BackgroundBoth modified Suanzaoren Decoction and estazolam serve as effective treatments for chronic insomnia disorder （CID）. Default mode network （DMN） dysfunction is recognized as the primary pathophysiological mechanism underlying CID. However， it remains unclear whether the two treatments exert their therapeutic effects via convergent modulation of DMN functional connectivity. ObjectiveTo investigate the convergent remodeling characteristics of bidirectional effective connectivity （EC） of core DMN nodes with both the intra-network and the remaining whole-brain regions in CID patients with Yin-deficiency and fire-hyperactivity syndrome following the treatment with modified Suanzaoren Decoction or estazolam， so as to provide neuroimaging evidence for the convergent neural mechanisms underlying the therapeutic effects of both therapies in treating CID. MethodsEighty-two patients diagnosed with CID according to the International Classification of Sleep Disorder， third edition （ICSD-3） were consecutively recruited from the outpatient clinic of the Inner Mongolia Autonomous Region Mental Health Center from October 2020 to September 2023. Based on treatment preference， patients were assigned to receive a 6-week intervention in either the modified Suanzaoren Decoction group （n=52） or the estazolam group （n=30）. Ultimately， 66 patients completed follow-up assessments （modified Suanzaoren Decoction group， n=41； estazolam group， n=25）. All CID patients underwent resting-state functional magnetic resonance imaging scanning before and after treatment. Core DMN nodes including medial prefrontal cortex （mPFC）， bilateral inferior parietal lobule （IPL）， and precuneus （PCUN） were selected as seed regions. Granger causality analysis （GCA） was employed to assess bidirectional EC between the seed regions and both the other intra-DMN nodes and the remaining whole-brain regions. Hepatic and renal function indices were detected pre- and post-treatment to evaluate the safety profiles of both treatments. ResultsAt baseline， significant between-group differences were identified in EC from the left IPL to the left middle fronto-orbital gyrus/gyrus rectus （t=5.24， Z=4.84， voxel-level P<0.001， cluster-level P<0.05， GRF-corrected）， with the modified Suanzaoren Decoction group exhibiting stronger EC than the estazolam group. No significant between-group differences were observed in EC between other core DMN nodes and remaining whole-brain regions （P>0.05）. Within-group pre- to post-treatment comparisons demonstrated consistent connectivity alterations in both groups. Specifically， EC from the left IPL to the supplementary motor area （SMA） decreased after treatment （modified Suanzaoren Decoction group： t=-6.28， Z=5.208； estazolam group： t=-5.58， Z=4.425）. Conversely， EC from the SMA to the left IPL increased （modified Suanzaoren Decoction group： t=5.89， Z=4.968； estazolam group： t=6.15， Z=4.720）. Furthermore， both groups demonstrated reduced EC from the PCUN to the left IPL （modified Suanzaoren Decoction group： t=-5.85， Z=4.94； estazolam group： t=-5.75， Z=4.515）， and elevated EC from the left IPL to the PCUN （modified Suanzaoren Decoction group： t=5.29， Z=4.579； estazolam group： t=4.55， Z=3.826） （voxel-level P<0.001， cluster-level P<0.05， GRF-corrected）. No significant pre- to post-treatment differences were observed in hepatic or renal function indices in either group （P>0.05）. ConclusionIn CID patients with Yin-deficiency and fire-hyperactivity syndrome， both modified Suanzaoren Decoction and estazolam induce convergent bidirectional remodeling of EC between the left IPL and the SMA and the PCUN. ［Funded by Natural Science Fund Project of Inner Mongolia Autonomous Region （number， 2019MS08099）； ClinicalTrials.gov number， NCT06452953］

Objective:To investigate the effect of early enteral nutrition on intestinal function in patients with complicated intra-abdominal infection.Methods:In this study,a prospective single-center randomized controlled trial was used to select 88 patients with severe abdominal infections in the surgical intensive care ward from January 2021 to December 2023.Among them,65 patients were eligible and were randomly divided into 33cases in the intervention group(who received early enteral nutrition),and 32cases in the control group(who did not receive early enteral nutrition).The clinical baseline characteristics of the two groups,conditions such as abdominal distension and diarrhea during enteral nutrition,intra-abdominal pressure,the time to reach the standard of complete enteral nutrition,and the indexes of pre-albumin,CRP,and leukocyte count on the third and the seventh day postoperative day were observed.The t-test was used to compare between groups for normally distributed measures.The Mann-Whitney U test was used to compare between groups for skewed measures.The χ2 test or continuity-corrected χ2 test was used to compare the count data between groups.Repeated measures data were analyzed by repeated measures ANOVA.Results:The clinical baseline characteristics of the two groups were completely matched;There were significant differences in the changes of intra-abdominal pressure over time between the two groups(Fgroup=9.665,P=0.004),There were significant differences in the changes of intra-abdominal pressure over time between the two intervention group(Ftime=64.124,P<0.001)and the control group.and the trend of intra-abdominal pressure reduction in the intervention group was more significant than that in the control group(Finteractive=3.938,P=0.023);The time required for the recovery of bowel sounds was significantly shorter in the experimental group than in the control group[(19.5±3.5)h vs(35.3±4.5)h,P<0.001,t=15.829];there was no significant difference in the frequency of abdominal distention,vomiting and aspiration between the two groups(P>0.05),and the difference in the frequency of diarrhea was statistically significant(P=0.003);The time to reach the standard of enteral nutrition in the intervention group was shorter than that in the control group[(6.3±1.2)d vs(7.4±1.5)d,P=0.002];The total hospital stay of the intervention group was significantly shorter than that of the control group[(11±3.2)d vs(14±4.1)d,P=0.007].The prealbumin(0.21±0.2,0.28±0.2)g/L,CRP(175.5±23.6,45.4±14.5)mg/L,and white blood cell count(11.7±2.9,9.1±3.5)109/L of the intervention group on the 3rd and 7th days after surgery were significantly improved compared with those of the control group(P<0.05).Conclusion:Early enteral nutrition can effectively promote the recovery of intestinal function in patients with complicated intra-abdominal infection.

A pyrene-phenol-based fluorescent probe PyP which showed typical intramolecular charge transfer(ICT)and monomer-excimer activities was synthesized by using pyrene carboxaldehyde hydrazone and 4-tert-butyl-2,6-diformylphenol as the raw materials.The effects of solvents on PyP were studied,and the results showed that the color of protic polar solvents(Ethanol,N,N-dimethylformamide,methanol and H2O)were successfully identified.Based on the solvent polarity-regulated PyP monomer-excimer switching,the rapid and highly sensitive ratiometric probe,"Turn-off"and"Turn-on"multimodal probes were established for detection of trace water content in organic solvents(Dimethyl sulfoxide,N,N-dimethylformamide,ethanol and methanol),with detection limits(3σ/k)of 0.0021％,0.046％,0.062％and 0.024％.The method was successfully used to detect water content in dimethyl sulfoxide,N,N-dimethy lformamide,ethanol and methanol commercial organic solvents,with recoveries ranging from 97.2％to 108.0％.The developed method showed good accuracy and stability,and had good application prospect.

Peroxynitrite anion(ONOO-),which is originated from the reaction of nitric oxide(NO)and superoxide anion(O2-),plays a pivotal role in immune defense and signal regulation.Excessive levels of ONOO-may induce the occurrence of various diseases such as Alzheimer's disease,inflammation,cardiovascular disease and cancer,etc.Existing detection methods for ONOO-have limitations such as complexity,time consumption,and low cell biocompatibility.In this study,a novel fluorescent probe QFPD was developed using quinoline and diphenylphosphinamide as fluorescent keleton and recognition group,respectively.The strong oxidizing property of ONOO-triggerd the cleavage of phosphoramide bond,leading to fluorescence quenching and a visible color change of the solution from yellow to purple,thereby enabling"ON-OFF"type recognition of ONOO-.QFPD exhibited excellent characteristics including good selectivity and high sensitivity in fluorescence detection(Limit of detection of 1.37 μmol/L),large Stokes shift(130 nm),rapid response(10 min),and strong anti-interference ability.Additionally,QFPD demonstrated good biocompatibility and could realize real-time dynamic monitoring of endogenous ONOO-.Furthermore,QFPD was successfully applied to environmental toxicology research by visualizing the oxidative stress effects induced by microplastics polymethyl methacrylate(PMMA)and Hg2+exposure,which might be a novel tool for the mechanism research on oxidative stress associated with microplastic pollution and heavy metal exposure.

Objective:To compare the effects of propofol and dexmedetomidine for sedation on the outcome in mechanically ventilated patients with severe pulmonary infection.Methods:Patients with severe pulmonary infection (Clinical Pulmonary Infection Score >7) requiring mechanical ventilation from the Medical Information Mart for Intensive Care Ⅳ database between 2008 and 2020 were selected and divided into propofol group and dexmedetomidine group based on the sedative agent used. The primary outcome was all-cause in-hospital mortality, and secondary outcomes included 90-day all-cause mortality and duration of mechanical ventilation. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounders, and logistic regression and linear regression were applied to analyze the effects of the two sedative drugs on the outcomes of mechanically ventilated patients with pulmonary infection. Kaplan-Meier survival curves were used to analyze survival outcomes.Results:A total of 6 204 critically ill patients with pulmonary infection requiring mechanical ventilation were included, with 3 439 cases in propofol group and 2 765 cases in dexmedetomidine group. The baseline characteristics between the two groups were well balanced (standardized mean difference < 0.1) after IPTW adjustment. In the IPTW-adjusted cohort, the in-hospital all-cause mortality and 90-day all-cause mortality were significantly lower in dexmedetomidine group than in propofol group (439.2[18.7%] vs 563.6[24.1%], 618.0[26.3%] vs 733.6[31.3%], P<0.001), the results of Further Kaplan-Meier survival curve analysis showed that the 90-day all-cause mortality was significantly lower in dexmedetomidine group than in propofol group ( P<0.01). Conclusions:Compared with propofol, dexmedetomidine can decrease the mortality rate and improve the prognosis in mechanically ventilated patients with severe pulmonary infection when used for sedation.

AIM To investigate the effects of Yiqi Juanbi Formula on chondrocyte pyroptosis in rat models of collagen-induced arthritis(CIA).METHODS Fifty rats were subcutaneously injected at the tail base with an emulsion containing equal volumes of bovine type Ⅱ collagen and incomplete Freund's adjuvant(IFA)to establish the CIA models.These rats were then randomly assigned to the model group,the methotrexate group(0.35 mg/kg),and the low-dose,medium-dose,and high-dose Yiqi Juanbi Formula groups(9.4,18.7,37.4 g/kg),in contrast to the ten intact rats serving in the normal control group.Following four weeks of intragastric administration,the rats had their general conditions observed;their joint swelling and arthritis indices measured;their ankle joint pathology assessed by HE staining;their serum levels of IL-1β,IL-18 and TNF-ɑ detected by ELISA;their mRNA expressions of NLRP3,Caspase-1,GSDMD,IL-1β,IL-18 and TNF-ɑ in ankle cartilage quantified by RT-qPCR;their protein expressions of NF-κB,NLRP3 and Caspase-1 in ankle cartilage analyzed by Western blot;and their NLRP3 and GSDMD positive expressions in ankle cartilage examined by immunohistochemistry.RESULTS Compared to the control group,the model group showed significantly increased joint swelling and arthritis indices(P＜0.01);elevated serum levels of IL-1 β,IL-18 and TNF-ɑ(P＜0.01);pathological changes including cartilage surface defects,reduced cell count,altered cellular morphology,irregular cell arrangement,and significant inflammatory cell infiltration in synovial tissue;upregulated mRNA expressions of NF-κB,NLRP3,Caspase-1,GSDMD,IL-1β,IL-18 and TNF-ɑ(P＜0.01)and increased protein expressions of NF-κB,NLRP3 and Caspase-1(P＜0.01)in ankle cartilage;enhanced positive expressions of NLRP3 and GSDMD in ankle cartilage(P＜0.01).Compared to the model group,the groups intervened with methotrexate or medium-or high-dose Yiqi Juanbi Formula exhibited reduced joint swelling and arthritis indices(P＜0.01);alleviated pathological damage in ankle joints;decreased serum levels of IL-1β,IL-18 and TNF-ɑ(P＜0.01);downregulated mRNA expressions of NF-κB,NLRP3,Caspase-1,GSDMD,IL-1β,IL-18 and TNF-ɑ(P＜0.05,P＜0.01),and reduced protein expressions of NF-κB,NLRP3 and Caspase-1(P＜0.05,P＜0.01)in ankle cartilage;and diminished positive expressions of NLRP3 and GSDMD in ankle cartilage(P＜0.01).CONCLUSION Yiqi Juanbi Formula alleviates inflammation in CIA rats,potentially by inhibiting the activation of the NF-κB/NLRP3/Caspase-1 signaling pathway,thereby suppressing chondrocyte pyroptosis.

Mechanical pain is one of the most common causes of clinical pain, but there remains a lack of effective treatment for debilitating mechanical and chronic forms of neuropathic pain. Recently, neurotoxin GsMTx4, a selective mechanosensitive (MS) channel inhibitor, has been found to be effective, while the underlying mechanism remains elusive. Here, with multiple rodent pain models, we demonstrated that a GsMTx4-based 17-residue peptide, which we call P10581, was able to reduce mechanical hyperalgesia and neuropathic pain. The analgesic effects of P10581 can be as strong as morphine but is not toxic in animal models. The anti-hyperalgesic effect of the peptide was resistant to naloxone (an μ-opioid receptor antagonist) and showed no side effects of morphine, including tolerance, motor impairment, and conditioned place preference. Pharmacological inhibition of TRPV4 by P10581 in a heterogeneous expression system, combined with the use of Trpv4 knockout mice indicates that TRPV4 channels may act as the potential target for the analgesic effect of P10581. Our study identified a potential drug for curing mechanical pain and exposed its mechanism.

Objective To investigate the correlation between myocardial fibrosis(MF)and left ventricular ejection fraction(LVEF)and myocardial injury markers in heart failure patients via cardiac magnetic resonance(CMR).Methods Seventy-six patients with heart failure were selected,including 32 cases of heart failure with preserved ejection fraction(HFpEF)(HFpEF group),15 cases of heart failure with mid-range ejection fraction(HFmEF)(HFmEF group),and 29 patients of heart failure with reduced ejection fraction(HFrEF)(HFrEF group).Additionally,7 healthy individuals undergoing physical examinations were included(control group).CMR parameters and biological markers for the heart failure groups were collected for all subjects.The differences in native T1 value and extracellular volume fraction(ECV)between the heart failure group and the control group were compared,respectively.The differences in native T1 value,ECV,late gadolinium enhancement(LGE)score,serum creatine kinase-MB(CK-MB),cardiac troponin Ⅰ knockdown(cTnI-KD),and N-terminal pro-brain natriuretic peptide(NT-proBNP)among heart failure subgroups were also compared,respectively.Spearman correlation analysis was used to examine the relationships between MF imaging indicators and LVEF,as well as NT-proBNP levels.Results The differences in native T1 value,ECV,LGE score,and NT-proBNP between the heart failure group and the control group,as well as between the heart failure subgroups were statistically significant(P＜0.05).The native T1 value,ECV,and LGE score in the heart failure group were positively correlated with NT-proBNP,and negatively correlated with LVEF.Conclusion The native T1 value,ECV value and LGE score are correlated with heart failure severity.CMR can detect myocardial injury early in patients with HFpEF and provide valuable information for risk stratification of MF.

Objective:To compare the effects of propofol and dexmedetomidine for sedation on the outcome in mechanically ventilated patients with severe pulmonary infection.Methods:Patients with severe pulmonary infection (Clinical Pulmonary Infection Score >7) requiring mechanical ventilation from the Medical Information Mart for Intensive Care Ⅳ database between 2008 and 2020 were selected and divided into propofol group and dexmedetomidine group based on the sedative agent used. The primary outcome was all-cause in-hospital mortality, and secondary outcomes included 90-day all-cause mortality and duration of mechanical ventilation. Inverse probability of treatment weighting (IPTW) was used to adjust for baseline confounders, and logistic regression and linear regression were applied to analyze the effects of the two sedative drugs on the outcomes of mechanically ventilated patients with pulmonary infection. Kaplan-Meier survival curves were used to analyze survival outcomes.Results:A total of 6 204 critically ill patients with pulmonary infection requiring mechanical ventilation were included, with 3 439 cases in propofol group and 2 765 cases in dexmedetomidine group. The baseline characteristics between the two groups were well balanced (standardized mean difference < 0.1) after IPTW adjustment. In the IPTW-adjusted cohort, the in-hospital all-cause mortality and 90-day all-cause mortality were significantly lower in dexmedetomidine group than in propofol group (439.2[18.7%] vs 563.6[24.1%], 618.0[26.3%] vs 733.6[31.3%], P<0.001), the results of Further Kaplan-Meier survival curve analysis showed that the 90-day all-cause mortality was significantly lower in dexmedetomidine group than in propofol group ( P<0.01). Conclusions:Compared with propofol, dexmedetomidine can decrease the mortality rate and improve the prognosis in mechanically ventilated patients with severe pulmonary infection when used for sedation.

Objective:To analyze the surveillance results of brucellosis in Shanxi Province, to gain a understanding of the epidemic characteristics and changing trend of brucellosis in Shanxi Province, and to provide scientific basis for formulating prevention and control strategies and measures for brucellosis.Methods:The surveillance data of brucellosis in Shanxi Province from Infectious Disease Reporting Information Management System of China Disease Prevention and Control Information System, and the active surveillance results of 5 national brucellosis surveillance sites from 2018 to 2023 were collected for descriptive analysis.Results:From 2018 to 2023, a total of 24 041 cases of human brucellosis were reported in Shanxi Province, with the number of cases increased from 2 800 in 2018 to 5 131 in 2023. The annual reported incidence was 11.22/100 000, ranging from 7.56/100 000 to 14.74/100 000, showing an overall upward trend (χ 2trend = 1 377.43, P < 0.001). The epidemic had affected all counties (cities and districts) in the province, mainly concentrated in Linfen City, Jinzhong City, Datong City, and Shuozhou City, with a total of 13 489 cases of human brucellosis reported, accounting for 56.11%. The population distribution was mainly composed of individuals aged 40 - 69 (17 682 cases), males (18 513 cases), farmers (20 295 cases), and household and unemployed individuals (1 017 cases). The onset of the disease showed obvious seasonality, with the peak time from March to August, accounting for 66.39% (15 961/24 041). A total of 14 130 occupational individuals were investigated at the surveillance sites, and 11 141 underwent serological tests, with a positive rate of 5.25% (585/11 141), including 299 new cases. The positive rate of serological tests was relatively high in Qinyuan County, at 8.51% (241/2 832). Etiological culture was conducted on 338 human blood samples, and 43 strains of Brucella were isolated, with a detection rate of 12.72%. All strains were Brucella melitensis, including 42 strains of Brucella melitensis biovar 3. Conclusions:The overall trend of human brucellosis epidemic in Shanxi Province from 2018 to 2023 is on the rise, and it is still at a high level. It is suggested to continue strengthening monitoring, study the epidemic situation in a timely manner, take comprehensive prevention and control measures, and effectively control the spread of brucellosis.