ObjectiveTo investigate the effects of modified Xiaoyaosan （JJXYS） on behavioral abnormalities and hippocampal mitochondrial quality control （MQC） in the rat model of post-myocardial infarction depression （PMD） and preliminarily explore its potential mechanism. MethodsA rat model of PMD was established by left anterior descending coronary artery ligation combined with chronic unpredictable mild stress （CUMS）. Rats were randomized into a control group， a model group， a fluoxetine （FLX， 10 mg·kg^-1） group， and low-， medium-， and high-dose JJXYS （JJXYS-L/M/H， 1.12， 2.24， 4.48 g·kg^-1， respectively） groups. Depressive-like behaviors were evaluated by body weight monitoring， sucrose preference test， open field test， and forced swimming test. Hematoxylin-eosin staining and Nissl staining were used to observe hippocampal histomorphology and neuronal changes. Enzyme-linked immunosorbent assay was conducted to determine the serum levels of 5-hydroxytryptamine （5-HT）， dopamine （DA）， interleukin-1 beta （IL-1β）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α）. The mRNA levels of MQC-related genes including peroxisome proliferator-activated receptor-gamma coactivator-1 alpha （PGC-1α）， nuclear respiratory factor 1 （Nrf1）， and transcription factor A， mitochondrial （TFAM） in the hippocampal tissue were measured by real-time PCR. The expression of proteins related to the dynamin-related protein 1 （Drp1）/PTEN-induced putative kinase 1 （PINK1）/Parkin signaling pathway was determined by Western blot. ResultsCompared with the control group， the model group showed restricted body weight gain， aggravated depressive-like behaviors， declined serum 5-HT and DA levels， evident hippocampal neuronal damage and reduced Nissl bodies， as well as downregulated expression of MQC-related genes and proteins （P<0.05）. Compared with the model group， both FLX and JJXYS alleviated the above changes to varying degrees. Moreover， the JJXYS-M and JJXYS-H groups showed more pronounced effects， improving behavioral performance， restoring 5-HT and DA levels， alleviating hippocampal pathological injury， and upregulating the expression of PGC-1α/Nrf1/TFAM mRNA and Drp1/PINK1/Parkin signaling pathway-related proteins （P<0.05）. ConclusionJJXYS can significantly alleviate depressive-like behaviors and neurotransmitter imbalance in the rat model of PMD by regulating hippocampal MQC and upregulating the Drp1/PINK1/Parkin-related pathway. This study provides experimental evidence for the intervention of PMD with JJXYS.

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 use multiple model integration to predict the potential distribution of suitable areas for Hedysari Radix in China and the main environmental factors affecting its distribution.Methods Based on 119 geographical distribution points obtained from species distribution databases,and incorporating 19 bioclimatic and topographic factors,a species distribution model was constructed using the Biomod2 software package 3.5-1 version ensemble modeling platform,integrating six algorithms including generalized linear model,gradient boosting machine,random forest,and others.Geographic information system spatial analysis methods were used to quantitatively assess the distribution characteristics of suitable habitats of Hedysari Radix under current climate conditions and under future climate scenarios,while identifying the primary environmental drivers of its distribution.Results The ensemble model showed significantly superior predictive performance.TSS value and AUC value were 0.924 and 0.992,respectively.Key environmental factors significantly influencing the distribution of Hedysari Radix included slope,aspect,daily average temperature difference,isothermity,seasonal variation coefficient of temperature,lowest temperature in the coldest month,annual precipitation,driest month precipitation,and seasonal variation coefficient of precipitation.Under current climate conditions,suitable habitats for Hedysari Radix were primarily concentrated in the regions of Longnan and Dingxi in Gansu Province,covering an area of approximately 26.17×104 km2.Under future climate scenarios,suitable habitats will gradually shift toward the northwest into lower temperature zones,with a significant reduction in area.Conclusion The habitat suitability model developed in this study provides a basis for the conservation and sustainable utilization of Hedysari Radix genetic resources,while also offering a methodological reference for ecological adaptability studies of medicinal plants.

Objective To use multiple model integration to predict the potential distribution of suitable areas for Hedysari Radix in China and the main environmental factors affecting its distribution.Methods Based on 119 geographical distribution points obtained from species distribution databases,and incorporating 19 bioclimatic and topographic factors,a species distribution model was constructed using the Biomod2 software package 3.5-1 version ensemble modeling platform,integrating six algorithms including generalized linear model,gradient boosting machine,random forest,and others.Geographic information system spatial analysis methods were used to quantitatively assess the distribution characteristics of suitable habitats of Hedysari Radix under current climate conditions and under future climate scenarios,while identifying the primary environmental drivers of its distribution.Results The ensemble model showed significantly superior predictive performance.TSS value and AUC value were 0.924 and 0.992,respectively.Key environmental factors significantly influencing the distribution of Hedysari Radix included slope,aspect,daily average temperature difference,isothermity,seasonal variation coefficient of temperature,lowest temperature in the coldest month,annual precipitation,driest month precipitation,and seasonal variation coefficient of precipitation.Under current climate conditions,suitable habitats for Hedysari Radix were primarily concentrated in the regions of Longnan and Dingxi in Gansu Province,covering an area of approximately 26.17×104 km2.Under future climate scenarios,suitable habitats will gradually shift toward the northwest into lower temperature zones,with a significant reduction in area.Conclusion The habitat suitability model developed in this study provides a basis for the conservation and sustainable utilization of Hedysari Radix genetic resources,while also offering a methodological reference for ecological adaptability studies of medicinal plants.

Pigeon circovirus(PiCV)is globally widespread and is considered a potential cause of young pigeon sickness syndrome(YPDS),which leads to severe immunosuppression and high mortality.Due to the inability of PiCV to be cultured in cells,the development of traditional vac-cines is severely limited,and no effective vaccines is currently available.To develop a novel PiCV DNA candidate vaccine,we cloned the △Cap gene lacking a nuclear localization signal(NLS),and fused it at its C-terminus with the transmembrane and cytoplasmic regions of the Newcastle dis-ease virus(NDV)F protein(△Cap-TMCT).Two DNA vaccine candidates were constructed:pCAGG-△Cap,targeting intracellular expression,and pCAGG-△Capt,for cell surface expression,respectively.The results of indirect immunofluorescence and Western blot analyses confirmed suc-cessful expression of both recombinant plasmids in DF1 cells.Immunization studies in mice re-vealed that pCAGG-△Capt induced significantly higher levels of specific IgG antibodies,T-cell re-sponses,and cytokine secretion compared to pCAGG-△Cap,as assessed by ELISA,flow cytome-try,and ELISpot assays.These findings suggest that targeting △Cap-TMCT fusion protein to the cell surface can effectively enhance its immunogenicity,highlighting its potential as a PiCV DNA vaccine candidate.This study provides new strategies and theoretical foundations for the design and development of PiCV DNA vaccines.

Sacroiliac complex injuries are commonly seen in high-energy pelvic fractures. The injuries make a big difference in treatment patterns due to the diverse injury types, posing considerable challenges in formulating optimal treatment strategies, and hence are persistent clinical difficulties in orthopedic trauma. The clinical management of sacroiliac complex injuries presents several key challenges such as a non-negligible rate of missed diagnoses in associated vascular and visceral injuries, absence of standardized protocols for surgical approaches and reduction-fixation strategies across different injury patterns, and ongoing controversies regarding surgical indications and optimal timing for patients combined with concomitant lumbosacral plexus injuries. Currently, no systematic clinical guidelines are available for the diagnosis and treatment of sacroiliac complex injuries both domestically and internationally. To this end, the Pelvic and Acetabular Surgery Group, Orthopedic Branch, China International Exchange and Promotive Association for Medical and Health Care and Orthopedic Physician Branch, Chinese Medical Doctor Association organized a panel of domestic experts in the field to develop the Clinical guideline for the diagnosis and treatment of sacroiliac complex injuries ( version 2025), based on evidence-based medicine and adhering to the principles of scientific rigor, clinical applicability, and innovation. These guidelines provided 11 recommendations covering diagnosis, therapeutic principles and techniques, management protocols for lumbosacral plexus injuries, outcome evaluation, and postoperative rehabilitation pathways, etc., aiming to standardize the clinical management of sacroiliac complex injuries.

Objective To study the effect and molecular mechanism of vitamin D(VitD)on Tfh cells of MRL/lpr lupus mice.Methods C57/B6 mice and MRL/lpr lupus mice were transfected with siRNA to construct VDR knockout mouse models.Splenic Tfh cells of C57/B6 mice and MRL/lpr lupus mice were divided into control group,lupus group and VDRsiRNA lupus group(treated with vitamin D 0,1 and 10 nmol·L-1,respectively)by siRNA transfection.The percentage of Tfh cells was detected by flow cytometry.MRL/lpr lupus mice Peyer node Tfh cells were randomly divided into 7 groups,blank control group,vitamin D dose groups of 1 and 10 nmol·L-1,paricalcitol group(VitD 10 nmol·L-1+PA),VDRsiRNA control group,VDRsiRNA group(VitD 10 nmol·L-1),CaN inhibitor group(VitD 10 nmol·L-1+CsA),and incubated for 72 h.The concentration of calcium ions in Tfh of each group was detected.The expressions of AT1R,NFAT,CaN and P-CaN in Tfh cells were determined by Western blotting.Results The percentage of Tfh cells decreased significantly with the increase of vitamin D dose.Vitamin D CaN reduce the intracellular calcium concentration of Tfh,up-regulate the expression of AT1 protein in Tfh cells,and down-regulate the expression of CAN,P-CaN and NFAT protein in a dose-dependent manner,and the effect is more obvious when combined with PA.Conclusion Vitamin D may regulate the activation of follicular T helper cells in MRL/lpr mice via the Ca-CaN-NFAT pathway.

Sacroiliac complex injuries are commonly seen in high-energy pelvic fractures. The injuries make a big difference in treatment patterns due to the diverse injury types, posing considerable challenges in formulating optimal treatment strategies, and hence are persistent clinical difficulties in orthopedic trauma. The clinical management of sacroiliac complex injuries presents several key challenges such as a non-negligible rate of missed diagnoses in associated vascular and visceral injuries, absence of standardized protocols for surgical approaches and reduction-fixation strategies across different injury patterns, and ongoing controversies regarding surgical indications and optimal timing for patients combined with concomitant lumbosacral plexus injuries. Currently, no systematic clinical guidelines are available for the diagnosis and treatment of sacroiliac complex injuries both domestically and internationally. To this end, the Pelvic and Acetabular Surgery Group, Orthopedic Branch, China International Exchange and Promotive Association for Medical and Health Care and Orthopedic Physician Branch, Chinese Medical Doctor Association organized a panel of domestic experts in the field to develop the Clinical guideline for the diagnosis and treatment of sacroiliac complex injuries ( version 2025), based on evidence-based medicine and adhering to the principles of scientific rigor, clinical applicability, and innovation. These guidelines provided 11 recommendations covering diagnosis, therapeutic principles and techniques, management protocols for lumbosacral plexus injuries, outcome evaluation, and postoperative rehabilitation pathways, etc., aiming to standardize the clinical management of sacroiliac complex injuries.

Objective To investigate whether exposure pathways influence the distribution pattern and toxicity of polystyrene nanoplastics(PSNPs)in hepatic cells.Methods Male C57BL/6J wild-type healthy mice aged 6 to 8 weeks old and weighed 18 to 22 g were administered with PSNPs via gavage or tail vein injection.Then,we tracked PSNPs distribution in the major organs of mice via an in vivo imaging system(IVIS).After that,we analyzed the cellular accumulation patterns in hepatic cell subpopulations(hepatocytes and Kupffer cells)using immunofluorescence and transmission electron microscopy(TEM).300 nm PSNPs were administered via gastric gavage or tail vein injection,and 70 nm PSNPs were injected via the portal vein.The cellular localization of PSNPs in the liver was analyzed using immunofluorescence.Subsequently,using AML-12 cells,a normal mouse liver cell line,as the parenchymal hepatocyte model,the uptake of PSNPs in AML-12 cells was analyzed by confocal laser scanning microscope(CLSM).Flow cytometry was performed to observe and quantify PSNPs uptake,and to analyze the underlying endocytosis mechanisms.IVIS was used to analyze PSNPs uptake features in vivo.Finally,using mouse macrophage line RAW264.7 as a Kupffer cell model and AML-12 cells as a parenchymal hepatocyte model,the cell-type-specific toxic effects induced by 100 μg/ml PSNPs were examined through transcriptomics and metabolomics analyses.Results IVIS revealed predominant hepatic accumulation of PSNPs regardless of exposure pathways via intragastric gavage or tail vein injection.Immunofluorescence/TEM demonstrated exposure pathway-dependent cellular distribution:intragastric PSNPs were localized mainly in hepatocytes,while intravenous PSNPs were accumulated in Kupffer cells.Changes in particle size(300 nm vs.70 nm)did not alter the cellular distribution pattern,while 70 nm PSNPs injected via the portal vein accumulated in Kupffer cells,which suggested that the cell-type-specific distribution of PSNPs in the liver was independent of PSNPs size and might be related to the transport of PSNPs in the gastrointestinal tract.Flow cytometry showed that PSNPs uptake by AML-12 was time-dependent and that the underlying endocytosis mechanism involved pathways mediated by clathrin(P<0.000 1),macropinocytosis(P=0.002 6),and lipid rafts(P<0.000 1).Findings on PSNPs distribution in blood revealed that the uptake of PSNPs by hepatocytes exhibited a rate saturation phenomenon.Multi-omics analysis identified distinct toxicity patterns:PSNPs disrupted lipid metabolism and neurotransmitter homeostasis in AML-12 cells and induced inflammation and oxidative stress in Kupffer cells.Conclusion Exposure pathways mediate the hepatic cell-type-specific distribution of PSNPs,thereby altering the downstream toxicological consequences induced by exposure to PSNPs.

BackgroundThe functional changes of the default mode network （DMN） are closely related to the onset of major depressive disorders. However， the relationship between the DMN subsystem （core subsystem， dorsomedial prefrontal cortex subsystem， medial temporal lobe subsystem） and symptoms of first-episode major depressive disorder remains unclear. ObjectiveTo investigate abnormal functional connectivity between DMN subsystems and the whole brain in first-episode major depressive disorder patients during the resting-state， and to analyse the correlations between these functional connectivity patterns and clinical symptoms， so as to reveal the potential neural mechanisms from the perspective of DMN subsystem. MethodsFrom September 2020 to September 2023， a total of 64 first-episode outpatients and inpatients meeting the diagnostic criteria for major depressive disorder in the Diagnostic and Statistical Manual of Mental Disorders， fourth edition （DSM-IV） were enrolled at the Inner Mongolia Autonomous Region Mental Health Center as the study group. During the same period， 54 healthy volunteers matched for age， gender， and years of education were recruited from the community as the control group. Both groups were assessed using the Hamilton Depression Scale-24 item （HAMD-24）. Resting-state functional magnetic resonance images （rs-fMRI） of the two groups were acquired using a Siemens 3.0 T scanner， and differences in functional connectivity between DMN subsystems （core subsystem， dorsomedial prefrontal cortex subsystem， medial temporal lobe subsystem） and the whole brain were compared. The functional connectivity values of brain regions with statistically significant differences between the two groups were extracted. Spearman's rank correlation coefficient analysis was used to investigate the correlation between these functional connectivity values and HAMD-24 scores of the study group. ResultsUltimately， 46 patients and 43 controls completed the study. Compared with the control group， the study group exhibited significantly stronger functional connectivity in the following pathways： between the right superior parietal lobule （core subsystem） and right cerebellar lobule VIII （t=3.954， P<0.05， GRF-corrected）， between the right lateral temporal cortex （dorsomedial prefrontal cortex subsystem） and right cerebellar lobule VIII， right and left hippocampi， right medial， and paracingulate gyrus （t=4.595， 4.208， 5.200， 4.038， P<0.05， GRF-corrected）， and between the temporoparietal junction （dorsomedial prefrontal cortex subsystem） and left lingual gyrus and right cerebellar lobule VIII （t=3.557， 4.274， P<0.05， GRF-corrected）. Conversely， weaker functional connectivity was observed between the right inferior frontal gyrus and left gyrus rectus （t=-3.824， P<0.05， GRF-corrected）. Furthermore， within the study group， the functional connectivity values between the right lateral temporal cortex and right hippocampus， as well as between the temporoparietal junction and right cerebellar lobule VIII， were both negatively correlated with the HAMD-24 cognitive impairment factor score （r=-0.306， -0.318， P<0.05）. ConclusionIncreased functional connectivity between the DMN （specifically its core and dorsomedial prefrontal cortex subsystems） and cerebellum， partial limbic system， and lingual gyrus may be associated with the neuropathology of first-episode major depressive disorder. Furthermore， alterations in functional connectivity between the dorsomedial prefrontal cortex subsystem and both the cerebellum and hippocampus in these patients may be related to cognitive function. ［Funded by 2019 Annual Inner Mongolia Autonomous Region Natural Science Foundation Project （number， 2019MS03038）； 2023 Annual Inner Mongolia Autonomous Region Natural Science Foundation Project （number， 2023MS08028）］