIBP and BIBP of Sinopharm; ClinicalTrials.gov number, NCT05293548).

Molecular mechanism analysis of Miao medicine Jinwujiangu decoction in treating osteoarthritis based on a network pharmacology approach.

OBJECTIVE: To investigate molecular mechanisms of Jinwujiangu decoction (, JWJG) in treating osteoarthritis (OA) using network pharmacology analysis. METHODS: Principal active compounds of JWJG were screened out via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and BATMAN-TCM, and potential targets for OA treatment were identified through Online Mendelian Inheritance in Man (OMIM) and GeneCards databases. The JWJG network diagrams of both principal chemical compound-action targets and OA treatment target-OA disease were constructed applying the Cytoscape 3.7.2 software. The diagram of protein-protein interaction network was plotted for core analysis. Meanwhile, the common targets and relevant signaling pathways involved in both networks were analyzed using the Gene Ontology function analysis and Kyoto Encyclopedia of Genes and Genomes pathway enrichment. The predicted results were ultimately verified through animal experiments. RESULTS: Effects of JWJG were indicated in acting on key targets interleukin-6, insulin, protein kinase B, glyceraldehyde-3-phosphate dehydrogenase, and mitosis-specific MRE11-RAD50-NBS1 associated protein by regulating signaling pathways of phosphoinositide 3-kinase- protein kinase B, mitogen-activated protein kinases, tumor necrosis factor, and colorectal cancer. Meanwhile, it inhibited the over-activation of signaling pathways and the release of inflammatory factors in OA treatment. Following a signaling pathway analysis utilizing network pharmacology technique, it was demonstrated that JWJG could treat OA through the Wnt/ß-catenin signaling pathway verified by animal experiments. CONCLUSIONS: The present study preliminarily analyzed the pharmacological mechanism of JWJG in treating OA on a network pharmacology approach and provided a great theoretical significance for clinical application.

Pseudomembranous necrotizing laryngotracheobronchitis due to Mycoplasma pneumoniae: a case report and literature review.

BACKGROUND: Pseudomembranous necrotizing laryngotracheobronchitis refers to an acute diffuse necrotizing inflammation in the mucosa of the larynx, trachea, and bronchus. It often occurs in infants and children having viral infections secondary to bacterial infections. Mycoplasma pneumoniae (M. pneumoniae) is a common pathogen that causes pneumonia in children. In recent years, serious complications due to M. pneumoniae infection, including necrotizing pneumonia, pulmonary embolism, and pleural effusion, have been increasingly reported. CASE PRESENTATION: An 11-year-old girl was admitted to our unit with cough, fever, and hoarseness persistent for a week. The results of the M. pneumoniae serological test, PCR examination with bronchial aspirate and bronchoalveolar lavage fluid (BALF), next-generation sequencing (mNGS) for BALF, all suggested the presence of M. pneumoniae infection. High-resolution CT scanning of the chest showed inflammation of the middle and lower lobes of the right lung. By bronchoscopy, the necrosis of the vocal cords, trachea, and bronchial mucosa was observed; each bronchial lumen contained a large amount of white viscous sputum. Pathological findings for bronchial mucosa suggested inflammatory necrosis. After administration of azithromycin and glucocorticoids, the symptoms of the patients were ameliorated. After 2 weeks post-discharge, the X-ray scan of her chest indicated the pneumonia resolution in the right lung. CONCLUSIONS: In patients with pneumonia due to M. pneumoniae infection, which causes obvious hoarseness, bronchoscopy is necessary even if the lung lesions are not massively consolidated. When necrotizing lesions of the larynx, trachea, and bronchi are detected by bronchoscopy, the necrotic tissues in the corresponding parts should be conducted tissue biopsy for pathological examination. Apart from macrolide antibiotics, the administration of small doses of glucocorticoids is necessary.

Constructions of the scale of difficulty in the extraction of impacted mandibular third molars by using Delphi method / 北京大学学报(医学版)

OBJECTIVE@#To evaluate the relevant indicators affecting difficulty in the extraction of impacted mandibular third molars and score difficulty of different operation and risk indicators, so as to build an intuitive and accurate scale to help operators make more accurate analysis and prediction of difficulty before the operation.@*METHODS@#Based on literature and the clinical review, the difficulty indicators of tooth extraction were summarized. Firstly, 10 doctors from Peking University School and Hospital of Stomatology who had been engaged in alveolar surgery for a long time established an expert nominal group, and then rated whether the summarized indicators needed to be retained in the form of face-to-face questionnaires. A level 1 and 2 item frame for evaluating difficulty in the tooth extraction was formed after discussion; Then Delphi method was used to send a questionnaire to 30 experts by e-mail. After two rounds of scoring and modification, the scale of difficulty in the extraction of impacted mandibular third molars was formed.@*RESULTS@#The recycling rate of two rounds of questionnaires was 100.0%, which showed that the experts were very enthusiastic about the study; The authority coefficients (Cr) of the two rounds of Delphi expert consultation were both 0.92, which showed that the results were representative and authoritative. After two rounds of grading and revision, the variable coefficient (CV) decreased and the Kendall's concordance coefficient (W) increased, which were statistically significant: In the first round, the CV was 0.24 and W was 0.56 (P < 0.001), and in the second, the CV was 0.19 and W was 0.72 (P < 0.001), which indicated that there was a good convergence among the expert opinions. Finally, a scale of difficulty in the tooth extraction containing 12 items at level A and 37 items at level B was formed, including operation difficulty indicators, risk difficulty indicators and common difficulty indicators.@*CONCLUSION@#Based on comprehensive literature retrieval, the study has put forward the concept that difficulty in the extraction of impacted mandibular third molars is composed of operation difficulty and risk difficulty. Using Delphi method, the long-term clinical experience and professional knowledge of experts are transformed into quantitative indicators as a scoring scale. The scale has certain representativeness and authority.

Structure and computation-guided design of a mutation-integrated trimeric RBD candidate vaccine with broad neutralization against SARS-CoV-2

The spike (S) protein receptor-binding domain (RBD) of SARS-CoV-2 is an attractive target for COVID-19 vaccine developments, which naturally exists in a trimeric form. Here, guided by structural and computational analyses, we present a mutation-integrated trimeric form of RBD (mutI tri-RBD) as a broadly protective vaccine candidate, in which three RBDs were individually grafted from three different circulating SARS-CoV-2 strains including the prototype, Beta (B.1.351) and Kappa (B.1.617). The three RBDs were then connected end-to-end and co-assembled to possibly mimic the native trimeric arrangements in the natural S protein trimer. The recombinant expression of the mutI tri-RBD, as well as the homo-tri-RBD where the three RBDs were all truncated from the prototype strain, by mammalian cell exhibited correct folding, strong bio-activities, and high stability. The immunization of both the mutI tri-RBD and homo-tri-RBD plus aluminum adjuvant induced high levels of specific IgG and neutralizing antibodies against the SARS-CoV-2 prototype strain in mice. Notably, regarding to the "immune-escape" Beta (B.1.351) variant, mutI tri-RBD elicited significantly higher neutralizing antibody titers than homo-tri-RBD. Furthermore, due to harboring the immune-resistant mutations as well as the evolutionarily convergent hotspots, the designed mutI tri-RBD also induced strong broadly neutralizing activities against various SARS-CoV-2 variants, especially the variants partially resistant to homo-tri-RBD. Homo-tri-RBD has been approved by the China National Medical Products Administration to enter clinical trial (No. NCT04869592), and the superior broad neutralization performances against SARS-CoV-2 support the mutI tri-RBD as a more promising vaccine candidate for further clinical developments.