OBJECTIVE To report the diagnosis and treatment process of 1 case of Streptomyces thermoviolaceus pneumonia， and provide reference for the diagnosis and treatment of this type of infection by combining literature on Streptomyces pneumonia. METHODS A case study was conducted on a patient with S. thermoviolaceus pneumonia treated at the First Affiliated Hospital of Army Medical University. Additionally， a systematic literature review of Streptomyces pneumonia cases was performed. RESULTS The patient with S. thermoviolaceus presented with left lung consolidation and mass-like opacity. Initial diagnosis via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry failed， but 16S rRNA gene amplification and sequencing confirmed S. thermoviolaceus as the causative pathogen. Six-month therapy with Amoxicillin capsules （1 g orally， three times daily） resulted in near-complete lesion resolution. The literature analysis of Streptomyces pneumonia revealed that 13 patients with Streptomyces pneumonia were included （including the patient reported in the article）， age range of 18-77 years， more males （8 cases）， and mostly suffering from underlying diseases. In terms of clinical symptoms， all enrolled cases exhibited cough， and some cases were accompanied by variable dyspnea. Imaging findings included that there was no characteristic predilection site for Streptomyces pneumonia lesions， and CT images commonly showed lung consolidation and bilateral nodules. Definitive diagnosis relied on 16S rRNA sequencing. Treatment regimens included tetracyclines， β -lactam drugs combined with enzyme inhibitors， ceftriaxone， aminoglycosides， macrolides， or carbapenems， administered for prolonged duration （6 months）. Follow-up indicated a good prognosis， and only one mortality occurred. CONCLUSIONS 16S rRNA gene sequencing should be prioritized for diagnosing S. pneumonia. Effective antimicrobial options include tetracyclines，β-lactam drugs combined with enzyme inhibitors， ceftriaxone， aminoglycosides， macrolides， and carbapenems. Prolonged therapy correlates with favorable prognosis.

Objective: To investigate the trends in incidence and mortality of esophageal cancer in cancer registration areas of Anhui Province from 2014 to 2020, so as to provide the basis for formulating prevention and control measures. Methods: The incidence and mortality data of esophageal cancer in Anhui Province from 2014 to 2020 was collected through the Cancer Registry in Anhui Province. The crude incidence and crude mortality were calculated. The Chinese population-standardized rate was standardized using the age structure of the standard population from the Fifth National Population Census in 2000. The trends in incidence and mortality of esophageal cancer were analyzed using the average annual percent change (APPC), stratified by genders, urban/rural areas, and ages. Results: In Anhui Province, the rank of esophageal cancer incidence dropped from the third in 2014 to the sixth in 2020. Concurrently, the crude incidence and Chinese population-standardized incidence declined from 28.74/100 000 and 20.74/100 000 to 19.23/100 000 and 10.59/100 000, respectively (AAPC=-5.846%, -9.658%, both P<0.05). The mortality rank remained stable at the fourth in 2014 and 2020, while the crude mortality and Chinese population-standardized mortality decreased from 19.96/100 000 and 14.09/100 000 to 16.00/100 000 and 8.41/100 000, respectively (AAPC=-3.542%, -7.784%, both P<0.05). The Chinese population-standardized incidence (AAPC=-9.682%, -9.188%, -6.175% and -12.575%, all P<0.05) and Chinese population-standardized mortality (AAPC=-7.734%. -7.447%. -5.366% and -10.209%, all P<0.05) showed declining trends in males, females, urban, and rural areas, respectively. From 2014 to 2020 in Anhui Province, the crude incidence and mortality of esophageal cancer generally increased with age. However, significant declining trends were observed in crude incidence (AAPC=-12.779%, -11.701%, -11.955% and -5.751%, all P<0.05) and crude mortality (AAPC=-12.255%, -11.120%, -10.985% and -5.751%, all P<0.05) for the age groups of 40-<50, 50-<60, 60-<70, 70-<80 years. A significant declining trend in crude incidence was also seen in the ≥80 years group (APPC=-6.334%, P<0.05), but the trend in crude mortality was no statistically significant (P>0.05). Conclusion In registration areas of Anhui Province, the incidence and mortality of esophageal cancer exhibited a declining trend from 2014 to 2020, calling for focused attention on the middle-aged and elderly population and enhanced health behaviors such as tobacco and alcohol control.

Addressing the enduring challenge of evaluating traditional Chinese medicines (TCMs), the integrated evidence chain-based effectiveness evaluation of TCMs (Eff-iEC) has emerged. This paper explored its capacity through a demonstration study that evaluated the effectiveness evidence of six commonly used anti-hepatic fibrosis Chinese patent medicines (CPMs), including Biejiajian Pill (BP), Dahuang Zhechong Pill (DZP), Biejia Ruangan Compound (BRC), Fuzheng Huayu Capsule (FHC), Anluo Huaxian Pill (AHP), and Heluo Shugan Capsule (HSC), using both Eff-iEC and the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system. The recognition of these CPMs within the TCM academic community was also assessed through their inclusion in relevant medical documents. Results showed that the evidence of BRC and FHC received higher assessments in both Eff-iEC and GRADE system, while the assessments for others varied. Analysis of community recognition revealed that Eff-iEC more accurately reflects the clinical value of these CPMs, exhibiting superior evaluative capabilities. By breaking through the conventional pattern of TCMs effectiveness evaluation, Eff-iEC offers a novel epistemology that better aligns with the clinical realities and reasoning of TCMs, providing a coherent methodology for clinical decision-making, new drug evaluations, and health policy formulation.

The translocator protein (TSPO) positron emission tomography (PET) can noninvasively detect neuroinflammation associated with epileptogenesis and epilepsy. This study explored the role of the TSPO-targeting radioligand [¹⁸F]F-TFQC, an m-trifluoromethyl ER176 analog, in the PET neuroimaging of epileptic rats. Initially, [¹⁸F]F-TFQC was synthesized with a radiochemical yield of 8%-10% (EOS), a radiochemical purity of over 99%, and a specific activity of 38.21 ± 1.73 MBq/nmol (EOS). After determining that [¹⁸F]F-TFQC exhibited good biochemical properties, [¹⁸F]F-TFQC PET neuroimaging was performed in epileptic rats at multiple time points in various stages of disease progression. PET imaging showed specific [¹⁸F]F-TFQC uptake in the right hippocampus (KA-injected site, i.e., epileptogenic zone), which was most pronounced at 1 week (T/NT 1.63 ± 0.21) and 1 month (T/NT 1.66 ± 0.20). The PET results were further validated using autoradiography and pathological analysis. Thus, [¹⁸F]F-TFQC can reflect the TSPO levels and localize the epileptogenic zone, thereby offering the potential for monitoring neuroinflammation and guiding anti-inflammatory treatment in patients with epilepsy.

Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation

Advancements in artificial intelligence (AI) and emerging technologies are rapidly expanding the exploration of chemical space, facilitating innovative drug discovery. However, the transformation of novel compounds into safe and effective drugs remains a lengthy, high-risk, and costly process. Comprehensive early-stage evaluation is essential for reducing costs and improving the success rate of drug development. Despite this need, no comprehensive tool currently supports systematic evaluation and efficient screening. Here, we present druglikeFilter, a deep learning-based framework designed to assess drug-likeness across four critical dimensions: 1) physicochemical rule evaluated by systematic determination, 2) toxicity alert investigated from multiple perspectives, 3) binding affinity measured by dual-path analysis, and 4) compound synthesizability assessed by retro-route prediction. By enabling automated, multidimensional filtering of compound libraries, druglikeFilter not only streamlines the drug development process but also plays a crucial role in advancing research efforts towards viable drug candidates, which can be freely accessed at https://idrblab.org/drugfilter/.

Drug development encompasses multiple processes, wherein protein subcellular localization is essential. It promotes target identification, treatment development, and the design of drug delivery systems. In this research, a deep learning framework called LocPro is presented for predicting protein subcellular localization. Specifically, LocPro is unique in (a) combining protein representations from the pre-trained large language model (LLM) ESM2 and the expert-driven tool PROFEAT, (b) implementing a hybrid deep neural network architecture that integrates convolutional neural network (CNN), fully connected (FC) layer, and bidirectional long short-term memory (BiLSTM) blocks, and (c) developing a multi-label framework for predicting protein subcellular localization at multiple granularity levels. Additionally, a dataset was curated and divided using a homology-based strategy for training and validation. Comparative analyses show that LocPro outperforms existing methods in sequence-based multi-label protein subcellular localization prediction. The practical utility of this framework is further demonstrated through case studies on drug target subcellular localization. All in all, LocPro serves as a valuable complement to existing protein localization prediction tools. The web server is freely accessible at https://idrblab.org/LocPro/.

OBJECTIVE To study the general situation and characteristics of the adverse drug reactions(ADRs) associated with polatuzumab vedotin(combined with bendamustine and rituximab), so as to provide reference for clinical rational drug use. METHODS The clinical data of all patients who were hospitalized at Tianjin Cancer Hospital Airport Hospital and treated with polatuzumab vedotin during hospitalization from January 2021 to August 2022 were collected by searching Hospital Information System. The basic patient information, medication status, incidence of adverse reactions, etc, were collected and analyzed. RESULTS A total of 7 patients were enrolled in the analysis, which there were 4 males(57.1%) and 3 females(42.8%). The toxicity profile of polatuzumab vedotin consisted mainly of neutropenia and leukopenia. ADRs mainly occured within 3 months after administration, and it could be recovered after symptomatic treatment or observation, and there was no death due to ADRs. CONCLUSION During the rational use of polatuzumab vedotin in clinical practice, clinicians and pharmacists should reinforce the monitoring on its using to ensure the safe and effective of polatuzumab vedotin clinical application.

Objective:To explore the effects of midazolam oral solution on preoperative sedation, hemodynamics, and awakening agitation in children undergoing tonsillectomy combined with adenoidectomy.Methods:A total of 267 pediatric patients who underwent tonsillectomy combined with adenoidectomy at the Children′s Hospital Affiliated to Zhejiang University School of Medicine from January to September 2022 were randomly divided into a low-dose group ( n=89), a high-dose group ( n=89), and a control group ( n=89) using a random number table method. 30 minutes before anesthesia, the low-dose group received 0.25 mg/kg of midazolam orally, the high-dose group received 0.5 mg/kg of midazolam orally, and the control group received 5 ml of 10% glucose mixture orally. We compared the extubation time and post anesthesia recovery room (PACU) retention time among three groups of pediatric patients; Mean arterial pressure (MAP) and heart rate (HR) levels before administration and 10, 20, and 30 minutes after administration; The Yale Modified Perioperative Anxiety Scale (mYPAS) score and restlessness incidence were measured before administration and 10 and 60 minutes after administration. Results:The retention time of PACU in the low-dose group was shorter than that in the high-dose group ( P<0.05), and there was no statistically significant difference between the low-dose group and the control group ( P>0.05). At 10, 20, and 30 minutes after administration, the levels of MAP and HR in the low-dose and high-dose groups were lower than before administration (all P<0.05), and at 10, 20, and 30 minutes after administration, the levels of MAP and HR in the low-dose and high-dose groups were lower than those in the control group (all P<0.05). Before administration, there was no statistically significant difference in mYPAS scores among the three groups (all P>0.05); At 10 and 60 minutes after administration, the mYPAS scores of the low-dose and high-dose groups were lower than before administration, and the mYPAS scores of the low-dose and high-dose groups were lower than those of the control group (all P<0.05); At 10 and 60 minutes after administration, there was no statistically significant difference in mYPAS scores between the control group and before administration (all P>0.05), while there was no statistically significant difference in mYPAS scores between the low-dose and high-dose groups (all P>0.05). There was no statistically significant difference in the incidence of agitation among the three groups ( P>0.05). Conclusions:Preoperative oral administration of 0.25 mg/kg or 0.5 mg/kg midazolam can effectively alleviate preoperative anxiety and improve hemodynamics in children undergoing tonsillectomy combined with adenoidectomy. However, due to the fast metabolism of midazolam, its effect on improving postoperative restlessness during the recovery period is not significant. The 0.25 mg/kg dose of midazolam can reduce the retention time of PACU compared to the 0.5 mg/kg dose, which is worthy of clinical recommendation.

Objective:To construct a prospective benefit evaluation model,and to explore its effect and value in the management of micro-injection pumps and infusion pumps in thoracic surgery.Methods:A prospective benefit evaluation model was constructed through three stages:data collection,data analysis,and data application.A total of 11 medical syringe pumps(6 micro-injection pumps and 5 infusion pumps)in clinical use in the Department of Thoracic Surgery of Chongqing General Hospital from 2021 to 2023 were selected,and the conventional management method was adopted during the equipment use period from January to December 2021,and the prospective benefit evaluation model management was adopted during the equipment use period from January 2022 to December 2023(referred to as prospective management).The equipment utilization efficiency and equipment operation benefit increase of the two management methods were compared.Results:The equipment availability rate,annual start-up rate,rate of return and utilization rate of equipment utilization efficiency using prospective management method were(0.98±0.12)%,(2.14±0.28)%,(1.31±0.19)%and(25.14±1.27)%,respectively,which were higher than those of conventional management method,and the difference was statistically significant(t=3.525,3.463,7.591,11.779,P＜0.05).The increase of equipment management cost,cost-effectiveness and social benefit using prospective management method were(0.65±0.23)%,(5.92±1.14)%and(6.31±1.29)%,respectively,the increase of management cost was lower than that of conventional management method,while the increase of cost-effectiveness and social benefit were higher than those of conventional management method,and the difference was statistically significant(t=3.099,3.763,4.798,P＜0.05).Conclusion:The application of prospective benefit evaluation model to the management of equipment of micro-injection pumps and infusion pumps in thoracic surgery can improve equipment utilization efficiency,strengthen equipment management quality,and improve the increase of equipment efficiency.