[The Efficacy and Safety of Venetoclax Combined with Azacitidine in the Treatment of Adult Patients with Acute Myeloid Leukemia Who Are Unfit for Intensive Chemotherapy].

OBJECTIVE: To observe the clinical efficacy and safety of venetoclax (VEN) combined with azacitidine (AZA) in the treatment of adult acute myeloid leukemia (AML) patients who are unfit for intensive chemotherapy. METHODS: The clinical data of 21 adult patients with unfit AML who were treated with VEN combined with AZA in the Second Hospital of Shanxi Medical University from January 2021 to May 2022 were collected, and the efficacy and safety were analyzed retrospectively. RESULTS: After one course of treatment with VEN and AZA, 16 out of 21 unfit AML patients reached complete remission (CR)/CR with incomplete hematologic recovery (CRi), 2 patients reached partial remission (PR), the overall response rate (ORR) was 85.7%. Among the 16 patients with CR/CRi, 13 achieved minimal residual disease (MRD) negativity. Among the 11 patients with adverse prognosis, 8 achieved CR/CRi. By the deadline of follow-up, the median overall suivival (OS) of the entire cohort was not reached, with 1-year OS rate of 61.7%. The main adverse events of VEN combined with AZA were myelosuppression, gastrointestinal reactions and infections. There were 13 cases of leukopenia, 7 cases of neutropenia, 7 cases of anemia, 4 cases of thrombocytopenia, and these hematologic adverse events were all grade 3-4. There were 11 cases with gastrointestinal reactions and 7 cases with infections. The above adverse events were controllable and tolerable. No tumor lysis syndrome or infection related death occurred. CONCLUSION: VEN combined with AZA can quickly achieve deep remission in adult patients with unfit AML, and it shows a good safety profile.

A deep learning-based 3D Prompt-nnUnet model for automatic segmentation in brachytherapy of postoperative endometrial carcinoma.

PURPOSE: To create and evaluate a three-dimensional (3D) Prompt-nnUnet module that utilizes the prompts-based model combined with 3D nnUnet for producing the rapid and consistent autosegmentation of high-risk clinical target volume (HR CTV) and organ at risk (OAR) in high-dose-rate brachytherapy (HDR BT) for patients with postoperative endometrial carcinoma (EC). METHODS AND MATERIALS: On two experimental batches, a total of 321 computed tomography (CT) scans were obtained for HR CTV segmentation from 321 patients with EC, and 125 CT scans for OARs segmentation from 125 patients. The numbers of training/validation/test were 257/32/32 and 87/13/25 for HR CTV and OARs respectively. A novel comparison of the deep learning neural network 3D Prompt-nnUnet and 3D nnUnet was applied for HR CTV and OARs segmentation. Three-fold cross validation and several quantitative metrics were employed, including Dice similarity coefficient (DSC), Hausdorff distance (HD), 95th percentile of Hausdorff distance (HD95%), and intersection over union (IoU). RESULTS: The Prompt-nnUnet included two forms of parameters Predict-Prompt (PP) and Label-Prompt (LP), with the LP performing most similarly to the experienced radiation oncologist and outperforming the less experienced ones. During the testing phase, the mean DSC values for the LP were 0.96 ± 0.02, 0.91 ± 0.02, and 0.83 ± 0.07 for HR CTV, rectum and urethra, respectively. The mean HD values (mm) were 2.73 ± 0.95, 8.18 ± 4.84, and 2.11 ± 0.50, respectively. The mean HD95% values (mm) were 1.66 ± 1.11, 3.07 ± 0.94, and 1.35 ± 0.55, respectively. The mean IoUs were 0.92 ± 0.04, 0.84 ± 0.03, and 0.71 ± 0.09, respectively. A delineation time < 2.35 s per structure in the new model was observed, which was available to save clinician time. CONCLUSION: The Prompt-nnUnet architecture, particularly the LP, was highly consistent with ground truth (GT) in HR CTV or OAR autosegmentation, reducing interobserver variability and shortening treatment time.

Retinal structure and vessel density changes in cerebral small vessel disease.

Background: Cerebral small vessel disease (CSVD) attaches people's attention in recent years. In this study, we aim to explore retinal structure and vessel density changes in CSVD patients. Methods: We collected information on retinal metrics assessed by optical coherence tomography (OCT) and OCT angiography and CSVD characters. Logistic and liner regression was used to analyze the relationship between retinal metrics and CSVD. Results: Vessel density of superficial retinal capillary plexus (SRCP), foveal density- 300 length (FD-300), radial peripapillary capillary (RPC) and thickness of retina were significantly lower in CSVD patients, the difference only existed in the thickness of retina after adjusted relevant risk factors (OR (95% CI): 0.954 (0.912, 0.997), p = 0.037). SRCP vessel density showed a significant downward trend with the increase of CSVD scores (ß: -0.087, 95%CI: -0.166, -0.008, p = 0.031). SRCP and FD-300 were significantly lower in patients with lacunar infarctions and white matter hypertensions separately [OR (95% CI): 0.857 (0.736, 0.998), p = 0.047 and OR (95% CI): 0.636 (0.434, 0.932), p = 0.020, separately]. Conclusion: SRCP, FD-300 and thickness of retina were associated with the occurrence and severity of total CSVD scores and its different radiological manifestations. Exploring CSVD by observing alterations in retinal metrics has become an optional research direction in future.

[Nutrients and Ecological Stoichiometry Characteristics of Typical Wetland Soils in the Lower Yellow River].

Carbon, nitrogen, phosphorus, and potassium in the soil are the necessary nutrient elements for plant growth, and their contents and ecological stoichiometry can reflect the status of soil quality and nutrient limitation. The Huayuankou Yellow River Floating Bridge Wetland in the lower Yellow River was selected as the research object. The methods of ANOVA, redundancy analysis, and linear regression fitting were used to study the contents of organic carbon (SOC), total nitrogen (TN), total phosphorus (TP), total potassium (TK), alkaline nitrogen (AN), available phosphorus (AP), available potassium (AK), and their ecological stoichiometric ratios as well as the limiting elements of soil nutrients, and the key physicochemical properties that affect soil nutrients and their ecological stoichiometry in the wetland were revealed. The results showed that the mean values of ω(SOC), ω(TN), ω(TP), ω(TK), ω(AN), ω(AP), and ω(AK) in wetland soil were 5.46 g·kg-1, 0.60 g·kg-1, 0.28 g·kg-1, 17.06 g·kg-1, 13.75 mg·kg-1, 6.54 mg·kg-1, and 158.56 mg·kg-1, respectively, which showed an increasing trend from the river bank to the shoaly land and were generally higher at the high vegetation coverage areas than at the low vegetation coverage areas. There were significant correlations among SOC, TN, TP, and TK. Soil C/P, C/K, N/P, and N/K showed a consistent trend with soil nutrients, whereas C/N showed the opposite. The coefficients of variation of SOC, TN, AN, N/P, and N/K in the soil exceeded 50.00%, with significant spatial differences. The average value of C/N in wetland soil was 11.882, which was close to the average level of soils in China, whereas the average values of C/P and N/P were 49.119 and 4.516, respectively, both of which were lower than the average level of soils in China, and the N/P of soil was far less than 14, which indicated that N was limited in the soil. The proportion of clay and electrical conductivity combined to explain 61.4% and 43.9% of the variation in the soil nutrients and their ecological stoichiometry, respectively, which were the dominant soil physicochemical properties affecting the soil nutrients and their ecological stoichiometry of Huayuankou Yellow River Floating Bridge Wetland. The research results are helpful to improve our knowledge of nutrients and their influencing factors in the wetland soil of the lower Yellow River and provide an important scientific basis for the ecological restoration and management of the wetland in the lower Yellow River.

Association between gardening and multiple sleep complaints: A nationwide study of 62,098 adults.

BACKGROUND: Physical activity was suggested to be related to sleep health, while the gardening-sleep association among the community population remained unrevealed. Therefore, this study aimed to explore whether gardening was associated with sleep complaints. METHODS: A total of 62,098 adults from the 2017 Behavioral Risk Factor Surveillance System (BRFSS) were included in this study and further categorized as non-exercisers, gardeners, and other exercisers, based on their self-reported exercise status. Sleep complaints including short/prolonged sleep duration, probable insomnia, daytime sleepiness, and sleep apnea were surveyed via a questionnaire. Primary outcome was multiple sleep complaints (coexistence of ≥2 sleep complaints) and secondary outcomes referred to individual sleep complaints. The adjusted odds ratios (ORs) and 95 % confidence intervals (CIs) were estimated to assess the associations between gardening or tertiles of gardening duration and the outcomes using multivariable logistic regression models. RESULTS: The sample included 16,707 non-exercisers, 4243 gardeners, and 41,148 other exercisers. Relative to non-exercisers, gardeners (OR 0.58, 95%CI 0.49-0.67) and other exercisers (OR 0.67, 95%CI 0.61-0.72) had a lower likelihood of experiencing multiple sleep complaints. The adjusted OR comparing the highest gardening duration tertile to non-exercise was 0.45 (95%CI 0.33-0.63) for multiple sleep complaints (P for trend <0.001). Similar patterns persisted in several individual sleep complaints, such as short sleep duration, probable insomnia, daytime sleepiness, and sleep apnea. LIMITATIONS: Cross-sectional study design and use of self-reported variables. CONCLUSIONS: This nationwide study observed an inverse association of gardening with multiple sleep complaints and several individual sleep complaints, in a dose-response manner.

Processable Pickering emulsion for composite cryogel with cellulose nanofibrils and nanochitin.

Cryogels that are constructed with cellulose nanofibrils (CNF) are important as green materials for a wide range of applications. However, their utilization is limited by inherent hydrophilicity and insufficient mechanical properties. Herein, a processable CNF/nanochitin (NCh)-stabilized Pickering emulsion that contains polylactide (PLA) in the oil phase is developed to directly produce ternary composite cryogels via freeze-drying. The complexation of CNF with NCh promotes CNF adsorption at the surface of PLA droplets, resulting in formation of uniform Pickering PLA droplets. The CNF/NCh complex-stabilized PLA droplets are easy to be translated to the internal structure of the cryogels, exhibiting lightweight nature and possessing highly porous structure. The interconnected network and lamellar structure formed by the CNF/NCh complexes, associating with inclusion of PLA particles, improve the cryogel structure integrity upon post-processing and endow hydrophilic cryogel with water resistance. This study offers a straightforward and eco-friendly Pickering emulsion template on fabrication of the CNF-based composite cryogel with controllable microstructure and mechanical performance, broadening construction of nanocellulose-based composites.

Can We Do Breast-Conserving Surgery Without Intraoperative Frozen Section of Margin?

PURPOSE: This study was a retrospective and nonrandomized study to assess the safety and reliability of identifying the surgical margin in breast cancer breast-conserving surgery (BCS) by using intraoperative ultrasonic location and specimen mammography instead of traditional intraoperative frozen pathological section. METHODS: Among the patients who underwent BCS from May 2019 to October 2021, according to the different methods of evaluating the intraoperative margin, 104 breast cancer patients were included in the frozen edge group, 53 breast cancer patients were included in the freeze-free group, and the surgeon judged whether extended resection was needed based on the results of pathological section or evaluation of intraoperative ultrasound and mammography. The surgical margins of the two groups were judged by postoperative pathological results as the gold standard. RESULTS: The median waiting pathology results time in the frozen edge group was 64 minutes, while the waiting time in the freeze-free group was 30 minutes, and the difference was statistically significant (P < .0001). The postoperative pathological results showed that the positive rate of the surgical margin in the frozen edge group was 0.96%. The coincidence rate of intraoperative frozen and postoperative pathological results was 99.04%. The coincidence rate between intraoperative mammography and postoperative pathological results was 100%. CONCLUSIONS: In BCS, the method of using intraoperative staining markers combined with mammography to evaluate the resection margin is highly accurate, reliable, economical and convenient, and at the same time reduces the waiting time of the operator during the operation. However, this was not a randomized controlled study, and there was patient selection bias, and its safety needs to be confirmed by long-term follow-up. In the future, it is expected to become the mainstream means of evaluating.

Why does HER2-positive breast cancer metastasize to the brain and what can we do about it?

Breast cancer is the most frequent malignancy in women. However, in the middle and late stages, some people develop distant metastases, which considerably lower the quality of life and life expectancy. The brain is one of the sites where metastasis frequently happens. According to epidemiological research, brain metastases occur at a late stage in 30-50% of patients with HER2-positive breast cancer, resulting in a poor prognosis. Additionally, few treatments are available for HER2-positive brain metastatic breast cancer, and the mortality rate is remarkable owing to the complexity of the brain's anatomical structure and physiological function. In this review, we described the stages of the brain metastasis of breast cancer, the relationship between the microenvironment and metastatic cancer cells, and the unique molecular and cellular mechanisms. It involves cancer cells migrating, invading, and adhering to the brain; penetrating the blood-brain barrier; interacting with brain cells; and activating signal pathways once inside the brain. Finally, we reviewed current clinically used treatment approaches for brain metastasis in HER2-positive breast cancer; summarized the traditional treatment, targeted treatment, immunotherapy, and other treatment modalities; compared the benefits and drawbacks of each approach; discussed treatment challenges; and emphasized the importance of identifying potential targets to improve patient survival rates and comprehend brain metastasis in breast cancer.

First report of Colletotrichum siamense causing fruit anthracnose on Acer fabric in China.

Acer fabric Hance is an evergreen tree widely cultivated in China for its ornamental value (Liu et al. 2021). In August 2021, serious fruit anthracnose, with brown to black irregular sunken lesions, occurred on A. fabric plants at the campus of Jiangxi Agricultural University (28°45'56″N, 115°50'21″E) in Nanchang, Jiangxi province, China. On average, 25% of the fruit per individual tree was affected. Small spots initially formed along the edge of the fruit and gradually expanded into dark brown spots, and eventually the diseased fruit withered. Small pieces (4 × 4 mm) from the affected fruits were surface sterilized in 70% ethanol for 30 s, followed by 2% NaOCl for 1 min, and then rinsed three times with sterile water (Liao et al. 2023). Tissues were placed on potato dextrose agar (PDA) and incubated at 25°C. Pure cultures were obtained by monosporic isolation, and the representative isolates, AFG-3, AFG-7, and AFG-12, were used for morphological studies and phylogenetic analyses. Colonies on the PDA of the three isolates were white to gray with cottony mycelia and grayish-white on the undersides of the culture under incubation at 25°C in the dark for 7 days. Conidia were single-celled, hyaline, cylindrical, clavate, and measured 12.6-17.3 × 4.2-5.6 µm (14.2 ± 0.9 × 4.5 ± 0.3 µm, n = 100). Appressoria were brown to dark brown, ovoid to clavate, slightly irregular to irregular, and ranged from 5.5-9.2 × 4.5-6.7 µm (7.2 ± 0.2 × 5.4 ± 0.5 µm, n=100). Morphological features were similar to Colletotrichum gloeosporioides species complex (Weir et al. 2012). The internal transcribed spacer (ITS) regions, actin (ACT), calmodulin (CAL), beta-tubulin 2 (TUB2), chitin synthase (CHS-1), and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) were amplified using primers ITS1/ITS4, ACT-512F/ACT-783R, CL1/CL2, T1/Bt2b, CHS-79F/CHS-354R and GDF/GDR (Weir et al. 2012), respectively. All sequences were deposited into GenBank (ITS, OQ184035 - OQ184037; ACT, OQ196109 - OQ196111; GAPDH, OQ196115 - OQ196117; TUB2, OQ196121 - OQ196123; CHS-1, OQ196112 - OQ196114; CAL, OQ196118 - OQ196120). A maximum likelihood and Bayesian posterior probability analysis using IQtree v. 1.6.8 and Mr. Bayes v. 3.2.6 with the concatenated sequences placed AFG-3, AFG-7, and AFG-12 in the clade of C. siamense. Based on the multi-locus phylogeny and morphology, three isolates were identified as C. siamense. Pathogenicity tests were conducted on six 9-year-old A. fabric plants. Healthy fruits were wounded with a sterile needle and inoculated by placing a drop on the surface of wounded tissue (106 conidia/mL; 20 µL) prepared from the three isolates. The conidial suspension of each isolate was inoculated onto three fruit per plant. Another nine fruit on three plants inoculated with sterile water served as the control (Wan et al. 2022). All the inoculated fruit were covered with plastic bags to keep the humidity for two days. All the inoculated fruit showed dark brown spots similar to those symptoms observed on naturally infected fruit on campus, whereas control fruit were asymptomatic. C. siamense was reisolated from the inoculated fruit. The pathogen was previously reported to cause fruit anthracnose on Carya illinoinensis (Zhuo et al. 2022), Chili Pepper (May et al. 2021), and Salix babylonica (Zhang et al. 2023). This study confirmed that C. siamense also causes anthracnose on fruit of A. fabric. This work contributes to a better understanding of the etiology of fruit anthracnose on A. fabric in south China and helps develop effective control strategies.

Separation of anti-TMV active components and modes of action of Omphalia lapidescens.

BACKGROUND: Omphalia lapidescens is a saprophytic and parasitic fungus belonging to the Polypora genus of Tricholomataceae. It has repellent, insecticidal, anti-inflammatory and immunomodulatory effects. RESULT: This study found that the extract of O. lapidescens had significant anti-TMV activity, and the main active component was homopolysaccharide LW-1 by Bioassay-guided fractionation. LW-1 is a glucan with ß-(1,3) glucoside bond as the main chain and ß-(1,6) glucoside bond as the branch chain, with molecular weight in the range of 172,916-338,827 Da. The protective and inactive efficacies of LW-1(100 mg/L) against TMV were 78.10% and 48.20%, but had no direct effect on the morphology of TMV particles. The results of mechanism of action showed that LW-1 induced the increase of the activity of defense enzymes such as POD, SOD and PAL in Nicotiana glutinosa. The overexpression of resistance genes such as NPR1, PR1 and PR5, and the increase of SA content. Further transcriptome sequencing showed that LW-1 activated MAPK signaling pathway, plant-pathogen interaction pathway and glucosinolide metabolic pathway in Arabidopsis thaliana. Besides, LW-1 induced crops resistance against plant pathogenic fungi. CONCLUSION: Taken together, the anti-TMV mechanism of LW-1 was to activate MAPK signaling pathway, inducing overexpression of resistance genes, activating plant immune system, and improving the synthesis and accumulation of plant defencins such as glucosinolide. LW-1-induced plant disease resistance has the advantages of broad spectrum and long duration, which has the potential to be developed as a new antiviral agent or plant immune resistance inducer.

Primary versus acquired epidermal growth factor receptor Thr790Met mutant non-small cell lung cancer: clinical features and prognoses.

PURPOSE: This study aimed to identify the impact of epidermal growth factor receptor (EGFR) T790M mutations on clinical characteristics and prognosis. METHODS: Retrospective analyses were conducted on the differences on clinicopathological features and prognosis between primary and acquired T790M mutations. Subgroup analyses were performed for primary T790M coexisting with other mutations. RESULTS: Patients with primary T790M mutations showed a 60.53% (23/38) incidence of concurrent L858R mutations, 18.42% (7/38) for 19del mutations and a 21.05% (8/38) occurrence of brain metastases. Conversely, those with acquired T790M mutations demonstrated respective frequencies of 36.53% (61/167), 58.68% (98/167) and 44.31% (74/167), with all comparisons yielding p < 0.05. The median overall survival differed significantly between the two groups, with a duration of 33 months for patients with primary T790M mutations as compared to 48 months for those with acquired mutations (p = 0.030). Notably, among patients with L858R co-mutations, when treated with third-generation EGFR-TKIs, those with acquired T790M mutations experienced a significantly prolonged median time to treatment failure compared to those with primary mutations (17 months vs. 9 months, p = 0.009). CONCLUSION: Patients with primary T790M have unique molecular features and had worse prognosis compared with acquired T790M. Resistance to third-generation EGFR-TKIs seems to be associated with the presence of EGFR co-mutations.

Single-cell transcriptomics analysis of cellular heterogeneity and immune mechanisms in neurodegenerative diseases.

Single-cell transcriptomics analysis is an advanced technology that can describe the intracellular transcriptome in complex tissues. It profiles and analyses datasets by single-cell RNA sequencing. Neurodegenerative diseases are identified by the abnormal apoptosis of neurons in the brain with few or no effective therapy strategies at present, which has been a growing healthcare concern and brought a great burden to society. The transcriptome of individual cells provides deep insights into previously unforeseen cellular heterogeneity and gene expression differences in neurodegenerative disorders. It detects multiple cell subsets and functional changes during pathological progression, which deepens the understanding of the molecular underpinnings and cellular basis of neurodegenerative diseases. Furthermore, the transcriptome analysis of immune cells shows the regulation of immune response. Different subtypes of immune cells and their interaction are found to contribute to disease progression. This finding enables the discovery of novel targets and biomarkers for early diagnosis. In this review, we emphasize the principles of the technology, and its recent progress in the study of cellular heterogeneity and immune mechanisms in neurodegenerative diseases. The application of single-cell transcriptomics analysis in neurodegenerative disorders would help explore the pathogenesis of these diseases and develop novel therapeutic methods.

Preparation and characterization of active films based on oregano essential oil microcapsules/soybean protein isolate/sodium carboxymethyl cellulose.

This study aimed to prepare oregano essential oil microcapsules (EOMs) by the active coalescence method using gelatin and sodium alginate as wall materials and oregano essential oil (OEO) as the core material. EOMs were added to the soybean protein isolate (SPI)/sodium carboxymethyl cellulose (CMC) matrix to prepare SPI-CMC-EOM active films, and the physical and chemical features of the active films and EOMs were characterized. The results showed that the microencapsulated OEO could protect its active ingredients. Scanning electron microscopy results showed that EOMs were highly compatible with the film matrix. The solubility of active films decreased upon adding EOMs, and their ultraviolet resistance and thermal stability also improved. When the added amount of EOMs was 5 %, the active films had the best mechanical properties and the lowest water vapor permeability. The active films prepared under this condition had excellent comprehensive performance. Also, adding EOMs considerably enhanced the antioxidant of the active films and endowed them with antibacterial properties. The application of the SPI-CMC-EOM films to A. bisporus effectively delayed senescence and maintained the freshness of the postharvest A. bisporus. This study provided a theoretical foundation for the incorporation of EOMs into active films based on biological materials.

Assembly of porous filaments by interfacial complexation of nanochitin-based Pickering emulsion and seaweed alginate.

Interfacial polyelectrolyte complexation spinning is an all-water, easy-to-operate method for production of composite filaments. Herein, this concept is extended to interfacial polyelectrolyte-emulsion complexation (IPEC) that better encodes structural and functional attributes of biomass substances into the filaments. This allows for formation of composite filaments by drawing contacting oppositely-charged chitin nanofiber-stabilized Pickering emulsion and seaweed alginate solution. The parameters affecting spinnability of the system including water-to-oil ratio, alginate concentration, and pH are comprehensively elucidated to support the design and application of IPEC. The composite filaments exhibit varied diameters and diverse porous structures that are adjustable by properties of Pickering droplets. The droplet diameter of precursor emulsion and pore size in the filaments are well correlated, revealing controllability of the IPEC spinning. The filaments are mechanically robust in dry condition and show stable performance even in wet condition. The release rate of filaments that is pre-loaded with hydrophilic drug is regulated by the internal pore size, showing capability on sustained release. This study offers a new perspective toward dry spinning via interfacial complexation of complicated nanochitin-based structural building blocks, aiming at developing high-performance fiber materials for advanced applications.

Shenxiang Suhe pill improves cardiac function through modulating gut microbiota and serum metabolites in rats after acute myocardial infarction.

CONTEXT: Shenxiang Suhe pill (SXSH), a traditional Chinese medicine, is clinically effective against coronary heart disease, but the mechanism of cardiac-protective function is unclear. OBJECTIVE: We investigated the cardiac-protective mechanism of SXSH via modulating gut microbiota and metabolite profiles. MATERIALS AND METHODS: Sprague-Dawley (SD) male rats were randomly divided into 6 groups (n = 8): Sham, Model, SXSH (Low, 0.063 g/kg; Medium, 0.126 g/kg; High, 0.252 g/kg), and Ato (atorvastatin, 20 mg/kg). Besides the Sham group, rats were modelled with acute myocardial infarction (AMI) by ligating the anterior descending branch of the left coronary artery (LAD). After 3, 7, 14 days' administration, ultrasound, H&E staining, serum enzymic assay, 16S rRNA sequencing were conducted to investigate the SXSH efficacy. Afterwards, five groups of rats: Sham, Model, Model-ABX (AMI with antibiotics-feeding), SXSH (0.126 g/kg), SXSH-ABX were administrated for 14 days to evaluate the gut microbiota-dependent SXSH efficacy, and serum untargeted metabolomics test was performed. RESULTS: 0.126 g/kg of SXSH intervention for 14 days increased ejection fraction (EF, 78.22%), fractional shortening (FS, 109.07%), and aortic valve flow velocities (AV, 21.62%), reduced lesion area, and decreased serum LDH (8.49%) and CK-MB (10.79%). Meanwhile, SXSH upregulated the abundance of Muribaculaceae (199.71%), Allobaculum (1744.09%), and downregulated Lactobacillus (65.51%). The cardiac-protective effect of SXSH was disrupted by antibiotics administration. SXSH altered serum metabolites levels, such as downregulation of 2-n-tetrahydrothiophenecarboxylic acid (THTC, 1.73%), and lysophosphatidylcholine (lysoPC, 4.61%). DISCUSSION AND CONCLUSION: The cardiac-protective effect and suggested mechanism of SXSH could provide a theoretical basis for expanding its application in clinic.

Efficacy and safety of Chinese herbal medicine in post-stroke epilepsy: a systematic review and meta-analysis.

Background: Poststroke epilepsy (PSE) is a common complication of strokes that seriously affects the recovery and quality of life of patients, and effective treatments are needed. Chinese herbal medicine (CHM) adjunctive therapy is a viable treatment option, but current evidence is insufficient to support its efficacy and safety. This study aimed to evaluate the efficacy and tolerability of CHM adjunctive therapy in the treatment of PSE. Methods: A systematic search of eight databases was conducted to identify PSE-related randomized clinical trials from the inception of each database through October 2023. The methodological quality assessment was conducted by RoB 2.0, meta-analysis was conducted by RevMan 5.3 and Stata 15.1, and evidence quality was evaluated by GRADE. Results: Twenty-three RCTs involving 1,901 PSE patients were identified. We found that orally administered CHM plus conventional Western medicine (CWM) was superior to CWM monotherapy in increasing the 75% responder rate (RR 1.46, 95% CI: 1.31 to 1.62, p < 0.00001), decreasing the seizure duration (MD -1.01, 95% CI: -1.30 to -0.72, p < 0.00001), improving total responder rate (RR 1.29, 95% CI: 1.20 to 1.37, p < 0.00001), reducing epileptiform discharges (EDs) (MD -2.02.46, 95% CI: -2.64 to -1.40, p < 0.00001), and decreasing the number of leads involved in epileptiform discharge (MD -3.92, 95% CI: -5.15 to -2.68, p < 0.00001). Furthermore, intravenously administered CHM plus CWM was superior regarding 75% responder rate (RR 1.39, 95% CI: 1.24 to 1.56, p < 0.00001), total responder rate (RR 1.29, 95% CI: 1.20 to 1.39, p < 0.00001), EDs (MD -3.92, 95% CI: -5.15 to -2.68, p < 0.00001), and the number of leads involved in epileptiform discharge (MD -1.82, 95% CI: -2.62 to -1.02, p < 0.00001). However, regarding the 50%-75% responder rate, there was no statistically significant difference between the two groups for either oral (RR 1.00, 95% CI: 0.77 to 1.29, p = 0.98) or injectable CHM (RR 0.95, 95% CI: 0.67 to 1.33, p = 0.75). Both orally administered CHM plus CWM (RR 0.56, 95% CI: 0.35 to 0.90, p = 0.02) and intravenously administered CHM plus CWM (RR 0.64, 95% CI: 0.45 to 0.90, p = 0.010) caused fewer AEs than CWM. Furthermore, the levels of evidence ranged from low to high due to publication bias and heterogeneity. Conclusion: CHM adjuvant therapy may be an effective and safe therapy for PSE. However, due to the poor quality of clinical data, more well-designed RCTs are needed to confirm these findings. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=364356, identifier PROSPERO (CRD42022364356).

Bisphenol AF Induces Prostatic Dorsal Lobe Hyperplasia in Rats through Activation of the NF-κB Signaling Pathway.

Bisphenol AF (BPAF) represents a common environmental estrogenic compound renowned for its capacity to induce endocrine disruptions. Notably, BPAF exhibits an enhanced binding affinity to estrogen receptors, which may have more potent estrogenic activity compared with its precursor bisphenol A (BPA). Notwithstanding, the existing studies on BPAF-induced prostate toxicity remain limited, with related toxicological research residing in the preliminary stage. Our previous studies have confirmed the role of BPAF in the induction of ventral prostatic hyperplasia, but its role in the dorsal lobe is not clear. In this study, BPAF (10, 90 µg/kg) and the inhibitor of nuclear transcription factor-κB (NF-κB), pyrrolidinedithiocarbamate (PDTC, 100 mg/kg), were administered intragastrically in rats for four weeks. Through comprehensive anatomical and pathological observations, as well as the assessment of PCNA over-expression, we asserted that BPAF at lower doses may foster dorsal prostatic hyperplasia in rats. The results of IHC and ELISA indicated that BPAF induced hyperplastic responses in the dorsal lobe of the prostate by interfering with a series of biomarkers in NF-κB signaling pathways, containing NF-κB p65, COX-2, TNF-α, and EGFR. These findings confirm the toxic effect of BPAF on prostate health and emphasize the potential corresponding mechanisms.

Integration of machine learning to identify diagnostic genes in leukocytes for acute myocardial infarction patients.

BACKGROUND: Acute myocardial infarction (AMI) has two clinical characteristics: high missed diagnosis and dysfunction of leukocytes. Transcriptional RNA on leukocytes is closely related to the course evolution of AMI patients. We hypothesized that transcriptional RNA in leukocytes might provide potential diagnostic value for AMI. Integration machine learning (IML) was first used to explore AMI discrimination genes. The following clinical study was performed to validate the results. METHODS: A total of four AMI microarrays (derived from the Gene Expression Omnibus) were included in bioanalysis (220 sample size). Then, the clinical validation was finished with 20 AMI and 20 stable coronary artery disease patients (SCAD). At a ratio of 5:2, GSE59867 was included in the training set, while GSE60993, GSE62646, and GSE48060 were included in the testing set. IML was explicitly proposed in this research, which is composed of six machine learning algorithms, including support vector machine (SVM), neural network (NN), random forest (RF), gradient boosting machine (GBM), decision trees (DT), and least absolute shrinkage and selection operator (LASSO). IML had two functions in this research: filtered optimized variables and predicted the categorized value. Finally, The RNA of the recruited patients was analyzed to verify the results of IML. RESULTS: Thirty-nine differentially expressed genes (DEGs) were identified between controls and AMI individuals from the training sets. Among the thirty-nine DEGs, IML was used to process the predicted classification model and identify potential candidate genes with overall normalized weights > 1. Finally, two genes (AQP9 and SOCS3) show their diagnosis value with the area under the curve (AUC) > 0.9 in both the training and testing sets. The clinical study verified the significance of AQP9 and SOCS3. Notably, more stenotic coronary arteries or severe Killip classification indicated higher levels of these two genes, especially SOCS3. These two genes correlated with two immune cell types, monocytes and neutrophils. CONCLUSION: AQP9 and SOCS3 in leukocytes may be conducive to identifying AMI patients with SCAD patients. AQP9 and SOCS3 are closely associated with monocytes and neutrophils, which might contribute to advancing AMI diagnosis and shed light on novel genetic markers. Multiple clinical characteristics, multicenter, and large-sample relevant trials are still needed to confirm its clinical value.

Efficacy and safety of acupuncture in post-stroke constipation: a systematic review and meta-analysis.

Background and objective: Post-stroke constipation (PSC) is a common complication of strokes that seriously affects the recovery and quality of life of patients, and effective treatments are needed. Acupuncture is a viable treatment option, but current evidence is insufficient to support its efficacy and safety. This study aims to evaluate the efficacy and safety of acupuncture in the treatment of PSC. Methods: A systematic search of eight databases was conducted to identify PSC-related randomized clinical trials from the inception of each database through May 2023. Methodological quality assessment was conducted by RoB 2.0, meta-analysis was conducted by RevMan 5.3 and Stata 15.1, and evidence quality was evaluated by GRADE. Moreover, reporting quality of acupuncture interventions was assessed using the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). Results: Thirty RCTs involving 2,220 patients were identified. We found that acupuncture was superior to conventional treatment (CT) in improving total responder rate [risk ratio (RR): 1.16, 95% confidence interval (CI): 1.09 to 1.25, p < 0.0001], decreasing constipation symptom scores [standardized mean difference (SMD): -0.65, 95% CI: -0.83 to -0.46, p < 0.00001], increasing serum P substance (SP) levels (SMD: 1.92, 95% CI: 0.47 to 3.36, p = 0.009), reducing the time to first bowel movement (BM) (SMD: -1.19, 95% CI: -2.13 to -0.25, p = 0.01), and lowing serum vasoactive intestinal peptide (VIP) levels (SMD: -2.11, 95% CI: -3.83 to -0.38, p = 0.02). Furthermore, acupuncture plus CT was superior regarding total responder rate (RR: 1.26, 95% CI: 1.17 to 1.35, p < 0.00001), serum SP levels (SMD: 2.00, 95% CI: 1.65-2.35, p < 0.00001), time to first BM (SMD: -2.08, 95% CI: -2.44 to -1.71, p < 0.00001), and serum VIP levels (SMD: -1.71, 95% CI: -2.24 to -1.18, p < 0.00001). However, regarding Bristol Stool Scale (BSS) score, acupuncture plus CT was superior to CT (SMD: -2.48, 95% CI: -3.22 to -1.73, p < 0.00001), while there was no statistically significant difference between acupuncture and CT (SMD: 0.28, 95% CI: -0.02 to 0.58, p = 0.07). Acupuncture causes fewer AEs than CT (RR: 0.13, 95% CI: 0.06 to 0.26, p < 0.00001), though there was no statistically significant difference between acupuncture plus CT vs. CT (RR: 1.30, 95% CI: 0.60 to 2.84, p = 0.51). Conclusion: Acupuncture may be an effective and safe therapy for PSC. However, given the inferior quality of clinical data, additional well-designed RCTs are required to confirm these findings.

Adaptive machine learning method for photoacoustic computed tomography based on sparse array sensor data.

BACKGROUND AND OBJECTIVE: Photoacoustic computed tomography (PACT) is a non-invasive biomedical imaging technology that has developed rapidly in recent decades, especially has shown potential for small animal studies and early diagnosis of human diseases. To obtain high-quality images, the photoacoustic imaging system needs a high-element-density detector array. However, in practical applications, due to the cost limitation, manufacturing technology, and the system requirement in miniaturization and robustness, it is challenging to achieve sufficient elements and high-quality reconstructed images, which may even suffer from artifacts. Different from the latest machine learning methods based on removing distortions and artifacts to recover high-quality images, this paper proposes an adaptive machine learning method to firstly predict and complement the photoacoustic sensor channel data from sparse array sampling and then reconstruct images through conventional reconstruction algorithms. METHODS: We develop an adaptive machine learning method to predict and complement the photoacoustic sensor channel data. The model consists of XGBoost and a neural network named SS-net. To handle data sets of different sizes and improve the generalization, a tunable parameter is used to control the weights of XGBoost and SS-net outputs. RESULTS: The proposed method achieved superior performance as demonstrated by simulation, phantom experiments, and in vivo experiment results. Compared with linear interpolation, XGBoost, CAE, and U-net, the simulation results show that the SSIM value is increased by 12.83%, 6.78%, 21.46%, and 12.33%. Moreover, the median R2 is increased by 34.4%, 8.1%, 28.6%, and 84.1% with the in vivo data. CONCLUSIONS: This model provides a framework to predict the missed photoacoustic sensor data on a sparse ring-shaped array for PACT imaging and has achieved considerable improvements in reconstructing the objects. Compared with linear interpolation and other deep learning methods qualitatively and quantitatively, our proposed methods can effectively suppress artifacts and improve image quality. The advantage of our methods is that there is no need for preparing a large number of images as the training dataset, and the data for training is directly from the sensors. It has the potential to be applied to a wide range of photoacoustic imaging detector arrays for low-cost and user-friendly clinical applications.