List prices and clinical value of anticancer drugs in China, Japan, and South Korea: a retrospective comparative study.

Background: High prices of anticancer drugs have raised concerns due to their financial impact on patients and healthcare systems. This study aimed to assess the initial and latest list prices and clinical value of reimbursed anticancer drugs in China, Japan, and South Korea. Methods: We identified anticancer drugs newly approved by the National Medical Products Administration of China from January 2012 to June 2022, and by the Pharmaceuticals and Medical Devices Agency of Japan and the Ministry of Food and Drug Safety of South Korea up until June 2022. We compared initial and latest treatment prices between countries and assessed clinical value using patients' survival, quality of life (QoL), and European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS). We calculated Spearman rank correlation coefficients of treatment prices with clinical value for individual countries and employed regression analyses to investigate whether the relationship between prices and clinical value was modified by the country setting. Findings: Our cohort included 91 anticancer drug indications, with 60 listed for reimbursement in China, 91 in Japan, and 87 in South Korea. Median treatment prices were highest in Japan, followed by South Korea, and lowest in China, both for initial prices (US$64082 vs. US$45529 vs. US$19144, p < 0.0001) and latest prices (US$50859 vs. US$31611 vs. US$18666, p < 0.0001). Over time, China (ß = -0.047, p < 0.0001) and South Korea (ß = -0.049, p < 0.0001) witnessed more significant price reductions compared to Japan (ß = -0.013, p = 0.011). The correlations between both initial and latest treatment prices and clinical value (QoL and ESMO-MCBS) were more significant and stronger in China and South Korea than in Japan, although Japan exhibited slightly stronger correlations in terms of survival compared to China and South Korea. The relationship between clinical value and treatment prices may not be modified by the country setting. Interpretation: In comparison, South Korea's list prices and their correlations with clinical value appear reasonable. Policymakers in Japan could enhance efficiency by controlling prices and aligning them with clinical value, while China would need to take substantial steps to expand anticancer drug coverage. Funding: National Natural Science Foundation of China (72374149 and 72074163), and China Center for South Asian Studies, Sichuan University.

Joint effects of green space and air pollutant exposure on preterm birth: evidence from a nationwide study in China.

An association between green space exposure and preterm birth has been reported. However, evidence on the joint effects of air pollutant and green space exposure on preterm birth from nationwide research is limited in China. Based on a nationwide cohort, this study aims to explore the effect of green space exposure on preterm birth and analyze the joint effects of green space and air pollutant. Logistic regression models were developed to analyze the effects of green space exposure, and interaction effects were evaluated by adding interaction terms between green space and air pollutants. From 2013 to 2019, this study included 2,294,188 records of newborn births, of which 82,921 were preterm births. The results show that for buffer zones with 250 m, 500 m, 1000 m, and 1500 m, every 0.1 unit increase in NDVI exposure was associated with a decrease in the risk of preterm birth by 5.5% (95% CI: 4.6-6.4%), 5.8% (95% CI: 4.9-6.6%), 6.1% (95% CI: 5.3-7.0%), and 5.6% (95% CI: 4.7-6.5%), respectively. Under high-level exposure to air pollutants, high-level NDVI exposure was more strongly negatively correlated with preterm birth than low-level NDVI exposure. High-level green space exposure might mitigate the adverse effect of air pollutants on preterm birth by promoting physical activity, reducing stress, and adsorbing pollutants. Further investigation is needed to explore how green space and air pollution interact and affect preterm birth, in order to improve risk management and provide a reference for newborn health.

Risk factors for treatment-related bone loss and osteoporosis in patients with follicular lymphoma.

The survival rate of non-Hodgkin lymphoma (NHL) has steadily improved. However, osteoporosis introduced by treatment is prevalent and associated with increased mortality and disability for patients with NHL. We aimed to investigate factors impacting bone mineral density (BMD) reduction and osteoporosis, and the trend of BMD after chemotherapy. Overall, 97 newly diagnosed patients with follicular lymphoma (FL) were retrospectively enrolled. CT attenuation values were measured to assess BMD levels. Although 73.2% of patients received calcium and vitamin D supplements, 44.3% showed significant BMD reduction, and baseline BMD and hemoglobin levels were the risk factors. 26.6% of patients newly developed osteoporosis post-chemotherapy where age and cumulative dose of glucocorticoid were risk factors. The results of 20 patients with consecutive follow-up showed that BMD continued to decline for 6 months post-chemotherapy and did not return to baseline values. Therefore, BMD evaluation and more positive anti-resorption treatments should be administered for high-risk patients.

A whole-slide foundation model for digital pathology from real-world data.

Digital pathology poses unique computational challenges, as a standard gigapixel slide may comprise tens of thousands of image tiles1-3. Prior models have often resorted to subsampling a small portion of tiles for each slide, thus missing the important slide-level context4. Here we present Prov-GigaPath, a whole-slide pathology foundation model pretrained on 1.3 billion 256 × 256 pathology image tiles in 171,189 whole slides from Providence, a large US health network comprising 28 cancer centres. The slides originated from more than 30,000 patients covering 31 major tissue types. To pretrain Prov-GigaPath, we propose GigaPath, a novel vision transformer architecture for pretraining gigapixel pathology slides. To scale GigaPath for slide-level learning with tens of thousands of image tiles, GigaPath adapts the newly developed LongNet5 method to digital pathology. To evaluate Prov-GigaPath, we construct a digital pathology benchmark comprising 9 cancer subtyping tasks and 17 pathomics tasks, using both Providence and TCGA data6. With large-scale pretraining and ultra-large-context modelling, Prov-GigaPath attains state-of-the-art performance on 25 out of 26 tasks, with significant improvement over the second-best method on 18 tasks. We further demonstrate the potential of Prov-GigaPath on vision-language pretraining for pathology7,8 by incorporating the pathology reports. In sum, Prov-GigaPath is an open-weight foundation model that achieves state-of-the-art performance on various digital pathology tasks, demonstrating the importance of real-world data and whole-slide modelling.

[Effect of Intelligent Health Education Based on Health Belief Model on Patients With Kinesophobia After Surgical Treatment of Cervical Spondylosis]. / åŸºäºŽå¥åº·ä¿¡å¿µæ¨¡å¼çš„æ™ºèƒ½å¥åº·æ•™è‚²åœ¨é¢ˆæ¤Žç— æœ¯åŽæåŠ¨ç—‡æ‚£è€ ä¸­çš„æ•ˆæžœç ”ç©¶.

Objective: To explore the application effect of intelligent health education based on the health belief model on patients with postoperative kinesophobia after surgical treatment of cervical spondylosis. Methods: A prospective cohort study was conducted with patients who underwent anterior cervical discectomy, decompression, and fusion surgery with a single central nerve and spine center, and who had postoperative kinesophobia, ie, fear of movement. The patients made voluntary decisions concerning whether they would receive the intervention of intelligent health education. The patients were divided into a control group and an intelligent education group and the intervention started on the second day after the surgery. The intelligent education group received intelligent education starting from the second day after surgery through a WeChat widget that used the health belief model as the theoretical framework. The intelligent health education program was designed according to the concept of patient problems, needs, guidance, practice, and feedbacks. It incorporated four modules, including knowledge, intelligent exercise, overcoming obstacles, and sharing and interaction. It had such functions as reminders, fun exercise, shadowing exercise, monitoring, and documentation. Health education for the control group also started on the second day after surgery and was conducted by a method of brochures of pictures and text and WeChat group reminder messages. The participants were surveyed before discharge and 3 months after their surgery. The primary outcome measure compared between the two groups was the degree of kinesophobia. Secondary outcome measures included differences in adherence to functional exercise (Functional Exercise Adherence Scale), pain level (Visual Analogue Scale score), degree of cervical functional impairment (Cervical Disability Index), and quality of life (primarily assessed by the Quality of Life Short Form 12 [SF-12] scale for psychological and physiological health scores). Results: A total of 112 patients were enrolled and 108 patients completed follow-up. Eventually, there were 53 cases in the intelligent education group and 55 cases in the control group. None of the patients experienced any sports-related injuries. There was no statistically significant difference in the primary and secondary outcome measures between the two groups at the time of discharge. At the 3-month follow-up after the surgery, the level of kinesophobia in the intelligent education group (25.72±3.90) was lower than that in the control group (29.67±6.16), and the difference between the two groups was statistically significant (P<0.05). In the intelligent education group, the degree of pain (expressed in the median [25th percentile, 75th percentile]) was lower than that of the control group (0 [0, 0] vs. 1 [1, 2], P<0.05), the functional exercise adherence was better than that of the control group (63.87±7.26 vs. 57.73±8.07, P<0.05), the psychological health was better than that of the control group (40.78±3.98 vs. 47.78±1.84, P<0.05), and the physical health was better than that of the control group (43.16±4.41 vs. 46.30±3.80, P<0.05), with all the differences being statistically significant. There was no statistically significant difference in the degree of cervical functional impairment between the two groups (1 [1, 2] vs. 3 [2, 7], P>0.05). Conclusion: Intelligent health education based on the health belief model can help reduce the degree of kinesophobia in patients with postoperative kinesophobia after surgical treatment of cervical spondylosis and improve patient prognosis.

Four New Isocoumarins from the Mangrove Fungus Alternaria Malorum with Antimicrobial Activities.

Four new isocoumarins, alternariethers A-C (1-3) and alternariester (4) were separated from the fermentation of the fungus Alternaria malorum FL39, purified from Myoporum bontioides. Their structures were ascertained using NMR and HR-ESI-MS spectroscopy. For compound 4, the absolute configuration was solved with the help of ECD calculation and the DP4+ method. Compared with the positive control triadimefon, compound 1 showed more potent antifungal effects on Colletotrichum musae. The antifungal effects of compounds 1, 2, and 3 on Fusarium oxysporum and Fusarium graminearum, of compound 4 on F. oxysporum, were equal to those of triadimefon. Except for compound 4 which was inactive against Escherichia coli with O78 serotype, all compounds showed moderate or weak antibacterial activity against Staphylococcus aureus ATCC 6538 and E. coli with O6 or O78 serotype.

The effect of the mitochondria-targeted antioxidant Mito-tempo during sperm ultra-rapid freezing.

During the freeze-thaw process, human spermatozoa are susceptible to oxidative stress, which may cause cryodamage and reduce sperm quality. As a novel mitochondria-targeted antioxidant, Mito-tempo has been used for sperm cryopreservation. However, it is currently unknown what role it will play in the process of sperm ultra-rapid freezing. The purpose of this study was to investigate whether Mito-tempo can improve sperm quality during ultra-rapid freezing. In this study, samples with the addition of Mito-tempo (0, 5, 10, 20, and 40 µM) to sperm freezing medium were selected to evaluate the changes in sperm quality, antioxidant capacity and ultrastructure after ultra-rapid freezing. After ultra-rapid freezing, the quality and antioxidant function of the spermatozoa were significantly reduced and the spermatozoa ultrastructure was destroyed. The addition of 10 µM Mito-tempo significantly increased post thaw sperm motility, viability, plasma membrane integrity and mitochondrial membrane potential (P < 0.05). Moreover, the DNA fragmentation index (DFI), ROS levels and MDA content were reduced, and the antioxidant enzyme (CAT and SOD) activities were enhanced in the 10 µM Mito-tempo group (P < 0.05). Moreover, Mito-tempo protected sperm ultrastructure from damage. In conclusion, Mito-tempo improved the quality and antioxidant function of sperm after ultra-rapid freezing while reducing freezing-induced ultrastructural damage.

Genetic and prognostic analysis of blastoid and pleomorphic mantle cell lymphoma: a multicenter analysis in China.

Blastoid or pleomorphic mantle cell lymphoma (B/P-MCL) is characterized by high invasiveness and unfavorable outcomes, which is still a challenge for treating MCL. This retrospective study was performed to comprehensively analyze the clinical, genomic characteristics and treatment options of patients with B/PMCL from multicenter in China. Data were obtained from 693 patients with B/PMCL from three centers in China between April 1999 and December 2019. Seventy-four patients with BMCL (n = 43) or PMCL (n = 31) were included in the analysis. The median age of the cohort was 60.0 years with a male-to-female ratio of 2.89:1. The 3-year progression-free survival (PFS) and overall survival (OS) rates were 44.1% and 46.0%, respectively. Mutations of TP53, ATM, NOTCH1, NOTCH2, NSD2, SMARCA4, CREBBP, KMT2D, FAT1, and TRAF2 genes were the most common genetic changes in B/P-MCL. Progression of disease within 12 months (POD12) could independently predict the poor prognosis of patients with blastoid and pleomorphic variants. Patients with POD12 carried a distinct mutation profile (TP53, SMARCA4, NSD2, NOTCH2, KMT2D, PTPRD, CREBBP, and CDKN2A mutations) compared to patients with non-POD12. First-line high-dose cytosine arabinoside exposure obtained survival benefits in these populations, and BTKi combination therapy as the front-line treatment had somewhat improvement in survival with no significant difference in the statistic. In conclusion, B/P-MCL had inferior outcomes and a distinct genomic profile. Patients with POD12 displayed a distinct mutation profile and a poor prognosis. New therapeutic drugs and clinical trials for B/P-MCL need to be further explored.

Embracing the era of antimicrobial peptides with marine organisms.

Covering: 2018 to Jun of 2023The efficiency of traditional antibiotics has been undermined by the proliferation of antibiotic-resistant pathogenic microorganisms, necessitating the pursuit of innovative therapeutic agents. Antimicrobial peptides (AMPs), which are part of host defence peptides found ubiquitously in nature, exhibiting a wide range of activity towards bacteria, fungi, and viruses, offer a highly promising candidate solution. The efficacy of AMPs can frequently be augmented via alterations to their amino acid sequences or structural adjustments. Given the vast reservoir of marine life forms and their distinctive ecosystems, marine AMPs stand as a burgeoning focal point in the quest for alternative peptide templates extracted from natural sources. Advances in identification and characterization techniques have accelerated the discoveries of marine AMPs, thereby stimulating AMP customization, optimization, and synthesis research endeavours. This review presents an overview of recent discoveries related to the intriguing qualities of marine AMPs. Emphasis will be placed upon post-translational modifications (PTMs) of marine AMPs and how they may impact functionality and potency. Additionally, this review considers ways in which marine PTM might support larger-scale, heterologous AMP manufacturing initiatives, providing insights into translational applications of these important biomolecules.

Assessment of the Binding of Pseudallecin A to Human Serum Albumin with Multi-Spectroscopic Analysis, Molecular Docking and Molecular Dynamic Simulation.

The binding of pseudallecin A (PA), a potential antibiotic with strong inhibitory activities against Gram-positive Escherichia coli and Gram-negative Staphylococcus aureus, to human serum albumin (HSA) was explored. The interaction between them was assessed by multi-spectroscopic analysis, binding site competitive analysis, molecular docking and molecular dynamic simulation, showing the results as follows: PA effectively quenched the innate fluorescence of HSA by a static quenching process, formed a complex at a molar ratio of approximately 1 : 1 and performed an effective non-radiative energy transfer; the binding of PA to HSA was a spontaneous exothermic reaction driven by enthalpy with strong affinity and had a slight effect on the conformation of HSA; PA bound at site III of HSA and hydrogen bonds were the major binding forces to maintain the stability of the PA-HSA complex. Molecular dynamic simulation was performed to calculate the root mean square deviation (RMSD), root mean square fluctuation (RMSF) and radius of gyration (Rg) for this complex and effectively supported the spectroscopic outcome. These results meant that the delivery and distribution of PA as a water-insoluble molecule can be efficiently accomplished via HSA in human blood and, it has a good potential for future drug application and pharmacological development.

Primary sources of HONO vary during the daytime: Insights based on a field campaign.

Nitrous acid (HONO) is an established precursor of hydroxyl (OH) radical and has significant impacts on the formation of PM2.5 and O3. Despite extensive research on HONO observation in recent years, knowledge regarding its sources and sinks in urban areas remains inadequate. In this study, we monitored the atmospheric concentrations of HONO and related pollutants, including gaseous nitric acid and particulate nitrate, simultaneously at a supersite in downtown Chengdu, a megacity in southwestern China during spring, when was chosen due to its tolerance for both PM2.5 and O3 pollution. Furthermore, we employed the random forest model to fill the missing data of HONO, which exhibited good predictive performance (R2 = 0.96, RMSE = 0.36 ppbv). During this campaign, the average mixing ratio of HONO was measured to be 1.0 ± 0.7 ppbv. Notably, during periods of high O3 and PM2.5 concentrations, the mixing ratio of HONO was >50 % higher compared to the clean period. We developed a comprehensive parameterization scheme for the HONO budget, and it performed well in simulating diurnal variations of HONO. Based on the HONO budget analysis, we identified different mechanisms that dominate HONO formation at different times of the day. Vehicle emissions and NO2 heterogeneous conversions were found to be the primary sources of HONO during nighttime (21.0 %, 30.2 %, respectively, from 18:00 to 7:00 the next day). In the morning (7:00-12:00), NO2 heterogeneous conversions and the reaction of NO with OH became the main sources (35.0 %, 32.2 %, respectively). However, in the afternoon (12:00-18:00), the heterogeneous photolysis of HNO3 on PM2.5 was identified as the most substantial source of HONO (contributing 52.5 %). This study highlights the significant variations in primary HONO sources throughout the day.

Evaluating the microbial aerosol generated by dental instruments: addressing new challenges for oral healthcare in the hospital infection.

BACKGROUND: Using a rotary instrument or ultrasonic instrument for tooth preparation is a basic operation in the dental clinic that can produce a significant number of droplets and aerosols. The dental droplet and aerosol can lead to the transfer of harmful germs. The goal of this study was to analyze the properties of microbiological aerosol created by droplets and aerosol generated by three common tooth-preparation instruments. METHODS: Streptococcus mutans UA159 was used as the biological tracer to visualize the droplets and aerosols. The passive sampling method was used to map the three-dimensional spatial distribution and the six-stage Andersen microbial sampler (AMS) was used as the active sampling method to catch aerosol particles at a specific time. RESULTS: The aerosol concentration is related to instruments, three-dimensional spatial distribution, and dissipation time. Most aerosols were generated by air turbines. More microorganisms are concentrated at the 1.5 m plane. The majority of the post dental procedure contamination was detected within the 0-10-min period and it decreased rapidly within 30 min. CONCLUSION: This study is conducive to the proposal and improvement of relevant infection control measures in dental procedures and provides a basis for the assessment of measures, reducing the risk of nosocomial infection.

White spot syndrome virus (WSSV) modulates lipid metabolism in white shrimp.

In addition to the Warburg effect, which increases the availability of energy and biosynthetic building blocks in WSSV-infected shrimp, WSSV also induces both lipolysis at the viral genome replication stage (12 hpi) to provide material and energy for the virus replication, and lipogenesis at the viral late stage (24 hpi) to complete virus morphogenesis by supplying particular species of long-chain fatty acids (LCFAs). Here, we further show that WSSV causes a reduction in lipid droplets (LDs) in hemocytes at the viral genome replication stage, and an increase in LDs in the nuclei of WSSV-infected hemocytes at the viral late stage. In the hepatopancreas, lipolysis is triggered by WSSV infection, and this leads to fatty acids being released into the hemolymph. ß-oxidation inhibition experiment reveals that the fatty acids generated by WSSV-induced lipolysis can be diverted into ß-oxidation for energy production. At the viral late stage, WSSV infection leads to lipogenesis in both the stomach and hepatopancreas, suggesting that fatty acids are in high demand at this stage for virion morphogenesis. Our results demonstrate that WSSV modulates lipid metabolism specifically at different stages to facilitate its replication.

Discovery of Novel Bactericides from Aspergillus alabamensis and Their Antibacterial Activity against Fish Pathogens.

The emerging outbreak of bacterial diseases is a major challenge for the aquaculture industry. The development of new antibacterial agents from natural resources to curb fish bacterial diseases in aquaculture is becoming increasingly popular. In this study, eight new benzoic acid-containing alkaloids, asperalin A-F (1-6), asperalumazine A (7), and N-(3-acetamidopropyl)-3,4-dihydroxybenzamide (8), along with four known compounds (9-12) were isolated and identified from a seagrass-derived Aspergillus alabamensis. Their chemical structures were established on the basis of extensive spectroscopic analyses (including HRESIMS, 1D and 2D NMR spectroscopy), NMR computational methods, and electronic circular dichroism (ECD) calculations. Compounds 1-6 exhibited moderate or potent inhibitory activities against at least one fish pathogenic bacterium, among Edwardsiella ictalurid, Streptococcus iniae, and Streptococcus parauberis, and these compounds represent the first report of the coupling of dihydroquinolone alkaloids with benzoic acid derivatives. Compounds 3 and 4 showed strong activities against Staphylococcus aureus, S. iniae, and S. parauberis, with an MIC value of 10.1, 5.0, and 10.1 µM, respectively. Compound 5, an N-alkylated product of 4, exhibited the strongest inhibitory effects against S. iniae, with an MIC value of 2.2 µM. Notably, compound 6, as a new natural bactericide, showed moderate to potent inhibitory activity toward all strains tested, including one Gram-negative bacterium E. ictalurid (10.9 µM, MIC) and four Gram-positive bacteria S. iniae (43.6 µM, MIC), S. aureus (21.8 µM, MIC), S. parauberis (87.3 µM, MIC), and Bacillus subtilis (21.8 µM, MIC). Compound 7 represents the first example of a lumazine derivative directly coupled to a benzoic acid moiety by a hydroxymethyl group.

Enhanced nitrate contribution to light extinction during haze pollution in Chengdu: Insights based on an improved multiple linear regression model.

In recent years, the annual mean concentration of PM2.5 has decreased in Chengdu, China; however, atmospheric visibility has not improved accordingly. Low-visibility events occurred even when the PM2.5 mass concentrations were below the national ambient air quality secondary standard (daily mean concentration, 75 µg/m3). In this study, the non-linear relationship between PM2.5 and visibility was analyzed under different NO3- mass fractions in PM2.5 based on 2-year field observation data. The results indicated that NO3- formation contributed to particulate pollution events and reduced atmospheric visibility. Multiple linear regression was used to propose a localized reconstruction equation for the light-scattering coefficient. According to the maximum likelihood estimation method and log-transformed residuals, the mass scattering coefficients (MSEs) of organic matter (OM), NH4NO3, and (NH4)2SO4 in Chengdu were 7.42, 3.83, and 3.80, respectively. OM and NH4NO3 contributed to more than 50% of the light-extinction coefficient (bext). NH4NO3 was the main pollutant causing the substantial increase in bext. Chengdu has a high relative humidity (annual mean 70%), and under such conditions, the contribution of NH4NO3 to bext was considerably enhanced through hygroscopic growth and heterogeneous reactions. This study estimated the localized MSEs of OM, NH4NO3, and (NH4)2SO4 in Chengdu and emphasized that effective control measures to reduce nitrate and its precursors could simultaneously ameliorate air quality and visibility in humid regions with poor atmospheric visibility.

Calibration and Uncertainty in Neural Time-to-Event Modeling.

Models for predicting the time of a future event are crucial for risk assessment, across a diverse range of applications. Existing time-to-event (survival) models have focused primarily on preserving pairwise ordering of estimated event times (i.e., relative risk). We propose neural time-to-event models that account for calibration and uncertainty while predicting accurate absolute event times. Specifically, an adversarial nonparametric model is introduced for estimating matched time-to-event distributions for probabilistically concentrated and accurate predictions. We also consider replacing the discriminator of the adversarial nonparametric model with a survival-function matching estimator that accounts for model calibration. The proposed estimator can be used as a means of estimating and comparing conditional survival distributions while accounting for the predictive uncertainty of probabilistic models. Extensive experiments show that the distribution matching methods outperform existing approaches in terms of both calibration and concentration of time-to-event distributions.

Melatonin Increases Proliferation and Decreases Apoptosis of GC-1 spg Cells by Upregulating the Expression of circTec.

Melatonin has been shown to be beneficial for the motility of human sperm, although its mechanism remains to be uncovered. Circular RNAs (circRNAs) have been shown to regulate cellular function in many diseases. However, there has been no relevant research on the effect of melatonin on sperm circRNAs. In this study, we aimed to explore the changes in circRNAs after melatonin treatment of GC-1 spg cells and identify key functional circRNAs. The results showed that melatonin enhanced the proliferation and reduced the apoptosis of GC-1 spg cells. A total of 1423 circRNAs were found to be significantly differentially expressed between groups with and without melatonin treatment. Of these circRNAs, 702 were upregulated and 721 were downregulated. circTec was one of the upregulated circRNAs. Suppressing the expression of circTec significantly reduced cell proliferation and mammalian target of rapamycin (mTOR) signaling pathway activation but promoted melatonin-treated GC-1 spg cell apoptosis. In conclusion, melatonin increased the expression of circTec to exert its physiological effects on GC-1 spg cells, possibly by activating the mTOR signaling pathway. These results enhance our understanding of the biological function of circTec and its regulation by melatonin in spermatogenesis and infertility.

Establishment of qRT-PCR for absolute quantitative detection of Chikungunya virus / 中国热带医学

@#Abstract: Objective　To develop a real-time fluorescent quantitative RT-PCR (qRT-PCR) method for qualitative and quantitative Chikungunya virus (CHIKV) analysis. Methods Based on the systematic analysis of the genomic sequences of Chikungunya and its related arboviruses, the specific nucleic acid sequences for Chikungunya virus were screened and identified, and then the primers and TaqMan probe were designed. Meanwhile, the human GAPDH gene was used as an internal reference. The reaction system for qRT-PCR was systematically optimized by L9(34) orthogonal design, and a rapid detection method for Chikungunya by qRT-PCR based on TaqMan probe methods was established. The sensitivity, specificity, reproducibility, and coverage of the established method were analyzed in detail. The standard curve was made, and the absolute quantitative method was established using the cloned nucleic acid fragments as positive samples. Results　A real-time fluorescent quantitative RT-PCR assay was developed for the qualitative and quantitative analysis of Chikungunya virus. The reaction system included Chikungunya virus and reference internal gene specific primers and probe, RT/Taq enzyme mixture, reaction buffer, and negative and positive reference. The established method obtained positive results with the ROSS strain of ECSA subtype, LR2006 strain of IOL branch, 181/25 strain of Asian type and Dongguan 2010 epidemic strains of Chikungunya virus, but there was no cross-reaction with other 18 arboviruses belonging to Flaviviruses, Alphaviruses and Bunyavirus. The minimum detection limit of the established method was 5.80 copies/mL, and a linear relationship was observed between the amount of input plasmid DNA and fluorescence signal value over a range of 5.80×102 copies/mL to 5.80×1010 copies/mL, and the correlation coefficient was 0.999 5. The qRT-PCR amplification efficiency was 91%, and the intra-assay variations and inter-assay variations were 0.01-0.07 and 0.03-0.11, respectively. Conclusions　The TaqMan qRT-PCR method developed in this study can qualitatively and quantitatively detect Chikungunya virus rapidly with specificity and sensitivity, providing a technical method for the prevention and control of this viral disease.

Development of a new risk scoring system based on spleen involvement and the lymphocyte/monocyte ratio for follicular lymphoma patients.

BACKGROUND: This study aimed to retrospectively evaluate a large Chinese cohort's baseline characters and develop a new predictive scoring system. METHODS: A total of 491 FL patients were reviewed, and 337newly diagnosed 1-3a FL patients from January 2010 to October 2020 were enrolled in our retrospective cohort. RESULTS: Progression-free survival (PFS) was assessed as the first endpoint; the 2-year and 5-year PFS were 81.4% and 67.8%, respectively. A new risk scoring system (SLMR) was established after the univariable and multivariable analyses, and four independent factors such as ß2-MG, LDH, LMR, the number of nodal areas ≥ 5, and spleen involvement were detected by FDG-PET imaging were included. The SLMR was compared with the existing models using discrimination and calibration, and k-fold cross-validation was performed for internal validation. Our cohort classified patients into three groups (low-, intermediate- and high) according to the SLMR and showed the best model performance, especially for FL3a and received rituximab maintenance after induction therapy patients.

Identification of six hub genes in mantle cell lymphoma patients with BTKi resistance.

Background: Bruton tyrosine kinase inhibitor (BTKi) resistance is an unsolved problem in the treatment of relapse/recurrence (R/R) mantle cell lymphoma (MCL). Although salvage therapy following ibrutinib resistance has been attempted in recent years, the survival of resistant patients was significantly reduced. Once ibrutinib-treated patients relapse, the 1-year survival rate is only 22%. Acquired drug resistance and primary drug resistance were found to relate closely to genetic mutations. The hub genes identification and clinical data analysis of patients resistant to BTKi based on the Chinese MCL gene mutation profile are worthy of exploration. Methods: Based on 28 MCL patients' mutation data and clinical data, 6 hub genes were screened by a gene panel of 69 genes and univariate Cox prognostic analysis. Prognosis and responses to salvage therapy regimen were analyzed. Results: Patients with BTKi had less favorable clinical features at baseline. Chimeric antigen receptor T-cell (CAR-T) therapy yielded the best response among salvage treatments. The 6 hub genes were screened by a gene panel of 69 genes (GP79) which might be a potential predictor for MCL patients with BTKi resistance. Conclusions: The clinical characteristics of BTKi resistance in MCL patients were summarized, and 6 hub genes were identified to provide ideas and suggestions for further research.