Aim To explore the mechanism by which the compound Chaijin Jieyu formula(CCJJY)regulates the TLR4/NLRP3 signaling pathway to inhibit central oxidative stress and improve hippocampal synaptic plasticity damage in depression.Methods SD rats were randomly divided into the control group,chronic unpredictable mild stress group,sleep deprivation group,chronic unpredictable mild stress combined with sleep deprivation group,positive drug group(venlafax-ine+melatonin),low-dose group of CCJJY,medium dose group of CCJJY,and high-dose group of CCJJY,with nine rats in each group.Except for the control group,a rat model of depression complicated with in-somnia was established using chronic unpredictable mild stress combined with sleep deprivation.Depres-sion-like and sleep behaviors in rats were evaluated through weight,food intake,water maze,and pento-barbital sodium tests.ELisa was used to detect ROS,AANAT,and HPLC-EC was used to detect 5-HT con-tent,while Western blot/RT-PCR was used to detect the expression of IL-1β,TLR4,NLRP3,PSD-95,and SYN related proteins and mRNA.HE and Golgic stai-ning were used to observe the pathological changes in the third ventricle,hippocampus,and neuronal synap-ses.Results Compared with the control group,the depression-like behaviors of the model group rats were significant.The expression of IL-1β,TLR4,and NL-RP3 in the hippocampus increased,while the expres-sion of PSD-95 and SYN decreased.Activation of NL-RP3 inflammasomes led to "sleeve like" pathological changes in the third ventricle,with hippocampal neu-rons undergoing apoptosis and significant damage to neuronal synaptic plasticity.Compared with the model group,after intervention with CCJJY,the expression of ROS,IL-1β,TLR4,and NLRP3 decreased,while the expression of AANAT,5-HT,PSD-95,and SYN in-creased.Pathological damage to the third ventricle and hippocampal neurons was repaired.Conclusion The CCJJY improves hippocampal synaptic plasticity dam-age in depression by regulating the TLR4/NLRP3 sig-naling pathway to inhibit central oxidative stress.

Objective To conduct a retrospective analysis of the correlation among bedaquiline(BDQ)plasma concentrations,relevant clinical factors,and disease prognosis.Methods In this retrospective study,22 patients diagnosed with rifampicin-resistant tuberculosis(RR-TB),multidrug-resistant tuberculosis(MDR-TB),or pre-extensively drug-resistant tuberculosis(pre-XDR-TB)were enrolled.These patients were admitted to the tuberculosis ward of our hospital between February 2022 and October 2024.All patients were administered a treatment regimen containing BDQ.The cohort comprised 6 RR-TB patients(27.27%),12 MDR-TB patients(54.55%),and 4 pre-XDR-TB patients(18.18%).Peripheral blood samples were collected 2 hours after the oral administration of Bedaquiline.The plasma concentration of Bedaquiline was measured using liquid chromatography-tandem mass spectrometry(LC-MS/MS).Spearman correlation analysis was performed using R studio software with the ggplot2 and corrplot packages.The factors included the blood concentration of bedaquiline,electrocardiogram QTcF(QT interval corrected by the Fridericia method),liver and kidney function parameters,weight,age,body mass index,sex,blood uric acid level,serum creatinine level,and other relevant indicators.Results In 22 patients treated with BDQ,the plasma concentration reached a peak after 1.5 weeks of administration,and gradually stabilized after 2 weeks.The plasma concentration was approximately 1-3 μg/mL.After 24 weeks of withdrawal of bedaquiline,patients were continued to monitor their bedaquiline concentration and found that BDQ blood concentration in peripheral blood was approximate 1 μg/mL up to 36 weeks.The serum concentration of BDQ was not correlated with age,body weight,BMI,ALT,AST,GGT,TDiL,urea,uric acid and QT interval,but correlated with sputum negative transformation and serum creatinine.The correlation analysis between serum concentration of BDQ and acid-fast staining of sputum smear showed,the difference was significant(r=0.35,P<0.05).In addition,the correlation analysis between serum BDQ concentration and serum creatinine showed,the difference was significant(r=0.34,P<0.05).The results of multiple linear regression analysis showed that BDQ blood concentration was positively correlated with Scr level,and Scr was an independent factor affecting BDQ blood concentration.20 cases(90.9%,20/22)were cured,1 case died of Covid-19 virus infection,1 case was recurrence.Conclusions Regimens containing bedaquiline seem to exhibit relatively high safety profiles and good tolerability among patients with rifampicin-resistant,multidrug-resistant,or pre-extensively drug-resistant tuberculosis,typically yielding favorable treatment outcomes.The BDQ shows a positive correlation with serum creatinine(SCr).Consequently,close surveillance of BDQ levels and renal function remains of utmost importance throughout the treatment course.

Objective:To conduct a study on pricing by service unit to address the problems of hospice and palliative care pricing and fee system in China.Methods:Combining theoretical research and empirical evidence,this study organized the pricing mechanism of initiative hospice and palliative care services and established a graded and categorized pricing strategy.Empirical research was conducted based on real-world data from 36 pilot institutions in typical areas.Results:This study developed a comprehensive pricing framework for value-based classification price standard of initiative hospice and palliative care services from the perspective of incentive regulation.We proposed a pricing plan based on service units,with inpatient bed fee ranging from 459 to 606 yuan or 459 to 1 102 yuan,and home visit fee ranging from 89 to 264 yuan.Conclusions and suggestions:This study proposes a pricing scheme based on the technique and service value with a gradient fluctuation by service unit,and forms a set of price standards with high economic and technical feasibility,which can provide scientific evidences for solving the pricing problem of hospice care.In addition,there is still a need to establish a multi-level incentive compensation mechanism to motivate all levels and types of organisations and healthcare provider,and to promote the high-quality and sustainable development of hospice and palliative care.

Aim To investigate the anti-acute lung injury(ALI)effect of Sterculiae Lychnophorae Semen(SLS)and its mechanism.Methods The main ac-tive components of SLS and their core targets and path-ways of action against ALI were obtained by network pharmacology methods.Subsequently,molecular doc-king technology and in vitro cellular experiments were applied for validation.Results A total of 19 core tar-gets were obtained,including HSP90AA1,CASP3,TNF,MAPK8 and MAPK14.The mechanisms may in-volve signaling pathways such as cancer,PI3K/Akt and MAPK.Molecular docking confirmed that the key targets of SLS formed a better binding activity with the relevant active ingredients.The in vitro results showed that SLS was able to protect the PM2.5-contaminated BEAS-2B cells,inhibit their NO,IL-1β and TNF-αlevels,and reduce the expression of p-p38 MAPK and p-JNK proteins.Conclusions The study successfully predicts the active ingredients,targets and signaling pathways of SLS against ALI,and in vitro experiments demonstrate that SLS might protect BEAS-2B cells from PM2.5 stimulus-induced inflammation and apoptosis by inhibiting the over-activation of p38 MAPK and JNK signaling pathways.

Anticipatory anxiety is a negative emotion that arises when individuals encounter potential threats or uncertainties in the future. It is the core symptom of a variety of anxiety disorders, and is closely associated with the occurrence, severity, treatment outcome, and prognosis of anxiety disorders, which has garnered a growing amount of focus in clinical practice. Nevertheless, scientific research on anticipatory anxiety continues to face obstacles such as unclear pathological mechanisms, the absence of simple and consistent self-assessment tools, and effective interventions. To improve understanding of the role of anticipatory anxiety in the diagnosis and treatment of anxiety disorders, this study reviews pertinent domestic and international literature, and briefly introduces the concept, assessment and measurement, activation paradigm, pathological mechanisms, and interventions of anticipatory anxiety.

Objective To explore curative effect of two thrombolytic regimens in the treatment of ultra-early acute cerebral infarction(ACI)of different age groups and different thrombolytic time windows.Methods A total of 166 patients with ACI were enrolled,with interval from onset to treatment≤4.5 h.According to different thrombolytic regiments,patients were divided into the recombinant tissue plasminogen activator(rt-PA)group(104 cases,intravenous thrombolysis with 0.9 mg/kg rt-PA)and the tenecteplase(TNK)group(62 cases,intravenous thrombolysis with 0.25 mg/kg TNK).According to different age groups and different thrombolytic time windows,patients were divided into the high age group(≥70 years),the low age group(＜70 years),the short time window group(＜3 h)and the long time window group(3-4.5 h).After thrombolysis,laboratory indexes[neutrophil(NEU),lymphocyte(LYM)],scores of National Institutes of Health Stroke Scale(NIHSS),modified Rankin scale(mRS)and incidence of adverse events were compared in different groups by factorial analysis method.Results There was no significant difference in any index between the rt-PA group and the TNK group(P＞0.05).Compared with the high age group at 7 d after thrombolysis,NIHSS score,NEU,neutrophil to lymphocyte ratio(NLR)and high sensitive C-reactive protein(hs-CRP)were lower,while LYM and albumin(ALB)were higher in the low age group(P＜0.05).Compared with the long time window group,NEU and NLR were lower,while LYM was higher in the short time window group(P＜0.05).There was no significant difference in total incidence of adverse events within 14 d of thrombolysis between the different age groups and the different thrombolytic time window groups(P＞0.05).Conclusion For patients with ultra-early ACI,0.9 mg/kg rt-PA and 0.25 mg/kg TNK have comparable efficacy in intravenous thrombolysis,and both have better effects when patient age is＜70 years old and the thrombolysis time window is＜3 hours.

Objective To explore curative effect of two thrombolytic regimens in the treatment of ultra-early acute cerebral infarction(ACI)of different age groups and different thrombolytic time windows.Methods A total of 166 patients with ACI were enrolled,with interval from onset to treatment≤4.5 h.According to different thrombolytic regiments,patients were divided into the recombinant tissue plasminogen activator(rt-PA)group(104 cases,intravenous thrombolysis with 0.9 mg/kg rt-PA)and the tenecteplase(TNK)group(62 cases,intravenous thrombolysis with 0.25 mg/kg TNK).According to different age groups and different thrombolytic time windows,patients were divided into the high age group(≥70 years),the low age group(＜70 years),the short time window group(＜3 h)and the long time window group(3-4.5 h).After thrombolysis,laboratory indexes[neutrophil(NEU),lymphocyte(LYM)],scores of National Institutes of Health Stroke Scale(NIHSS),modified Rankin scale(mRS)and incidence of adverse events were compared in different groups by factorial analysis method.Results There was no significant difference in any index between the rt-PA group and the TNK group(P＞0.05).Compared with the high age group at 7 d after thrombolysis,NIHSS score,NEU,neutrophil to lymphocyte ratio(NLR)and high sensitive C-reactive protein(hs-CRP)were lower,while LYM and albumin(ALB)were higher in the low age group(P＜0.05).Compared with the long time window group,NEU and NLR were lower,while LYM was higher in the short time window group(P＜0.05).There was no significant difference in total incidence of adverse events within 14 d of thrombolysis between the different age groups and the different thrombolytic time window groups(P＞0.05).Conclusion For patients with ultra-early ACI,0.9 mg/kg rt-PA and 0.25 mg/kg TNK have comparable efficacy in intravenous thrombolysis,and both have better effects when patient age is＜70 years old and the thrombolysis time window is＜3 hours.

Aim To investigate the anti-acute lung injury(ALI)effect of Sterculiae Lychnophorae Semen(SLS)and its mechanism.Methods The main ac-tive components of SLS and their core targets and path-ways of action against ALI were obtained by network pharmacology methods.Subsequently,molecular doc-king technology and in vitro cellular experiments were applied for validation.Results A total of 19 core tar-gets were obtained,including HSP90AA1,CASP3,TNF,MAPK8 and MAPK14.The mechanisms may in-volve signaling pathways such as cancer,PI3K/Akt and MAPK.Molecular docking confirmed that the key targets of SLS formed a better binding activity with the relevant active ingredients.The in vitro results showed that SLS was able to protect the PM2.5-contaminated BEAS-2B cells,inhibit their NO,IL-1β and TNF-αlevels,and reduce the expression of p-p38 MAPK and p-JNK proteins.Conclusions The study successfully predicts the active ingredients,targets and signaling pathways of SLS against ALI,and in vitro experiments demonstrate that SLS might protect BEAS-2B cells from PM2.5 stimulus-induced inflammation and apoptosis by inhibiting the over-activation of p38 MAPK and JNK signaling pathways.

In view of the few studies on the influence of Armillaria spp. infection on the content of the chemical components in different parts of Polyporus umbellatus sclerotia, this study determined the biomass of P. umbellatus sclerotia and the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in the separated cavity wall of the sclerotia and the uninfected part of the sclerotia in different harvesting years under the conditions of A. gallica and A. mellea infection respectively. According to the difference of content and dynamic changes of the polysaccharide and the steroid substances, the superior Armillaria sp. was screened to obtain the best harvest years of P. umbellatus. Using HPLC and UV-VIS spectrophotometry methods, the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in P. umbellatus sclerotia infected by the two Armillaria spp. in different years were determined. In addition, the differentially expressed genes related to P. umbellatus polysaccharide synthesis were screened according to the transcriptomic data of different parts of P. umbellatus after A. mellea infection. With the increase of years, the biomass of sclerotia infected by different Armillaria spp. had significant differences, and there were significant differences in the four components of sclerotia. The four components of the separated cavity wall of the sclerotia were significantly higher than those of the uninfected part. The best harvest time was the third year after cultivation. Transcriptomic analysis showed that the infection of Armillaria spp. could significantly promote polysaccharide synthesis, which provided a basis for polysaccharide content determination at the molecular level. The study clarified the influence of different Armillaria spp. infection on the accumulation of chemical components of P. umbellatus sclerotia, laying a foundation for exploring the symbiosis mechanism and provided a scientific clue for screening superior Armillaria sp. and guiding the artificial cultivation of P. umbellatus sclerotia.

Aim To explore the mechanism by which the compound Chaijin Jieyu formula(CCJJY)regulates the TLR4/NLRP3 signaling pathway to inhibit central oxidative stress and improve hippocampal synaptic plasticity damage in depression.Methods SD rats were randomly divided into the control group,chronic unpredictable mild stress group,sleep deprivation group,chronic unpredictable mild stress combined with sleep deprivation group,positive drug group(venlafax-ine+melatonin),low-dose group of CCJJY,medium dose group of CCJJY,and high-dose group of CCJJY,with nine rats in each group.Except for the control group,a rat model of depression complicated with in-somnia was established using chronic unpredictable mild stress combined with sleep deprivation.Depres-sion-like and sleep behaviors in rats were evaluated through weight,food intake,water maze,and pento-barbital sodium tests.ELisa was used to detect ROS,AANAT,and HPLC-EC was used to detect 5-HT con-tent,while Western blot/RT-PCR was used to detect the expression of IL-1β,TLR4,NLRP3,PSD-95,and SYN related proteins and mRNA.HE and Golgic stai-ning were used to observe the pathological changes in the third ventricle,hippocampus,and neuronal synap-ses.Results Compared with the control group,the depression-like behaviors of the model group rats were significant.The expression of IL-1β,TLR4,and NL-RP3 in the hippocampus increased,while the expres-sion of PSD-95 and SYN decreased.Activation of NL-RP3 inflammasomes led to "sleeve like" pathological changes in the third ventricle,with hippocampal neu-rons undergoing apoptosis and significant damage to neuronal synaptic plasticity.Compared with the model group,after intervention with CCJJY,the expression of ROS,IL-1β,TLR4,and NLRP3 decreased,while the expression of AANAT,5-HT,PSD-95,and SYN in-creased.Pathological damage to the third ventricle and hippocampal neurons was repaired.Conclusion The CCJJY improves hippocampal synaptic plasticity dam-age in depression by regulating the TLR4/NLRP3 sig-naling pathway to inhibit central oxidative stress.