Effects of combined intervention of physical exercise and cognitive training on cognitive function in stroke survivors with vascular cognitive impairment: a randomized controlled trial.

OBJECTIVE:: This study evaluated the possible effect of the combined intervention of physical exercise and cognitive training on cognitive function in stroke survivals with vascular cognitive impairment. DESIGN:: A single-blind (investigator-blinded but not subject-blinded) randomized controlled trial. SETTING:: Medical Rehabilitation Center of Shanghai General Hospital, China. SUBJECTS:: A total of 225 patients (mean age 64.59 years, SD = 4.27) who exhibited vascular cognitive impairment were included in this study. INTERVENTIONS:: Patients were randomly allocated into one of the four groups: (1) physical exercise ( n = 56; 50-minute session), (2) cognitive training ( n = 57; 60-minute session), (3) combined intervention of physical exercise and cognitive training ( n = 55; 50-minute session + 60-minute session), or (4) control groups ( n = 57; 45-minute session). All participants received training for 36 sessions, three days per week, for 12 weeks. PRIMARY MEASURES:: Measures were recorded at baseline, after the intervention and at a six-month follow-up. Primary measurements included the Trail Making Part B, Stroop, forward digit span, and mental rotation tests. RESULTS:: A total of 179 participants (79.56% response rate) completed the study. Cognitive performances on all four tasks in the combined training group improved significantly after the intervention ( P < 0.01). Changes in cognitive performance were greater in the combined intervention group than those in the physical exercise group (e.g. forward digit span, 13.61% vs. 2.18%, P = 0.003), the cognitive training group (e.g. mental rotation, 17.36% vs. 0.87%, P = 0.002), and the control group (e.g. Stroop, -4.11% vs. -0.72%, P = 0.026). CONCLUSION:: The combined intervention produced greater benefits on cognitive function compared to either training alone in stroke survivors with vascular cognitive impairment.

Auxin enhances grafting success in Carya cathayensis (Chinese hickory).

MAIN CONCLUSION: Application of auxin to root stock and scion increases the success rate of grafting in Chinese hickory. The nuts of the Chinese hickory (Carya cathayensis) tree are considered both delicious and healthy. The popularity and high demand result is that the hickory nuts are of very high economical value for horticulture. This is particularly true for the Zhejiang province in eastern China where this tree is widely cultivated. However, there are several difficulties surrounding the hickory cultivation, such as for example long vegetative growth, tall trees, labour-intensive nut picking, and slow variety improvements. These complications form a great bottleneck in the expansion of the hickory industry. The development of an efficient grafting procedure could surpass at least some of these problems. In this study, we demonstrate that application of the auxin indole-3-acetic acid promotes the grafting process in hickory, whereas application of the auxin transport inhibitor 1-N-naphthylphthalamic acid inhibits the grafting process. Furthermore, we have identified hickory genes in the PIN, ABCB, and AUX/LAX-families known to encode influx and efflux carriers in the polar transport of auxin. We show that increased expression of several of these genes, such as CcPIN1b and CcLAX3, is correlating with successful grafting.

Low-Latency and Energy-Efficient Data Preservation Mechanism in Low-Duty-Cycle Sensor Networks.

Similar to traditional wireless sensor networks (WSN), the nodes only have limited memory and energy in low-duty-cycle sensor networks (LDC-WSN). However, different from WSN, the nodes in LDC-WSN often sleep most of their time to preserve their energies. The sleeping feature causes serious data transmission delay. However, each source node that has sensed data needs to quickly disseminate its data to other nodes in the network for redundant storage. Otherwise, data would be lost due to its source node possibly being destroyed by outer forces in a harsh environment. The quick dissemination requirement produces a contradiction with the sleeping delay in the network. How to quickly disseminate all the source data to all the nodes with limited memory in the network for effective preservation is a challenging issue. In this paper, a low-latency and energy-efficient data preservation mechanism in LDC-WSN is proposed. The mechanism is totally distributed. The data can be disseminated to the network with low latency by using a revised probabilistic broadcasting mechanism, and then stored by the nodes with LT (Luby Transform) codes, which are a famous rateless erasure code. After the process of data dissemination and storage completes, some nodes may die due to being destroyed by outer forces. If a mobile sink enters the network at any time and from any place to collect the data, it can recover all of the source data by visiting a small portion of survived nodes in the network. Theoretical analyses and simulation results show that our mechanism outperforms existing mechanisms in the performances of data dissemination delay and energy efficiency.

Correlation analysis between driver gene mutation and clinicopathological features in lung adenocarcinoma based on real-world cumulative clinical data.

Background: Driver genes are essential predictors of targeted therapeutic efficacy. Detecting driver gene mutations in lung adenocarcinoma (LUAD) patients can help to screen for targeted drugs and improve patient survival benefits. This study aims to investigate the mutation characterization of driver genes and their correlation with clinicopathological features in LUAD. Methods: A total of 440 LUAD patients were selected from Sir Run Run Shaw Hospital between July 2019 and September 2022. Postoperative tissue specimens were analyzed for gene mutations using next-generation sequencing technology, focusing, including epidermal growth factor receptor EGFR, ALK, ROS1, RET, KRAS, MET, BRAF, HER2, PIK3CA and NRAS. At the same time, clinicopathological data were collected and organized for multidimensional correlation analysis. Results: Of 440 LUAD patients, driver gene mutations were not detected in 48 patients. The proportion of patients with driver gene mutations was as high as 89.09%. The top three driver genetic mutations were EGFR, KRAS, and MET. Sixty-nine types of EGFR mutations were detected and distributed in the protein tyrosine kinase catalytic domain (56, 81.16%), Furin-like cysteine-rich region (9, 13.04%), receptor binding domain (3, 4.35%), and EGFR transmembrane domain (1, 1.45%). Single gene locus mutation occurred in 343 LUAD patients, but the mutation gene types covered all tested genes. Our findings showed that EGFR mutations were more commonly observed in non-smoking and female patients (P<0.01), KRAS mutations were more prevalent in male patients and smokers (P<0.01), ROS1 mutations had larger tumor diameters (P<0.01) and RET mutations were more prevalent in smokers (P<0.05). Conclusions: LUAD patients exhibit diverse genetic mutations, which may co-occur simultaneously. Integrated analysis of multiple mutations is essential for accurate diagnosis and effective treatment of the disease. The use of NGS can significantly expand our understanding of gene mutations and facilitate integrated analysis of multiple gene mutations, providing critical evidence for targeted treatment methods.

Immune-mediated diseases after vaccinations with AZD1222, BNT-162b2, &/or mRNA-1273: An observational investigation of 78 patients.

BACKGROUND: Immune-mediated diseases (IMDs) after nucleic acid-based vaccines have been sporadically reported since their introduction during the worldwide COVID-19 crisis. Confirming their cause-effect association remains challenging. We analysed the effects of AZD1222 (ChAdOx1 nCoV-19), BNT-162b2, and/or mRNA-1273 on the development &/or deterioration of IMDs in terms of the time of clinical onsets of IMDs after exposure to these vaccines. METHODS: We retrospectively reviewed 78 in-patients in Taipei Veterans General Hospital, who presented with IMDs within 120 days after receiving AZD1222, BNT-162b2, &/or mRNA-1273 vaccinations in Taiwan from May 2021 to April 2022. The duration from inoculation to development of IMD was analysed by two-tailed Kolmogorov-Smirnov (K-S) test for goodness of fit. RESULTS: The average time to new IMDs or flare-up of the diseases following vaccinations was 36 ± 26 days for all 91 events in these 78 patients. The onset time of IMDs after vaccinations was not haphazard as analysed by two-tailed K-S test for overall 91 events (40 new and 51 deteriorating episodes, p < 0.001). The IMDs presenting as non-connective tissue diseases (non-CTDs) have a shorter duration of incubation after vaccinations than those of CTDs (<14.7 days, 95 % confidence interval [CI], 3.0 to 26.4, p = 0.014). Furthermore, systemic vasculitis and type 2 inflammatory diseases were observed exclusively in those receiving AZD1222. CONCLUSION: AZD1222, BNT-162b2, or mRNA-1273 influence the activities of IMDs in ways yet to be explored. High index of suspicion to IMDs after nucleic acid-based vaccine inoculation against COVID-19 may be important for primary care physicians.

Anti-VEGF Therapy Possibly Extends Survival in Patients With Colorectal Brain Metastasis by Protecting Patients From Neurologic Disability.

BACKGROUND: Colorectal brain metastases (CBMs) are rare with poor prognosis. There is still no standard systemic treatment for multiple or unresectable CBM. our study aimed to explore the impact of anti-VEGF therapy on overall survival, brain-specific disease control, and neurologic symptom burden in patients with CBM. METHODS: A total of 65 patients with CBM under treatment were retrospectively enrolled and divided into anti-VEGF based systemic therapy or non-anti-VEGF based therapy. A total of 25 patients who received at least 3 cycles of anti-VEGF agent and 40 patients without anti-VEGF therapy were analyzed by endpoints of overall survival (OS), progression-free survival (PFS), intracranial PFS (iPFS) and neurogenic event-free survival (nEFS). Gene expression in paired primary metastatic colorectal cancer (mCRC), liver, lung and brain metastasis from NCBI data was analyzed using top Gene Ontology (GO) and cBioPortal. RESULTS: Patients who treated with anti-VEGF therapy had significantly longer OS (19.5 vs. 5.5 months, P = .009), iPFS (14.6 vs. 4.1 months, P < .001) and nEFS (17.6 vs. 4.4 months, P < .001). Patients who received anti-VEGF therapy beyond any disease progression presented with superior OS (19.7 vs. 9.4 months, P = .039). Top GO and cBioPortal analysis revealed a stronger molecular function of angiogenesis in intracranial metastasis. CONCLUSIONS: Anti-VEGF based systemic therapy showed favorable efficacy that was reflected in longer overall survival, iPFS and NEFS in patients with CBM.

Fostering Green Innovation Adoption through Green Dynamic Capability: The Moderating Role of Environmental Dynamism and Big Data Analytic Capability.

Though the concept of green dynamic capability has been increasingly gaining traction among academics, practitioners, and policymakers, its association with green innovation adoption remains unclear. The present study addresses this gap and aims to provide clarity by distinguishing green innovation adoption in the context of developing countries. Drawing on dynamic capability and stakeholder theory, this research shed light on the significance of green dynamic capability for green innovation adoption. Additionally, this study examines the moderating role of environmental dynamism and big data analytics capability in the link between green dynamic capability and green innovation adoption. Adopting a two-wave research design, the sample for this study contained SMEs from Pakistan and Malaysia. Data was obtained from 220 SMEs (105 from Pakistan, 115 from Malaysia). To test the hypotheses, covariance-based structural equation modelling was performed to analyze causal relationships in the model, by using AMOS 23 software. The results showed that green dynamic capability positively impacts green innovation adoption, but environmental dynamism does not positively moderate between green dynamic capability and green innovation adoption. In addition, big data analytics capability positively moderates between green dynamic capability and green innovation adoption. We believe that this study opens a new avenue in the environmental literature under which green innovation adoption is useful for SMEs.

Chyme Reinfusion Reducing the Postoperative Complications After Definitive Surgery for Small Intestinal Enteroatmospheric Fistula: A Cohort Study.

Purpose: This study is aimed to reveal the role of preoperative chyme reinfusion (CR) in reducing the complications occurring after definitive surgery (DS) for small intestinal enteroatmospheric fistula (EAF). Methods: In this study, from January 2012 to December 2019, the patients with small intestinal EAF and receiving a definitive surgery were recruited. Depending on whether the CR has been performed, these patients were divided into either the CR group or the non-CR group. Then, propensity scores matching (PSM) was used to further divide these patients into the PSM CR group or the PSM none-CR group. The clinical characteristics exhibited by the groups were analyzed, and the effect of preoperative CR was investigated. Result: A total of 159 patients were finally recruited with 72 patients in the CR group and 87 patients in the non-CR group. The postoperative complications were manifested in a total of 126 cases (79.3%). There were 49 cases in the CR group, and 77 cases in the non-CR group. CR was associated with the occurrence of postoperative complications (multivariate odds ratio [OR] = 0.289; 95% CI: 0.123-0.733; p = 0.006). After 1:1 PSM, there were 92 patients included. The postoperative complications were observed in 67 out of these 92 patients. There were 26 patients in the PSM CR group, and 41 patients in the PSM non-CR group. CR was associated with postoperative complications (multivariate OR = 0.161; 95% CI: 0.040-0.591; p = 0.002). In addition, CR played a role in reducing the recurrence of fistula both before (multivariate OR = 0.382; 95% CI: 0.174-0.839; p = 0.017) and after (multivariate OR = 0.223; 95% CI: 0.064-0.983; p = 0.034) PSM. In addition, there is a protective factor at play for those patients with postoperative ileus before (multivariate OR = 0.209; 95% CI: 0.095-0.437; p < 0.001) and after (multivariate OR = 0.222; 95% CI: 0.089-0.524; p < 0.001) PSM. However, the relationship between CR and incision-related complications was not observed in this study. Conclusion: Preoperative CR is effective in reducing postoperative complications after definitive surgery was performed for EAF.

Chyme reinfusion improved outcomes after definitive surgery for small-intestinal enteroatmospheric fistula in patients with enteral nutrition.

PURPOSE: In patients suffering from small-intestinal enteroatmospheric fistula who are receiving enteral nutrition (EN), although the function of the small intestine is sufficient, without chyme reinfusion (CR), disuse of the distal intestine of enteroatmospheric fistula may occur. However, CR reverses such pathological changes and have an influence on improving outcomes following definitive surgery (DS) for small-intestinal enteroatmospheric fistula. This study attempted to investigate the effect of preoperative CR in patients with EN on the outcomes after DS for small-intestinal enteroatmospheric fistula. METHODS: According to whether CR was performed between January 2012 and December 2019, patients receiving DS for small intestinal enteroatmospheric fistula were divided into the CR group and non-CR group. The effect of preoperative CR was then investigated. RESULTS: A total of 159 patients were finally enrolled, of which 72 patients were in the CR group and 87 patients were in the non-CR group. A total of 47 (29.56%) patients were found to have recurrent fistula after DS, the recurrent fistula rate in the CR group (multivariate odds ratio = 0.557; 95% CI, 0.351-0.842; P = 0.019) was lower. CR was also shown to promote postoperative recovery of bowel function (hazard ratio [HR] = 1.982; 95% CI, 1.199-3.275; P = 0.008), and shorten postoperative length of stay (LOS) (HR = 1.739; 95% CI, 1.233-2.453; P = 0.002). CONCLUSION: Preoperative CR may reduce the incidence of recurrent fistula, time to return of bowel function and postoperative LOS following DS for small-intestinal enteroatmospheric fistula.

SPRC Suppresses Experimental Periodontitis by Modulating Th17/Treg Imbalance.

Object: The aims of the study were to explore the protective effects of S-propargyl-cysteine (SPRC) on periodontitis and to determine the underlying mechanisms. Methods: A rat periodontitis model was constructed by injecting LPS and SPRC (0, 25, and 50 mg/kg/d) was administered intraperitoneally. H2S and CSE level were detected. The alveolar bone level was evaluated by micro-CT, HE staining and methylene blue staining analysis. Inflammation-related factors, Treg and Th17 cells were detected by immunohistochemistry, RT-PCR, immunofluorescence, Western blot and flow cytometry. Phosphorylation levels of ERK1/2 and CREB were analysed. Results: The administration of SPRC significantly increased the expression of CSE in the gingival tissue and the concentration of endogenous H2S in the peripheral blood. Simultaneously, SPRC significantly inhibited the resorption of alveolar bone based on the H&E staining, micro-CT and methylene blue staining analysis. Compared with the periodontitis group, the levels of IL-17A, IL-10 were downregulated and IL-6,TGF-ß1 were upregulated in the SPRC groups. In the SPRC group, the percentage of TH17 cells and the expression of ROR-γt were downregulated, while the percentage of Tregs and the expression of Foxp3 were upregulated accompanied with inhibition of phosphorylation ERK1/2 and CREB. Conclusion: SPRC can prevent the progression of periodontitis by regulating the Th17/Treg balance by inhibition of the ERK/CREB signalling pathway.

Testosterone and non-alcoholic fatty liver disease in men and women: A Mendelian randomization study / 中华内分泌代谢杂志

Objective:To investigate the causal association between testosterone and nonalcoholic fatty liver disease(NAFLD) in men and women using a two-sample Mendelian randomization(MR) approach.Methods:Genetic variation in testosterone(total testosterone, bioavailable testosterone) and sex hormone-binding globulin(SHBG) in females and males was used as an instrumental variable using the genome-wide association study(GWAS) pooled data, and the inverse variance weighting method was applied. Inverse variance weighted(IVW) was used as the main analytical method, along with six univariate MR methods based on other modeling assumptions to assess the causal relationship between testosterone(total testosterone, bioavailable testosterone) as well as SHBG and NAFLD in women and men. In addition, NAFLD data from Finnish Biobank(FinnGen) were applied to validate the results of the exploratory analysis. Further, sensitivity analyses were performed to assess the level of heterogeneity, genetic pleiotropy, and stability of the instrumental variables using Cochran′ s Q test, MR-Egger regression, and leave-one-out methods. Results:The results of exploratory analysis of IVW model showed that bioavailable testosterone and SHBG were causally associated with NAFLD in women, for each unit increase in bioavailable testosterone levels, the risk of developing non-alcoholic fatty liver disease(NAFLD) rose by 24%( OR=1.24, 95% CI 1.07-1.43, P=0.004); and with each unit decrease in women′s SHBG, the NAFLD risk increased by 31%( OR=0.69, 95% CI 0.57-0.83, P<0.001). However, testosterone(total testosterone, bioavailable testosterone) as well as SHBG in men and female total testosterone did not show a causal relationship with NAFLD. The results of the other six MR methods were generally consistent with the IVW method. The results of the external validation data provided further evidence of a causal relationship between female bioavailable testosterone and SHBG and NAFLD. Conclusion:Elevated levels of bioavailable testosterone along lower levels of SHBG may increase the risk of developing NAFLD in women.

Effects of Zhuyu Pill （茱萸丸） and its Ingredient on Aortic Plaque and the NLRP3/Asc/Caspase-1 Signaling Pathway in Aortic Tissue of Mice in Atherosclerosis Model / 中医杂志

ObjectiveTo investigate the possible mechanism of action and combination of medicinals of Zhuyu Pill （茱萸丸） in the treatment of atherosclerosis. MethodsThirteen normal C57BL/6J mice were used as blank group， and 40 ApoE-/- mice of the same strain were randomly divided into model group， Huanglian （Coptis chinensis Franch.） group， Wuzhuyu （Tetradium ruticarpum） group， and Zhuyu Pill group， with 10 mice in each group. Except the blank group， the other groups were fed with high-fat diet for modeling， and the total modeling cycle was 12 weeks. After modelling， Huanglian group was given Huanglian solution 143.34 mg/（kg·d）， Wuzhuyu group with Wuzhuyu solution 301.78 mg/（kg·d）， Zhuyu Pill group with 261.07 mg/（kg·d） of Zhuyu Pill solution， blank group and model group were given 0.3ml of normal saline. Mice in all groups were gavaged for 12 weeks. The levels of total cholesterol （TC）， triglyceride （TG）， low density lipoprotein cholesterol （LDL-C） and fasting blood glucose were measured by biochemical method； fasting insulin in serum was detected by enzyme-linked immunosorbent assay （ELISA） and insulin resistance index was calculated； HE staining was used to observe the pathological and morphological changes of aortic tissue， liver and epididymal fat in mice， and oil red O staining was used to observe the lipid deposition of aortic tissue in mice， and the percentage of positive area of aortic HE staining， the percentage of positive area of aortic oil red O staining， the non-alcoholic fatty liver activity score （NAS） score， and the cross-sectional area of epididymal fat were calculated； serum levels of interleukin 1β （IL-1β） and interleukin 18 （IL-18） were detected by ELISA； protein expression of nucleotide-binding oligomerisation structural domain-like receptor family pyridoxal structural domain protein 3 （NLRP3） in aortic tissues was detected by Western blot； and immunofluorescence was used to detect the levels of apoptosis-associated granulocyte-like protein （ASC）， which contains the CARD structural domain （ASC） and cysteine-containing aspartic protease 1 （Caspase-1） protein expression； and real-time fluorescence PCR was used to detect NLRP3， ASC， Caspase-1， IL-1β， and IL-18 mRNA expression in mouse aortic tissues. ResultsCompared with blank group， serum TC， TG and LDL-C were increased， insulin was decreased， fasting blood glucose and insulin resistance index were increased in model group （P＜0.01）. Aortic plaque area increased， liver lipid deposition increased， epididymal fat cells volume increased， liver NAS score increased， and epididymal fat cross-sectional area increased. Serum IL-1β and IL-18 increased， and the expression levels of NLRP3， ASC， Caspase-1 protein and mRNA in aortic tissue increased （P＜0.01）. Compared with model group， serum TC， TG and LDL-C in Huanglian group， Wuzhuyu group and Zhuyu Pill group decreased， fasting insulin increased， fasting blood glucose and insulin resistance index decreased （P＜0.01）； aortic plaque area decreased significantly， liver lipid deposition decreased， liver NAS score decreased， epididymal fat cell volume decreased， epididymal fat cross section area decreased， serum IL-1β and IL-18 were decreased， the expression levels of NLRP3， ASC， Caspase-1 protein and mRNA in aortic tissue were decreased （P＜0.01）， and the improvement of all indexes in the Zhuyu Pill group was better than that in Huanglian and Wuzhuyu groups （P＜0.01）. ConclusionZhuyu Pill has a good therapeutic effect on atherosclerosis in mice， and the combination of Huanglian and Wuzhuyu has a synergistic effect， the mechanism of which may be related to regulation of the NLRP3/ASC/Caspase-1 aortic signaling pathway， and thus reducing the vascular inflammatory response.

Treating Chronic Urticaria with the Method of Dredging Sanjiao （三焦） / 中医杂志

The membranous tube of sanjiao （三焦） is not only the path of the transport of fluid and qi， but the way of the invasion of pathogenic factors， therefore， it cooperates with the skin mucous membrane physically and influence on each other pathologically. It is believed that the core pathogenesis of chronic urticaria is pathogens intruding sanjiao， membrane collaterals acute spasm， and fluid and qi disturbance， of which defense qi insufficiency and pathogens intruding sanjiao initiates the disease， while struggle between healthy and pathogenic qi and membrane collaterals acute spasm is the intermediate stage， and disturbed fluid， qi and blood movement is the terminal stage. Following the core treatment principle of dredging sanjiao， the internal treatment is to open striae and interstices and dispel pathogens out using self-made Guben Shufeng Decoction（固本疏风汤）modifications， and the external treatment is to dredge and regulate membrane collaterals， move qi and fluid， and treat sanjiao simultaneously， commonly using cutting therapy on Danzhong （RN 17） to move qi and fluid， seal umbilical therapy on Shenque （RN 8） to supplement and nourish ying-wei （营卫）， and natural moxibustion on Xuehai （SP 10） to move blood and unblock collaterals.

Study on the correlation between cystatin C,microglobulin and ischemic cerebral small vessel disease / 中国现代医生

@#Objective To explore the the correlation between cystatin C(Cys C),beta-2 microglobulin(β2-MG)and ischemic cerebral small vessel disease(CSVD)and its subgroups.Methods Totally 234 patients with CSVD were assigned to the study group,and 92 elderly people with no abnormal findings in head MRI were selected as controls.The CSVD patients were further divided into the subgroups of lacunar infarction(LI),white matter lesion(WML)and LI+WML.Each group was compared risk factors include the blood level of Cys C and β2-MG.Results There were statistically significant differences between CSVD group and control group in cystatin C(Cys C)and β2-MG(P<0.05).Cystatin C(Cys C)and β2-MG there were statistically significant differences between WML group and control group(P<0.05),and also between WML+LI group and control group(P<0.05).Logistic regression analysis and comparison across subgroups showed Cys C and β2-MG to be the common risk factors for WML group and WML+LI group inpatients with ischemic cerebral small vessel disease.Conclusion Cys C and β2-MG are the common risk factors for WML group and WML+LI group inpatients with ischemic cerebral small vessel disease.The risk factors vary across different CSVD subgroups.

Evaluation of chemiluminescence immunoassay kit for detection of hepatitis D virus IgG antibody / 中华检验医学杂志

Objective:This study evaluates the performance of chemiluminescence assay, which is designed to detect Hepatitis D Virus (HDV) Immunoglobulin G (IgG) antibodies.Methods:A comparative analysis was conducted among chemiluminescence anti-HDV IgG reagent, the magnetic particle-based domestic reagent A and domestic reagent B, and the Robo Gene HDV RNA kit, using 1909 HBsAg-positive plasma samples. This comparison aimed to delineate clinical specificity and detection accuracy. The anti-HDV IgG reagent precision was assessed at three different concentration levels following the Clinical Laboratory Standards Institute EP5-A2 guidelines. The specificity of the assay was validated using 200 HAV IgM positive, 545 HBsAg-positive but anti-HDV IgG-negative, 350 anti HCV positive plasma samples and 200 healthy human blood samples. Additionally, a concordance study was conducted with 545 HBsAg-positive and 37 anti-HDV IgG-positive plasma samples, comparing the anti-HDV IgG reagent against reagent A.Results:1 909 HBsAg-positive plasma samples were tested using 3 anti HDV IgG reagent and 1 HDV RNA reagent, 19 samples were identified as anti-HDV IgG-positive. The anti-HDV IgG demonstrated superior accuracy and specificity. The assay exhibited excellent precision, with intra-assay coefficient of variation (CV) values ranging from 1.57% to 4.30%, and inter-assay CV values between 1.71% and 4.67% for detecting samples at high, medium, and low concentration levels. Concordance with Reagent A showed consistent results in both positive and negative detections.Conclusion:In this study, the anti-HDV IgG reagent (chemiluminescence method) displayed outstanding specificity in detecting clinical samples and exhibited a high conformity rate with commercialized reagents, making it potentially suitable for screening anti-HDV IgG in HBsAg-positive samples.

Assessment and preliminary clinical application of a domestic nucleic acid detection reagent for hepatitis D virus / 中华检验医学杂志

Objective:This study aims to evaluate the quality and explore the preliminary clinical applications of a domestically developed hepatitis D virus nucleic acid quantification reagent (abbreviated as"domestic HDV RNA reagent").Methods:The sensitivity and accuracy of the reagent were evaluated in accordance with the WHO HDV RNA international standard, employing the Bio-Rad CFX Opus 96 real-time fluorescence quantitative PCR analysis system. Serial dilutions of pseudo-viruses or cell culture-derived virus were used to determine the linear range of the domestic HDV RNA reagent. Specificity was assessed using positive samples of HAV, HBV, HCV infection, and HEV national reference materials. Precision was evaluated with samples at both high and low concentrations. In a comparative analysis, 30 HDV IgG positive samples were tested using both the domestic HDV RNA reagent and the RoboGene HDV RNA kit based on the ABI 7500 FAST DX system. The Pearson correlation coefficient (r) was used to examine the correlation between the two reagents.Results:The domestic HDV RNA reagent demonstrated a high sensitivity of up to 6 IU/ml, consistent with that of the comparator reagent. The calibration curve for WHO HDV RNA standards had a slope of -3.286, with an amplification efficiency of 101.6%. The linear detection range spanned from 10 to 10 8 IU/ml for eight HDV genotypes. The domestic HDV RNA reagent exhibited exceptional specificity, without cross-reactivity observed with HAV, HBV, HCV, or HEV. Accuracy assessments at five concentration levels met the required standards, with intra-assay precision coefficient of variation ( CV) ranging from 1.20% to 4.20%, and inter-assay precision CV from 1.20% to 7.90%. The detection results for HDV IgG positive samples were highly correlated with the comparator reagent ( r=0.984, P<0.001), achieving a diagnostic accuracy of 100% compared to sequencing results. Conclusion:In this study, the domestic HDV RNA reagent possesses excellent specificity, accuracy, precision, and a broad linear range, attaining a sensitivity level on par with international reagents of the same type.

Application of plasma SARS-CoV-2 quantitative antigen detection in the diagnosis and treatment of COVID-19 / 中华预防医学杂志

The corona virus disease 2019(COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), has created an urgent need of scientific and effective biomarkers for the purpose of prevention and control. Currently, commonly employed viral nucleic acids, antibodies, and rapid antigen test detection technologies all exhibit a range of limitations, including restricted applicability, inadequate sensitivity and specificity. Plasma SARS-CoV-2 quantitative antigen, as an emerging biomarker, has garnered significant attention due to its potential clinical value in the diagnosis and management of COVID-19. This article comprehensively analyzes the principles and clinical applications of quantitative detection technology for plasma SARS-CoV-2 antigen. Additionally, it explores the challenges encountered in this field and provides insights into future prospects.

Application of plasma SARS-CoV-2 quantitative antigen detection in the diagnosis and treatment of COVID-19 / 中华预防医学杂志

The corona virus disease 2019(COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), has created an urgent need of scientific and effective biomarkers for the purpose of prevention and control. Currently, commonly employed viral nucleic acids, antibodies, and rapid antigen test detection technologies all exhibit a range of limitations, including restricted applicability, inadequate sensitivity and specificity. Plasma SARS-CoV-2 quantitative antigen, as an emerging biomarker, has garnered significant attention due to its potential clinical value in the diagnosis and management of COVID-19. This article comprehensively analyzes the principles and clinical applications of quantitative detection technology for plasma SARS-CoV-2 antigen. Additionally, it explores the challenges encountered in this field and provides insights into future prospects.

Analysis of morphometric changes in the anterior alveolar bone in bimaxillary protrusion adult patients after retraction with cone-beam CT / 中华口腔医学杂志

Objective: To measure and analyze the morphometric changes in the anterior alveolar bone during treatment and retention stage after retraction in bimaxillary adults using cone-beam CT(CBCT). Methods: Fifteen adult patients, four males and 11 females, aged 19 to 28 years[(22.2±3.1) years], who have completed orthodontic treatment and extracted four first premolar teeth for retraction in the Department of Orthodontics, The Affiliated Stomatological Hospital of Nanchang University from January 2016 to December 2018 were selected. CBCT was taken to assess the labial and palatal vertical bone level, total bone thickness at crest area, middle root area and apical area in pre-treatment (T1), post-treatment (T2) and at follow-up (maintained for more than two years) (T3). The differences in alveolar bone morphology at different stages were compared by single factor repeated measure ANOVA, and Pearson correlation analysis was performed on the amount of alveolar bone change in treatment stage and retention stage. Results: There were statistically significant differences in the alveolar bone height of the palatal side of maxillary anterior teeth, the labial side of maxillary lateral incisors and canine among three time points (P<0.05). The height difference of palatal alveolar bone of anterior teeth in T1-T2 stage was statistically significant (P<0.05). Palatal alveolar bone of upper and lower central incisors decreased by (1.52±0.32) and (4.96±0.46) mm, respectively. The height difference of anterior palatal alveolar bone was statistically significant in T2-T3 stage(P<0.05), the palatal alveolar bone height of central incisors increased by (1.20±0.27) and (3.14±0.35) mm respectively. The height difference of palatal alveolar bone in the anterior teeth of T1-T3 stage was statistically significant (P<0.05), and the height of palatal alveolar bone of central incisors was decreased (0.33±0.11) and (1.82±0.39) mm, respectively. There were statistically significant differences in the thickness of the cervical and middle root alveolar bone of anterior teeth among three time points (P<0.05). The difference of alveolar bone thickness of the cervical and middle root of anterior teeth at T1-T2 was statistically significant (P<0.05). decreased by (0.63±0.10) and (0.67±0.09) mm in lateral incisors, respectively. In the T2-T3 stage, the alveolar bone thickness of the crest area of the lower anterior teeth was significantly different (P<0.05), the alveolar bone thickness of mandibular central incisor crest area increased (0.09±0.03) mm. There were statistically significant differences in alveolar bone thickness in crest area and middle root of the incisors during T1-T3 stage (P<0.05), among which the middle root decreased by (0.38±0.16) mm and (0.63±0.13) mm, respectively. There was no statistically significant difference in other areas (P>0.05). The change of alveolar bone height in palatal side of upper anterior teeth at T2-T3 was very strongly negatively correlated with the change in T1-T2. The change of alveolar bone height in labial side of upper anterior teeth and lingual side of lower anterior teeth and the thickness of incisor root and neck were moderately strongly negatively correlated (r≤-0.8, P<0.001), the change of alveolar bone height in labial side of upper anterior teeth and lingual side of lower anterior teeth and the thickness of incisor crest area were moderately strongly negatively correlated (-0.8<r≤-0.4, P<0.05). Conclusions: For adult patients after retraction, anterior alveolar bone decreased significantly. In the retention stage, the same degree of bone apposition will occur, but still have alveolar bone loss compared with pre-treatment. The amount of alveolar bone change in the retention stage correlated with the amount of alveolar bone change in the treatment stage.

Progress and challenges in RET-targeted cancer therapy / 医学前沿

The rearranged during transfection (RET) is a receptor protein tyrosine kinase. Oncogenic RET fusions or mutations are found most often in non-small cell lung cancer (NSCLC) and in thyroid cancer, but also increasingly in various types of cancers at low rates. In the last few years, two potent and selective RET protein tyrosine kinase inhibitors (TKIs), pralsetinib (BLU-667) and selpercatinib (LOXO-292, LY3527723) were developed and received regulatory approval. Although pralsetinib and selpercatinib gave high overall response rates (ORRs), < 10% of patients achieved a complete response (CR). The RET TKI-tolerated residual tumors inevitably develop resistance by secondary target mutations, acquired alternative oncogenes, or MET amplification. RET G810 mutations located at the kinase solvent front site were identified as the major on-target mechanism of acquired resistance to both selpercatinib and pralsetinib. Several next-generation of RET TKIs capable of inhibiting the selpercatinib/pralsetinib-resistant RET mutants have progressed to clinical trials. However, it is likely that new TKI-adapted RET mutations will emerge to cause resistance to these next-generation of RET TKIs. Solving the problem requires a better understanding of the multiple mechanisms that support the RET TKI-tolerated persisters to identify a converging point of vulnerability to devise an effective co-treatment to eliminate the residual tumors.