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2.
J Chromatogr A ; 1726: 464975, 2024 May 08.
Article in English | MEDLINE | ID: mdl-38735118

ABSTRACT

In conventional chromatographic ligand screening, underperforming ligands are often dismissed. However, this practice may inadvertently overlook potential opportunities. This study aims to investigate whether these underperforming ligands can be repurposed as valuable assets. Hydrophobic charge-induction chromatography (HCIC) is chosen as the validation target for its potential as an innovative chromatographic mode. A novel dual-ligand approach is employed, combining two suboptimal ligands (5-Aminobenzimidazole and Tryptamine) to explore enhanced performance and optimization prospects. Various dual-ligand HCIC resins with different ligand densities were synthesized by adjusting the ligand ratio and concentration. The resins were characterized to assess appearance, functional groups, and pore features using SEM, FTIR, and ISEC techniques. Performance assessments were conducted using single-ligand mode resins as controls, evaluating the selectivity against human immunoglobulin G and human serum albumin. Static adsorption experiments were performed to understand pH and salt influence on adsorption. Breakthrough experiments were conducted to assess dynamic adsorption capacity of the novel resin. Finally, chromatographic separation using human serum was performed to evaluate the purity and yield of the resin. Results indicated that the dual-ligand HCIC resin designed for human antibodies demonstrates exceptional selectivity, surpassing not only single ligand states but also outperforming certain high-performing ligand types, particularly under specific salt and pH conditions. Ultimately, a high yield of 83.9 % and purity of 96.7 % were achieved in the separation of hIgG from human serum with the dual-ligand HCIC, significantly superior to the single-ligand resins. In conclusion, through rational design and proper operational conditions, the dual-ligand mode can revitalize underutilized ligands, potentially introducing novel and promising chromatographic modes.

3.
Nat Plants ; 2024 May 13.
Article in English | MEDLINE | ID: mdl-38740943

ABSTRACT

In plants, the rapid accumulation of proline is a common response to combat abiotic stress1-7. Delta-1-pyrroline-5-carboxylate synthase (P5CS) is a rate-limiting enzyme in proline synthesis, catalysing the initial two-step conversion from glutamate to proline8. Here we determine the first structure of plant P5CS. Our results show that Arabidopsis thaliana P5CS1 (AtP5CS1) and P5CS2 (AtP5CS2) can form enzymatic filaments in a substrate-sensitive manner. The destruction of AtP5CS filaments by mutagenesis leads to a significant reduction in enzymatic activity. Furthermore, separate activity tests on two domains reveal that filament-based substrate channelling is essential for maintaining the high catalytic efficiency of AtP5CS. Our study demonstrates the unique mechanism for the efficient catalysis of AtP5CS, shedding light on the intricate mechanisms underlying plant proline metabolism and stress response.

4.
Eur J Med Chem ; 271: 116404, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38631262

ABSTRACT

Hearing loss (HL) is a health burden that seriously affects the quality of life of cancer patients receiving platinum-based chemotherapy, and few FDA-approved treatment specifically targets this condition. The main mechanisms that contribute to cisplatin-induced hearing loss are oxidative stress and subsequent cell death, including ferroptosis revealed by us as a new mechanism recently. In this study, we employed the frontier molecular orbital (FMO) theory approach as a convenient prediction method for the glutathione peroxidase (GPx)-like activity of isoselenazolones and discovered new isoselenazolones with great GPx-like activity. Notably, compound 19 exhibited significant protective effects against cisplatin-induced hair cell (HC) damage in vitro and in vivo and effectively reverses cisplatin-induced hearing loss through oral administration. Further investigations revealed that this compound effectively alleviated hair cell oxidative stress, apoptosis and ferroptosis. This research highlights the potential of GPx mimics as a therapeutic strategy against cisplatin-induced hearing loss. The application of quantum chemistry (QC) calculations in the study of GPx mimics sheds light on the development of new, innovative treatments for hearing loss.


Subject(s)
Cisplatin , Glutathione Peroxidase , Hearing Loss , Cisplatin/pharmacology , Glutathione Peroxidase/metabolism , Animals , Hearing Loss/drug therapy , Hearing Loss/chemically induced , Humans , Quantum Theory , Molecular Structure , Mice , Structure-Activity Relationship , Small Molecule Libraries/chemistry , Small Molecule Libraries/pharmacology , Small Molecule Libraries/chemical synthesis , Oxidative Stress/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Drug Discovery , Dose-Response Relationship, Drug , Apoptosis/drug effects
5.
Heliyon ; 10(7): e29242, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38623198

ABSTRACT

Objective: The ultrasonic cardiac output monitor (USCOM), an instrument that monitors the evolution of a patient's hemodynamic status and determines the type of shock, has become an important tool for assessing cardiac pathology and predicting changes in disease, but there are some variations in the instrumental findings for different physical conditions of patients. This article examines whether there are differences in the quality of USCOM waveforms measured in different types of critically ill patients based on clinical characteristics and test parameters. Methods: Baseline data, diagnoses, echocardiograms, ventilation patterns, and USCOM results were retrospectively collected from patients in the emergency intensive care unit. Waveform quality was quantified using the Fremantle score to determine the extent to which age, body mass index (BMI), chronic obstructive pulmonary disease (COPD), respiratory failure, cardiac enlargement, valvular heart disease, and ventilation pattern influenced USCOM waveform quality. Results: Age, body mass index, chronic obstructive pulmonary disease, respiratory failure, right and left heart enlargement, aortic valve disease (excluding aortic stenosis), and ventilation mode did not have a significant effect on USCOM waveform quality in critically ill patients (P > 0.05). Conclusions: Various physical conditions of critically ill patients may have limited effect on the quality of the USCOM waveform, potentially rendering USCOM suitable for early assessment of hemodynamic status during ICU admission.

6.
BMC Plant Biol ; 24(1): 261, 2024 Apr 10.
Article in English | MEDLINE | ID: mdl-38594606

ABSTRACT

BACKGROUND: Rhubarb is one of common traditional Chinese medicine with a diverse array of therapeutic efficacies. Despite its widespread use, molecular research into rhubarb remains limited, constraining our comprehension of the geoherbalism. RESULTS: We assembled the genome of Rheum palmatum L., one of the source plants of rhubarb, to elucidate its genome evolution and unpack the biosynthetic pathways of its bioactive compounds using a combination of PacBio HiFi, Oxford Nanopore, Illumina, and Hi-C scaffolding approaches. Around 2.8 Gb genome was obtained after assembly with more than 99.9% sequences anchored to 11 pseudochromosomes (scaffold N50 = 259.19 Mb). Transposable elements (TE) with a continuous expansion of long terminal repeat retrotransposons (LTRs) is predominant in genome size, contributing to the genome expansion of R. palmatum. Totally 30,480 genes were predicted to be protein-coding genes with 473 significantly expanded gene families enriched in diverse pathways associated with high-altitude adaptation for this species. Two successive rounds of whole genome duplication event (WGD) shared by Fagopyrum tataricum and R. palmatum were confirmed. We also identified 54 genes involved in anthraquinone biosynthesis and other 97 genes entangled in flavonoid biosynthesis. Notably, RpALS emerged as a compelling candidate gene for the octaketide biosynthesis after the key residual screening. CONCLUSION: Overall, our findings offer not only an enhanced understanding of this remarkable medicinal plant but also pave the way for future innovations in its genetic breeding, molecular design, and functional genomic studies.


Subject(s)
Rheum , Rheum/genetics , Plant Breeding , Anthraquinones , Chromosomes , Genome Size , Evolution, Molecular
7.
Front Neurol ; 15: 1302874, 2024.
Article in English | MEDLINE | ID: mdl-38601339

ABSTRACT

Background and purpose: Irregular pulsation of the aneurysmal wall has been suggested as a novel predictor for aneurysm rupture. Aneurysm volume variations during the cardiac cycle and the association between irregular pulsation and morphological features have been discussed, but the clinical significance remains unclear. The purpose of this study was to quantify changes in morphological characteristics over the cardiac cycle and examine their correlation with irregular pulsation to facilitate comprehension of aneurysm dynamics. Materials and methods: Fourteen unruptured intracranial aneurysms (UIAs) from 11 patients were included in this study, and each of them underwent 4D-CTA after diagnosis by DSA. The R-R intervals were divided into 20-time phases at 5% intervals to determine whether an aneurysm had irregular pulsation throughout the cardiac cycle. CT images from the 20-time phases were used to reconstruct 3D aneurysm models, measure 14 morphological parameters, and quantify each parameter's absolute change and relative rates of change during the cardiac cycle. Results: Seven of 14 UIAs exhibited irregular pulsation over the cardiac cycle by 4D-CTA, 5 of which were small aneurysms (< 7 mm). The UIAs with irregular pulsation exhibited greater changes in morphological characteristics. As aneurysm size increased, the absolute change in aneurysm volume increased (p = 0.035), but the relative rates of change in aneurysm size (p = 0.013), height (p = 0.014), width (p = 0.008), height-to-width ratio (p = 0.009), dome-to-neck ratio (p = 0.019) and bottleneck factor (p = 0.012) decreased. Conclusion: Although the larger the aneurysm, the greater the amplitude of its volumetric variation, small aneurysms are prone to irregular pulsation during the cardiac cycle and have more pronounced and dramatic morphological changes during the cardiac cycle that may increase the risk of rupture. This proof-of-concept study could help to explain the importance of dynamic changes using 4D-CTA in assessing the rupture risk of UIAs.

8.
Biochem Genet ; 2024 Apr 20.
Article in English | MEDLINE | ID: mdl-38642176

ABSTRACT

In this cohort of 217 bladder cancer patients and 484 healthy controls, we explored the association between CYP24A1 variants (rs2762934, rs1570669, rs6068816, rs2296241) and bladder cancer risk in the Chinese Han population. Utilizing the Agena MassARRAY system, we genotyped four selected CYP24A1 polymorphisms. Logistic regression revealed a significant association of rs2762934 and rs1570669 with elevated bladder cancer risk, while rs6068816 exhibited a protective effect. Bioinformatics analysis of CYP24A1 expression in normal and cancerous bladder tissues indicated higher expression in normal tissue. In conclusion, our findings highlight the potential role of CYP24A1 variants in bladder cancer susceptibility.

9.
Appl Opt ; 63(9): 2352-2361, 2024 Mar 20.
Article in English | MEDLINE | ID: mdl-38568591

ABSTRACT

Improving the spectrum efficiency (SE) is an effective method to further enhance the data rate of bandwidth-limited underwater wireless optical communication (UWOC) systems. Non-orthogonal frequency-division multiplexing (NOFDM) with a compression factor of 0.5 can save half of the bandwidth without introducing any inter-carrier-interference (ICI) only if the total number of subcarriers is large enough, and we termed it as half-spectrum OFDM (HS-OFDM). To the best of our knowledge, this is the first reported work on a closed-form HS-OFDM signal in the discrete domain from the perspective of a correlation matrix. Due to the special mathematical property, no extra complex decoding algorithm is required at the HS-OFDM receiver, making it as simple as the conventional OFDM receiver. Compared with traditional OFDM, HS-OFDM can realize the same data rate, but with a larger signal-to-noise ratio (SNR) margin. To fully use the SNR resource of the communication system, we further propose a digital power division multiplexed HS-OFDM (DPDM-HS-OFDM) scheme to quadruple the SE of conventional OFDM for the bandwidth-starved UWOCs. The experimental results show that HS-OFDM can improve the receiver sensitivity by around 4 dB as opposed to conventional 4QAM-OFDM with the same data rate and SE. With the help of the DPDM-HS-OFDM scheme, the data rate of multi-user UWOC can reach up to 4.5 Gbps under the hard-decision forward error correction (HD-FEC) limit of a bit error rate (BER) of 3.8×10-3. Although there is some performance degradation in comparison with single-user HS-OFDM, the BER performance of multi-user DPDM-HS-OFDM is still superior to that of conventional single-user 4QAM-OFDM. Both single-user HS-OFDM and multi-user DPDM-HS-OFDM successfully achieve 2 Gbps/75 m data transmission, indicating that the DPDM-HS-OFDM scheme is of great importance in bandwidth-limited UWOC systems and has guiding significance to underwater wireless optical multiple access.

10.
Materials (Basel) ; 17(8)2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38673227

ABSTRACT

As the most stable phase of gallium oxide, ß-Ga2O3 can enable high-quality, large-size, low-cost, and controllably doped wafers by the melt method. It also features a bandgap of 4.7-4.9 eV, a critical electric field strength of 8 MV/cm, and a Baliga's figure of merit (BFOM) of up to 3444, which is 10 and 4 times higher than that of SiC and GaN, respectively, showing great potential for application in power devices. However, the lack of effective p-type Ga2O3 limits the development of bipolar devices. Most research has focused on unipolar devices, with breakthroughs in recent years. This review mainly summarizes the research progress fora different structures of ß-Ga2O3 power diodes and gives a brief introduction to their thermal management and circuit applications.

11.
PLoS One ; 19(4): e0298314, 2024.
Article in English | MEDLINE | ID: mdl-38662750

ABSTRACT

OBJECTIVE: While growing psychological health issues among pregnant women during the COVID-19 pandemic have been clearly validated, most research was conducted in countries with relatively lax quarantine measures. This study aimed to compare the prevalence of prenatal depression among pre-, peak-, and post-COVID-19 in Beijing, the region with a stringent response policy in China. We also explore predictors of prenatal depression throughout the outbreak. METHODS: We investigated prenatal depression among 742 pregnant women who received antenatal checkups in Beijing from March 28, 2019 to May 07, 2021 using the Edinburgh Postnatal Depression Scale and associative demographic, pregnancy-related, and psychosocial characteristics were measured. The phase was divided into pre-, peak-, and post-COVID-19 in light of the trajectory of COVID-19. Pearson's Chi-square test was used after the examination of confounders homogeneity. The bivariable and multivariable logistic regression was conducted to explore predictors. RESULTS: The pooled prevalence of prenatal depression was 11.9% throughout the COVID-19 pandemic. Rates at different phases were 10.6%, 15.2%, and 11.1% respectively and no significant difference was observed. Multivariable logistic regression revealed that history of mental illness, number of boy-preference from both pregnant women and husband's family, social support, occupation, and living space were independent predictors of prenatal depression in Beijing. CONCLUSION: Our data suggested that the impact of this pandemic on prenatal depression in Beijing appears to be not significant, which will strengthen confidence in adhering to current policy for decision-makers and provide important guidance for the development of major outbreak control and management policies in the future. Our findings may also provide a more efficient measure to identify high-risk pregnant women for professionals and help raise gender equity awareness of pregnant women and their husbands' families. Future studies should focus on the value of targeted care and family relations on the mental health of pregnant women.


Subject(s)
COVID-19 , Depression , Humans , COVID-19/epidemiology , COVID-19/psychology , Female , Pregnancy , Adult , Prevalence , Beijing/epidemiology , Depression/epidemiology , SARS-CoV-2 , Pandemics , Pregnancy Complications/epidemiology , Pregnancy Complications/psychology , Pregnant Women/psychology , Young Adult , China/epidemiology
14.
medRxiv ; 2024 Mar 22.
Article in English | MEDLINE | ID: mdl-38562806

ABSTRACT

INTRODUCTION: Intravenous (IV) medications are a fundamental cause of fluid overload (FO) in the intensive care unit (ICU); however, the association between IV medication use (including volume), administration timing, and FO occurrence remains unclear. METHODS: This retrospective cohort study included consecutive adults admitted to an ICU ≥72 hours with available fluid balance data. FO was defined as a positive fluid balance ≥7% of admission body weight within 72 hours of ICU admission. After reviewing medication administration record (MAR) data in three-hour periods, IV medication exposure was categorized into clusters using principal component analysis (PCA) and Restricted Boltzmann Machine (RBM). Medication regimens of patients with and without FO were compared within clusters to assess for temporal clusters associated with FO using the Wilcoxon rank sum test. Exploratory analyses of the medication cluster most associated with FO for medications frequently appearing and used in the first 24 hours was conducted. RESULTS: FO occurred in 127/927 (13.7%) of the patients enrolled. Patients received a median (IQR) of 31 (13-65) discrete IV medication administrations over the 72-hour period. Across all 47,803 IV medication administrations, ten unique IV medication clusters were identified with 121-130 medications in each cluster. Among the ten clusters, cluster 7 had the greatest association with FO; the mean number of cluster 7 medications received was significantly greater in patients in the FO cohort compared to patients who did not experience FO (25.6 vs.10.9. p<0.0001). 51 of the 127 medications in cluster 7 (40.2%) appeared in > 5 separate 3-hour periods during the 72-hour study window. The most common cluster 7 medications included continuous infusions, antibiotics, and sedatives/analgesics. Addition of cluster 7 medications to a prediction model with APACHE II score and receipt of diuretics improved the ability for the model to predict fluid overload (AUROC 5.65, p =0.0004). CONCLUSIONS: Using ML approaches, a unique IV medication cluster was strongly associated with FO. Incorporation of this cluster improved the ability to predict development of fluid overload in ICU patients compared with traditional prediction models. This method may be further developed into real-time clinical applications to improve early detection of adverse outcomes.

15.
Arch Oral Biol ; 163: 105941, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38599038

ABSTRACT

OBJECTIVE: Crown dimensions data of deciduous teeth hold anthropological, forensic, and archaeological value. However, such information remains scarce for the Chinese population. This multi-center study aimed to collect a large sample of deciduous crown data from Chinese children using three-dimensional measurement methods and to analyze their dimensions. DESIGN: A total of 1592 children's deciduous dentition samples were included, and the sample size was distributed according to Northeast, North, East, Northwest, Southwest and South China. Digital dental models were reconstructed from plaster dental models. Independent sample t test, paired t test, principal component analysis (PCA), and factor analysis (FA) were used to analyze the tooth crown dimensions. RESULT: 18,318 deciduous teeth from 1592 children were included. Males exhibited slightly larger values than females. The range of sexual dimorphism percentages for each measurement was as follows: mesiodistal diameter (0.40-2.08), buccolingual diameter (0.13-2.24), and maxillogingival diameter (0.48-3.37). The FA results showed that the main trend of crown dimensions changes was the simultaneous increase or decrease in mesiodistal diameter, buccolingual diameter and maxillogingival diameter in three directions. CONCLUSION: This is the first large-scale survey of deciduous tooth crown dimensions in China, which supplements the data of deciduous tooth measurement and provides a reference for clinical application.


Subject(s)
Tooth Crown , Tooth, Deciduous , Humans , Tooth, Deciduous/anatomy & histology , China , Male , Female , Cross-Sectional Studies , Child , Tooth Crown/anatomy & histology , Principal Component Analysis , Models, Dental , Child, Preschool , Imaging, Three-Dimensional/methods , Odontometry/methods , Factor Analysis, Statistical , Sex Characteristics
16.
J Integr Med ; 2024 Apr 23.
Article in English | MEDLINE | ID: mdl-38688809

ABSTRACT

BACKGROUND: Yiqi Peiyuan (YQPY) prescription, a composite prescription of traditional Chinese medicine, has been used to prevent or delay the continued deterioration of renal function after acute kidney injury (AKI) in some institutions and has shown considerable efficacy. OBJECTIVE: This is the first randomized controlled trial to assess efficacy and safety of YQPY for improving short-term prognosis in adult patients with AKI. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This is a prospective, double-blind, multicenter, randomized, and placebo-controlled clinical trial. A total of 144 enrolled participants were randomly allocated to two groups according to a randomization schedule. Participants, caregivers and investigators assessing the outcomes were blinded to group assignment. Patients in the YQPY group received 36 g YQPY granules twice a day for 28 days. Patients in the placebo group received a placebo in the same dose as the YQPY granules. MAIN OUTCOME MEASURES: The primary outcome was the change in the estimated glomerular filtration rate (eGFR) between baseline and after 4 and 24 weeks of treatment. The secondary outcomes were the change of serum creatinine (Scr) level between baseline and after treatment, and the incidence of endpoint events, defined as eGFR increasing by more than 25% above baseline, eGFR >75 mL/min per 1.73 m2 or the composite endpoint, which was defined as the sum of patients meeting either of the above criteria. RESULTS: Data from a total of 114 patients (59 in the YQPY group and 55 in the control group) were analyzed. The mean changes in eGFR and Scr in weeks 4 and 24 had no difference between the two groups. In further subgroup analysis (22 in the YQPY group and 31 in the control group), the mean change in eGFR after treatment for 4 weeks was 27.39 mL/min per 1.73 m2 in the YQPY group and 5.78 mL/min per 1.73 m2 in the placebo group, and the mean difference between groups was 21.61 mL/min per 1.73 m2 (P <0.001). Thirteen (59.1%) patients in the YQPY group and 5 (16.1%) in the placebo group reached the composite endpoints (P = 0.002). During the intervention, 2 and 4 severe adverse events were reported in the YQPY and placebo groups, respectively. CONCLUSION: The YQPY granules can effectively improve the renal function of patients 4 weeks after the onset of AKI, indicating that it has good efficacy for improving short-term renal outcomes in patients with AKI. The YQPY granules may be a promising therapy for adults with AKI. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100051723. Please cite this article as: Wu JJ, Zhang TY, Qi YH, Zhu MY, Fang Y, Qi CJ, et al. Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with acute kidney injury: a multicenter, double-blind, placebo-controlled, randomized trial. J Integr Med. 2024; Epub ahead of print.

17.
J Adv Res ; 2024 Apr 27.
Article in English | MEDLINE | ID: mdl-38685529

ABSTRACT

INTRODUCTION: Effective targeting drugs for KRAS mutation-mediated Lung Adenocarcinoma (LUAD) are currently are limited. OBJECTIVES: Investigating and intervening in the downstream key target genes of KRAS is crucial for clinically managing KRAS mutant-driven LUAD. GTF3C6, a newly identified member of the general transcription factor III (GTF3) family, plays a role in the transcription of RNA polymerase III (pol III)-dependent genes. However, its involvement in cancer remains unexplored. METHODS: This study examined the expression, roles, and potential molecular mechanisms of GTF3C6 in LUAD tissues, LSL-KrasG12D/+;LSL-p53-/- LUAD mouse models, and LUAD patients-derived organoid using Western blot, qRT-PCR, immunofluorescence, immunohistochemistry, and gene manipulation assays. RESULTS: We present the first evidence that GTF3C6 is highly expressed in LUAD tissues, LSL-KrasG12D/+;LSL-p53-/- LUAD mouse models, and LUAD organoids, correlating with poor clinical prognosis. Furthermore, GTF3C6 was found to promote anchorage-independent proliferation, migration, and invasion of LUAD cells. Mechanistically, KRAS mutation drives GTF3C6 expression through the PI3K pathway, and GTF3C6 knockdown reverses the malignant phenotype of KRAS mutation-driven LUAD cells. Additionally, the FAK pathway emerged as a crucial downstream signaling pathway through which GTF3C6 mediates the malignant phenotype of LUAD. Finally, GTF3C6 knockdown suppresses LUAD organoid formation and inhibits tumor growth in vivo. CONCLUSION: Our findings demonstrate that GTF3C6, driven by KRAS mutation, promotes LUAD development by regulating FAK phosphorylation, suggesting its potential as a biomarker and therapeutic target in KRAS mutant-driven LUAD.

18.
Article in English | MEDLINE | ID: mdl-38527247

ABSTRACT

Objective: Pyrotinib, a new irreversible dual pan-human epidermal growth factor receptor 2 (HER2) receptor tyrosine kinase inhibitor blocking EGFR and HER2, has achieved a promising efficacy for advanced HER2-positive (HER2+) breast cancer. This study intended to further investigate the efficacy and safety of neoadjuvant pyrotinib and trastuzumab plus chemotherapy for HER2+ breast cancer treatment. Methods: Thirty-eight HER2+ breast cancer patients who received neoadjuvant pyrotinib and trastuzumab plus chemotherapy (docetaxel and carboplatin) were retrospectively reviewed. Clinical response by Response Evaluation Criteria in Solid Tumors (RECIST), pathological complete response (pCR), and adverse events data was retrieved. Results: According to the RECIST, the complete response rate was 0.0%, 10.5%, and 15.8% after second-cycle, fourth-cycle, and sixth-cycle therapy, respectively; whereas the objective response rate was 76.3%, 92.1%, and 100.0%, accordingly. The total pCR (tpCR) rate was 52.6%, the pCR rate of the breast was also 52.6%, and the pCR rate of lymph nodes was 86.8%. The tpCR rate was lower in patients with HER2 immunohistochemistry (IHC)++ and amplification by fluorescent in situ hybridization (FISH) than in those with HER2 IHC+++ (14.3% vs. 61.3%, p = 0.024), which was also lower in patients with Ki-67 expression ≥30% than in those with Ki-67 expression <30% (40.0% vs. 76.9%, p = 0.031). The common adverse events included diarrhea (84.2%), anemia (73.7%), nausea and vomiting (63.2%), fatigue (50.0%), hypomagnesemia (44.7%), leukopenia (42.1%), thrombocytopenia (39.5%), elevated transaminase (36.8%), and pruritus (31.6%). Conclusions: Pyrotinib and trastuzumab plus chemotherapy serve as an acceptable neoadjuvant regimen exhibiting good efficacy and tolerance in HER2+ breast cancer patients, while further large-scale validation is warranted.

19.
Heliyon ; 10(6): e27769, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38515672

ABSTRACT

Objective: This review aims to conduct a comprehensive study of the diagnostic accuracy of interleukin-6 (IL-6) for multiple diseases by utilizing existing systematic reviews and meta-analyses. Methods: We performed a thorough search of Embase, Web of Science, PubMed, and Cochrane Database of Systematic Reviews up to April 2023 to gather meta-analyses that investigate the diagnostic accuracy of IL-6. To assess the methodological quality of the studies, we employed the Assessing the Methodological Quality of Systematic Reviews-2 and Grading of Recommendations, Assessment, Development and Evaluation criteria. Results: We included 34 meta-analyses out of the 3024 articles retrieved from the search. These meta-analyses covered 9 categories of diseases of the International Classification of Diseases-11. Studies rated as "Critically Low" or "Very Low" in the quality assessment process were excluded, resulting in a total of 6 meta-analyses that encompassed sepsis, colorectal cancer, tuberculous pleural effusion (TPE), endometriosis, among others. Among these diseases, IL-6 demonstrated a relatively high diagnostic potential in accurately identifying TPE and endometriosis. Conclusions: IL-6 exhibited favorable diagnostic accuracy across multiple diseases, suggesting its potential as a reliable diagnostic biomarker in the near future. Substantial evidence supported its high diagnostic accuracy, particularly in the cases of TPE and endometriosis.

20.
Eur J Clin Invest ; : e14202, 2024 Mar 30.
Article in English | MEDLINE | ID: mdl-38553975

ABSTRACT

BACKGROUND: High-altitude pulmonary oedema (HAPE) is a form of noncardiogenic pulmonary oedema. Studies have found that long noncoding RNA (lncRNA) plays an important role in HAPE. ANRIL is significant in pulmonary illnesses, which implies that alterations in ANRIL expression levels may be involved in the beginning and development of HAPE. However, the specific mechanism is indistinct. The present study is meant to explore the effect and mechanism of ANRIL on hypoxic-induced injury of pulmonary microvascular endothelial cells (PMEVCs). METHODS: In the hypoxic model of PMVECs, overexpression of ANRIL or knockdown of miR-181c-5p was performed to assess cell proliferation, apoptosis, and migration. Furthermore, the levels of apoptosis-related proteins, inflammatory factors, and vascular active factors were also measured. RESULTS: The results showed that, after 24 h of hypoxia, PMVECs proliferation and migration were suppressed in comparison to the control group, along with an increase in apoptosis, a decrease in the expression of ANRIL, and an increase in the expression of miR-181c-5p (all p < .05). The damage caused by hypoxia in PMVECs can be lessened by overexpressing ANRIL, which also inhibits the production of TNF-α, iNOS, and VEGF as well as BAX and cleaved caspase-3 (all p < .05). Further experimental results showed that overexpression of ANRIL and knockdown of miR-181c-5p had the same protection against hypoxic injury in PMVECs (all p < .05). CONCLUSIONS: Our study suggests that ANRIL may prevent hypoxia injury to PMVECs in HAPE through the negative regulation of miR-181c-5p.

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