Malignant pleural effusion (MPE) refers to the accumulation of pleural fluid caused by metastasis from primary pleural malignancies or tumors originating elsewhere. It is associated with a poor prognosis. Current treatment strategies primarily include systemic anti-tumor therapy and local management of MPE based on the primary tumor. Numerous studies have documented diverse approaches for the local control of MPE. This review summarizes recent advances in local treatment strategies for primary tumor-related MPE, highlighting emerging pharmacological agents and innovative techniques.
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Humans ; Pleural Effusion, Malignant/drug therapy*

Microglial functions are linked to Ca²⁺ signaling, with endoplasmic reticulum (ER) calcium stores playing a crucial role. Microglial abnormality is a hallmark of Alzheimer's disease (AD), but how ER Ca²⁺ receptors regulate microglial functions under physiological and AD conditions remains unclear. We found reduced ryanodine receptor 2 (Ryr2) expression in microglia from an AD mouse model. Modulation of RyR2 using S107, a RyR-Calstabin stabilizer, blunted spontaneous Ca²⁺ transients in controls and normalized Ca²⁺ transients in AD mice. S107 enhanced ATP-induced migration and phagocytosis while reducing ramification in control microglia; however, these effects were absent in AD microglia. Our findings indicate that RyR2 stabilization promotes an activation state shift in control microglia, a mechanism impaired in AD. These results highlight the role of ER Ca²⁺ receptors in both homeostatic and AD microglia, providing insights into microglial Ca²⁺ malfunctions in AD.
Animals ; Microglia/pathology* ; Alzheimer Disease/pathology* ; Phagocytosis/drug effects* ; Ryanodine Receptor Calcium Release Channel/metabolism* ; Disease Models, Animal ; Mice ; Cell Movement/drug effects* ; Mice, Transgenic ; Calcium Signaling/physiology* ; Calcium/metabolism* ; Mice, Inbred C57BL ; Male ; Endoplasmic Reticulum/metabolism*

Influenza virus causes serious threat to human life and health. Due to the inherent high variability of influenza virus, clinically resistant mutant strains of currently approved anti-influenza virus drugs have emerged. Therefore, it is urgent to develop antiviral drugs with new targets or mechanisms of action. RNA-dependent RNA polymerase is directly responsible for viral RNA transcription and replication, and plays key roles in the viral life cycle, which is considered an important target of anti-influenza drug design. From the point of view of medicinal chemistry, this review summarizes current advances in diverse small-molecule inhibitors targeting influenza virus RNA-dependent RNA polymerase, hoping to provide valuable reference for development of novel antiviral drugs.

Currently, clinically used drugs for the treatment of gout inflammation, such as colchicine, nonsteroidal anti-inflammatory drugs, and glucocorticoids, can only relieve the pain of joint inflammation and have severe hepatorenal toxicity and multiple organ adverse reactions. The NOD-like receptor thermal protein domain associated protein 3 (NLRP3) inflammasome is a key complex that induces the onset of gout inflammation and has become a crucial target in the development of anti-gout drugs. This article reviews the research progress of anti-gout small molecules targeting the NLRP3 inflammasome and their bioactivity evaluation methods in the past five years, in order to provide information for the development of specific drugs for the treatment of gout inflammation.

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a serious impact on global public health and the economy. SARS-CoV-2 infiltrates host cells via its surface spike protein, which binds to angiotensin-converting enzyme 2 on the host cell membrane. As a result, small molecules targeting spike protein have emerged as a hotspot in anti-SARS-CoV-2 drug research. Activity screening is an important step in seeking small molecule drugs. Therefore, this article aims to review the biological activity evaluation methods of small molecule inhibitors targeting SARS-CoV-2 spike protein, with the goal of laying the foundation for the discovery of new anti-SARS-CoV-2 drugs.

Objective:To analyze the clinical efficacy of three-dimensional(3D) reconstruction guided uniportal fluorescence thoracoscopic subsegmentectomy for the pulmonary nodules.Methods:We retrospectively analyzed 50 patients with nodules who underwent uniportal fluorescence thoracoscopic subsegmentectomy from December 2021 to February 2024. All patients underwent thin-slice CT scanning and 3D reconstruction preoperatively. 12 patients were given CT-guided hookwire localization preoperatively.The intersegmental plane was identified by fluorescence method.Results:One patient was converted to right upper lobectomy due to no lesion found in S1b. The mean blood loss was(23.4±16.5)ml and the mean operative time was(126.5±38.5)min. The mean duration of postoperative drainage was(2.6±0.8)days. Mean postoperative hospitalization was(4.8±1.8)days. There were 2 cases with postoperative pulmonary infections, including one with encapsulated pleural effusion. There was no air leakage over 3 days, and no death within 30 days after surgery.Conclusion:3D reconstruction guided uniportal fluorescence thoracoscopic subsegmentectomy is a safe and feasible technique for resection of pulmonary nodules in lung subsegments, and surgical indications must be strictly controlled.

Objective To compare the effects of two arc(TA)and dual arc(DA)techniques on the dose distribution to the planning target volume(PTV)and organs at risk(OAR)in volumetric modulated arc therapy(VMAT)for lower mid-thoracic esophageal cancer.Methods Ten patients with lower mid-thoracic esophageal cancer who received radiation therapy at some hospital from July 2020 to June 2022 were selected retrospectively.A TA radiation therapy plan and a DA radiation therapy plan were developed for each patient using the Ray Arc module of RayStation 4.7.5.4 planning system,and the two kinds of radiation plans were compared in terms of dosimetric parameters including D2,D5,D50,D95,D98,homogeneity index(HI),conformity index(CI),beam-on time and total monitor unit for PTV and lung V5,V10,V20,V30 and Dmean and heartV30,V40 and Dmean and spine cord Dmax for OAR.SPSS 22.0 was used for statistical analysis.Results TA and DA radiation therapy plans had no significant differences in PTV CI,HI,D2,D5,D50,D95 and beam-on time(P＞0.05),and DA plan had D98 and total monitor unit higher obviously than those of TA plan(P＜0.05).In terms of OARs protection,DA plan had heart V30,V40 and Dmean slightly lower than those of TA plan with non-significantly differences(P＞0.05),while lung V5,V30 and Dmean and spine cordDmax significantly lower(P＜0.05).Conclusion DA technique gains advantages over TA technique in PTV dose distribution and dose to OAR,and the involvement of DA technique in preparing the VMAT plan for esophageal cancer contributes to enhancing the treatment efficacy.[Chinese Medical Equipment Journal,2024,45(1):62-66]

AIM To establish a UPLC-MS/MS method for the simultaneous content determination of liquiritin apioside,alibiflorin,swertiamarin,methyl gallate,benzoylpaeoniflorin,sweroside,6′-O-β-D-glucosylgentiopicroside,isoliquiritigenin,loganic acid,liquiritigenin,gallic acid,paeoniflorin,oxypaeoniflorin,gentiopicroside,glycyrrhizic acid,isoliquiritoside and liquiritin in Yangxue Ruanjian Capsules.METHODS The analysis was performed on a 40℃thermostatic Waters BEH C18column(2.1 mm×100 mm,1.7 μm),with the mobile phase comprising of 2 mmol/L ammonium acetate(containing 0.1%formic acid)-acetonitrile flowing at 0.3 mL/min in a gradient elution manner,and electron spray ionization source was adopted in negative ion scanning with multiple reaction monitoring mode.RESULTS Seventeen constituents showed good linear relationships within their own ranges(r>0.999 6),whose average recoveries were 91.33%-104.03%with the RSDs of 1.58%-3.50%.CONCLUSION This rapid,accurate and stable method can be used for the quality control of Yangxue Ruanjian Capsules.

Objective To explore the therapeutic mechanism of Modified Lugen Formula(Phragmitis Rhizoma,Cicadae Periostracum,Batryticatus Bombyx,Lonicerae Japonicae Flos,Glycyrrhiza,Menthae Haplocalycis Herba,Notopterygii Rhizoma et Radix,Puerariae Lobatae Radix,Bupleuri Radix)in treating influenza from the virus-host interaction interface.Methods The phytocompounds were first collected from the HERB database,and then potential active compounds were screened out by Lipinski's rules of five.The targets of active compounds were further predicted through the SwissTargetPrediction platform.Differentially expressed genes(DEGs)were determined from the human H1N1 influenza dataset GSE90732 available in the Gene Expression Omnibus database(GEO).H1N1-Homo sapiens-related protein-protein interactions(PPIs)were gathered from the Pathogen-Host Interaction Search Tool(PHISTO).The above mentioned bioinformatic datasets were integrated.Then a PPI network and a Formula-virus-host interaction network were constructed using Cytoscape.Functional enrichment analyses were performed by using R software.Finally,molecular docking was carried out to evaluate the binding activities between the key compounds and targets.Results A total of 1 252 active compounds,1 415 targets,951 influenza-related DEGs,and 10 142 H1N1-Homo sapiens-related PPIs were obtained.There were 72 intersection targets between the Modified Lugen Formula and influenza.Functional enrichment analyses showed that these targets are closely related to host defense and programmed cell death.The network topological analysis showed that active compounds in the Modified Lugen Formula,such as oleanolic acid,γ-undecalactone,and longispinogenin,regulate viral proteins M2,NA,NS1,and HA and/or the host factors HSP90AA1,NRAS,and ITGB1,thus exert therapeutic effect.Molecular docking results confirmed that these compounds had a good binding ability with the targets.Conclusion Multiple active ingredients in Modified Lugen Formula directly target influenza virus proteins and/or host factors,thereby play an anti-influenza role in multiple dimensions,including inhibiting virus replication,regulating host defense and cell death.This study provides a theoretical basis for further experimental analysis of the action mechanism of the Modified Lugen Formula in treating influenza.

Objective:To evaluate the effect of gender on dose-effect relationship of remimazolam combined with alfentanil in painless gastroscopy.Methods:Subjects who planned to undergo elective painless gastroscopy,aged 18-60 years old,body mass index 19-24 kg/m2,American Society of Anesthesiologists physical status Ⅰ or Ⅱ,were enrolled.They were divided into male group and female group.The first subject in both groups received afentanil 5 μg/kg and remimazolam 0.2 mg/kg,and was implanted into a gastroscope 2 minutes later.Positive reactions were defined as body movement,coughing,swallowing and frowning during gastroscopy placement and examination.Remimazolam 0.05 mg/kg was used as a dose gradient by using modified Dixon's up-and-down method.The dose of the next subject was adjusted according to whether the subject had a positive reaction.If there was a positive reaction,the dose of the next subject was increased by one level of gradient,otherwise,the dose was decreased by one level of gradient,and so on.The process was terminated at the seventh intersection point of positive-negative reaction.And 50% effective dose(ED50),95% effective dose(ED95)and 95% confidence interval(CI)of remimazolam for inhibiting gastroscopic implantation reaction was calculated by Probit method.Results:A total of 46 subjects were included,with 23 subjects in each group.There was no significant difference in general data between the two groups.The ED50 of afentanil combined with remimazolam was 0.193 mg/kg(95% CI:0.145-0.286),and the ED95 was 0.293 mg/kg(95% CI:0.237-0.903)in male group.The ED50 of afentanil combined with remimazolam was 0.215 mg/kg(95% CI:0.155-0.293),and the ED95 was 0.316 mg/kg(95% CI:0.261-0.968)in female group.The ED50 and ED95(P＜0.05).Conclusion:When combined with 5 μg/kg of afentanil,remimazolam is more effective in inhibiting responses to gastroscopy inserting in male subjects than in female subjects.