Objective To explore the mechanism of Medicoscab tincture in the treatment of second-degree burns based on network pharmacology and molecular docking technology. Methods The effective components of the tincture were screened by the TCMSP; the effective components of the tincture and burn related targets were screened by GeneCards and OMIM database; Cytoscape 3.7.2 software was used to draw “Chinese medicine-disease-effective components-targets” network diagram; the related gene ontology （GO） functions and pathways of the tincture were obtained through GO enrichment analysis and Kyoto encyclo-pedia of genes and geomes （KEGG） pathway analysis on the targets through Metascape platform; the pathway bubble diagram was constructed by the pathways enriched in the KEGG database, and finally verified by AutoDockTools for molecular alignment. Results 19 effective components and 179 target intersections of Medicoscab tincture were selected. GO analysis showed the intervention burns process mainly involved the reaction of inorganic substances, the reaction of cells to nitrogen compounds, and the response to xenobiotic stimuli, as well as biological processes such as membrane rafts, vesicular cavities, transcriptional regulatory factor complexes, receptor complexes, and endoplasmic reticulum cavities. KEGG analysis showed the function mainly includes AGE-RAGE signal pathway, PI3K-Akt signal pathway, IL-17 signal pathway, TNF signal pathway, etc. Analysis of cytoscape software showed the core targets were AKT1, TNF, IL-6, GAPDH, TP53, etc. Molecular docking showed that the active components of Medicoscab tincture were docking with multiple targets, among which β- sitosterol had strong binding activity with AKT1, GAPDH and TP53. Conclusion Quercetin, kaempferol, baicalein, β-sitosterol and other core active ingredients in the tincture of making scabs, which could assist in the relief of burns, regulate the signalling pathways such as AGE-RAGE, PI3K-Akt, IL-17, TNF and so on by acting on the targets of AKT1, GAPDH, TP53, IL-6 and so on. This study laid a theoretical foundation for clarifying the mechanism of action of tincture of scab making for the treatment of burn-like diseases.

Astrocytes are a crucial type of glial cells in the central nervous system, not only maintaining brain homeostasis, but also actively participating in the transmission of information within the brain. Astrocytes have a complex structure that includes the soma, various levels of processes, and end-feet. With the advancement of genetically encoded calcium indicators and imaging technologies, researchers have discovered numerous localized and small calcium activities in the fine processes and end-feet. These calcium activities were termed as microdomain calcium activities, which significantly differ from the calcium activities in the soma and can influence the activity of local neurons, synapses, and blood vessels. This article elaborates the detection and analysis, characteristics, sources, and functions of microdomain calcium activities, and discusses the impact of aging and neurodegenerative diseases on these activities, aiming to enhance the understanding of the role of astrocytes in the brain and to provide new insights for the treatment of brain disorders.
Astrocytes/cytology* ; Humans ; Animals ; Calcium/metabolism* ; Calcium Signaling/physiology* ; Brain/physiology* ; Aging/physiology* ; Membrane Microdomains/physiology* ; Neurodegenerative Diseases/physiopathology*

Objective To explore the effects of S100 calcium-binding protein A9 (S100A9) gene knockout on the phenotype of systemic lupus erythematosus (SLE) in mice and to clarify the role of S100A9 in the pathogenesis of SLE. Methods Ten female C57BL/6 wild-type and S100A9 knockout (S100A9-KO ) mice were selected, with five wild-type and five S100A9-KO B6 mice receiving imiquimod (IMQ) cream to establish SLE mouse model. The other five wild-type and five S100A9-KO B6 mice were treated as control groups by wiping the skin of the right ear with a cotton swab. After 8 weeks, the mice were sacrificed. The serum was collected from each mouse to detect the levels of anti-double-stranded DNA (dsDNA) antibodies, immunoglobulin G (IgG), B cell activating factor (BAFF), and interleukin 6 (IL-6) using ELISA. The levels of serum creatinine were determined using a sarcosine oxidase method. Urine was collected to measure urinary protein concentration. Kidneys were collected and stained with hematoxylin and eosin (H&E) for evaluating histological changes. Results After IMQ treatment, the length and weight of spleen, levels of serum creatinine, anti-dsDNA antibodies, IgG, BAFF, IL-6, and urinary protein in the IMQ B6 group and IMQ S100A9-KO B6 group were significantly higher than those of the control groups. Lupus-like changes including increased glomerular volume and tubular epithelial swelling were observed in kidneys from the IMQ and IMQ S100A9-KO groups. However, compared with the IMQ B6 group, the IMQ S100A9-KO B6 group exhibited milder levels of serum and urine indicators as well as the lupus-like symptoms. Conclusion IMQ could induce lupus-like symptoms in both wild-type B6 mice and S100A9-KO B6 mice, but the lesions in S100A9 knockout mice are milder. Theses results suggested that S100A9 is involved in and promotes the pathogenesis of SLE.
Animals ; Lupus Erythematosus, Systemic/chemically induced* ; Female ; Calgranulin B/genetics* ; Mice, Knockout ; Mice, Inbred C57BL ; Phenotype ; Mice ; Interleukin-6/blood* ; Disease Models, Animal ; Antibodies, Antinuclear/blood* ; B-Cell Activating Factor/blood* ; Immunoglobulin G/blood* ; Kidney/pathology*

OBJECTIVE To report a case of hepatitis B virus （HBV） reactivation induced by iparomlimab and tuvonralimab， summarize the clinical characteristics and potential mechanisms of such adverse reactions induced by immune-checkpoint inhibitors （ICIs）， and provide references for clinical application. METHODS From the perspective of a clinical pharmacist， a retrospective analysis was conducted on the treatment course of a patient with metastatic cervical cancer who experienced HBV reactivation after receiving iparomlimab and tuvonralimab. Additionally， an analysis of the correlation with adverse reactions was performed， and the clinical characteristics， risk factors， potential mechanisms， key points of treatment approaches and pharmaceutical care associated with HBV reactivation induced by ICIs were summarized. RESULTS & CONCLUSIONS The patient developed HBV reactivation and severe liver injury after using iparomlimab and tuvonralimab. The condition improved following drug discontinuation， and symptomatic treatment such as glucocorticoids. According to Naranjo’s Assessment Scale and China’s Measures for the Reporting and Monitoring of Adverse Drug Reactions， the association between iparomlimab and tuvonralimab and HBV reactivation was judged as “highly probable”， and it was identified as a new adverse reaction； the correlation between iparomlimab and tuvonralimab， paclitaxel and liver injury was “highly probable”. HBV reactivation in hepatitis B patients receiving standardized antiviral therapy is very rare after ICIs treatment； HBV reactivation is related to the overactivation of the immune system and disruption of immune balance induced by ICIs. For such patients， glucocorticoids should be administered for treatment， accompanied by pharmaceutical care， including pre- medication risk assessment and monitoring of relevant indicators during treatment.

Objective To analyze therapeutic effect of savolitinib in patients with stage Ⅲ/Ⅳ non-small cell lung cancer (NSCLC). Methods A total of 95 patients with MET 14 exon (METex14) jumping mutation in stage Ⅲ/Ⅳ NSCLC were divided into a control group (47 cases) and an observation group (48 cases) through a random-number table method. The patients in the control group were treated with crizotinib, whereas those in the observation group were treated with savolitinib. The clinical efficacy and incidence of toxic side effects in both groups were evaluated through a chi-square test, and survival was evaluated through Kaplan-Meier survival analysis. Results Compared with control group (31.91% and 70.21%), the objective response rate and disease control rate of the observation group were 52.08% and 87.50%, respectively (P<0.05). According to Kaplan-Meier survival analysis, the overall survival and progression free survival rates in the observation group were higher than those in the control group (Log rank χ²=8.003, 4.528; P=0.005, 0.033). No statistically significant difference in the degree of toxic side effects was found between the groups (P>0.05). Conclusion Savolitinib can improve the efficacy of treatment for stage Ⅲ/Ⅳ METex14 skip mutation NSCLC patients, prolong survival, enhance the tolerance of patients to savolitinib, and facilitate the management of adverse reactions.

OBJECTIVE To observe the efficacy of vericiguat in the treatment of acute decompensated heart failure （HF） and its effect on left ventricular ejection fraction （LVEF） in patients with different left ventricular end-diastolic internal diameters （LVDd）. METHODS A total of 52 patients with acute decompensated HF who were hospitalized in Anqing Municipal Hospital from September 2022 to May 2023 and were stabilized by intravenous injection of diuretics or vasodilators and then given vericiguat orally were selected. Clinical baseline data were collected， and blood creatinine （Scr）， estimated glomerular filtration rate （eGFR）， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， echocardiographic indexes（LVEF， LVDd）， and Kansas City cardiomyopathy questionnaire （KCCQ） scores and so on were recorded and analyzed at 1 and 6 months after treatment. The patients were divided into two subgroups according to whether they had dilated cardiomyopathy or not， the baseline data were compared between the two subgroups， and the changes in the above follow-up indexes for the entire population and two subgroups of patients were analyzed by using mixed effect model. RESULTS Patients in the dilated cardiomyopathy group were significantly younger than those in the nondilated cardiomyopathy group， while the former had a lower proportion of patients with combined coronary artery disease， longer LVDd， lower LVEF levels， and more HF patients with reduced ejection fraction （P＜0.05）. Compared with baseline values， KCCQ scores were significantly higher in patients in the whole population， non-dilated cardiomyopathy group and dilated cardiomyopathy group at 1 month after treatment （P＜0.001）. The difference between the whole population in terms of elevated KCCQ scores and decreased lg（NT-proBNP） levels was statistically significant at 6 months after treatment （P＜0.05）； the levels of lg（NT-proBNP）of two subgroups were significantly decreased and KCCQ scores were significantly increased （P＜0.05）， but the difference was not statistically significant （P＞0.05）； LVEF levels of the patients E-mail：guangf4-508@163.com in both subgroups were significantly elevated （P＜0.05） and the difference between the subgroups amounted to 7.52% （P＝0.030）. Mixed effect model result showed that whether patients had coronary artery disease and different baseline levels of LVDd were likely to affect follow-up LVEF levels， with coronary artery disease contributing to follow-up LVEF elevation （P＝0.043）， but the coronary artery disease subgroup × time interaction was not significant （P＞0.05）；compared with patients with baseline LVDd ≥62 mm， patients with baseline LVDd≤61 mm had a faster LVEF improvement （P＜0.05）. CONCLUSIONS Vericiguat is able to improve cardiac function and quality of life in patients with acute decompensated HF without negatively affecting their renal function. The drug is able to significantly improve LVEF levels in patients with baseline LVDd ≤61 mm.

OBJECTIVE To observe the efficacy of vericiguat in the treatment of acute decompensated heart failure （HF） and its effect on left ventricular ejection fraction （LVEF） in patients with different left ventricular end-diastolic internal diameters （LVDd）. METHODS A total of 52 patients with acute decompensated HF who were hospitalized in Anqing Municipal Hospital from September 2022 to May 2023 and were stabilized by intravenous injection of diuretics or vasodilators and then given vericiguat orally were selected. Clinical baseline data were collected， and blood creatinine （Scr）， estimated glomerular filtration rate （eGFR）， N-terminal pro-B-type natriuretic peptide （NT-proBNP）， echocardiographic indexes（LVEF， LVDd）， and Kansas City cardiomyopathy questionnaire （KCCQ） scores and so on were recorded and analyzed at 1 and 6 months after treatment. The patients were divided into two subgroups according to whether they had dilated cardiomyopathy or not， the baseline data were compared between the two subgroups， and the changes in the above follow-up indexes for the entire population and two subgroups of patients were analyzed by using mixed effect model. RESULTS Patients in the dilated cardiomyopathy group were significantly younger than those in the nondilated cardiomyopathy group， while the former had a lower proportion of patients with combined coronary artery disease， longer LVDd， lower LVEF levels， and more HF patients with reduced ejection fraction （P＜0.05）. Compared with baseline values， KCCQ scores were significantly higher in patients in the whole population， non-dilated cardiomyopathy group and dilated cardiomyopathy group at 1 month after treatment （P＜0.001）. The difference between the whole population in terms of elevated KCCQ scores and decreased lg（NT-proBNP） levels was statistically significant at 6 months after treatment （P＜0.05）； the levels of lg（NT-proBNP）of two subgroups were significantly decreased and KCCQ scores were significantly increased （P＜0.05）， but the difference was not statistically significant （P＞0.05）； LVEF levels of the patients E-mail：guangf4-508@163.com in both subgroups were significantly elevated （P＜0.05） and the difference between the subgroups amounted to 7.52% （P＝0.030）. Mixed effect model result showed that whether patients had coronary artery disease and different baseline levels of LVDd were likely to affect follow-up LVEF levels， with coronary artery disease contributing to follow-up LVEF elevation （P＝0.043）， but the coronary artery disease subgroup × time interaction was not significant （P＞0.05）；compared with patients with baseline LVDd ≥62 mm， patients with baseline LVDd≤61 mm had a faster LVEF improvement （P＜0.05）. CONCLUSIONS Vericiguat is able to improve cardiac function and quality of life in patients with acute decompensated HF without negatively affecting their renal function. The drug is able to significantly improve LVEF levels in patients with baseline LVDd ≤61 mm.

BACKGROUND: Ventricular remodeling after acute anterior wall ST-segment elevation myocardial infarction (AAMI) is an important factor in occurrence of heart failure which additionally results in poor prognosis. Therefore, the treatment of ventricular remodeling needs to be further optimized. Compound Danshen Dripping Pills (CDDP), a traditional Chinese medicine, exerts a protective effect on microcirculatory disturbance caused by ischemia-reperfusion injury and attenuates ventricular remodeling after myocardial infarction. OBJECTIVE: This study is designed to evaluate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function after AAMI on a larger scale. METHODS: This study is a multi-center, randomized, double-blind, placebo-controlled, parallel-group clinical trial. The total of 268 patients with AAMI after primary percutaneous coronary intervention (pPCI) will be randomly assigned 1:1 to the CDDP group (n=134) and control group (n=134) with a follow-up of 48 weeks. Both groups will be treated with standard therapy of ST-segment elevation myocardial infarction (STEMI), with the CDDP group administrating 20 tablets of CDDP before pPCI and 10 tablets 3 times daily after pPCI, and the control group treated with a placebo simultaneously. The primary endpoint is 48-week echocardiographic outcomes including left ventricular ejection fraction (LVEF), left ventricular end-diastolic volume index (LVEDVI), and left ventricular end-systolic volume index (LVESVI). The secondary endpoint includes the change in N terminal pro-B-type natriuretic peptide (NT-proBNP) level, arrhythmias, and cardiovascular events (death, cardiac arrest, or cardiopulmonary resuscitation, rehospitalization due to heart failure or angina pectoris, deterioration of cardiac function, and stroke). Investigators and patients are both blinded to the allocated treatment. DISCUSSION This prospective study will investigate the efficacy and safety of CDDP in improving ventricular remodeling and cardiac function in patients undergoing pPCI for a first AAMI. Patients in the CDDP group will be compared with those in the control group. If certified to be effective, CDDP treatment in AAMI will probably be advised on a larger scale. (Trial registration No. NCT05000411).
Humans ; ST Elevation Myocardial Infarction/therapy* ; Stroke Volume ; Ventricular Remodeling ; Prospective Studies ; Microcirculation ; Ventricular Function, Left ; Myocardial Infarction/etiology* ; Treatment Outcome ; Percutaneous Coronary Intervention/adverse effects* ; Heart Failure/drug therapy* ; Drugs, Chinese Herbal/therapeutic use* ; Randomized Controlled Trials as Topic ; Multicenter Studies as Topic

COVID-19 has been prevalent for three years. The virulence of SARS-CoV-2 is weaken as it mutates continuously. However, elderly patients, especially those with underlying diseases, are still at high risk of developing severe infections. With the continuous study of the molecular structure and pathogenic mechanism of SARS-CoV-2, antiviral drugs for COVID-19 have been successively marketed, and these anti-SARS-CoV-2 drugs can effectively reduce the severe rate and mortality of elderly patients. This article reviews the mechanism, clinical medication regimens, drug interactions and adverse reactions of five small molecule antiviral drugs currently approved for marketing in China, so as to provide advice for the clinical rational use of anti-SARS-CoV-2 in the elderly.

Background The urban heat island effect has a significant negative impact on human health. Urban green space can effectively improve the urban thermal environment while enhancing human thermal comfort. Objective To investigate the effects of vegetation configuration structure on temperature and humidity and on human thermal comfort, with a view to providing reference for the landscape planning of urban reserve, preventing and reducing the impact of urban heat island effect on the health of urban residents. Methods The study was carried out on a typical clear and cloudless summer day without extreme weather in a university reserve area in Hefei. The numerical simulation accuracy of ENVI-met software was verified by measured data. Based on the quantitative definition of vegetation configuration structure scheme from vertical and horizontal perspectives, nine simulation scenarios were established based on three aspects including vegetation configuration type (grass, shrub + grass, tree + grass, tree + shrub + grass), planting layout (column planting, uniform spot planting), and planting density [the aspect ratio of trees (ART) between plants was 0.75, 1.13, 1.50, and 2.25, respectively] to quantitatively evaluate the cooling and humidifying effects and human thermal comfort [physiological equivalent temperature (PET)] of the vegetation configurations. Results The change trends of the cooling and humidifying effects of all the simulated scenarios were consistent, basically first increasing and then decreasing. Among all the simulated scenarios, the cooling and humidifying effects of scenario 8 (tree + grass, ART=2.25, uniform spot planting) were the best, with the greatest cooling of 1.36 ℃ and humidification of 6.29% in comparison to the worst scenario 1 in the reserve area. The human thermal comfort of scenario 9 (tree + shrub + grass, ART=2.25, uniform spot planting) was the best, with the PET of 35.37 ℃. The order of improvement effect of different vegetation configurations on thermal comfort from strong to weak was tree + shrub + grass structure (scenario 9) > tree + grass structure (scenario 8) > shrub + grass structure (scenario 2) > grass structure (scenario 1). At 15:00, the PET value of tree + shrub + grass structure (scenario 9) decreased by 7.44 ℃ in comparison to that of grass structure (scenario 1). The higher the planting density among trees, the higher the difference in temperature and relative humidity between the simulated and the original scenarios. In case of holding the same amount of greenery, uniform spot planting showed better human comfort when the vegetation was planted sparsely, but the difference between the PET value of scenario 3 (tree + grass, ART=0.75, uniform spot planting) and scenario 5 (tree + grass, ART=1.5, column planting) was only 0.15 ℃; when the vegetation was planted densely, column planting was more favorable to wind circulation and more effective in reducing the temperature of the site, with a lower PET value of 0.87 ℃ for scenario 7 (tree + grass, ART=2.25, column planting) than for scenario 4 (tree + grass, ART=1.13, uniform spot planting). Conclusion Urban green space has obvious cooling and humidifying effects in summer. The human comfort of tree + shrub + grass structure with uniform spot planting is optimal, and the cooling and humidifying effects of tree + grass structure with uniform spot planting are the most obvious. The optimization of vegetation configuration structure is crucial for reducing urban heat island, improving human thermal comfort, and promoting residents’ health.