A head-to-head comparison of humoral and cellular immune responses of five COVID-19 vaccines in adults in China.

Introduction: Various COVID-19 vaccine trials have shown that vaccines can successfully prevent symptomatic cases of COVID-19 and death. Head-to-head comparisons help to better understand the immune response characteristics of different COVID-19 vaccines in humans. Methods: We randomly selected 20 participants from each of five ongoing Phase II trials of COVID-19 vaccines. Here, SARS-CoV 2-specific immune responses to DNA vaccine (INO-4800), mRNA vaccine (BNT162b2), Adenovirus-vectored vaccine (CONVIDECIA), Protein subunit vaccine (Recombinant COVID- 19 Vaccine (Sf9 Cells)), Inactivated Vaccine (KCONVAC) were examined longitudinally in healthy adults between Jan 15, 2021 and July 5, 2021 for 6 months. RBD-IgG titres were detected by ELISA, neutralising antibody titer were detected by pseudoviral neutralization and immune cell response were detected by flow cytometry. Results: At the first visit (V1), 100% of individuals who received the BNT162b2, CONVIDECIA, or KCONVAC vaccines experienced seroconversion of neutralizing and binding antibodies in the serum. Except for the Recombinant COVID-19 Vaccine (Sf9 Cells) vaccine having the highest neutralizing antibody GMT at the second visit (although there was no statistically significant difference in geometric mean titers between V1 and V2), the rest of the vaccines had the highest levels of binding antibodies and neutralizing antibodies at V1. The neutralizing antibodies GMT of all vaccines showed a significant decrease at V3 compared to V1. The neutralizing antibody GMT against the omicron variant of all vaccines at V1 showed a significant decrease compared to the wild strain. We observed statistically significant differences in Tcm cells and RBD-specific memory B cells among various vaccines. Discussion: BNT162b2 (mRNA vaccine) exhibits the highest antibody levels among the five vaccines evaluated, regardless of whether the target is the wild-type virus or its variants. However, its cellular immune response may be weaker compared to CONVIDECIA (adenovirus type 5 vector vaccine).

Effectiveness of seven oral traditional Chinese medicines against mild or moderate COVID-19: An updated systematic review and network meta-analysis.

Background: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for the outbreak of COVID-19 in Wuhan, China. As a highly infectious epidemic, SARS-CoV-2 rapidly evolves. Presently, COVID-19 coexists with humans, mainly with mild or moderate disease. The latest Guidelines for the Diagnosis and Treatment of COVID-19 (trial version of the 10th Edition) recommend several oral traditional Chinese medicines (TCMs) for treatment. This study aims to evaluate the evidence-based benefits of these TCMs as adjunctive therapies to conventional western medicine (CWM) for patients with mild or moderate COVID-19. Methods: We conducted a systematic review and meta-analysis adhering to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, utilizing the PRISMA checklist. We searched PubMed, Cochrane Library, Embase, CNKI, and Wan-Fang databases to retrieve randomized controlled trials and retrospective cohort studies of TCM in combination with CWM on the treatment of mild or moderate COVID-19 that were published as of December 25, 2023. A network meta-analysis using the frequency model was employed to evaluate the benefits of different interventions. Results: A total of 30 eligible studies, enrolling 4144 participants, utilized 7 marketed oral TCMs in China. Compared with CWM alone, the integration of TCMs with CWM can significantly reduce severe conversion rate. This combined approach also enhances the clinical effective rate, shortens the negative conversion time of nucleic acid, and improves both symptoms and blood biochemical markers in patients. The network meta-analysis provided preliminary evidence of the superiority of specific TCMs for various outcomes: Qingfei Paidu for raising the CT improvement rate and clinical effective rate, and shortening the negative conversion time of nucleic acid; Huashi Baidu for reducing severe conversion and improving cough; Xuanfei Baidu for improving fatigue; Jinhua Qinggan for improving fever; Lianhua Qingwen for shortening the recovery time of fatigue and cough; and Shufeng Jiedu for shortening the recovery time of fever. Conclusions: TCM in combination with CWM may be beneficial for patients with mild or moderate COVID-19. Each TCM may have distinct benefits in COVID-19.

Effect of mutation of phaC on carbon supply, extracellular polysaccharide production, and pathogenicity of Xanthomonas oryzae pv. oryzae.

Xanthomonas oryzae pv. oryzae (Xoo) causes bacterial blight in rice. Polyhydroxyalkanoates (PHAs) consitute a diverse group of biopolyesters synthesized by bacteria under nutrient-limited conditions. The phaC gene is important for PHA polymerization. We investigated the effects of phaC gene mutagensis in Xoo strain PXO99A. The phaC gene knock-out mutant exhibited reduced swarming ability relative to that of the wild-type. Under conditions where glucose was the sole sugar source, extracellular polysaccharide (EPS) production by ΔphaC declined by 44.8%. ΔphaC showed weak hypersensitive response (HR) induction in the leaves of non-host Nicotiana tabacum, concomitant with downregulation of hpa1 gene expression. When inoculated in rice leaves by the leaf-clipping method, ΔphaC displayed reduced virulence in terms of lesion length compared with the wild-type strain. The complemented strain showed no significant difference from the wild-type strain, suggesting that the deletion of phaC in Xoo induces significant alterations in various physiological and biological processes. These include bacterial swarming ability, EPS production, transcription of hrp genes, and glucose metabolism. These changes are intricately linked to the energy utilization and virulence of Xoo during plant infection. These findings revealed involvement of phaC in Xoo is in the maintaining carbon metabolism by functioning in the PHA metabolic pathway.

Cost-Effectiveness Analysis of Herpes Zoster Vaccination in a Chinese Population: Recombinant Subunit Vaccine versus Live Attenuated Vaccine.

BACKGROUND: Currently, the recombinant subunit vaccine and live attenuated vaccine in the prevention of herpes zoster are approved for marketing in China. This study aims to evaluate the cost-effectiveness of the recombinant subunit vaccine and the live attenuated vaccine in the Chinese population. METHODS: A decision tree-Markov analysis model was utilized to estimate expected costs and quality-adjusted life years (QALYs), comparing the lifetime cost-effectiveness of vaccination with the recombinant subunit vaccine (London, United Kingdom, Shingrix, GSK) to that of the live attenuated vaccine (Changchun, China, Ganwei, Changchun Bcht) in the Chinese population, with the primary outcome measure being the incremental cost-effectiveness ratio (ICER). RESULTS: In the base-case analysis, the ICERs for the recombinant subunit vaccine ranged by age from USD 3428 to USD 5743 per QALY, while the ICERs for the live attenuated vaccine ranged from USD 4017 to USD 18,254 per QALY, compared with no vaccination. Among all age groups, the category of 60 to 69 years was the optimal age for vaccination. The results were most sensitive to changes in herpes zoster incidence, vaccine efficacy, and discount rate. Even with a two-dose compliance rate of 20% for the recombinant subunit vaccine, vaccination remained cost-effective. ZVL would need to reduce costs by at least 12.2% compared to RZV to have a cost-effectiveness advantage. CONCLUSIONS: The recombinant subunit vaccine and the live attenuated vaccine were both cost-effective in the Chinese population, but, relatively, the recombinant subunit vaccine had a greater advantage in disease prevention and cost-effectiveness in all age groups above 50 years.

Molecular mechanism of vivipary as revealed by the genomes of viviparous mangroves and non-viviparous relatives.

Vivipary is a prominent feature of mangroves, allowing seeds to complete germination while attached to the mother plant, and equips propagules to endure and flourish in challenging coastal intertidal wetlands. However, vivipary-associated genetic mechanisms remain largely elusive. Genomes of two viviparous mangrove species and a non-viviparous inland relative were sequenced and assembled at the chromosome level. Comparative genomic analyses between viviparous and non-viviparous genomes revealed that DELAY OF GERMINATION 1 (DOG1) family genes (DFGs), the proteins from which are crucial for seed dormancy, germination, and reserve accumulation, are either lost or dysfunctional in the entire lineage of true viviparous mangroves but are present and functional in their inland, non-viviparous relatives. Transcriptome dynamics at key stages of vivipary further highlighted the roles of phytohormonal homeostasis, proteins stored in mature seeds, and proanthocyanidins in vivipary under conditions lacking DFGs. Population genomic analyses elucidate dynamics of syntenic regions surrounding the missing DFGs. Our findings demonstrated the genetic foundation of constitutive vivipary in Rhizophoraceae mangroves.

Bacillus velezensis HN-2: a potent antiviral agent against pepper veinal mottle virus.

Background: Pepper veinal mottle virus (PVMV) belongs to the genus Potyvirus within the family Potyviridae and is a major threat to pepper production, causing reduction in yield and fruit quality; however, efficient pesticides and chemical treatments for plant protection against viral infections are lacking. Hence, there is a critical need to discover highly active and environment-friendly antiviral agents derived from natural sources. Bacillus spp. are widely utilized as biocontrol agents to manage fungal, bacterial, and viral plant diseases. Particularly, Bacillus velezensis HN-2 exhibits a strong antibiotic activity against plant pathogens and can also induce plant resistance. Methods: The experimental subjects employed in this study were Bacillus velezensis HN-2, benzothiadiazole, and dufulin, aiming to evaluate their impact on antioxidant activity, levels of reactive oxygen species, activity of defense enzymes, and expression of defense-related genes in Nicotiana benthamiana. Furthermore, the colonization ability of Bacillus velezensis HN-2 in Capsicum chinense was investigated. Results: The results of bioassays revealed the robust colonization capability of Bacillus velezensis HN-2, particularly in intercellular spaces, leading to delayed infection and enhanced protection against PVMV through multiple plant defense mechanisms, thereby promoting plant growth. Furthermore, Bacillus velezensis HN-2 increased the activities of antioxidant enzymes, thereby mitigating the PVMV-induced ROS production in Nicotiana benthamiana. Moreover, the application of Bacillus velezensis HN-2 at 5 dpi significantly increased the expression of JA-responsive genes, whereas the expression of salicylic acid-responsive genes remained unchanged, implying the activation of the JA signaling pathway as a crucial mechanism underlying Bacillus velezensis HN-2-induced anti-PVMV activity. Immunoblot analysis revealed that HN-2 treatment delayed PVMV infection at 15 dpi, further highlighting its role in inducing plant resistance and promoting growth and development. Conclusions: These findings underscore the potential of Bacillus velezensis HN-2 for field application in managing viral plant diseases effectively.

Comparison of 1 Versus 2 Doses of Quadrivalent Influenza Vaccine in 3-8-Year-Old Children with Different Immunological States - Jiangsu Province, China, 2021.

What is already known about this topic?: The quadrivalent influenza vaccine (QIV) provides protection against a broader range of influenza strains by including strains of influenza A/H1N1, A/H3N2, B/Yamagata, and B/Victoria. What is added by this report?: This study aimed to assess the immunogenicity and safety of administering a single dose compared to two doses of QIV in children, taking into consideration their previous influenza vaccination history. What are the implications for public health practice?: This study provides evidence supporting the use of a single dose of the QIV in children aged 3-8 years who have previously received two or more doses of influenza vaccine. However, children who have not been previously vaccinated with influenza vaccine should still adhere to the recommended schedule of receiving two doses.

The feasibility of using pathobiome strains as live biotherapeutic products for human use.

The evaluation of pathobiome strains should be conducted at the strain level, involving the identification of the functional genes, while considering the impact of ecological niche and drug interactions. The safety, efficacy, and quality management of live biotherapeutic products (LBPs), especially pathobiome strains, have certain peculiarities. Promising development methods include the recombinant LBP and active metabolites.

Oleanane triterpenoids with PTP1B and α-glucosidase inhibitory activities from Caulophyllum robustum.

Eleven oleanane triterpenoids (1-11) including two new ones (1 and 2) were isolated from the roots and stems of Caulophyllum robustum. Their structures were established by extensive spectroscopic analysis, comparison with literature, and NMR calculations. Compounds 1 and 2 represent the first examples of 23-hydroxy-28-nor-oleanane and 21-hydroxy-olean-3-one triterpenoids, respectively. All isolates were evaluated for their PTP1B and α-glucosidase inhibitory activities in vitro. Among them, the triterpene aglycones 1-5 showed almost equivalent PTP1B inhibitory activities to oleanolic acid and ursolic acid, while 1, 2, and the triterpene saponins 6-11 showed significant α-glucosidase inhibitory activities. Furthermore, compounds 1 and 3 were proved to regulate the expression of proteins implicated the PTP1B/IRS-1/pIRS-1 signalling pathway to improve insulin resistance.

Stepwise Charge/Energy Transfer in MR-TADF Molecule-Doped Exciplex for Ultralong Persistent Luminescence Activated with Visible Light.

Organic long-persistent luminescence (OLPL), which relies on energy storage for delayed light emission by the charge separation state, has attracted intense attention in various optical applications. However, charge separation (CS) is efficient only under ultraviolet excitation in most OLPL systems because it requires a driving force from the large energy difference between the local excited (LE) and charge transfer (CT) states. In this study, a multiresonance thermally activated delayed fluorescence (MR-TADF) molecule is incorporated into an exciplex system to achieve efficient OLPL in a composite material activated by visible light via a stepwise charge/energy transfer process. The enhanced absorption of the composite material facilitated a tenfold increase in the duration of the OLPL, which can last for several hours under visible light excitation. The excited state of the MR-TADF molecule tends to charge transfer to the acceptor, followed by energy transfer to the exciplex, which benefits from the small difference between the LE and CT states owing to the inherent CS characteristics of the opposing resonance effect. Afterglow displays of these composite materials are fabricated to demonstrate their considerable potential in encryption patterns and emergency lights, which take advantage of their excellent processability, visible light activation, and tunable luminescence properties.

Protein function annotation and virulence factor identification of Klebsiella pneumoniae genome by multiple machine learning models.

Klebsiella pneumoniae is a type of Gram-negative bacterium which can cause a range of infections in human. In recent years, an increasing number of strains of K. pneumoniae resistant to multiple antibiotics have emerged, posing a significant threat to public health. The protein function of this bacterium is not well known, thus a systematic investigation of K. pneumoniae proteome is in urgent need. In this study, the protein functions of this bacteria were re-annotated, and their function groups were analyzed. Moreover, three machine learning models were built to identify novel virulence factors. Results showed that the functions of 16 uncharacterized proteins were first annotated by sequence alignment. In addition, K. pneumoniae proteins share a high proportion of homology with Haemophilus influenzae and a low homology proportion with Chlamydia pneumoniae. By sequence analysis, 10 proteins were identified as potential drug targets for this bacterium. Our model achieved a high accuracy of 0.901 in the benchmark dataset. By applying our models to K. pneumoniae, we identified 39 virulence factors in this pathogen. Our findings could provide novel clues for the treatment of K. pneumoniae infection.

Nasal Staphylococcus aureus Carriage and Antimicrobial Resistance Profiles Among Community-Dwelling Adults in Jiangsu, China.

INTRODUCTION: Persistent nasal carriage has been associated with Staphylococcus aureus infection. Previous S. aureus studies in Asia have primarily focused on clinical patients, providing limited information on persistent nasal carriage among the general adult population. METHODS: This study examined 143 healthy adults in a community in Jiangsu, China. Nasal swab samples were collected 10 times. The colonization status was identified using SPA typing. We also determined antimicrobial susceptibility, genotype, and genomic characteristics of S. aureus. RESULTS: The prevalence of S. aureus nasal carriage among the community individuals was on average 16.78%. The carriage rates of methicillin-resistant S. aureus and multidrug-resistant S. aureus were 6.29% and 7.69%, respectively. We identified 8.39% persistent carriers, 39.16% intermittent carriers, and 52.45% noncarriers. Furthermore, family members displayed concordance in terms of genotype and genomic characteristics. CONCLUSION: Persistent nasal sampling captured intermittent carriers that were missed during short-term sampling, thus highlighting the necessity for regular community testing. SPA typing can serve as a rapid method for determining S. aureus colonization. The potential for intrafamilial transmission of S. aureus is evident, with persistent carriers being the most probable source of infection.

Relative effectiveness of a heterologous booster dose with adenovirus type 5 vectored COVID-19 vaccine versus three doses of inactivated COVID-19 vaccine in adults during a nationwide outbreak of omicron predominance, in China: a retrospective, individually matched cohort-control study.

Effectiveness of heterologous booster regimes with ad5 vectored COVID-19 vaccine in a large, diverse population during the national-scale outbreak of SARS-CoV-2 omicron predominance in China has not been reported, yet. We conducted a large-scale cohort-control study in six provinces in China, and did a retrospective survey on the COVID-19 attack risk during this outbreak. Participant aged ≥18 years in five previous trials who were primed with 1 to 3 doses of ICV received heterologous booster with either intramuscular or orally inhaled ad5 vectored COVID-19 vaccine were included in the heterologous-trial cohort. We performed propensity score-matching at a ratio of 1:4 to match participants in the heterologous-trial cohort individually with the community individuals who received three-dose of ICV as a control (ICV-community cohort). From February 4 to April 10, 2023, 41504 (74.5%) of 55710 individuals completed the survey. The median time since the most recent vaccination to the onset of the symptoms of COVID-19 was 303.0 days (IQR 293.0-322.0). The attack rate of COVID-19 in the heterologous-trial cohort was 55.8%, while that in the ICV-community cohort was 64.6%, resulting in a relative effectiveness of 13.7% (95% CI 11.9 to 15.3). In addition, a higher relative effectiveness against COVID-19 associated outpatient visits, and admission to hospital was demonstrated, which was 25.1% (95% CI 18.9 to 30.9), and 48.9% (95% CI 27.0 to 64.2), respectively. The heterologous booster with ad5 vectored COVID-19 vaccine still offered some additional protection in preventing COVID-19 breakthrough infection versus homologous three-dose regimen with ICV, 10 months after vaccination.

Quantitative differentiation of non-invasive bladder urothelial carcinoma and inverted papilloma based on CT urography.

PURPOSE: To investigate the value of CT urography (CTU) indicators in the quantitative differential diagnosis of bladder urothelial carcinoma (BUC) and inverted papilloma of the bladder (IPB). MATERIAL AND METHODS: The clinical and preoperative CTU imaging data of continuous 103 patients with histologically confirmed BUC or IPB were retrospectively analyzed. The imaging data included 6 qualitative indicators and 7 quantitative measures. The recorded clinical information and imaging features were subjected to univariate and multivariate logistic regression analysis to find independent risk factors for BUC, and a combined multi-indicator prediction model was constructed, and the prediction model was visualized using nomogram. ROC curve analysis was used to calculate and compare the predictive efficacy of independent risk factors and nomogram. RESULTS: Junction smoothness, maximum longitudinal diameter, tumor-wall interface and arterial reinforcement rate were independent risk factors for distinguishing BUC from IPB. The AUC of the combined model was 0.934 (sensitivity = 0.808, specificity = 0.920, accuracy = 0.835), and its diagnostic efficiency was higher than that of junction smoothness (AUC=0.667, sensitivity = 0.654, specificity = 0.680, accuracy = 0.660), maximum longitudinal diameter (AUC=0.757, sensitivity = 0.833, specificity = 0.604, accuracy = 0.786), tumor-wall interface (AUC=0.888, sensitivity = 0.755, specificity = 0.808, accuracy = 0.816) and Arterial reinforcement rate (AUC=0.786, sensitivity = 0.936, specificity = 0.640, accuracy = 0.864). CONCLUSION: Above qualitative and quantitative indicators based on CTU and the combination of them may be helpful to the differential diagnosis of BUC and IPB, thus better assisting in clinical decision-making. KEY POINTS: 1. Bladder urothelial carcinoma (BUC) and inverted papilloma of the bladder (IPB) exhibit similar clinical symptoms and imaging presentations. 2. The diagnostic value of CT urography (CTU) in distinguishing between BUC and IPB has not been documented. 3. BUC and IPB differ in lesion size, growth pattern and blood supply. 4. The diagnostic efficiency is optimized by integrating multiple independent risk factors into the prediction model.

Cost-effectiveness of edaravone dexborneol versus dl-3-n-butylphthalide for the treatment of acute ischemic stroke: a Chinese health care perspective.

BACKGROUND: Edaravone dexborneol and dl-3-n-butylphthalide are two innovative brain cytoprotective drugs from China that have been approved and widely prescribed for acute ischemic stroke, and the cost of the two drugs are partially paid by the Chinese medical insurance system. This study aimed to investigate and compare the cost-effectiveness of edaravone dexborneol versus dl-3-n-butylphthalide for acute ischemic stroke from the Chinese healthcare system's perspective. METHODS: A model combining a short-term decision tree model with 90 days and a long-term Markov model with a life-time horizon (40 years) was developed to simulate the cost-effectiveness of edaravone dexborneol versus dl-3-n-butylphthalide for acute ischemic stroke over a lifetime horizon. Since the absence of a head-to-head clinical comparison of two therapies, an unanchored matching-adjusted indirect comparison (MAIC) was conducted by adjusting the patient characteristics using individual patient data from pivotal phase III trial of edaravone dexborneol and published aggregated data of dl-3-n-butylphthalide. Health outcomes were measured in quality-adjusted life years (QALYs). Utilities and costs (Chinese Yuan, CNY) were derived from publications and open-access database. One-way and probabilistic sensitivity analyses were performed to evaluate the robustness of results. RESULTS: Compared with patients in dl-3-n-butylphthalide arm, edaravone dexborneol arm was found to be cost-effective in 90 days and highly cost-effective as the study horizons extended. With a similar direct medical cost, patients in edaravone dexborneol arm slightly gained an additional 0.1615 QALYs in life-time. In the long term (40 years), patients in edaravone dexborneol arm and dl-3-n-butylphthalide arm yielded 8.0351 and 7.8736 QALYs with the overall direct medical cost of CNY 29,185.23 and CNY 29,940.28, respectively. The one-way sensitivity analysis suggested that the incremental cost-effectiveness ratio was most sensitive to the price of edaravone dexborneol and dl-3-n-butylphthalide. CONCLUSION: Edaravone dexborneol is a cost-effective alternative compared with dl-3-n-butylphthalide for acute ischemic stroke patients in current medical setting of China.

Favorable Loci Identified for Stripe Rust Resistance in Chinese Winter Wheat Accessions via Genome-Wide Association Study.

Stripe rust (or yellow rust), caused by Puccinia striiformis f. sp. tritici (Pst), is one of the most devastating diseases of wheat worldwide. Currently, the utilization of resistant cultivars is the most viable way to reduce yield losses. In this study, a panel of 188 wheat accessions from China was evaluated for stripe rust resistance, and genome-wide association studies were performed using high-quality Diversity Arrays Technology markers. According to the phenotype and genotype data, a total of 26 significant marker-trait associations were identified, representing 18 quantitative trait loci (QTLs) on chromosomes 1B, 2A, 2B, 3A, 3B, 5A, 5B, 6B, 7B, and 7D. Of the 18 QTLs, almost all were associated with adult plant resistance (APR) except QYr.nwsuaf-6B.2, which was associated with all-stage resistance (also known as seedling resistance). Three of the 18 QTLs were mapped far from previously identified Pst resistance genes and QTLs and were considered potentially new loci. The other 15 QTLs were mapped close to known resistance genes and QTLs. Subsequent haplotype analysis for QYr.nwsuaf-2A and QYr.nwsuaf-7B.3 revealed the degrees of resistance of the panel in the APR stage. In summary, the favorable alleles identified in this study may be useful in breeding for disease resistance to stripe rust.

Two cases report of febuxostat-induced acute liver injury: acute heart failure as a probable risk factor?

Drug induced liver injury, as a sub-type of hepatotoxicity, is rare but practical problem, producing challenges for clinicians. Within the recent two months, two patients with heart failure develop febuxostat-induced acute liver injury during hospital stay. To the best of our knowledge, very few cases of febuxostat-induced hepatotoxicity have been reported up to now. In this paper, two unusual cases of febuxostat-induced acute liver injury are herein described. The medical history, drug treatment, clinical symptoms, liver function tests, diagnosis and prognosis are fully given in this paper. It should be noticed that, two liver injury happen in patients of heart failure with reduced ejection fraction. Whether heart failure is a risk factor of febuxostat related liver injury, deserves further research. This paper reminds the clinicians that more attention should be paid to the acute liver injury caused by febuxostat, and liver function tests are suggested especially for patients of heart failure.

Potentially inappropriate medications among older patients with Parkinson's disease: a cross-sectional analysis of a national health insurance database in China.

BACKGROUND: With the rapid aging trend of China's population, the issue of drug rational use in older adults has become more and more prominent. Parkinson's disease (PD) is the one of the most common age-related neurodegenerative disorders. Pharmaceutical treatment plays a cardinal role in alleviating motor and non-motor symptoms to improve the quality of life of patients with PD. Patients with PD have complex medical needs yet little is known about the use of potentially inappropriate medications (PIM) among them in China. We quantify the prevalence of PIM use and identify its predictors among older persons with PD in China. METHODS: We conducted a cross-sectional analysis using a national representative database of all medical insurance beneficiaries across China, extracting records of ambulatory visits of older adults with PD between 2015 and 2017. Beneficiaries aged 65 and above were eligible for inclusion. The prevalence of patients exposed to overall PIMs and PIMs related to motor and cognitive impairment was calculated based on Beers Criteria 2015 version. Potential predictors of PIM concerning patients' characteristics were estimated using multivariate logistic regression. RESULTS: A total of 14,452 older adults with PD were included. In total, 8,356 (57.8%) patients received at least one PIM; 2,464 (17.1%) patients received at least one motor-impairing PIM and 6,201 (42.9%) patients received at least one cognition-impairing PIM. The prevalence of overall PIM use was higher in patients of older age group (54.7% [65-74] vs. 59.5% [75-84; OR, 1.22; 95% CI, 1.14-1.31] vs.65.5% [≥ 85; OR, 1.58; 95% CI, 1.38-1.80) and females (61.4% [female] vs. 55.0% [males; OR, 0.77; 95% CI, 0.72-0.82). CONCLUSIONS: Prescribing PIMs for older adults with PD was common in China, especially for females and older age groups, yet younger patients were more inclined to be prescribed with motor or cognition-impaired PIMs. Our findings represent a clear target awaiting multidimensional efforts to promote the rational prescribing of medications for this vulnerable population.

Inner Surface Morphology and Roughness Evolution of Pilgering Thick-Walled Tubes.

A hot-working die steel thick-walled tube Pilger rolling test was carried out using an LG40 Pilger mill, and the morphology and roughness evolution of the inner surface were examined using a white-light interferometer. The experimental results showed that micro-wrinkles formed on the basis of the original inner surface morphology, the altitude difference (Sz) between the peaks and valleys of the inner surface profile increased from 3.18 to 3.686 µm, and Sa increased from 0.722 to 0.892 µm in the diameter reduction zone. As the tube continued to feed into the wall thickness reduction zone, the micro-wrinkles gradually flattened, Sz and Sa were decreased to 1.625 and 0.174 respectively, and Sa maintained a slight fluctuation of 0.174~0.2 µm in the final sizing zone. From the diameters of the roller groove and taper of the mandrel, the three-dimensional strain of the tube in the wall thickness reduction zone was calculated, and the strain state of the tube in the complete deformation zone could be analyzed by finite element simulations. We found that in the diameter reduction zone, the inner surface was not supported by the mandrel and was free, while micro-wrinkles formed under circumferential compressive strain. In the wall thickness reduction zone, the deformation of the inner surface was controlled by the mandrel, and the micro-wrinkles were gradually flattened by radial compressive strain. The ratio of radial to circumferential strain was the key to flattening the micro-wrinkles, and when the ratio increased, the inner surface roughness (Sa) was reduced to 0.174 µm. In the sizing zone, the radial and circumferential strains were small, and the inner surface roughness showed no obvious fluctuation.

The 6-Month Antibody Durability of Heterologous Convidecia Plus CoronaVac and Homologous CoronaVac Immunizations in People Aged 18-59 Years and over 60 Years Based on Two Randomized Controlled Trials in China.

Previous reports have shown that heterologous boosting with the AD5-vectored COVID-19 vaccine Convidecia based on a primary series of two doses of inactivated vaccine induces increasing immune responses. However, the immune persistence until 6 months after the heterologous prime-boost immunization was limited. Participants were from two single-center, randomized, controlled, observer-blinded trials, which involved individuals of 18-59 years of age and over 60 years of age. Eligible participants who previously primed with one dose or two doses of CoronaVac were stratified and randomly assigned to inoculate a booster dose of Convidecia or CoronaVac. Neutralizing antibodies against a live SARS-CoV-2 prototype virus and Delta and Omicron (B.1.1.529) variants, pseudovirus neutralizing antibodies against Omicron BA.4/5 variants, and anti-SARS-CoV-2 RBD antibodies at month 6 were detected, and the fold decreases and rate difference were calculated by comparing the levels of antibodies at month 6 with the peak levels at month 1. The neutralizing antibody titers against prototype SARS-CoV-2, RBD-specific IgG antibodies, and the Delta variant in the heterologous regimen of the CoronaVac plus Convidecia groups were significantly higher than those of the homologous prime-boost groups. In three-dose regimen groups, the geometric mean titers (GMTs) of neutralizing antibodies against prototype SARS-CoV-2 were 30.6 (95% CI: 25.1; 37.2) in the heterologous boosting group versus 6.9 (95% CI: 5.6; 8.6) in the homologous boosting group (p < 0.001) at month 6 in participants aged 18-59 years, and in the two-dose regimen, the neutralizing antibody GMTs were 8.5 (95% CI: 6.2; 11.7) and 2.7 (2.3 to 3.1) (heterologous regimen group versus CoronaVac regimen group, p < 0.001). Participants aged over 60 years had similar levels of neutralizing antibodies against the prototype, with GMTs of 49.1 (38.0 to 63.6) in the group receiving two doses of CoronaVac plus one dose of Convidecia versus 9.4 (7.7 to 11.4) in the group receiving three doses of CoronaVac (p < 0.001) and 11.6 (8.4 to 16.0) in the group receiving one dose of CoronaVac and one dose of Convidecia versus 3.3 (2.7 to 4.0) in the group receiving two doses of CoronaVac (p < 0.001). Compared with day 14, over sixfold decreases in neutralizing antibody GMTs were observed in the heterologous groups of the three- or two-dose regimen groups of younger and elderly participants, while in the homologous regimen groups, the GMTs of neutralizing antibodies decreased about fivefold in the two age groups. The heterologous prime-boost regimen with two doses of CoronaVac and one dose of Convidecia was persistently more immunogenic than the regimen of the homologous prime-boost with three doses of CoronaVac.