OBJECTIVES: To evaluate the inhibitory effect of Macrothele raveni crude venom against proliferation of different cancer cells and identify the active components in the venom. METHODS: Different cancer cell lines were treated with different concentrations of Macrothele raveni venom for 48 h, and cell proliferation and the half-maximal inhibitory concentrations (IC₅₀) of the venom were assessed with CCK-8 assay. The apoptosis rate of breast cancer MCF7 cells following the treatment was analyzed with flow cytometry, and the changes in cellular caspase-8 and caspase-9 expressions were detected. The crude venom was separated into protein, peptide, and small-molecule compound fractions using gel filtration chromatography and high-performance liquid chromatography (HPLC). The protein and peptide components were identified using proteomics analysis, and small-molecule compounds were structurally characterized using nuclear magnetic resonance (NMR), mass spectrometry (MS), and HPLC. RESULTS The crude venom exhibited strong concentration-dependent inhibitory effects on proliferation of MCF7 cells and nasopharyngeal carcinoma SUNE1 and HONE1 cells (IC₅₀ of 2.14±0.29, 1.57±0.14, and 2.85±0.15 µg/mL, respectively), with less potent inhibitory effects in gastric cancer HGC27 cells and colorectal cancer SW620 cells (IC₅₀ of 3.02±0.27 and 3.02±0.28 µg/mL, respectively). The crude venom significantly promoted MCF7 cell apoptosis likely via the caspase 8 signaling pathway. The protein fraction from the crude venom showed a weak inhibitory effect in MCF7 cells, whereas the peptide fraction exhibited a much stronger inhibitory effect (IC₅₀ of 6.41±0.31 µg/mL). The peptides in the peptide fraction, with relative molecular mass around 10 000, were homologous to those found in Macrothele gigas venom. The small-molecule fraction consisted mainly of nucleotide metabolites without obvious inhibitory effects in MCF7 cells, but its combination with the peptide fraction showed significantly enhanced inhibitory activity. Conclusion The inhibitory effects of Macrothele raveni venom, which vary significantly across different cancer cell lines, are attributed primarily to its peptide components, which may act synergistically with the nucleotide metabolites.
Humans ; Cell Proliferation/drug effects* ; Apoptosis/drug effects* ; Animals ; Cell Line, Tumor ; MCF-7 Cells ; Caspase 8/metabolism* ; Peptides/pharmacology* ; Caspase 9/metabolism*

The ventral anterior (VA) nucleus of the thalamus is a major target of the basal ganglia and is closely associated with the pathogenesis of Parkinson's disease (PD). Notably, the VA receives direct innervation from the hypothalamic histaminergic system. However, its role in PD remains unknown. Here, we assessed the contribution of histamine to VA neuronal activity and PD motor deficits. Functional magnetic resonance imaging showed reduced VA activity in PD patients. Optogenetic activation of VA neurons or histaminergic afferents significantly alleviated motor deficits in 6-OHDA-induced PD rats. Furthermore, histamine excited VA neurons via H1 and H2 receptors and their coupled hyperpolarization-activated cyclic nucleotide-gated channels, inward-rectifier K⁺ channels, or Ca²⁺-activated K⁺ channels. These results demonstrate that histaminergic afferents actively compensate for Parkinsonian motor deficits by biasing VA activity. These findings suggest that targeting VA histamine receptors and downstream ion channels may be a potential therapeutic strategy for PD motor dysfunction.
Animals ; Histamine/metabolism* ; Male ; Oxidopamine/toxicity* ; Rats ; Ventral Thalamic Nuclei/physiopathology* ; Rats, Sprague-Dawley ; Disease Models, Animal ; Parkinson Disease/metabolism* ; Neurons/physiology* ; Humans ; Optogenetics

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

AIM To study the chemical constituents from the leaves of Cyanocarya paliurus(Batalin)Iljinskaja and their α-glucosidase inhibitory activities.METHODS The 95%ethanol extract from the leaves of C.paliurus was isolated and purified by macroporous resin,silica gel,Sephadex LH-20,polyamide,C18 reversed-phase silica gel and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their α-glucosidase inhibitory activities were evaluated by PNPG.RESULTS Fifteen compounds were isolated and identified as cyclopaloside C(1),cyclopaloside A(2),juglanosides E(3),vaccinin A(4),ent-murin A(5),kaempferol 3-O-α-L-rhamnopyranoside(6),kaempferol-3-O-β-D-glucopyranoside(7),kaempferol-3-O-β-D-glucuronide methyl ester(8),kaempferol-3-O-β-D-glucuronide ethyl ester(9),kaempferol-3-O-β-D-glucuronide butyl ester(10),quercetin-3-O-α-L-rhamnopyranoside(11)quercetin-3-O-β-D-glucopyranoside(12),quercetin-3-O-β-D-galactopyranoside(13),quercetin-3-O-β-D-glucuronide butyl ester(14),dihydrokaempferol(15).The IC50 value of total extracts ihibited α-glucosidase was(1.83±0.04)μg/mL,and the IC50 values of compounds 1,4-5 were(29.48±1.86),(0.50±0.07),(0.71±0.07)μmol/L,respectively.CONCLUSION Compound 1 is a new tetrahydronaphthalene glycoside.Compounds 4-5,8-10 and 14 are isolated from the leaves of C.paliurus for the first time.Compounds 4-5 are relatively rare flavonoid lignans with potential inhibitory activities against α-glucosidase.

italic>Lamiophlomis rotata is an important medicinal plant species endemic to the Tibetan Plateau, which is prone to strong climate change impacts on its habitable range due to the high sensitivity of the Tibetan Plateau to climate change. Accurate quantification of species vulnerability to climate change is essential for assessing species extinction risk and developing effective conservation strategies. Therefore, we carried out the α-shape analysis to determine the habitat of L. rotata. We then carried out the climate-niche factor analysis (CNFA) to assess the vulnerability of L. rotata to climate change based on five climate variables (i.e., mean diurnal range, temperature seasonality, mean temperature of warmest quarter, precipitation of driest month and precipitation of warmest quarter) in the context of two shared socioeconomic pathways (i.e., SSP126 and SSP585) and three global climate models (CMCC-ESM2: Centro Euro-Mediterraneo sui Cambiamenti Climatici-Earth System Model version 2; HadGEM3-GC31-LL: Hadley Global Environment Model version 3-Global Coupled configuration 3.1; IPSL-CM6A-LR: Institut Pierre Simon Laplace-Climate Model version 6) during two different periods (2041-2060 and 2081-2100). The vulnerability of L. rotata to climate change was calculated by integrating the sensitivity and exposure indices of L. rotata to five climate variables. The results showed that L. rotata had the highest vulnerability to the precipitation of warmest quarter. Its vulnerability within its habitat range generally showed a spatial pattern of high value in the southern region and low in the northern region, high in the western region and low in the eastern region. In general, the vulnerability of L. rotata under the SSP585 scenario was higher than that under the SSP126 scenario. The climate data of different global climate models have some influence on the results, while the resulted uncertainty can be reduced by data integration methods. As a result of climate change, the pressure on the survival of L. rotata in the future will be intensified in the low-altitude areas such as the Yarlung Zangbo River, Yigongzangbu River, Zayu River, and Jiaomuzu River, etc., while the highly weathered scree flats or stony alpine meadows in the high-altitude zones, such as the eastern Tanggula Mountain Range, the northern part of Hengduan Mountain Range, and the western part of the Qinling Mountains, may become its refuge. It is necessary to focus on and strengthen the protection and management of L. rotata resources in these vulnerble and critical areas.

Objective To investigate the effects of different angles of pulmonary surfactant(PS)administration on the incidence of bronchopulmonary dysplasia and intracranial hemorrhage in preterm infants.Methods A prospective study was conducted on 146 preterm infants(gestational age＜32 weeks)admitted to the Department of Neonatology,Provincial Hospital Affiliated to Anhui Medical University from January 2019 to May 2023.The infants were randomly assigned to different angles for injection of pulmonary surfactant groups:0° group(34 cases),30° group(36 cases),45° group(38 cases),and 60° group(38 cases).Clinical indicators and outcomes were compared among the groups.Results The oxygenation index was lower in the 60° group compared with the other three groups,with shorter invasive ventilation time and oxygen use time,and a lower incidence of bronchopulmonary dysplasia than the other three groups(P＜0.05).The incidence of intracranial hemorrhage was lower in the 60° group compared to the 0° group(P＜0.05).The cure rate in the 60° group was higher than that in the 0° group and the 30° group(P＜0.05).Conclusions The clinical efficacy of injection of pulmonary surfactant at a 60° angle is higher than other angles,reducing the incidence of intracranial hemorrhage and bronchopulmonary dysplasia in preterm infants.[Chinese Journal of Contemporary Pediatrics,2024,26(4):337-342]

Objective To explore the clinical value of vaginoscopy in the diagnosis and treatment of uterine cavity diseases in virgins.Methods We retrospectively reviewed the data of 450 patients who underwent vaginoscopy and traditional hysteroscopy in Obstetrics and Gynecology Hospital,Fudan University from Jan 2020 to Dec 2023,including vaginoscopy group(n=232)and traditional hysteroscopy group(n=218).The average ages of the two groups were 24.9±4.7 years and 25.5±5.4 years,and there was no significant difference between the two groups(P>0.05).The operation time,estimated blood loss,fluid deficit,false passage,surgical failure,incidence of complications and postoperative pain score were compared between vaginoscopy group and traditional hysteroscopy group.Results Compared with the traditional hysteroscopy group,the average operation time in the vaginoscopy group was shorter,the fluid deficit was less,and the VAS pain score was lower,but the rate of surgical failure was higher(7.8%vs.0),all the differences were statistically significant(P<0.05).In terms of complications,the incidence of false passage in the vaginoscopy group was less(0 vs.3.2%)and the rate of hymen injury was lower(0 vs.85.3%),the differences were statistically significant(P<0.05).There was no significant difference in the estimated blood loss between the two groups,and the incidence of postoperative infection was similar in both groups.There were no complications such as uterine perforation and air embolism in both groups.Conclusion Vaginoscopy is safe and effective,more minimally invasive than traditional hysteroscopy,does not damage the hymen,and is suitable for virgins.This technology is worthy of clinical application.

Objective:To investigate the laboratory detection methods for immune hemolytic transfusion reactions caused by anti-tigecycline antibody and the clinical diagnosis and treatment of one patient.Methods:The correlation between hemolysis-related laboratory indexes of the patient and the duration of medication was analyzed. Blood samples of the patient were tested using direct anti-human globulin test, free antibody test, and release test. Erythrocyte sensitization method and immune complexome analysis were used to detect the antibody against tigecycline in the serum of the patient. The properties and the titers of anti-tigecycline antibody were analyzed.Results:Anti-tigecycline antibody was found in the patient through the erythrocyte sensitization method and the immune complexome analysis, and the result of the direct anti-human globulin test was positive. The clinical symptoms and physical signs of the patient improved rapidly after withdrawal of tigecycline and blood transfusion. The patient was discharged after 14-day treatment with immunoglobulin and hormone.Conclusions:Tigecycline can cause hemolytic transfusion reactions. Serological tests are essential for the diagnosis of drug-induced hemolytic anemia. Withdrawal of medications and symptomatic treatment should be conduceted immediately when patients develop drug-related hemolytic anemia.

Piperazines are a class of new psychoactive substances with hallucinogenic effects that af-fect the central nervous system by affecting the level of monoamine neurotransmitters.Abuse of pipera-zines will produce stimulating and hallucinogenic effects,accompanied by headache,dizziness,anxiety,insomnia,vomiting,chest pain,tachycardia,hypertension and other adverse reactions,and may even cause cardiovascular diseases and multiple organ failure and lead to death,seriously affecting human physical and mental health and public safety.The abuse of new psychoactive substance piperazines has attracted extensive attention from the international community.The study of its pharmacological toxi-cology and analytical methods has become a research hotspot in the field of forensic medicine.This paper reviews the in vivo processes,sample treatment and analytical methods of existing piperazines,in order to provide reference for forensic identification.

Objective To analyze the incidence and mortality of malignant tumors among the middle-aged and elderly population in Chengguan district of Lanzhou from 2011 to 2021,and to discuss the related risk factors.Methods Using the research data of REACTION in Lanzhou,an epidemiological survey was conducted through cluster sampling in three communities in Chengguan district of Lanzhou since April 2011.The target population was middle-aged and elderly residents over 40 years old.Two follow-up surveys were carried out in 2014-2016 and 2021 successively,and 6543 people with complete follow-up data were finally included.The incidence and mortality rates of malignant tumors were calculated,as well as their age standardized rates with reference to the age composition of Segi's world standard population.Multivariate Cox regression analysis was used to screen the risk factors affecting the incidence and mortality of malignant tumors.Results After an average follow-up of 10.6 years,314 new cases of malignant tumors were found in middle-aged and elderly residents in Chengguan district of Lanzhou,with an incidence rate and age standardized incidence rate of 454.30/100 000 and 128.93/100 000,respectively.A total of 158 deaths were attributed to malignant tumors,with a mortality rate and age standardized rate of 228.41/100 000 and 607.9/100 000,respectively;The age standardized incidence rate and mortality rate of malignant tumors males were both higher than those females(P＜0.05).During the follow-up period,the age standardized incidence rate of malignant tumors in the general population showed an significant upward trend(P＜0.05),whereas the age standardized mortality rate gradually decreased after a brief increase(P＜0.05).Lung cancer,colorectal cancer,gastric cancer,and liver cancer were the main types of malignant tumors ranking in the top five in terms of incidence and mortality by gender.Multivariate Cox regression results indicate that male,age≥60 years old,college education level or above,smoking history,drinking history,having been hit by major stressful events,central obesity,hypertension,and coronary heart disease are risk factors for the onset or death of malignant tumors(HR＞1).Married,with family size≥4,frequent consumption of fresh fruit,frequent consumption of fresh vegetables,frequent consumption of grains and tubers are protective factors for the onset or death of malignant tumors(HR＜1).Conclusion The incidence of malignant tumors among middle-aged and elderly people in Chengguan district of Lanzhou from 2011 to 2021 showed an increasing trend,while the overall mortality was decreasing.Our study indicates early cancer screening in elderly populations,maintaining a healthy lifestyle and strengthening the management of chronic diseases are crucial for the prevention and treatment of malignant tumors.