Long-term efficacy of a recombinant hepatitis E vaccine in adults: 10-year results from a randomised, double-blind, placebo-controlled, phase 3 trial.

BACKGROUND: Hepatitis E virus (HEV) is a frequently overlooked causative agent of acute hepatitis. Evaluating the long-term durability of hepatitis E vaccine efficacy holds crucial importance. METHODS: This study was an extension to a randomised, double-blind, placebo-controlled, phase-3 clinical trial of the hepatitis E vaccine conducted in Dontai County, Jiangsu, China. Participants were recruited from 11 townships in Dongtai County. In the initial trial, a total of 112 604 healthy adults aged 16-65 years were enrolled, stratified according to age and sex, and randomly assigned in a 1:1 ratio to receive three doses of hepatitis E vaccine or placebo intramuscularly at month 0, month 1, and month 6. A sensitive hepatitis E surveillance system including 205 clinical sentinels, covering the entire study region, was established and maintained for 10 years after vaccination. The primary outcome was the per-protocol efficacy of hepatitis E virus vaccine to prevent confirmed hepatitis E occurring at least 30 days after administration of the third dose. Throughout the study, the participants, site investigators, and laboratory staff remained blinded to the treatment assignments. This study is registered with ClinicalTrials.gov (NCT01014845). FINDINGS: During the 10-year study period from Aug 22, 2007, to Oct 31, 2017, 90 people with hepatitis E were identified; 13 in the vaccine group (0·2 per 10 000 person-years) and 77 in the placebo group (1·4 per 10 000 person-years), corresponding to a vaccine efficacy of 83·1% (95% CI 69·4-91·4) in the modified intention-to-treat analysis and 86·6% (73·0 to 94·1) in the per-protocol analysis. In the subsets of participants assessed for immunogenicity persistence, of those who were seronegative at baseline and received three doses of hepatitis E vaccine, 254 (87·3%) of 291 vaccinees in Qindong at the 8·5-year mark and 1270 (73·0%) of 1740 vaccinees in Anfeng at the 7·5-year mark maintained detectable concentrations of antibodies. INTERPRETATION: Immunisation with this hepatitis E vaccine offers durable protection against hepatitis E for up to 10 years, with vaccine-induced antibodies against HEV persisting for at least 8·5 years. FUNDING: National Natural Science Foundation of China, Fujian Provincial Natural Science Foundation, Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences, and the Fundamental Research Funds for the Central Universities.

Urine is a viral antigen reservoir in hepatitis E virus infection.

BACKGROUND AND AIMS: HEV ORF2 antigen (Ag) in serum has become a tool for diagnosing current HEV infection. Particularly, urinary shedding of HEV Ag has been gaining increasing interest. We aim to uncover the origin, antigenicity, diagnostic performance, and diagnostic significance of Ag in urine in HEV infection. APPROACH AND RESULTS: Clinical serum and urine samples from patients with acute and chronic HEV infection were analyzed for their Ag levels. Ag in urine was analyzed by biochemical and proteomic approaches. The origin of urinary Ag and Ag kinetics during HEV infection was investigated in mouse and rabbit models, respectively. We found that both the Ag level and diagnostic sensitivity in urine were higher than in serum. Antigenic protein in urine was an E2s-like dimer spanning amino acids 453-606. pORF2 entered urine from serum in mice i.v. injected with pORF2. Ag in urine originated from the secreted form of pORF2 (ORF2 S ) that abundantly existed in hepatitis E patients' serum. HEV Ag was specifically taken up by renal cells and was disposed into urine, during which the level of Ag was concentrated >10-fold, resulting in the higher diagnosing sensitivity of urine Ag than serum Ag. Moreover, Ag in urine appeared 6 days earlier, lasted longer than viremia and antigenemia, and showed good concordance with fecal RNA in a rabbit model. CONCLUSIONS: Our findings demonstrated the origin and diagnostic value of urine Ag and provided insights into the disposal of exogenous protein of pathogens by the host kidney.

The presence and clinical significance of autoantibodies in amyotrophic lateral sclerosis: a narrative review.

Amyotrophic lateral sclerosis (ALS) is a debilitating and rapidly fatal neurodegenerative disease, which is characterized by the selective loss of the upper and lower motor neurons. The pathogenesis of ALS remains to be elucidated and has been connected to genetic, environmental and immune conditions. Evidence from clinical and experimental studies has suggested that the immune system played an important role in ALS pathophysiology. Autoantibodies are essential components of the immune system. Several autoantibodies directed at antigens associated with ALS pathogenesis have been identified in the serum and/or cerebrospinal fluid of ALS patients. The aim of this review is to summarize the presence and clinical significance of autoantibodies in ALS.

[Network Meta-analysis of different Chinese medicine injections combined with conventional western medicine in treatment of acute heart failure].

This study aims to evaluate the efficacy and safety of Chinese medicine injection in the treatment of acute heart failure. PubMed, Cochrane Library, EMbase, Web of Science, CNKI, VIP, Wanfang, and SinoMed were searched for the randomized controlled trial(RCT) of Chinese medicine injection combined with conventional western medicines in the treatment of acute heart failure with the time interval from the inception to July 10, 2023. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. Stata 15.1 was used to perform network Meta-analysis. A total of 117 RCTs were included, involving 10 529 patients and 7 Chinese medicine injections: Shenfu Injection, Shenmai Injection, Danhong Injection, Puera-rin Injection, Xinmailong Injection, Shengmai Injection, and Yiqi Fumai Injection. Network Meta-analysis yielded the following results.(1) In terms of improving the total response rate, the surface under the cumulative ranking curve(SUCRA) ranking was Shengmai Injection + conventional western medicine > Danhong Injection + conventional western medicine > Shenmai Injection + conventio-nal western medicine > Shenfu Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Puerarin Injection + conventional western medicine > conventional western medicine.(2)In terms of reducing brain natriuretic peptide(BNP), the SUCRA ranking was Danhong Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Puerarin Injection + conventional wes-tern medicine > Shengmai Injection + conventional western medicine > conventional western medicine.(3)In terms of reducing N-terminal pro-brain natriuretic peptide(NT-proBNP), the SUCRA ranking was Shenmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Puerarin Injection + conventional western medicine > Danhong Injection + conventional western medicine > conventional western medicine.(4) In terms of improving the left ventricular ejection fraction(LVEF), the SUCRA ranking was Shenmai Injection + conventional western medicine > Xinmailong Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > Puerarin Injection + conventional western medicine > Danhong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > conventional western medicine.(5) In terms of decreasing the left ventricular end-diastolic diameter(LVEDD), the SUCRA ranking was Shenmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine=Xinmailong Injection + conventional western medicine > Shengmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > conventional western medicine > Puerarin Injection + conventional western medicine.(6) In terms of increasing the 6-min walk trail(6MWT), the SUCRA ranking was Xinmailong Injection + conventional western medicine > Shenfu Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Yiqi Fumai Injection + conventional western medicine > conventional western medicine.(7) In terms of reducing the Minnesota heart failure quality of life scale(MLHFQ) scores, the SUCRA ranking was Xinmailong Injection + conventional western medicine > Shenmai Injection + conventional western medicine > Shenfu Injection + conventional western medicine > conventional western medicine.(8)In terms of safety, the group of Chinese medicine injection combined with conventional western medicine had lower incidence of adverse reactions than the control group. The current evidence shows that combining Chinese medicine injection with conventional western medicine treatment can improve the therapeutic effect on acute heart failure, with high safety. Due to the limited number and quality of included studies, the above conclusions need to be verified by more high-quality studies.

Global analysis of seed transcriptomes reveals a novel PLATZ regulator for seed size and weight control in soybean.

Seed size and weight are important factors that influence soybean yield. Combining the weighted gene co-expression network analysis (WGCNA) of 45 soybean accessions and gene dynamic changes in seeds at seven developmental stages, we identified candidate genes that may control the seed size/weight. Among these, a PLATZ-type regulator overlapping with 10 seed weight QTLs was further investigated. This zinc-finger transcriptional regulator, named as GmPLATZ, is required for the promotion of seed size and weight in soybean. The GmPLATZ may exert its functions through direct binding to the promoters and activation of the expression of cyclin genes and GmGA20OX for cell proliferation. Overexpression of the GmGA20OX enhanced seed size/weight in soybean. We further found that the GmPLATZ binds to a 32-bp sequence containing a core palindromic element AATGCGCATT. Spacing of the flanking sequences beyond the core element facilitated GmPLATZ binding. An elite haplotype Hap3 was also identified to have higher promoter activity and correlated with higher gene expression and higher seed weight. Orthologues of the GmPLATZ from rice and Arabidopsis play similar roles in seeds. Our study reveals a novel module of GmPLATZ-GmGA20OX/cyclins in regulating seed size and weight and provides valuable targets for breeding of crops with desirable agronomic traits.

Identification of new bisabosqual-type meroterpenoids reveals non-enzymatic conversion of bisabosquals into seco-bisabosquals.

Bisabosqual-type meroterpenoids are fungi-derived polyketide-terpenoid hybrids bearing a 2,3,3a,3a1,9,9a-hexahydro-1H-benzofuro[4,3,2-cde]chromene skeleton (6/6/6/5 ring system) or its seco-C-ring structure, and exhibit diverse bioactivities. Their unique structural architecture and impressive biological activities have led to considerable interest in discovering new analogues. However, to date, only nine analogues have been identified. Herein, we reported the isolation and identification of six new bisabosqual-type meroterpenoids stachybisbins C-H (1-6), together with one known compound bisabosqual C (7), from Stachybotrys bisbyi PYH05-7. Intriguingly, we found that 7, which contains the intact tetracyclic skeleton, can be non-enzymatically converted into its seco derivative stachybisbin I (8), unveiling the biosynthetic relationship between bisabosquals and seco-bisabosquals. Moreover, based on CRISPR/Cas9-mediated gene disruption, we revealed that the three-gene cluster responsible for the formation of LL-Z1272ß is associated with the biosynthesis of bisabosqual-type meroterpenoids, and then proposed a plausible route to 1-8.

Antibody preparation and age-dependent distribution of TLR8 in Bactrian camel spleens.

BACKGROUND: Toll-like receptor 8 (TLR8) can recognize specific pathogen-associated molecular patterns and exert multiple immunological functions through activation of signaling cascades. However, the precise distribution and age-related alterations of TLR8 in the spleens of Bactrian camels have not yet been investigated. This study aimed to prepare a rabbit anti-Bactrian camel TLR8 polyclonal antibody and elucidate the distribution of TLR8 in the spleens of Bactrian camels at different age groups. The methodology involved the construction of the pET-28a-TLR8 recombinant plasmid, followed by the expression of TLR8 recombinant protein via prokaryotic expression. Subsequently, rabbits were immunized with the purified protein to prepare the TLR8 polyclonal antibody. Finally, twelve Alashan Bactrian camels were categorized into four groups: young (1-2 years), pubertal (3-5 years), middle-aged (6-16 years) and old (17-20 years). These camels received intravenous sodium pentobarbital (20 mg/kg) anesthesia and were exsanguinated to collect spleen samples. Immunohistochemical techniques were employed to observe and analyze the distribution patterns and age-related changes of TLR8 in the spleen. RESULTS: The results showed that the TLR8 recombinant protein was expressed in the form of inclusion body with a molecular weight of 52 kDa, and the optimal induction condition involved 0.3 mmol/L IPTG induction for 8 h. The prepared antibody yielded a titer of 1:32 000, and the antibody demonstrated specific binding to TLR8 recombinant protein. TLR8 positive cells exhibited a consistent distribution pattern in the spleen across different age groups of Bactrian camels, primarily scattered within the periarterial lymphatic sheath of the white pulp, marginal zone, and red pulp. The predominant cell type expressing TLR8 was macrophages, with expression also observed in neutrophils and dendritic cells. Statistical analysis revealed that there were significant differences in the distribution density of TLR8 positive cells among different spleen regions at the same age, with the red pulp, marginal zone, and white pulp showing a descending order (P<0.05). Age-related changes indicated that the distribution density in the marginal zone and red pulp exhibited a similar trend of initially increasing and subsequently decreasing from young to old camels. As camels age, there was a significant decrease in the distribution density across all spleen regions (P<0.05). CONCLUSIONS: The results confirmed that this study successfully prepared a rabbit anti-Bactrian camel TLR8 polyclonal antibody with good specificity. TLR8 positive cells were predominantly located in the red pulp and marginal zone of the spleen, signifying their pivotal role in the innate immune response of the spleen. Aging was found to significantly reduce the density of TLR8 positive cells, while leaving their scattered distribution characteristics unaffected. These findings provide valuable support for further investigations into the immunomorphology and immunosenescence of the spleen in Bactrian camels.

Quantitative Review of Anesthesia in Liver Tumor Ablation: A Bibliometric Study from 1999 to 2022.

BACKGROUND Ablation has been developed as a radical surgical procedure for liver tumors. Local anesthesia in combination with general anesthesia or intravenous sedation is needed in ablative procedures. Although many studies have been published, a related bibliometric study is lacking. The present bibliometric analysis aimed to further understand the current situation of anesthesia for liver tumor ablation and discover candidate novel research directions. MATERIAL AND METHODS Web of Science Core Collection (WoSCC) was searched to identify studies associated with anesthesia for liver tumor ablation. Also, countries, journals, authors, and institutes contribution together with co-occurrence relations were analyzed by R, VOSviewer, and CiteSpace software; meanwhile, relevant research hotspots together with potential future trends were identified. RESULTS This work obtained 183 English-language documents during 1999-2022, and the annual growth rate was 8.83%. Most studies were conducted in the United States (24.04%, 44/183). The Oslo Univ Hosp contributed the most publications (n=11, 6.01%). Livraghi T (n=6), De Baere T (n=5), and Goldberg SN (n=4) ranked top in terms of cited authors and top authors. Keywords from that co-cited network were aggregated and identified, which revealed a shift in the liver tumor ablation anesthesia field. Initially, hotspots were predominantly "alcohol injection", "radiofrequency tissue ablation", and "metastases", but hotspots shifted to "efficacy", "ablation", "pain", "microwave ablation", "management", "analgesia", "safety", "irreversible electroporation", and "anesthesia" recently. CONCLUSIONS Anesthesia has received increased attention as liver tumor ablation advances. Bibliometric study findings provide insight into the current state and trends of anesthesia in liver tumor ablation research.

MsNRAMP2 Enhances Tolerance to Iron Excess Stress in Nicotiana tabacum and MsMYB Binds to Its Promoter.

Iron(Fe) is a trace metal element necessary for plant growth, but excess iron is harmful to plants. Natural resistance-associated macrophage proteins (NRAMPs) are important for divalent metal transport in plants. In this study, we isolated the MsNRAMP2 (MN_547960) gene from alfalfa, the perennial legume forage. The expression of MsNRAMP2 is specifically induced by iron excess. Overexpression of MsNRAMP2 conferred transgenic tobacco tolerance to iron excess, while it conferred yeast sensitivity to excess iron. Together with the MsNRAMP2 gene, MsMYB (MN_547959) expression is induced by excess iron. Y1H indicated that the MsMYB protein could bind to the "CTGTTG" cis element of the MsNRAMP2 promoter. The results indicated that MsNRAMP2 has a function in iron transport and its expression might be regulated by MsMYB. The excess iron tolerance ability enhancement of MsNRAMP2 may be involved in iron transport, sequestration, or redistribution.

Zinc-finger protein GmZF351 improves both salt and drought stress tolerance in soybean.

Abiotic stress is one of the most important factors reducing soybean yield. It is essential to identify regulatory factors contributing to stress responses. A previous study found that the tandem CCCH zinc-finger protein GmZF351 is an oil level regulator. In this study, we discovered that the GmZF351 gene is induced by stress and that the overexpression of GmZF351 confers stress tolerance to transgenic soybean. GmZF351 directly regulates the expression of GmCIPK9 and GmSnRK, leading to stomata closing, by binding to their promoter regions, which carry two CT(G/C)(T/A)AA elements. Stress induction of GmZF351 is mediated through reduction in the H3K27me3 level at the GmZF351 locus. Two JMJ30-demethylase-like genes, GmJMJ30-1 and GmJMJ30-2, are involved in this demethylation process. Overexpression of GmJMJ30-1/2 in transgenic hairy roots enhances GmZF351 expression mediated by histone demethylation and confers stress tolerance to soybean. Yield-related agronomic traits were evaluated in stable GmZF351-transgenic plants under mild drought stress conditions. Our study reveals a new mode of GmJMJ30-GmZF351 action in stress tolerance, in addition to that of GmZF351 in oil accumulation. Manipulation of the components in this pathway is expected to improve soybean traits and adaptation under unfavorable environments.

GmJAZ3 interacts with GmRR18a and GmMYC2a to regulate seed traits in soybean.

Seed weight is usually associated with seed size and is one of the important agronomic traits that determine yield. Understanding of seed weight control is limited, especially in soybean plants. Here we show that Glycine max JASMONATE-ZIM DOMAIN 3 (GmJAZ3), a gene identified through gene co-expression network analysis, regulates seed-related traits in soybean. Overexpression of GmJAZ3 promotes seed size/weight and other organ sizes in stable transgenic soybean plants likely by increasing cell proliferation. GmJAZ3 interacted with both G. max RESPONSE REGULATOR 18a (GmRR18a) and GmMYC2a to inhibit their transcriptional activation of cytokinin oxidase gene G. max CYTOKININ OXIDASE 3-4 (GmCKX3-4), which usually affects seed traits. Meanwhile, the GmRR18a binds to the promoter of GmMYC2a and activates GmMYC2a gene expression. In GmJAZ3-overexpressing soybean seeds, the protein contents were increased while the fatty acid contents were reduced compared to those in the control seeds, indicating that the GmJAZ3 affects seed size/weight and compositions. Natural variation in JAZ3 promoter region was further analyzed and Hap3 promoter correlates with higher promoter activity, higher gene expression and higher seed weight. The Hap3 promoter may be selected and fixed during soybean domestication. JAZ3 orthologs from other plants/crops may also control seed size and weight. Taken together, our study reveals a novel molecular module GmJAZ3-GmRR18a/GmMYC2a-GmCKXs for seed size and weight control, providing promising targets during soybean molecular breeding for better seed traits.

Genome-Wide Association Study of Partial Resistance to P. sojae in Wild Soybeans from Heilongjiang Province, China.

Phytophthora root rot (PRR) is a destructive disease of soybeans (Glycine max (L.) Merr) caused by Phytophthora sojae (P. sojae). The most effective way to prevent the disease is growing resistant or tolerant varieties. Partial resistance provides a more durable resistance against the pathogen compared to complete resistance. Wild soybean (Glycine soja Sieb. & Zucc.) seems to be an extraordinarily important gene pool for soybean improvement due to its high level of genetic variation. In this study, 242 wild soybean germplasms originating from different regions of Heilongjiang province were used to identify resistance genes to P. sojae race 1 using a genome-wide association study (GWAS). A total of nine significant SNPs were detected, repeatedly associated with P. sojae resistance and located on chromosomes 1, 10, 12, 15, 17, 19 and 20. Among them, seven favorable allelic variations associated with P. sojae resistance were evaluated by a t-test. Eight candidate genes were predicted to explore the mechanistic hypotheses of partial resistance, including Glysoja.19G051583, which encodes an LRR receptor-like serine/threonine protein kinase protein, Glysoja.19G051581, which encodes a receptor-like cytosolic serine/threonine protein kinase protein. These findings will provide additional insights into the genetic architecture of P. sojae resistance in a large sample of wild soybeans and P. sojae-resistant breeding through marker-assisted selection.

Cardiovascular disease in type 2 diabetes mellitus: progress toward personalized management.

Cardiovascular diseases (CVDs) are the main cause of death among patients with type 2 diabetes mellitus (T2DM), particularly in low- and middle-income countries. To effectively prevent the development of CVDs in T2DM, considerable effort has been made to explore novel preventive approaches, individualized glycemic control and cardiovascular risk management (strict blood pressure and lipid control), together with recently developed glucose-lowering agents and lipid-lowering drugs. This review mainly addresses the important issues affecting the choice of antidiabetic agents and lipid, blood pressure and antiplatelet treatments considering the cardiovascular status of the patient. Finally, we also discuss the changes in therapy principles underlying CVDs in T2DM.

FLAIR vascular hyperintensity predicts early neurological deterioration in patients with acute ischemic stroke receiving endovascular thrombectomy.

Fluid-attenuated inversion recovery vascular hyperintensity (FVH) is frequently observed in patients with acute ischemic stroke (AIS). FVH is associated with functional outcome at 3 months in AIS patients receiving endovascular thrombectomy. In the present study, we assessed whether FVH predicted early neurological deterioration (END) and hemorrhagic transformation (HT) within 72 h in AIS patients receiving endovascular thrombectomy. We retrospectively analyzed 104 patients with acute internal-carotid-artery or proximal middle-cerebral-artery occlusion within 16 h after symptom onset. Before thrombectomy, all patients underwent brain magnetic resonance imaging. END was defined as an increase of 4 points or more from baseline National Institutes of Health Stroke Scale (NIHSS) during 72 h following onset. HT was assessed by brain computed tomography. Statistical analyses were performed to predict END and HT. The proportion of high FVH score, high American Society of Intervention and Therapeutic Neuroradiology/Society of Interventional Radiology (ASITN/SIR) grade in non-END group was higher than that in END group (p < 0.001, p < 0.001, respectively). FVH score was positively correlated with ASITN/SIR grade (r = 0.461, p < 0.001). FVH score was a predictor factor for END (adjusted OR, 13.552; 95% CI, 2.408-76.260; p = 0.003), while FVH score was not a predictor factor for HT. Furthermore, NIHSS at admission (adjusted OR, 1.112; 95% CI, 1.006-1.228; p = 0.038) and high-density lipoprotein cholesterol (adjusted OR, 18.865; 95% CI, 2.998-118.683; p = 0.002) were predictor factors for HT. To assess FVH score before thrombectomy might be useful for predicting END in AIS patients receiving endovascular thrombectomy.

Viral neutralization by antibody-imposed physical disruption.

In adaptive immunity, organisms produce neutralizing antibodies (nAbs) to eliminate invading pathogens. Here, we explored whether viral neutralization could be attained through the physical disruption of a virus upon nAb binding. We report the neutralization mechanism of a potent nAb 8C11 against the hepatitis E virus (HEV), a nonenveloped positive-sense single-stranded RNA virus associated with abundant acute hepatitis. The 8C11 binding flanks the protrusion spike of the HEV viruslike particles (VLPs) and leads to tremendous physical collision between the antibody and the capsid, dissociating the VLPs into homodimer species within 2 h. Cryo-electron microscopy reconstruction of the dissociation intermediates at an earlier (15-min) stage revealed smeared protrusion spikes and a loss of icosahedral symmetry with the capsid core remaining unchanged. This structural disruption leads to the presence of only a few native HEV virions in the ultracentrifugation pellet and exposes the viral genome. Conceptually, we propose a strategy to raise collision-inducing nAbs against single spike moieties that feature in the context of the entire pathogen at positions where the neighboring space cannot afford to accommodate an antibody. This rationale may facilitate unique vaccine development and antimicrobial antibody design.

Mortality rates for hip fracture patients managed surgically and conservatively in a dedicated unit in Singapore.

INTRODUCTION: At our hospital, an unusually high proportion of patients and families opted for conservative management of hip fractures. This study aimed to compare the mortality rates of patients with hip fractures treated conservatively to that of operatively managed patients in a dedicated hip fracture unit. MATERIALS AND METHODS: Retrospective analysis was done for patients who were treated for hip fractures between January 2015 and October 2017 in a Hip Fracture Unit at a tertiary hospital. Patients were managed non-operatively or surgically after discussion with the multi-disciplinary team. RESULTS: 233 patients were treated conservatively and 781 underwent operative management for hip fractures. Patients managed non-operatively had a higher inpatient, 30-day and 1-year mortality rates. Inpatient mortality was 6.01% for conservatively managed compared to 0% for operative management. 30-day mortality for conservatively managed patients was 8.58% as compared to 0% for operatively managed patients, and 1-year mortality was 33.05% as opposed to 8.96%. There was an association seen with the type of management of hip fractures and that of inpatient death (p = 0.000), death in 30 days (p = 0.000) and death in 1 year (p = 0.000). The type of management was a predictive factor in 1-year mortality (p = 0.000). The average number of co-morbidities in conservatively managed patients was 5.2 compared to surgically managed patients of 4.0. Conservatively managed hip patients had a higher prevalence of stroke, chronic kidney disease and ischemic heart disease. Complications during hospital stay were comparable for both groups. The mean length of hospital stay was similar for both groups. CONCLUSION: Surgical intervention for hip fractures is associated with lower inpatient, 30-day and 1-year mortality rates. However, patient co-morbidities and pre-morbid conditions should also be considered. LEVEL OF EVIDENCE: IV.

[Value of nomogram based on the ultrasonographic features of prostatic calcification and varicocele and serological indicators in differential diagnosis of prostate cancer].

OBJECTIVE: To explore the diagnostic performance of the nomogram based on the transabdominal ultrasonographic features of prostatic calcification and varicocele (VC) and serological indicators in differentiating PCa with BPH from simple BPH. METHODS: This retrospective study included 108 cases of PCa with BPH and 317 cases of simple BPH, all pathologically confirmed after surgery from January 2014 to December 2021. Using t test or χ2/Fisher test, we compared the clinicopathologic data, transabdominal ultrasonographic features of prostatic calcification, VC severity and serological indicators between the two groups of patients. We identified the significant independent factors for differentiating PCa with BPH from simple BPH by multivariate logistic regression analysis and constructed a nomogram for visualizing the differential diagnostic performance. RESULTS: There were significant differences in the types and diameters of prostatic calcification, PSA density (PSAD), total PSA (tPSA), VC severity, and serum testosterone level between the two groups (P < 0.05). The types of calcification, PSAD and VC severity were identified as independent factors for differentiating PCa with BPH from simple BPH. Nomogram analysis of the above factors showed a good predicting performance, with an AUC of 0.805, a sensitivity of 83.28% and a specificity of 70.37%. CONCLUSION: Transabdominal ultrasonographic features and types of prostatic calcification, PSAD and VC severity are correlated with the development and progression of PCa. Nomogram analysis of the above factors contributes to the differentiation of PCa with BPH from simple BPH.

[Network Meta-analysis of six Chinese patent medicines for replenishing Qi and activating blood in treatment of chronic heart failure].

The efficacy of six commonly used Chinese patent medicines for replenishing Qi and activating blood in the treatment of chronic heart failure was evaluated systematically by network Meta-analysis. Randomized controlled trials(RCTs) about the treatment of chronic heart failure were searched against CNKI, Wanfang, SinoMed, PubMed, and Cochrane library. Network Meta-analysis was performed in Stata 16. A total of 154 RCTs involving 15 620 patients were eventually included. The network Meta-analysis showed that Qili Qiangxin Capsules+conventional western medicine had the highest total effective rate, followed by Tongxinluo Capsules+conventional western medicine, Qishen Yiqi Drop Pills+conventional western medicine, Naoxintong Capsules+conventional western medicine, Shexiang Tongxin Drop Pills+conventional western medicine, Yangxinshi Tablets+conventional western medicine, and conventional western medicine. As for left ventricular ejection fraction(LVEF), Yangxinshi Tablets+conventional western medicine had the highest value, followed by Shexiang Tongxin Drop Pills+conventional western medicine, Qili Qiangxin Capsules+conventional western medicine, Tongxinluo Capsules+conventional western medicine, Qishen Yiqi Drop Pills+conventional western medicine, Naoxintong Capsules+conventional western medicine, and conventional western treatments. As for N-terminal pro-B type natriuretic peptide(NT-proBNP), Qishen Yiqi Drop Pills+conventional western medicine was the most effective treatment, followed by Yangxinshi Tablets+conventional western medicine, Shexiang Tongxin Drop Pills+conventional western medicine, Qili Qiangxin Capsules+conventional western medicine, Tongxinluo Capsules+conventional western medicine, and conventional the most effective treatment was. As for left ventricular end-diastolic diameter(LVEDD), Naoxintong Capsules+conventional western medicine was the best therapy, followed by Tongxinluo Capsules+conventional western medicine, Shexiang Tongxin Drop Pills+conventional western medicine, Yangxinshi Tablets+conventional western medicine, Qili Qiangxin Capsules+conventional western medicine, Qishen Yiqi Drop Pills+conventional western medicine, and conventional western medicine. In summary, the combination of Chinese patent medicines for replenishing Qi and activating blood with western medicines is superior to conventional western medicine alone in the treatment of chronic heart failure. It effectively improves cardiac function indicators such as LVEF, NT-proBNP, and LVEDD, and thus is worthy of popularization in clinical practice. The results of this study provide evidence-based options for the clinical treatment of chronic cardiac failure by combining the Chinese patent medicines for replenishing Qi and activating blood with western medicine.

Clinical significance of stroke nurse in patients with acute ischemic stroke receiving intravenous thrombolysis.

BACKGROUND: Reports have proven that shorter door-to-needle time (DTN time) indicates better outcomes in AIS patients received intravenous thrombolysis. Efforts have been made by hospitals and centers to minimize DTN time in many ways including introducing a stroke nurse. However, there are few studies to discuss the specific effect of stroke nurse on patients' prognosis. This study aimed to compare consecutive AIS patients before and after the intervention to analyze the effect of stroke nurse on clinical outcome of AIS patients. METHODS: In this retrospective study, we observed 1003 patients from November 2016 to December 2020 dividing in two groups, collected and analyzed AIS patients' medical history, clinical assessment information, important timelines, 90 mRS score, etc. Comparative analysis and mediation analysis were also used in this study. RESULTS: A total of 418 patients was included in this study, and 199 patients were enrolled in the stroke nurse group and 219 was in the preintervention group. Baseline characteristics of patients showed no significant difference except there seems more patients with previous ischemic stroke history in the group of stroke nurse. (p = 0.008). The median DTN time significantly decreased in the stroke nurse group (25 min versus 36 min, p < 0.001) and multivariate logistic regression analysis showed the 90-day mRS clinical outcome significantly improved in the stroke nurse group (p = 0.001). Mediation analysis indicated the reduction of DTN time plays a partial role on the 90 days mRS score and the stroke nurse has some direct effect on the improvement of clinical outcome (p = 0.006). CONCLUSIONS: The introduction of stroke nurse is beneficial to clinical outcome of AIS patients and can be use of reference in other hospitals or centers.

Participation in a free medication program among non-registered permanent residents with severe mental disorders in Bao'an district, Shenzhen, China and its influencing factors.

BACKGROUND: In 2016, the government of Bao'an District, Shenzhen, China launched a free medication program for all non-registered permanent residents with severe mental disorders (SMD) within its jurisdiction, in efforts to reduce the relapse caused by intermittent medication or non-medication. Participation in the program has not been analyzed since its inauguration. This study aimed to evaluate the participation of non-registered permanent residents with SMD in the program from 2016 to 2020 and to explore its influencing factors. METHODS: This is a retrospective cross-sectional study of 3760 non-registered permanent residents with SMD in Bao'an District, Shenzhen, China (response rate: 78.64%). Data have been obtained from two sources: the Shenzhen Information System for Psychosis in 2020 and the free medication program's management files from 2016 to 2020. We employ descriptive statistics to analyze the participation rate of the free medication program among non-registered permanent patients. Logistic regression analysis is used to explore the factors affecting the patients' participation in the program. RESULTS: The participation rate of the free medication program among non-registered permanent patients has shown an upward trend, rising from 28.83% in 2016 to 58.32% in 2020. High participation rates have been registered among the following patient subgroups: those aged between 30 and 39 (63.11%), those with high school/technical secondary school (62.33%), those from rural areas (61.62%), those living in poverty (67.79%), those suffering schizoaffective disorder (72.26%), those having SMD for less than 5 years (59.89%), and those with family history of mental illness (71.23%).Logistics regression analysis shows that age, patient-guardian relationship, place of residence, financial condition, types of disease, duration of illness and family history are the main factors affecting the patients' decision to participate in the free medication program. CONCLUSION: The steadily increasing participation rate of the free medication program indicates that the program has been gradually accepted and recognized by non-registered permanent residents with SMD. However, nearly half of the patients have yet to join the program. To further raise the participation rate, special attention should be given to patients who are financially secure, aged below 20, without guardians, intellectually disabled or suffering SMD for over 5 years.