Objective To explore the application of plasma 7 microRNA (miR7) testing in the differential diagnosis of very early-stage hepatocellular carcinoma (HCC). Methods This study is a multicenter real-world study. Patients with single hepatic lesion (maximum diameter≤2 cm) who underwent plasma miR7 testing at Zhongshan Hospital, Fudan University, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Anhui Provincial Hospital, and Peking University People’s Hospital between January 2019 and December 2024 were retrospectively enrolled. Patients were divided into very early-stage HCC group and non-HCC group, and the clinical pathological characteristics of the two groups were compared. The value of plasma miR7 levels, alpha-fetoprotein (AFP), and des-gamma-carboxy prothrombin (DCP) in the differential diagnosis of very early-stage HCC was evaluated using receiver operating characteristic (ROC) curves and area under the curve (AUC). In patients with both negative AFP and DCP (AFP＜20 ng/mL, DCP＜40 mAU/mL), the diagnostic value of plasma miR7 for very early-stage HCC was analyzed. Results A total of 64 528 patients from 4 hospitals underwent miR7 testing, and 1 682 were finally included, of which 1 073 were diagnosed with very early-stage HCC and 609 were diagnosed with non-HCC. The positive rate of miR7 in HCC patients was significantly higher than that in non-HCC patients (67.9% vs 24.3%, P＜0.001). ROC curves showed that the AUCs for miR7, AFP, and DCP in distinguishing HCC patients from the non-HCC individuals were 0.718, 0.682, and 0.642, respectively. The sensitivities were 67.85%, 43.71%, and 44.45%, and the specificities were 75.70%, 92.78%, and 83.91%, respectively. The pairwise comparison of AUCs showed that the diagnostic efficacy of plasma miR7 detection was significantly better than that of AFP or DCP (P＜0.05). Although its specificity was slightly lower than AFP and DCP, the sensitivity was significantly higher. Among patients negative for both AFP and DCP, miR7 maintained an AUC of 0.728 for diagnosing very early-stage HCC, with 67.82% sensitivity and 77.73% specificity. Conclusions Plasma miR7 testing is a potential molecular marker with high sensitivity and specificity for the differential diagnosis of small hepatic nodules. In patients with very early-stage HCC lacking effective molecular markers (negative for both AFP and DCP), miR7 can serve as a novel and effective molecular marker to assist diagnosis.

Drug repurposing offers a promising alternative to traditional drug development and significantly reduces costs and timelines by identifying new therapeutic uses for existing drugs. However, the current approaches often rely on limited data sources and simplistic hypotheses, which restrict their ability to capture the multi-faceted nature of biological systems. This study introduces adaptive multi-view learning (AMVL), a novel methodology that integrates chemical-induced transcriptional profiles (CTPs), knowledge graph (KG) embeddings, and large language model (LLM) representations, to enhance drug repurposing predictions. AMVL incorporates an innovative similarity matrix expansion strategy and leverages multi-view learning (MVL), matrix factorization, and ensemble optimization techniques to integrate heterogeneous multi-source data. Comprehensive evaluations on benchmark datasets (Fdataset, Cdataset, and Ydataset) and the large-scale iDrug dataset demonstrate that AMVL outperforms state-of-the-art (SOTA) methods, achieving superior accuracy in predicting drug-disease associations across multiple metrics. Literature-based validation further confirmed the model's predictive capabilities, with seven out of the top ten predictions corroborated by post-2011 evidence. To promote transparency and reproducibility, all data and codes used in this study were open-sourced, providing resources for processing CTPs, KG, and LLM-based similarity calculations, along with the complete AMVL algorithm and benchmarking procedures. By unifying diverse data modalities, AMVL offers a robust and scalable solution for accelerating drug discovery, fostering advancements in translational medicine and integrating multi-omics data. We aim to inspire further innovations in multi-source data integration and support the development of more precise and efficient strategies for advancing drug discovery and translational medicine.

OBJECTIVE To analyze the types and control measures of major microorganisms in pharmaceutical water systems, so as to provide guidance for effective control of pharmaceutical water systems. METHODS The main microbial species, abundance and harmfulness of drinking water, purified water and water for injection were reviewed, and the control measures on microorganisms in pharmaceutical water were discussed. RESULTS There were differences in the main microbial types in pharmaceutical water. Burkholderia cepacia complex and Ralstonia pickettii were conditioned pathogens in pharmaceutical water, thus causing certain biological safety hazards. CONCLUSION Pharmaceutical companies can strengthen the control of microorganisms in the water system by establishing microbial databases and common microbial strain banks at all levels. Trend analysis should to be conducted based on alert limits and action limits, so as to strengthen the control of microorganisms in the water system.

Objective Intracranial hemorrhage(ICH),the second most common subtype of stroke,exacerbates the disruption of the blood-brain barrier(BBB),leading to vasogenic edema,plasma protein extravasation,and infiltration of neurotoxic substances.The clearance capacity of the brain plays a crucial role in maintaining BBB homeostasis and facilitating patient recovery after hemorrhage.This study aimed to investigate the effect of circadian rhythms on BBB function,neuronal damage,and clearance capabilities. Methods The transwell model and hemoglobin were co-cultured to simulate the BBB environment after ICH.After intervention with different light groups,neuronal apoptosis was determined,glial phagocytosis was analyzed,the expression of endogenous clearing-related proteins aquaporin 4(AQP4)and low-density lipoprotein receptor-related protein 1(LRP1)was detected by western blotting and immunofluorescence dual standard method,and the expression of the tight junction protein occludin and melatonin receptor 1A(MTNR1A)was quantitatively analyzed. Results Circadian rhythms play a key role in maintaining the integrity of the BBB,reducing oxidative stress-induced neuronal damage,and improving microglial phagocytosis.Meanwhile,the expression of occludin and MTNR1A in neurovascular unit(NVU)co-cultured with hemoglobin improved the expression of AQP4 and LRP1,the key proteins in the NVU's endogenous brain clearance system. Conclusion Circadian rhythm(alternating black and white light)protects the NVU BBB function after ICH,promotes the expression of proteins related to the clearance of the hematoma,provides new evidence for the clinical treatment of patients recovering from ICH,and improves the circadian rhythm to promote brain metabolism and hematoma clearance.

Objective:To investigate the distribution and seasonal fluctuations of flies in Hangzhou, study the resistance of Musca domestica ( M. domestica) to five commonly used sanitary insecticides and changing patterns in Hangzhou and provide a basis for scientific control of flies. Methods:From April to November 2023, the cage trap method was used for ecological monitoring of flies. From May to June 2023, the swing net method was used to collect M. domestica from various districts (counties and cities) in Hangzhou. After indoor breeding, the resistance of F1 generation female adult flies to five commonly used sanitary insecticides was determined using the micro-drop method. Probit regression model was used to calculate the median lethal dose (LD 50), 95% confidence interval ( CI) and virulence regression equation. Results:In 2023, the fly density in Hangzhou was 5.99 flies/cage, with a higher density of flies belonging to the Sarcophagus family (2.39 flies/cage), making it the dominant fly species in Hangzhou. Among different monitoring points, the fly density in Linping District was relatively high (20.97 flies/cage). In different habitats, the fly density in agricultural markets was relatively high (fly density from April to November: 2.86, 5.39, 8.86, 16.86, 31.32, 6.39, 3.75 and 1.89 flies/cage). The seasonal fluctuation of fly density showed a unimodal pattern, with the higher density in August (13.45 flies/cage). The M. domestica population in Hangzhou was sensitive to dichlorvos [resistance ratio ( RR): 3.08 times]. Different degrees of resistance were developed to propoxur, deltamethrin, beta-cypermethrin, and beta-cyhalothrin. The degree of resistance from high to low was propoxur (> 336.36 times), beta-cypermethrin (906.61 times), beta-cyhalothrin (432.29 times), and deltamethrin (72.56 times). Based on the monitoring results from 2003 to 2023, the RR of dichlorvos reached the higher level in 2008 (33.47 times) and gradually decreased to a sensitive level. The resistance level of propoxur had been at an extremely high level over the years. Three types of pyrethroid insecticides all had high resistance. Conclusions:The species of flies in the Sarcophagus family are the dominant population in Hangzhou, and M. domestica has developed high resistance to four commonly used insecticides except for dichlorvos. The use of physical control techniques is advocated to reduce the use of chemical pesticides, and prevent the continuous increase of resistance in M. domestica.

Objective:To study the dosimetry effects of differently selected values of control point(CP)in Monaco radiotherapy planning system on dynamic intensity modulated radiation therapy(dIMRT)for esophageal cancer of middle and lower segment.Methods:Thirteen patients with esophageal cancer at middle and lower segment who received dIMRT in Shangluo Central Hospital from January to June 2023 were selected.In the Monaco radiotherapy planning system,nine groups of dIMRT plans were designed for each patient according to the 9 kinds of CP limit values(10,20,30,40,50,60,70,80 and 90).There were not changes in other optimized parameters except CP parameter.The differences of the dosimetry between target region and organs at risk(OAR)included lung,heart and spinal cord were analyzed.Results:With the increase of the CP limit value,the maximum dose of the target region which was radiation dose(D2%)of 2%volume of target region,the mean dose,which was radiation dose(D50%)of 50%volume of target region,and the homogeneity index(HI)appeared a trend of gradual stability after reduction,and the radiation dose(D98%)of 98%volume of target region which was the minimum dose of target region and the conformance index(CI)appeared a trend of gradual stability after increase.There was not significant in each dose indicator of OAR(P>0.05).The variation ranges of lung at 5,10,20,30 Gy dose(V5,V10,V20 and V30)were respectively 1.13%,0.75%,0.29%and 0.19%,and the maximum deviation of mean dose(Vmean)of lung was 18.7 cGy.The variation ranges of V10,V20,V30 and V40 in the heart were respectively 2.2%,1.23%,1.39%and 1.12%,and the maximum deviation of Vmean in the heart was 63.85 cGy,and the maximum deviation of Dmax in the spinal-cord was 70.78 cGy.There were statistically significant differences in the actual CP number(CPs),execution time(DT)of plan,and ratio value of machine unit(MU)of the complexity of plan to CPs(MU/CPs)among the plans of 9 groups(F=2.857,25.145,135.467,P<0.05),respectively.Conclusion:In the dIMRT plan of esophageal cancer of middle and lower segment,the maximum CP value is set at between 40-50,which can reduce the optimization time of the plan,the number of subfields and the treatment time of patients under the premise of meeting the dose of the target region and the OAR.

Objective:To evaluate the early efficacy and safety of transnasal endoscopic decompression in the annulus of zinn (AZ) region for refractory dysthyroid optic neuropathy (DON) and to preliminarily analyze the correlated factors of postoperative visual function outcome.Methods:From July 2021 to January 2023, 35 patients (56 eyes) with DON who received AZ area decompression in Peking University Third Hospital were included retrospectively, including 9 males (13 eyes) and 26 females (43 eyes), aging (52.2±12.0) years. Among them, 35 eyes underwent two-wall (medial and inferior) orbital decompression using an endonasal endoscopic approach, while 21 eyes received three-wall (medial, lateral, and inferior) orbital decompression through a combined approach. Key parameters such as best corrected visual acuity (BCVA), visual field (MD value), eyeball prominence, intraocular pressure, and complications were recorded. Postoperative data were collected one month after surgery. The statistical analysis was performed using paired t-test and Spearman correlation analysis. Results:Significant outcomes were observed post surgery in BCVA, visual field, intraocular pressure and proptosis ( t value was 8.37, 6.17, 4.50, and 9.20, respectively, all P<0.001). The reduction in proptosis was statistically significant between the 2-wall and 3-wall orbital decompression groups ( t=-2.82, P=0.007). Changes in BCVA, visual field, and intraocular pressure before and after surgery was greater in the 3-wall orbital decompression group compared to 2-wall orbital decompression group, although the difference was not statistically significant (all P>0.05). Change in postoperative visual acuity and visual field was significantly positively correlated with preoperative visual acuity and preoperative visual field (all P<0.001). Similarly, change in intraocular pressure and proptosis was positively correlated with preoperative intraocular pressure and preoperative protrusion (all P<0.001). Preoperative diplopia was reported in seven patients (20.0%), and two new cases (5.7%) were noted post-operation, which resolved within 3 months after surgery. Conclusions:Endoscopic endonasal decompression of the AZ area is a safe and effective surgical treatment for DON, with notable improvements in BCVA. Furthermore, three-orbital wall decompression seems to yield better outcomes in terms of eye retraction.

ObjectiveTo systematically evaluate the safety of interferon β-1a for treatment of corona virus disease 2019 （COVID-19）， and to provide references for interferon β-1a's clinical application. MethodsThis study was conducted with the database from US Food and Drug Administration adverse event reporting system （FAERS） from January 1， 2015 to March 31， 2021. Information component （IC） and reporting odds ratio （ROR） methods were applied for signal mining. ResultsA total of 463 700 records of COVID-19 were selected for analysis， and 45 positive drug adverse event signals were detected. Headache （IC₀₂₅=1.09， ROR₀₂₅=2.28）， pyrexia （IC₀₂₅=0.51， ROR₀₂₅=1.51） and multiple sclerosis relapse （IC₀₂₅=3.67， ROR₀₂₅=14.71） were positive adverse events with higher frequency. Autoimmune disorder （IC₀₂₅=4.42， ROR₀₂₅=24.03）， streptococcal infection （IC₀₂₅=4.12， ROR₀₂₅=19.82）， and multiple sclerosis relapse （IC₀₂₅=3.67， ROR₀₂₅=14.71） were positive adverse events. Acute lung injury， cardio-respiratory arrest and metabolic acidosis were associated with a higher proportion and frequency of death. ConclusionThere are certain safety issues with interferon β-1a in the treatment of COVID-19， and some adverse events with high frequency and high death rate deserve further attention by medical staffs.

BACKGROUND: Ovarian cancer is one of the most widespread malignant diseases of the female reproductive system worldwide. The plurality of ovarian cancer is diagnosed with metastasis in the abdominal cavity. Epithelial-mesenchymal transition (EMT) exerts a vital role in tumor cell metastasis. However, it remains unclear whether long non-coding RNA (lncRNA) are implicated in EMT and influence ovarian cancer cell invasion and metastasis. This study was designed to investigate the impacts of lncRNA AC005224.4 on ovarian cancer. METHODS: LncRNA AC005224.4, miR-140-3p, and snail family transcriptional repressor 2 ( SNAI2 ) expression levels in ovarian cancer and normal ovarian tissues were determined using real-time quantitative polymerase chain reaction (qRT-PCR). Cell Counting Kit-8 (CCK-8) and Transwell (migration and invasion) assays were conducted to measure SKOV3 and CAOV-3 cell proliferation and metastasis. E-cadherin, N-cadherin, Snail, and Vimentin contents were detected using Western blot. Nude mouse xenograft assay was utilized to validate AC005224.4 effects in vivo . Dual-luciferase reporter gene assay confirmed the targeted relationship between miR-140-3p and AC005224.4 or SNAI2 . RESULTS: AC005224.4 and SNAI2 upregulation and miR-140-3p downregulation were observed in ovarian cancer tissues and cells. Silencing of AC005224.4 observably moderated SKOV3 and CAOV-3 cell proliferation, migration, invasion, and EMT process in vitro and impaired the tumorigenesis in vivo . miR-140-3p was a target of AC005224.4 and its reduced expression level was mediated by AC005224.4. miR-140-3p mimics decreased the proliferation, migration, and invasion of ovarian cancer cells. SNAI2 was identified as a novel target of miR-140-3p and its expression level was promoted by either AC005224.4 overexpression or miR-140-3p knockdown. Overexpression of SNAI2 also facilitated ovarian cancer cell viability and metastasis. CONCLUSION AC005224.4 was confirmed as an oncogene via sponging miR-140-3p and promoted SNAI2 expression, contributing to better understanding of ovarian cancer pathogenesis and shedding light on exploiting the novel lncRNA-directed therapy against ovarian cancer.
Animals ; Mice ; Humans ; Female ; MicroRNAs/metabolism* ; RNA, Long Noncoding/metabolism* ; Ovarian Neoplasms/metabolism* ; Cell Line, Tumor ; Epithelial-Mesenchymal Transition/genetics* ; Cell Movement/genetics* ; Cell Proliferation/genetics* ; Gene Expression Regulation, Neoplastic/genetics* ; Snail Family Transcription Factors/metabolism*

Objective:To investigate the prevalence of the decline of intrinsic capacity(IC)and to explore the effect of intrinsic capacity decline on falls and hospital readmission during 1 year follow-up.Methods:A total of 311 elderly patients treated in Geriatrics Department of Zhejiang Hospital were enrolled.General information and intrinsic ability data, including cognitive(simple mental state inventory), motor(Tinetti-Balance Scale and 4 m test), vitality(grip strength and mini-nutrition assessment table), perception(self-rated vision or hearing impairment), and psychosocial(Geriatric depression scale), were collected at admission.Falls and hospital readmission within 1 year after discharge were followed up.Multivariate Logistic regression analysis was used to investigate the relationship of baseline intrinsic ability at admission with falls and hospital readmission during 1-year follow-up.Results:Of 311 elderly hospitalized patients, 282(90.7%)had intrinsic capacity decline.During 1 year follow-up, 38 elderly patients(12.2%)had falls and 69 elderly patients(22.2%)were hospital readmitted.After adjusting for confounding factors such as age, gender, education level, comorbidities, multiple medications, fear of falling, and assistive tool use and so on, Logistic regression analysis showed that decreased balance ability was a risk factor for falls within 1 year in elderly patients( OR=3.515, 95% CI: 1.089-11.346, P=0.036), and slow walking speed was a risk factor for one-year hospital readmission( OR=2.426, 95% CI: 1.181-4.983, P=0.016). Conclusions:Decreased motor capacity is closely associated with falls and hospital readmission within 1 year in older patients.Great attention should be paid to the assessment and intervention of motor ability in elderly patients.