mNGS helped diagnose scrub typhus-associated HLH in children: a report of two cases.

Background: Scrub typhus, caused by the Orientia tsutsugamushi (Ot), is a widespread vector-borne disease transmitted by chigger mites. Hemophagocytic lymphohistiocytosis (HLH) is considered to be one of the potentially severe complications. The diagnosis of scrub typhus-associated HLH may be overlooked due to the non-specific clinical characteristics and the absence of pathognomonic eschar. Case presentation: We obtained clinical data from two patients in the South of Sichuan, China. The first case involved a 6-year-old girl who exhibited an unexplained fever and was initially diagnosed with sepsis, HLH, and pulmonary infection. The other patient presented a more severe condition characterized by multiple organ dysfunction and was initially diagnosed with septic shock, sepsis, HLH, acute kidney injury (AKI), and pulmonary infection. At first, a specific examination for scrub typhus was not performed due to the absence of a characteristic eschar. Conventional peripheral blood cultures yielded negative results in both patients, and neither of them responded to routine antibiotics. Fortunately, the causative pathogen Orientia tsutsugamushi (Ot) was detected in the plasma samples of both patients using metagenomics next-generation sequencing (mNGS) and further confirmed by polymerase chain reaction. Subsequently, they both were treated with doxycycline and recovered quickly. Conclusion: The unbiased mNGS provided a clinically actionable diagnosis for an uncommon pathogen-associated infectious disease that had previously evaded conventional diagnostic approaches.

Dose-response relationships between body-mass index and pressure injuries occurrence in hospitalized patients: A multi-center prospective study.

BACKGROUND: Pressure injuries (PIs) are one of the leading potentially preventable hospital-acquired complications associated with prolonged hospital length, poor quality of life and financial burden. The relationship between body mass index (BMI) and PIs occurrence is controversial. OBJECTIVE: The aim of this study was to further examine relationships between BMI and PIs occurrence in hospitalized patients. DESIGN: A multi-center prospective study. SETTING: 39 hospitals located in northwest China from April 2021 to July 2023. PARTICIPANTS: 175,960 hospitalized patients aged over 18 years were enrolled, and 170,800 patients were included in the final analysis. METHODS: BMI and clinical characteristics were assessed at baseline. PIs assessment were performed by trained nurses, with data recorded for the presence, the location and stage of each PI. For staging PIs, the National Pressure Ulcer Advisory Panel（NPUAP） staging system were used. The multivariate logistic regressions analysis and restricted cubic splines (RCS) models were used to explore associations between BMI and PIs, adjusting for potential confounders. RESULTS: Of 175,960 participants, 5160 were excluded from analyses. The multivariate logistic regression model identified a positive relationship between under-weight BMI and risk of PIs occurrence (OR = 1.60, 95% CI:1.18-2.17). We also found U shaped association between BMI and PIs occurrence (non-linear P < 0.001). BMI less than 23 kg/m2 significantly increased risk of PIs, and there was a tendency to increase risk of PIs at BMI higher than 30 kg/m2. We stratified participants by sex to further investigate their association and found the risk of PIs increases substantially in women at BMI below 17 kg/m2 and in men at BMI below 23 kg/m2. CONCLUSIONS: The present study indicated that there was an approximate U shaped relationship between BMI and PIs occurrence, and this association was potentially different between men and women.

Feasible CT features to distinguish incidental rib enhancement from sclerotic metastasis in patients with malignancies.

OBJECTIVE: To investigate the CT features of incidental rib enhancement (RE) and to summarize the CT characteristics for distinguishing the RE from sclerotic metastasis (SM) in patients with malignancies. MATERIAL AND METHODS: This retrospective observational study enrolled 79 patients with RE (involved 133 ribs) during October 2014 and December 2021. Another 53 patients with SM (160 SM) in the same period were selected randomly for comparison. The location, enhancement patterns of RE were reviewed. The CT values of RE regions and SM were measured and statistically analyzed. RESULTS: Most REs (70 patients, 88.6%) were in the 1st to 6th ribs. 50 patients had solitary RE and 29 with multiple REs in a regional distribution. All the REs were closely connected to the intercostal venous plexus (ICVP) ipsilateral to the injection site. No visible abnormalities on unenhanced scans were detected in all REs. One hundred and twenty REs (90.2%) had nodular/patchy enhancement. The CT value of RE regions in the venous phase was lower than that in the arterial phase (589.8 ± 344.2 HU versus 1188.5 ± 325.3 HU, p < 0.001). During the venous phase, most REs (125, 94.0%) shrank or disappeared. SM appeared similar on both contrast-enhanced and unenhanced scans in terms of shape and CT values. CONCLUSION: The RE demonstrated characteristic CT features. The manifestations of nodular/patchy enhancement in the arterial phase, decreased density and shrinkage or disappearance during the venous phase, and no abnormality on unenhanced scans, as well as a close connection with the ICVP, may help differentiate RE from SM.

Perioperative toripalimab and chemotherapy in locally advanced gastric or gastro-esophageal junction cancer: a randomized phase 2 trial.

Perioperative chemotherapy is the standard treatment for locally advanced gastric or gastro-esophageal junction cancer, and the addition of programmed cell death 1 (PD-1) inhibitor is under investigation. In this randomized, open-label, phase 2 study (NEOSUMMIT-01), patients with resectable gastric or gastro-esophageal junction cancer clinically staged as cT3-4aN + M0 were randomized (1:1) to receive either three preoperative and five postoperative 3-week cycles of SOX/XELOX (chemotherapy group, n = 54) or PD-1 inhibitor toripalimab plus SOX/XELOX, followed by toripalimab monotherapy for up to 6 months (toripalimab plus chemotherapy group, n = 54). The primary endpoint was pathological complete response or near-complete response rate (tumor regression grade (TRG) 0/1). The results showed that patients in the toripalimab plus chemotherapy group achieved a higher proportion of TRG 0/1 than those in the chemotherapy group (44.4% (24 of 54, 95% confidence interval (CI): 30.9%-58.6%) versus 20.4% (11 of 54, 95% CI: 10.6%-33.5%)), and the risk difference of TRG 0/1 between toripalimab plus chemotherapy group and chemotherapy group was 22.7% (95% CI: 5.8%-39.6%; P = 0.009), meeting a prespecified endpoint. In addition, a higher pathological complete response rate (ypT0N0) was observed in the toripalimab plus chemotherapy group (22.2% (12 of 54, 95% CI: 12.0%-35.6%) versus 7.4% (4 of 54, 95% CI: 2.1%-17.9%); P = 0.030), and surgical morbidity (11.8% in the toripalimab plus chemotherapy group versus 13.5% in the chemotherapy group) and mortality (1.9% versus 0%), and treatment-related grade 3-4 adverse events (35.2% versus 29.6%) were comparable between the treatment groups. In conclusion, the addition of toripalimab to chemotherapy significantly increased the proportion of patients achieving TRG 0/1 compared to chemotherapy alone and showed a manageable safety profile. ClinicalTrials.gov registration: NCT04250948 .

Effect of different noninvasive ventilation interfaces on the prevention of facial pressure injury: A network meta-analysis.

OBJECTIVE: To assess the effect of different noninvasive ventilation interfaces on preventing the facial pressure injury. METHODS: This network meta-analysis was conducted following the PRISMA reporting guidelines. Seven electronic databases were systematically searched for randomised controlled trials about the comparative effectiveness of different interfaces in preventing facial pressure injury with noninvasive ventilation in adults and newborns from inception to June 2023. The acronym of PICOS was used and the keywords as well as inclusion/exclusion criteria were determined. Study selection and data extraction were performed by two independent reviewers. The Cochrane risk of bias assessment tool was used to assess the methodological quality. RESULTS: A total of 78 randomised controlled trials involving 7,291 patients were included. The results of network meta-analysis showed that the effectiveness of the eight noninvasive ventilation interfaces on the prevention of facial pressure injury was in the order of: nasal cannula > full-face mask > rotation of nasal mask with nasal prongs > helmet > nasal mask > oronasal mask > nasal prongs > face mask. The use of full-face mask in adults and nasal cannula in newborns had the best effect on preventing the incidence of facial pressure injury. CONCLUSIONS: The use of full-face mask in adults and nasal cannula in newborns had the most clinical advantage in preventing the incidence of facial pressure injury and were worthy promoting in clinical practice. IMPLICATIONS FOR CLINICAL PRACTICE: This study provides a certain theoretical basis for the selection of appropriate interface for patients with noninvasive ventilation. Clinical practitioners should choose the appropriate interfaces based on the patient's specific condition to reduce the incidence of facial pressure injury, enhance patient comfort, and improve the effectiveness of respiratory therapy.

Semi-automatic fine delineation scheme for pancreatic cancer.

BACKGROUND: Pancreatic cancer fine delineation in medical images by physicians is a major challenge due to the vast volume of medical images and the variability of patients. PURPOSE: A semi-automatic fine delineation scheme was designed to assist doctors in accurately and quickly delineating the cancer target region to improve the delineation accuracy of pancreatic cancer in computed tomography (CT) images and effectively reduce the workload of doctors. METHODS: A target delineation scheme in image blocks was also designed to provide more information for the deep learning delineation model. The start and end slices of the image block were manually delineated by physicians, and the cancer in the middle slices were accurately segmented using a three-dimensional Res U-Net model. Specifically, the input of the network is the CT image of the image block and the delineation of the cancer in the start and end slices, while the output of the network is the cancer area in the middle slices of the image block. Meanwhile, the model performance of pancreatic cancer delineation and the workload of doctors in different image block sizes were studied. RESULTS: We used 37 3D CT volumes for training, 11 volumes for validating and 11 volumes for testing. The influence of different image block sizes on doctors' workload was compared quantitatively. Experimental results showed that the physician's workload was minimal when the image block size was 5, and all cancer could be accurately delineated. The Dice similarity coefficient was 0.894 ± 0.029, the 95% Hausdorff distance was 3.465 ± 0.710 mm, the normalized surface Dice was 0.969 ± 0.019. By completing the accurate delineation of all the CT images, the speed of the new method is 2.16 times faster than that of manual sketching. CONCLUSION: Our proposed 3D semi-automatic delineative method based on the idea of block prediction could accurately delineate CT images of pancreatic cancer and effectively deal with the challenges of class imbalance, background distractions, and non-rigid geometrical features. This study had a significant advantage in reducing doctors' workload, and was expected to help doctors improve their work efficiency in clinical application.

Bioactive compound composition and cellular antioxidant activity of fig (Ficus carica L.).

BACKGROUND: Fig (Ficus carica L.) fruit is consumed worldwide as a functional food. It contains phytochemicals that have been related to health benefits. However, the characteristic chemicals remain unclear. In this work, phytochemicals were prepared from figus by ultrasound-assisted extraction under optimized conditions. The chemical composition of fig fruit and leaves was characterized by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). RESULTS: One hundred and fifty-seven compounds were identified, including 58 flavonoids, 29 coumarins, 19 acids, 15 terpenoids, 11 alkaloids, and 25 other compounds. The mass spectrum (MS) fragmentation pathways of representative chemicals were elucidated. Flavonoid glycosides and prenylated flavonoids were mainly present in fig fruit, whereas coumarins were abundant in leaves. Both fig fruit and leaf extracts showed good cellular antioxidant activity. CONCLUSION: The full phytochemical profile of fig was revealed by UPLC-MS/MS. Prenylated flavonoids and prenylated coumarins were the characteristic phytochemicals. These data provided useful information for the extensive utilization of fig fruit in functional food. © 2023 Society of Chemical Industry.

New insights of flavonoid glycosidases and their application in food industry.

Flavonoids are significant natural nutraceuticals and a key component of dietary supplements. Given that flavonoid glycosides are more plentiful in nature and less beneficial to human health than their aglycone counterparts, they serve as potential precursors for flavonoid production. Glycosidases have shown substantial potential within the food industry, particularly in enhancing the organoleptic properties of juice, wine, and tea. When applied to food resources, glycosidases can amplify their biological activities, thereby improving the performance of functional foods. This review provides up-to-date information on flavonoid glycosidases, including their catalytic mechanisms, biochemical properties, and natural sources, as well as their applications within the food industry. The use of flavonoid glycosidases in improving food quality is also reviewed.

A primary pediatric acute myelomonocytic leukemia with t(3;21)(q26;q22): A case report.

RATIONALE: The rare t(3;21)(q26;q22) translocation results in gene fusion and generates multiple fusion transcripts, which are typically associated with therapy-related myelodysplastic syndrome, acute myeloid leukemia, and chronic myelogenous leukemia. Here, we report a rare case of de novo acute myelomonocytic leukemia in a young child with t(3;21)(q26;q22). PATIENT CONCERNS: A 2-and-a-half-year-old female patient presented with abdominal pain, cough, paleness, and fever for 3 weeks, without any history of malignant diseases. DIAGNOSES: Chest computed tomography revealed pneumonia. Bone marrow smear confirmed acute myelomonocytic leukemia. Cytogenetic analysis and Sanger sequencing identified RUNX1-MECOM and RUNX1-RPL22 fusion genes as a result of t(3;21)(q26;q22). INTERVENTIONS: The patient received 3 courses of chemotherapy, but bone marrow smear examination showed no remission. According to the wishes of the patient family, the allogeneic hematopoietic stem cell transplantation (Allo-HSCT) was chosen. OUTCOMES: The patient did not experience any adverse reactions after Allo-HSCT. The red blood cells and platelets increased without transfusion. The pneumonia recovered after antibiotic treatment. LESSONS: The patient recovered well after Allo-HSCT. Therefore, for patients with RUNX1-MECOM and RUNX1-RPL22 fusion genes, transplantation may be a good choice when chemotherapy is not effective.

Molecular epidemiology and clinical characteristics of enteroviruses associated HFMD in Chengdu, China, 2013-2022.

OBJECTIVES: This study aims to investigate molecular epidemiology and clinical characteristics of enterovirus associated hand-foot-mouth disease (HFMD) in Chengdu, China, 2013-2022. Monitoring the molecular epidemiology and clinical features of HFMD for up to 10 years may provide some ideas for future protection and control measures. METHODS: We conducted a retrospective analysis of the medical records of all patients with laboratory-confirmed HFMD-related enterovirus infection at the West China Second University Hospital from January 2013 to December 2022. We described the characteristics in serotype, age, sex distribution and hospitalization of enterovirus infection cases using data analysis and graphic description. RESULTS: A total of 29,861 laboratory-confirmed cases of HFMD-related enterovirus infection were reported from 2013 to 2022. There was a significant reduction in the number and proportion of EV-A71 cases after 2016, from 1713 cases (13.60%) in 2013-2015 to 150 cases (1.83%) in 2017-2019. During the COVID-19 pandemic, EV-A71 cases even disappeared. The proportion of CV-A16 cases decreased from 13.96% in 2013-2015 to 10.84% in 2017-2019 and then to 4.54% in 2020-2022. Other (non-EV-A71 and non-CV-A16) serotypes accounted for 95.45% during 2020-2022, with CV-A6 accounting for 50.39% and CV-A10 accounting for 10.81%. Thus, CV-A6 and CV-A10 became the main prevalent serotypes. Furthermore, There was no significant difference in the enterovirus prevalence rate between males and females. The hospitalization rate of EV-A71 patients was higher that of other serotypes. In general, the proportion of HFMD hospitalizations caused by other pathogens except for EV-A71, CV-A16, CV-A10 and CV-A16 was second only to that caused by EV-A71. The proportion of children over 4 years old infected with enterovirus increased. CONCLUSION: The incidence of HFMD associated with enterovirus infection has decreased significantly and CV-A6 has been the main pathogen of HFMD in Chengdu area in recent years. The potential for additional hospitalizations for other untested enterovirus serotypes suggested that attention should also be paid to the harms of infections with unknown enterovirus serotypes. Children with HFMD were older. The development of new diagnostic reagents and vaccines may play an important role in the prevention and control of enterovirus infection.

Fungal-Algal Association Drives Lichens' Mutualistic Symbiosis: A Case Study with Trebouxia-Related Lichens.

Biotic and abiotic factors influence the formation of fungal-algal pairings in lichen symbiosis. However, the specific determinants of these associations, particularly when distantly related fungi are involved, remain poorly understood. In this study, we investigated the impact of different drivers on the association patterns between taxonomically diverse lichenized fungi and their trebouxioid symbiotic partners. We collected 200 samples from four biomes and identified 41 species of lichenized fungi, associating them with 16 species of trebouxioid green algae, of which 62% were previously unreported. The species identity of both the fungal and algal partners had the most significant effect on the outcome of the symbiosis, compared to abiotic factors like climatic variables and geographic distance. Some obviously specific associations were observed in the temperate zone; however, the nestedness value was lower in arid regions than in cold, polar, and temperate regions according to interaction network analysis. Cophylogenetic analyses revealed congruent phylogenies between trebouxioid algae and associated fungi, indicating a tendency to reject random associations. The main evolutionary mechanisms contributing to the observed phylogenetic patterns were "loss" and "failure to diverge" of the algal partners. This study broadens our knowledge of fungal-algal symbiotic patterns in view of Trebouxia-associated fungi.

Regulating the properties of XQ-2d for targeted delivery of therapeutic agents to pancreatic cancers.

Enhanced recognition ability, cell uptake capacity, and biostability are characteristics attributed to aptamer-based targeted anticancer agents, and are possibly associated with increased accumulation at the tumor site, improved therapeutic efficacy and reduced negative side effects. Herein, a phosphorothioate backbone modification strategy was applied to regulate the biomedical properties of pancreatic cancer cell-targeting aptamer for efficient in vivo drug delivery. Specifically, the CD71- targeting aptamer XQ-2d was modified into a fully thio-substituted aptamer S-XQ-2d, improving the plasma stability of S-XQ-2d and mitomycin C (MMC)-functionalized S-XQ-2d (MFSX), thus considerably prolonging their half-life in mice. Moreover, the binding and uptake capacities of S-XQ-2d were significantly enhanced. MFSX showed the same level of cytotoxicity as that of MMC against targeted cancer cells, but lower toxicity to non-targeted cells, highlighting its specificity and biosafety. Brief mechanistic studies demonstrated that XQ-2d and S-XQ-2d had different interaction modes and internalization pathways with the targeted cells.

Two novel species and three new records of Torulaceae from Yunnan Province, China.

While investigating the diversity of lignicolous fungi in Yunnan Province, China, six fresh collections of Torulaceae were collected and identified based on morphological examination and phylogenetic analyses of combined LSU, ITS, SSU, tef1-α, and rpb2 sequence data. Two new species, viz. Neopodoconisyunnanensis and Torulasuae, and three new records, viz. T.canangae (new freshwater habitat record), T.masonii (new host record), and T.sundara (new freshwater habitat record) are reported. Detailed descriptions, illustrations, and a phylogenetic tree to show the placement of these species are provided.

How does patient-centered hospital culture affect clinical physicians' medical professional attitudes and behaviours in chinese public hospitals: a cross-sectional study?

BACKGROUND: An increasing number of studies on physicians' professionalism have been done since the 2002 publication of Medical Professionalism in the New Millennium: A Physician Charter. The Charter proposed three fundamental principles and ten responsibilities. However, most studies were done in developed countries, and few have been done in China. Additionally, few studies have examined the effect of patient-centered hospital culture (PCHC) on physicians' professionalism. We aimed to investigate physicians' medical professionalism in public hospitals in China, and to assess mediating effect of professional attitudes in the relationship of PCHC with professional behaviours. METHODS: Self-administered questionnaires including professional attitudes (20 items) and behaviours (10 items) survey and PCHC scale (22 items) were given to clinical physicians in five public hospitals, China. The mediating effect of professional attitudes in the relationship of PCHC with professional behaviours was tested. RESULT: 232 valid questionnaires were collected. More than 90% (208) respondents agreed with 15 of 20 specific statements on medical professionalism. As for the responsibility of improving quality of care, 54 (23%) respondents disagreed with reporting of incompetent colleagues and as for the responsibility of maintaining professional competence, 49 (21%) disagreed with recertification. More than 185 (83%) respondents reported that they sometimes, usually, or always showed the four positive behaviours on the questionnaire, and 173 (77%) reported that they never showed the six negative behaviours. Mediating effect analysis revealed that two dimensions of PCHC (i.e. value/institution culture and behaviour/material culture) had a significant positive impact on physicians' professional behaviour, and professional attitude played a complete mediation role between them, but another dimension of PCHC (i.e. negative evaluation of hospital) directly affected professional behaviour without influencing professional attitude. CONCLUSION: Chinese physicians showed positive professional attitudes and behaviours. Different dimensions of PCHC affected physicians' attitudes and behaviours in different ways.

Leishmania donovani visceral leishmaniasis diagnosed by metagenomics next-generation sequencing in an infant with acute lymphoblastic leukemia: a case report.

Background: Visceral leishmaniasis (VL) is a neglected vector-borne tropical disease caused by Leishmania donovani (L. donovani) and Leishmania infantum (L. infantum). Due to the very small dimensions of the protozoa impounded within blood cells and reticuloendothelial structure, diagnosing VL remains challenging. Case presentation: Herein, we reported a case of VL in a 17-month-old boy with acute lymphoblastic leukemia (ALL). The patient was admitted to West China Second University Hospital, Sichuan University, due to repeated fever after chemotherapy. After admission, chemotherapy-related bone marrow suppression and infection were suspected based on clinical symptoms and laboratory test results. However, there was no growth in the conventional peripheral blood culture, and the patient was unresponsive to routine antibiotics. Metagenomics next-generation sequencing (mNGS) of peripheral blood identified 196123 L. donovani reads, followed by Leishmania spp amastigotes using cytomorphology examination of the bone marrow specimen. The patient was given pentavalent antimonials as parasite-resistant therapy for 10 days. After the initial treatment, 356 L. donovani reads were still found in peripheral blood by mNGS. Subsequently, the anti-leishmanial drug amphotericin B was administrated as rescue therapy, and the patient was discharged after a clinical cure. Conclusion: Our results indicated that leishmaniasis still exists in China. Unbiased mNGS provided a clinically actionable diagnosis of a specific infectious disease from an uncommon pathogen that eluded conventional testing.

Research into the correlation between positional skull deformation and motor performance of infants aged under 4 months.

OBJECTIVE: To investigate the correlation between positional skull deformation (PD) and motor performance of infants under 4 months of age. METHODS: Infants aged under 4 months were enrolled in the children's healthcare and the premature infants follow-up Clinic of the Second Affiliated Hospital of Army Military Medical University. The cranial vault asymmetry (CVA) and cephalic index (CI) were calculated in all infants, and the infant motor performance test (TIMP) was used to evaluate the infant motor performance. The motor performances of infants with different types and degrees of PD were compared, so were the incidences of PD in infants with different motor performance levels. RESULTS: Overall, 2118 infants were recruited and divided according to the types of PD and TIMP scores. The comparison of TIMP scores within different types of PD at different months of age showed that, regardless of the types of PD, TIMP scores of infants with PD were lower than those of normal infants. In particular, the difference in TIMP scores was statistically significant (P < 0.05) in infants with dolichocephaly, plagiocephaly,dolicho-plagiocephaly and brachy-plagiocephy. In addition, the comparison of CVA values of infants with different TIMP score levels at different months of age showed that the CVA values of the extremely low-level group were significantly higher than those of the medium-level and high-level group, especially in the 3-month-old and 4-month-old groups, which showed significant statistical differences (P < 0.05). CONCLUSIONS: PD and motor performance of infants aged under 4 months seem to interact and influenc each other. The more serious the severity of PD were,the worse the motor performance of infants. Conversely, the incidence of PD increased in infants with poor motor performance.

Circulating HDAC4 reflects lipid profile, coronary stenosis and inflammation in coronary heart disease patients.

Aim: To investigate the clinical value of HDAC4 in coronary heart disease (CHD) patients. Methods: The serum HDAC4 levels were determined by ELISA in 180 CHD patients and 50 healthy controls. Results: HDAC4 was decreased in CHD patients compared with healthy controls (p < 0.001). HDAC4 was negatively linked with serum creatinine (p = 0.014), low-density lipoprotein cholesterol (p = 0.027) and C-reactive protein (p = 0.006) in CHD patients. Moreover, HDAC4 was inversely related to TNF-α (p = 0.012), IL-1ß (p = 0.002), IL-6 (p = 0.034), IL-17A (p = 0.023), VCAM1 (p = 0.014) and Gensini score (p = 0.001). Unfortunately, neither HDAC4 high (vs low) (p = 0.080) nor HDAC4 quartile (p = 0.268) estimated major adverse cardiovascular event risk. Conclusion: Circulating HDAC4 levels have disease monitoring value but are less valuable in estimating prognosis in CHD patients.

What was this article about? This study aimed to assess the clinical significance of identifying a marker named histone deacetylase 4 (HDAC4) in coronary heart disease (CHD) patients. What was done? Blood was taken from 180 CHD patients and 50 healthy controls, and their blood HDAC4 levels were evaluated. What were the results? HDAC4 levels were higher in CHD patients than in the controls. The CHD patients with a higher HDAC4 level had good kidney health and lower lipid profile, milder inflammation, good vascular status and less narrowing in their blood vessels. However, the HDAC4 level was not found to predict the risk of future cardiovascular disease. What do the results mean? A higher HDAC4 level in the blood of CHD patients suggests a better symptomatic disease status.

The landscape of objective response rate of anti-PD-1/L1 monotherapy across 31 types of cancer: a system review and novel biomarker investigating.

BACKGROUND: Immune checkpoint inhibitors (ICIs) have dramatically changed the landscape of cancer treatment. However, only a few patients respond to ICI treatment. Thus, uncovering clinically accessible ICI biomarkers would help identify which patients will respond well to ICI treatment. A comprehensive objective response rate (ORR) data of anti-PD-1/PD-L1 monotherapy in pan-cancer would offer the original data to explore the new biomarkers for ICIs. METHODS: We systematically searched PubMed, Cochrane, and Embase for clinical trials on July 1, 2021, limited to the years 2017-2021, from which we obtained studies centering around anti-PD-1/PD-L1 monotherapy. Finally, 121 out of 3099 publications and 143 ORR data were included. All of the 31 tumor types/subtypes can be found in the TCGA database. The gene expression profiles and mutation data were downloaded from TCGA. A comprehensive genome-wide screening of ORR highly correlated mutations among 31 cancers was conducted by Pearson correlation analysis based on the TCGA database. RESULTS: According to the ORR, we classified 31 types of cancer into high, medium, and low response types. Further analysis uncovered that "high response" cancers had more T cell infiltration, more neoantigens, and less M2 macrophage infiltration. A panel of 28 biomarkers reviewed from recent articles were investigated with ORR. We also found the TMB as a traditional biomarker had a high correlation coefficient with ORR in pan-cancer, however, the correlation between ITH and ORR was low across pan-cancer. Moreover, we primarily identified 1044 ORR highly correlated mutations through a comprehensive screening of TCGA data, among which USH2A, ZFHX4 and PLCO mutations were found to be highly correlated to strengthened tumor immunogenicity and inflamed antitumor immunity, as well as improved outcomes for ICIs treatment among multiple immunotherapy cohorts. CONCLUSION: Our study provides comprehensive data on ORR of anti-PD-1/PD-L1 monotherapy across 31 tumor types/subtypes and an essential reference of ORR to explore new biomarkers. We also screened out a list of 1044 immune response related genes and we showed that USH2A, ZFHX4 and PLCO mutations may act as good biomarkers for predicting patient response to anti-PD-1/PD-L1 ICIs.

Serum Amyloid a Predicts Prognosis and Chemotherapy Efficacy in Patients with Advanced Pancreatic Cancer.

Purpose: There is an urgent need to discover a predictive biomarker to help patients with advanced pancreatic cancer (APC) choose appropriate chemotherapy regimens. This study aimed to determine whether baseline serum amyloid A (SAA) levels were associated with overall survival (OS), progression-free survival (PFS), and treatment response in patients with APC received chemotherapy. Patients and Methods: This retrospective study included 268 patients with APC who received first-line chemotherapy at the Sun Yat-Sen University Cancer Center between January 2017 and December 2021. We examined the effect of baseline SAA on OS, PFS and chemotherapy response. The X-Tile program was used to determine the critical value for optimizing the significance of segmentation between Kaplan-Meier survival curves. The Kaplan-Meier curves and Cox regression analyses were used to analyze OS and PFS. Results: The best cut-off value of baseline SAA levels for OS stratification was 8.2 mg/L. Multivariate analyses showed that SAA was an independent predictor of OS (Hazard Ratio (HR) = 1.694, 95% Confidence Interval (CI) = 1.247-2.301, p = 0.001) and PFS (HR = 1.555, 95% CI = 1.152-2.098, p = 0.004). Low SAA was associated with longer OS (median, 15.7 months vs 10.0 months, p < 0.001) and PFS (median, 7.6 months vs 4.8 months, p < 0.001). The patients with a low SAA who received mFOLFIRINOX had longer OS (median, 28.5 months vs 15.1 months, p = 0.019) and PFS (median, 12.0 months vs 7.4 months, p = 0.035) than those who received nab-paclitaxel plus gemcitabine (AG) or SOXIRI, whereas there was no significant difference among the three chemotherapy regimens in patients with a high SAA. Conclusion: Owing to the rapid and simple analysis of peripheral blood, baseline SAA might be a useful clinical biomarker, not only as a prognostic biomarker for patients with APC, but also as a guide for the selection of chemotherapy regimens.