OBJECTIVE To investigate the effects of borneol on pharmacodynamic and pharmacokinetic effects of Corydalis saxicola total alkaloids in depression model rats. METHODS Thirty male SD rats were divided into blank control group， negative control group， positive control group （fluoxetine 10 mg/kg， i.g.）， single drug group （C. saxicola total alkaloids 210 mg/kg， i.g.） and combined drug group （C. saxicola total alkaloids 210 mg/kg+borneol 50 mg/kg， i.g.） according to the random number table method， with 6 rats in each group. By lipopolysaccharide （LPS） induction modeling， except blank control group （no model and no administration） received intraperitoneal injection of the same amount of normal saline， the rats in the other groups were intraperitoneally injected with LPS once a day to establish a rat model of depression. After 1 week of modeling， each administration group was given relevant drug intragastrically according to the corresponding dose， and blank control group and negative control group （without drug treatment） were administered intragastrically with an equal volume of solvent to dissolve the drug； continued modeling while administering the drug. After two weeks of continuous administration， the effects of C. saxicola total alkaloids versus the combination of C. saxicola total alkaloids and borneol on the behavior of depressed rats were tested by behavioral experiments； the levels of tumor necrosis factor-α， interleukin-1β and interleukin-6 in rats were determined； the histopathological changes of the hippocampus of rats were observed. Blood sample was collected from the orbit at different time points after administration on the 15th day， and the upper plasma was obtained. Ultra-performance liquid chromatography-triple quadrupole tandem mass spectrometry was established for the simultaneous determination of dehydrocarvedine， tetrahydropalmatine， coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine in rat plasma. The average plasma concentration-time curve was depicted， the area under the curve （AUC） was calculated， and the pharmacokinetic parameters were analyzed by DAS 3.2.2 software. RESULTS Compared with blank control group， the negative control group had a decrease in body mass and sugar water preference rate， a decrease in the total distance of open field， a prolonged swimming immobility time， and a increased in the expression of inflammatory factors in serum （P＜0.05）； compared with negative control group, the single drug group and the combined drug group increased the preference rate of sugar water， increased the total distance of open field， shortened the time of swimming immobility， and decreased the expression of inflammatory factors in serum （P＜0.05）. There was no significant difference in the above indicators between the single drug group and the combined drug group in rats （P＞0.05）. Pharmacokinetic results showed that compared with single drug group， AUC0-t of coptisine， AUC0-t， AUC0-∞， tmax and cmax of jatrorrhizine， AUC0-t， AUC0-∞， t1/2 and cmax of berberrubine， and AUC0-t of epiberberine， cmax of dehydrocarvedine， cmax of palmatine were significantly increased in combined drug group， but there was no significant difference， indicating that borneol didn’t have a significant effect on the efficacy of Corydalis saxicola nigra at this dose. CONCLUSIONS Both C. saxicola total alkaloids alone and in combination with borneol can improve depression-like behavior in depression model rats， reduce serum inflammatory cytokine levels， and protect hippocampal neurons. Compared with the use of Corydalis saxicola base alone， the combination with borneol do not show significant pharmacodynamic differences， bu can improve the absorption of coptisine， jatrorrhizine in model rats.

ObjectiveTo investigate the effect of total alkaloids of Corydalis saxicola on a rat model of lipopolysaccharide（LPS）-induced depression， as well as the pharmacokinetic characteristics of 8 of its major components. MethodTwenty-four male SD rats were randomly divided into normal group， model group， fluoxetine group（10 mg·kg^-1） and total alkaloids of C. saxicola group（210 mg·kg^-1）， with 6 rats in each group. In addition to the normal group， the rats were injected intraperitoneally with LPS to establish the inflammation model of depression， and the drug administration was started 1 week after modeling， and the administration groups were gavaged according to the corresponding dose， and the normal and model groups were intragastric administration with equal volume of distilled water， and the administration was performed along with the modeling. After two weeks of continuous administration， the effect of total alkaloids of C. saxicola on the behavior of depressed rats were tested by sucrose preference， forced swimming and open field experiments， the levels of tumor necrosis factor-α（TNF-α）， interleukin（IL）-1β and IL-6 in serum of rats were determined by enzyme-linked immunosorbent assay（ELISA）， the histopathological changes of rat hippocampus were observed by hematoxylin-eosin（HE） staining. After the last administration， blood was collected from orbit according to the set time， and ultra-high performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS） was established to simultaneously detect the concentrations of dehydrocavidine， tetrahydropalmatine， coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine in plasma， and drug-time curves were drawn. The pharmacokinetic parameters were analyzed by DAS 2.0 software. ResultCompared with the normal group， the model group exhibited a decrease in sucrose preference rate， total distance traveled in the open field， as well as an increase in swimming immobility time and serum inflammatory factor expression（P<0.01）. In contrast， compared with the model group， rats in each administration group showed an increase in sucrose preference rate and total distance traveled in the open field， a decrease in swimming immobility time， and a reduction in serum inflammatory factor expression（P<0.05， P<0.01）. Additionally， HE staining results revealed that neurons in the hippocampus of rats from the model group were characterized by loss， disorganization and residual vacuoles， whereas those from the total alkaloids of C.saxicola group displayed an increase in number with orderly arrangement and clear cytoplasm. Pharmacokinetic results showed that the time to peak（t_max） and half-life（t_1/2） of the 8 active ingredients were 0.19-2.06 h and 3.71-8.70 h after continuous administration of total alkaloids of C. saxicola. Among them， the area under the curve（AUC_0-∞） of tetrahydropalmatine was the highest and the t_1/2 was the shortest， and the AUC_0-∞ of coptisine， palmatine， jatrorrhizine， berberine， berberrubine and epiberberine were low. The curves of dehydrocavidine， coptisine， palmatine， berberine and epiberberine showed obvious double peak phenomenon. ConclusionTotal alkaloids of C. saxicola can improve the depression-like behavior of rats， inhibit the expression of inflammatory factors in serum， improve the pathological injury of hippocampus， and has the antidepressant effect. Meanwhile， the effective site is absorbed quickly and eliminated slowly in the depressed model rats， and the efficacy is maintained for a long time.

ObjectiveTo investigate the pharmacodynamics， pharmacokinetics and brain distribution of seven main components of Jiaotaiwan alone and Jiaotaiwan combined with borneol in lipopolysaccharide（LPS）-induced depression rats. MethodRats were randomly divided into the control group， model group， fluoxetine group（10 mg·kg^-1）， Jiaotaiwan group（1.5 g·kg^-1） and combination group（1.5 g·kg^-1 of Jiaotaiwan+0.05 g·kg^-1 of borneol）， with 8 rats in each group. Except for the control group， the depression model was established by intraperitoneal injection of LPS for 7 consecutive days， and each group was given the corresponding drugs or the same volume of pure water by gavage for 14 consecutive days. The behavioral indicators and levels of serum inflammatory factors［interleukin-1β（IL-1β）， IL-6 and tumor necrosis factor-α（TNF-α）］ of rats in each group were compared. The morphological changes of hippocampal neurons were observed by hematoxylin-eosin（HE） and Nissl staining. After the behavioral tests of sucrose preference， open field and forced swimming were completed， blood samples were collected from Jiaotaiwan group and combination group at the set time points after gavage， the contents of seven components in plasma were determined by ultra performance liquid chromatography-triple quadrupole tandem mass spectrometry（UPLC-QqQ-MS/MS）， and the pharmacokinetic parameters of each component were analyzed by DAS 3.2.2. Brains were rapidly removed on ice after blood collection was completed， and UPLC-QqQ-MS/MS was used to compare the content changes of the 7 components in brain tissue. ResultCompared with the control group， rats in the model group showed decreased sucrose preference rate and total distance of open field， prolonged swimming immobility time， and increased expression of inflammatory factors in serum（P<0.01）. Compared with the model group， the sucrose preference rate and total distance of open field were increased， and the swimming immobility time was shortened in the rats of each administration group， and the expression of inflammatory factors in serum was decreased in rats from Jiaotaiwan group and combination group（P<0.05， P<0.01）. The results of HE and Nissl staining showed that Jiaotaiwan group and combination group had a certain protective effect on hippocampal neurons. The pharmacokinetic results showed that compared with Jiaotaiwan group， the area under the curve（AUC_0-t， AUC_0-∞）， peak concentration（C_max） and the average steady-state plasma concentration（C_av） of berberine and epiberberine in the combination group were increased（P<0.05， P<0.01）， AUC_0-t， AUC_0-∞， mean residence time（MRT_0-∞） and C_av of coptisine were significantly increased（P<0.05， P<0.01）， C_max of jatrorrhizine increased significantly（P<0.05）， but the pharmacokinetic changes of the seven alkaloids were consistent. The results of brain tissue distribution showed that compared with Jiaotaiwan group， the contents of jatrorrhizine， epiberberine， coptisine， palmatine and berberine in the brain tissue of combination group were increased（P<0.05， P<0.01）， the content of magnoflorine increased and that of berberrubine decreased， but the difference was not statistically significant. ConclusionJiaotaiwan alone or combined with borneol can improve the depression-like behavior of rats， reduce the levels of serum inflammatory factors， improve the pathological damage of hippocampus， and have antidepressant effect. Compared with Jiaotaiwan alone， the combination of Jiaotaiwan and borneol can increase the exposure of multiple active components of Jiaotaiwan in the plasma and brain tissue of rats， improve its bioavailability， promote its absorption， and improve the brain targeting of the drug， which is more conducive to the antidepressant effect of Jiaotaiwan.

Objective To investigate the independent risk factors for postoperative deep vein thrombosis in lung cancer patients and to construct a risk prediction model.Methods Clinical data of 354 inpatients who underwent thoracoscopic surgery for lung cancer in Department of Thoracic Surgery of First Affiliated Hospital of Army Medical University between May 2019 and May 2023 were retrospectively collected and analyzed.LASSO regression was used to screen potential factors,followed by multivariate logistic regression to identify risk factors,and then a nomogram prediction model was constructed.Calibration curves,receiver operating characteristic(ROC)curves,and decision curves were drawn to evaluate the model's calibration,discrimination,sensitivity,specificity,and clinical utility.The net reclassification improvement(NRI)and integrated discrimination improvement(IDI)indices were employed to compare the predictive performance of the constructed model with the Caprini score for outcome events.Results LASSO regression identified 17 potential influencing factors.Multivariate regression analysis showed that D-dimer,central venous catheter(CVC)placement,and lower extremity varicose veins were independent risk factors for postoperative DVT in lung cancer patients(P＜0.05).Calibration curve analysis showed the model had good agreement between the predicted and observed values.ROC curve analysis indicated that the sensitivity and specificity of the model was 0.812 and 0.963,respectively,with an area under the curve(AUC)value of 0.912(95％CI:0.840～0.983).In comparison,the Caprini model had a sensitivity and specificity of 0.625 and 0.860,respectively,with an AUC value of 0.752(95％CI:0.657～0.846).The NRI and IDI for the model group compared to the Caprini model were 0.709 and 0.431,respectively.Decision curve analysis showed that the net benefit of applying the model from this study was higher than that of the Caprini model.Conclusion D-dimer,CVC,and varicose veins of lower extremities are independent risk factors for DVT after thoracoscopic surgery in patients with lung cancer.Our constructed nomogram model can effectively predict the risk of DVT after thoracoscopic surgery in patients with lung cancer.

Humans ; COVID-19 ; Pandemics ; SARS-CoV-2 ; Anxiety ; Brain ; Depression

BACKGROUND: Patients with schizophrenia (SCZ) and major depressive disorder (MDD) share significant clinical overlap, although it remains unknown to what extent this overlap reflects shared neural profiles. To identify the shared and specific abnormalities in SCZ and MDD, we performed a whole-brain voxel-based meta-analysis using magnetization transfer imaging, a technique that characterizes the macromolecular structural integrity of brain tissue in terms of the magnetization transfer ratio (MTR). METHODS: A systematic search based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines was conducted in PubMed, EMBASE, International Scientific Index (ISI) Web of Science, and MEDLINE for relevant studies up to March 2022. Two researchers independently screened the articles. Rigorous scrutiny and data extraction were performed for the studies that met the inclusion criteria. Voxel-wise meta-analyses were conducted using anisotropic effect size-signed differential mapping with a unified template. Meta-regression was used to explore the potential effects of demographic and clinical characteristics. RESULTS: A total of 15 studies with 17 datasets describing 365 SCZ patients, 224 MDD patients, and 550 healthy controls (HCs) were identified. The conjunction analysis showed that both disorders shared higher MTR than HC in the left cerebellum ( P =0.0006) and left fusiform gyrus ( P =0.0004). Additionally, SCZ patients showed disorder-specific lower MTR in the anterior cingulate/paracingulate gyrus, right superior temporal gyrus, and right superior frontal gyrus, and higher MTR in the left thalamus, precuneus/cuneus, posterior cingulate gyrus, and paracentral lobule; and MDD patients showed higher MTR in the left middle occipital region. Meta-regression showed no statistical significance in either group. CONCLUSIONS The results revealed a structural neural basis shared between SCZ and MDD patients, emphasizing the importance of shared neural substrates across psychopathology. Meanwhile, distinct disease-specific characteristics could have implications for future differential diagnosis and targeted treatment.
Humans ; Depressive Disorder, Major/drug therapy* ; Schizophrenia/pathology* ; Brain/pathology* ; Prefrontal Cortex ; Frontal Lobe ; Magnetic Resonance Imaging/methods*

In this study, we synthesized six tetrazine-dipyrromethene boron difluoride (BODIPY) probes and achieved a remarkable up to 14-fold increase in singlet oxygen yield via tetrazine bioorthogonal click-to-release reactions. We systematically investigated the photodynamic activity of these probes, revealing crucial structure-activity relationships. Additionally, we evaluated the stability and release kinetics of these probes and identified P5 and P6 as ideal candidates for photodynamic therapy in live cells. This innovative strategy opens new avenues for fine-tuning the photodynamic properties of BODIPY dyes, thereby expanding their utility in cancer therapy.

Cardiac-resident macrophages (CRMs) play important roles in homeostasis, cardiac function, and remodeling. Although CRMs play critical roles in cardiac regeneration of neonatal mice, their roles are yet to be fully elucidated. Therefore, this study aimed to investigate the dynamic changes of CRMs during cardiac ontogeny and analyze the phenotypic and functional properties of CRMs in the promotion of cardiac regeneration. During mouse cardiac ontogeny, four CRM subsets exist successively: CX₃CR1⁺CCR2^-Ly6C^-MHCII^- (MP1), CX₃CR1^lowCCR2^lowLy6C^-MHCII^- (MP2), CX₃CR1^-CCR2⁺Ly6C⁺MHCII^- (MP3), and CX₃CR1⁺CCR2^-Ly6C^-MHCII⁺ (MP4). MP1 cluster has different derivations (yolk sac, fetal liver, and bone marrow) and multiple functions population. Embryonic and neonatal-derived-MP1 directly promoted cardiomyocyte proliferation through Jagged-1-Notch1 axis and significantly ameliorated cardiac injury following myocardial infarction. MP2/3 subsets could survive throughout adulthood. MP4, the main population in adult mouse hearts, contributed to inflammation. During ontogeny, MP1 can convert into MP4 triggered by changes in the cellular redox state. These findings delineate the evolutionary dynamics of CRMs under physiological conditions and found direct evidence that embryonic and neonatal-derived CRMs regulate cardiomyocyte proliferation. Our findings also shed light on cardiac repair following injury.

Nonselective β-receptor blockers (NSBBs) are first-line drugs for the prevention and treatment of complications in cirrhotic patients with portal hypertension and are widely used in the primary and secondary prevention of esophagogastric variceal bleeding. In recent years, studies have shown that in patients with clinically significant portal hypertension (CSPH), NSBBs can used to prevent liver decompensation events besides variceal bleeding, such as ascites and hepatic encephalopathy. However, in patients without CSPH, current research evidence does not support the use of NSBBs. Although reliable data currently support the use of NSBBs in end-stage liver cirrhosis, there are still drug safety issues in patients with refractory ascites and spontaneous bacterial peritonitis, and further studies are needed to explore the dose and timing of administration. This article reviews the clinical research advances in the use of NSBBs (especially carvedilol) in patients with liver cirrhosis and summarizes the therapeutic window used reasonably in the whole-course management of liver cirrhosis, so as to provide a basis for clinical decision-making.

Objective To understand the etiological characteristics and risk factors of respiratory virus infection in children with bronchial asthma, and to provide theoretical basis for the prevention and treatment of respiratory virus infection in children with bronchial asthma. Methods A total of 374 children with bronchial asthma who were treated in Jianyang People's Hospital from December 2018 to December 2020 were enrolled. Pharyngeal swabs were collected from the outpatient children on the day of treatment, and 2 mL of nasopharyngeal secretions were collected from the hospitalized children within 24 hours by negative pressure aspirator. Seven viral antigens including RSV, ADV, IVA, IVB, PIVI, PIV II, and PIV III were detected. According to whether the virus test results were positive or not, they were divided into the experimental group (n=191) and the control group (n=183). Logistic regression analysis was used to screen the risk factors of respiratory virus infection in children with bronchial asthma. Results Among the 374 samples, the virus positive rate was 51.07% (191/374), and the top 3 virus species in the positive samples were RSV, ADV, and PIV III, accounting for 41.36% (79/191), 30.36% (58/191), and 9.42% (18/191), respectively. In addition, IVA accounted for 5.24% (10/191), PIV II accounted for 5.24% (10/191), PIVI accounted for 3.66% (7/191), and IVB accounted for 1.57% (3 /191). The positive rates of virus were 47.96% (94/196) and 54.49% (97/178) in male and female children, respectively, with no significant difference (χ²=1.597，P>0.05). The positive rate of 1~3 years old children was significantly higher than that of >3 years old group (χ²=6.412，P<0.05). There were significant differences in the frequency of asthma attack, intravenous glucocorticoid application and the onset season between the two groups (P<0.05). Further analysis showed that the frequency of asthma attack >3 times, intravenous glucocorticoid application and onset season were independent risk factors for respiratory virus infection in children with bronchial asthma (P<0.05). Conclusion The infection season of acute respiratory tract infection in children with asthma is mainly concentrated in autumn and winter, with RSV as the main viral pathogen. Targeted preventive measures should be given to children with bronchial asthma who have more than 3 asthma attacks and intravenous glucocorticoid application, which can reduce respiratory virus infection in children with asthma.