ObjectiveTo analyze the differences in color， odor and volatile components of Citri Reticulatae Pericarpium（CRP） before and after being stir-fried with Halloysitum Rubrum， and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and the volatile components were analyzed by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. According to the principle of variable importance in the projection（VIP） value>1.5， volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose， the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum， of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected， including α-pinene， β-myrcene， linalool， sabinene， ocimene isomer mixture， A-ocimene， and δ-elemene. After being processed with Halloysitum Rubrum， the brightness value（L^*）， yellow-blue value（b^*） and total chromatic value（E^*_ab） of CRP were decreased（P<0.01）， and red-green value（a^*） was increased（P<0.01）， the response values of S4， S5， S10 and S13 sensors were significantly increased（P<0.05）， and the response values of S3 and S8 sensors were significantly decreased（P<0.05）. Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L^* and E^*_ab， but positively correlated with a^*. Sabinene was positively correlated with L^* and E^*_ab. Linalool was positively correlated with L^* and E^*_ab， and negatively correlated with a^*. The ocimene isomer mixture was positively correlated with the L^*. ConclusionAfter being processed with Halloysitum Rubrum， the appearance color， odor and volatile components of CRP change significantly， and α-pinene， β-myrcene， sabinene， linalool and A-ocimene are the characteristic volatile components before and after processing， which can provide references for the quality evaluation and clinical application of CRP and its processed products.

ObjectiveTo analyze the differences in color， odor and volatile components of Citri Reticulatae Pericarpium（CRP） before and after being stir-fried with Halloysitum Rubrum， and to explore the material basis of enhancing the effect of strengthening spleen after processing and the scientific connotation of decoction pieces processed with Halloysitum Rubrum as the auxiliary material. MethodsThe volatile components of the samples before and after processing were identified and relatively quantified by headspace gas chromatography-mass spectrometry（HS-GC-MS）， and the volatile components were analyzed by principal component analysis（PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）. According to the principle of variable importance in the projection（VIP） value>1.5， volatile differential components before and after processing were screened. And combined with intelligent sensory technologies such as colorimeter and electronic nose， the chroma and odor information of CRP before and after being stir-fried with Halloysitum Rubrum were identified. Pearson correlation analysis was used to explore the correlation between volatile differential components and chroma values. ResultsA total of 112 volatile components were identified from CRP and CRP stir-fried with Halloysitum Rubrum， of which 84 were from CRP and 97 were from CRP stir-fried with Halloysitum Rubrum. And 7 differential components were selected， including α-pinene， β-myrcene， linalool， sabinene， ocimene isomer mixture， A-ocimene， and δ-elemene. After being processed with Halloysitum Rubrum， the brightness value（L^*）， yellow-blue value（b^*） and total chromatic value（E^*_ab） of CRP were decreased（P<0.01）， and red-green value（a^*） was increased（P<0.01）， the response values of S4， S5， S10 and S13 sensors were significantly increased（P<0.05）， and the response values of S3 and S8 sensors were significantly decreased（P<0.05）. Correlation analysis showed that α-pinene and β-myrcene were negatively correlated with L^* and E^*_ab， but positively correlated with a^*. Sabinene was positively correlated with L^* and E^*_ab. Linalool was positively correlated with L^* and E^*_ab， and negatively correlated with a^*. The ocimene isomer mixture was positively correlated with the L^*. ConclusionAfter being processed with Halloysitum Rubrum， the appearance color， odor and volatile components of CRP change significantly， and α-pinene， β-myrcene， sabinene， linalool and A-ocimene are the characteristic volatile components before and after processing， which can provide references for the quality evaluation and clinical application of CRP and its processed products.

Objective To investigate the effects of cucurbitacin B (CucB) on alleviating skin lesions and inflammation in psoriasis mice via the cGAS-STING signaling pathway. Methods The expression of genes associated with the cGAS-STING signaling pathway in psoriatic lesions and non-lesional skin was analyzed, and hallmark gene set enrichment analysis was performed. The cytotoxicity of CucB on BMDMs was evaluated using the CCK-8 assay. The expression levels of genes and proteins related to the cGAS-STING signaling pathway, along with the secretion of inflammatory cytokines, were measured at different concentrations of CucB using quantitative PCR, Western blotting, and ELISA. Imiquimod-induced psoriasis BALB/c mice were divided into four groups: normal group, model group, low-dose CucB group [0.1 mg/ (kg.d)], and high-dose CucB group [0.4 mg/ (kg.d)], with five mice per group. PASI scoring was performed to assess the severity of psoriasis after 6 days of treatment, and HE staining was conducted to observe pathological damage. Meanwhile, the mRNA levels of inflammatory cytokines and their secretion were detected by qPCR and ELISA. Results Most cGAS-STING signaling-related genes were upregulated in lesional skin of psoriasis patients, and the hallmark gene set enrichment analysis revealed that the most significantly upregulated genes were primarily associated with immune response signaling pathways. CucB inhibited dsDNA-induced phosphorylation of interferon regulatory factor 3 (IRF3) and STING proteins in both bone-marrow derived macrophages(BMDMs) and THP-1 cells. CucB also suppressed dsDNA-induced mRNA expression of IFNB1, TNF, IFIT1, CXCL10, ISG15, and reduced the secretion of cytokines such as IFN-β, IL-1β, and TNF-α in THP-1 cells. In the imiquimod-induced psoriasis mouse model, CucB treatment reduced psoriatic symptoms, alleviated skin lesions, and attenuated inflammation. ELISA and qPCR results showed that CucB significantly reduced serum secretion levels of IL-6, TNF-α, and IL-1β, as well as the mRNA levels of IL23A, IL1B, IL6, TNF, and IFNB1. Conclusion CucB inhibits cytoplasmic DNA-induced activationc of the GAS-STING pathway. CucB significantly attenuates skin lesions and inflammation in IMQ-induced psoriatic mice, and the potential molecular mechanism may be related to the down-regulation of the cGAS-STING pathway.
Animals ; Psoriasis/pathology* ; Signal Transduction/drug effects* ; Membrane Proteins/genetics* ; Mice ; Nucleotidyltransferases/genetics* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism* ; Triterpenes/therapeutic use* ; Humans ; Cytokines/metabolism* ; Inflammation/drug therapy* ; Male

Hypertrophic scar is a fibrous hyperplastic disorder that arises from skin injuries. The current therapeutic modalities are constrained by the dense and rigid scar tissue which impedes effective drug delivery. Additionally, insufficient autophagic activity in fibroblasts hinders their apoptosis, leading to excessive matrix deposition. Here, we developed an active microneedle (MN) system to overcome these challenges by integrating micromotor-driven drug delivery with autophagy regulation to remodel the scar microenvironment. Specifically, sodium bicarbonate and citric acid were introduced into the MNs as a built-in engine to generate CO₂ bubbles, thereby enabling enhanced lateral and vertical drug diffusion into dense scar tissue. The system concurrently encapsulated curcumin (Cur), an autophagy activator, and triamcinolone acetonide (TA), synergistically inducing fibroblast apoptosis by upregulating autophagic activity. In vitro studies demonstrated that active MNs achieved efficient drug penetration within isolated scar tissue. The rabbit hypertrophic scar model revealed that TA-Cur MNs significantly reduced the scar elevation index, suppressed collagen I and transforming growth factor-β1 (TGF-β1) expression, and elevated LC3 protein levels. These findings highlight the potential of the active MN system as an efficacious platform for autonomous augmented drug delivery and autophagy-targeted therapy in fibrotic disorder treatments.

Rice (Oryza sativa L.), as a thermophilic crop, is highly susceptible to cold stress during its growth process. Chilling injury at the plumule stage and seedling stage often affects the morphological development and leads to yield reduction of rice. The exploration and utilization of cold tolerance genes are among the most direct and effective approaches to address cold stress in rice. To identify quantitative trait loci (QTLs) associated with cold tolerance at plumule and seedling stages, in this study, we measured the seedling rates and survived seedling rates of the indica rice cultivar 'HZ', the japonica cultivar 'Nekken2', and their 120 recombinant inbred lines (RILs) under cold stress. A previously constructed high-density genetic linkage map was used for the mapping of the QTLs conferring cold tolerance at the plumule and seedling stages. A total of 4 QTLs for plumule-stage cold tolerance and 9 QTLs for seedling-stage cold tolerance were detected, with the maximum limit of detection reaching 5.20. Notably, a genetically overlapping QTL for both plumule and seedling stages was identified on chromosome 8, spanning a physical interval of 24 432 953-25 295 129 bp. Candidate genes within the detected QTL intervals were screened, and quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to analyze the gene expression during the plumule and seedling stages. The results revealed that LOC_Os03g06570, LOC_Os03g07100, LOC_Os06g08280, LOC_Os08g38440, LOC_Os08g39100, and LOC_Os08g39540 exhibited significantly differential expression between the parental lines. These genes were either significantly downregulated or upregulated under cold stress. Among them, the first three gene (LOC_Os03g06570, LOC_Os03g07100, and LOC_Os06g08280) were hypothesized to be key candidates regulating the cold tolerance of rice seedlings, while the latter three genes (LOC_Os08g38440, LOC_Os08g39100, and LOC_Os08g39540) were identified as comprehensive regulators of cold tolerance during both plumule and seedling stages. These findings lay a foundation for the fine mapping and cloning of cold tolerance genes at the plumule and seedling stages, providing valuable insights for breeding cold-tolerant rice varieties.
Quantitative Trait Loci/genetics* ; Oryza/growth & development* ; Seedlings/growth & development* ; Cold Temperature ; Chromosome Mapping ; Gene Expression Regulation, Plant

OBJECTIVE To investigate the improvement effects of 3，5，6，7，8，3′，4′-heptamethoxyflavone （HMF） of Fructus Aurantii on rats with damp blockage of the middle energizer. METHODS The rats were randomly divided into normal group， model group， positive control group （Raceanisodamine tablet， 1 mg/kg）， HMF low-dose， medium-dose and high-dose groups （0.3， 0.6， 0.9 mg/kg）， with 7 rats in each group. Except for the normal group， the other groups were modeled by internal and external composite factors. After successful modeling， the rats in each group were given the corresponding drug or normal saline， once a day， for 14 days. The general behavioral states such as dietary intake， water intake and mental state of the rats were observed， and the fecal water content rate and saliva flow rate were measured. Hematoxylin-eosin （HE） staining was used to observe the pathological and morphology in gastric and small intestinal tissues of rats. The plasma content of aldosterone was detected， and the expression of aquaporins （AQP3） in the gastric tissue of rats was determined. RESULTS Compared with the normal group， the dietary intake and water intake of the model group rats were significantly decreased （P＜0.01）， the fecal water content rate， salivary flow rate， plasma content of aldosterone and the expression of AQP3 in gastric tissue were increased significantly （P＜0.01）. Gastric tissue injury invaded the mucosal muscle layer， resulting in mucosal muscle layer rupture； pathological and morphological changes such as small intestinal villous erosion and glandular structure destruction were observed in the small intestine. Compared with the model group， the dietary intake and water intake of rats were increased in HMF groups； fecal water content rate， salivary flow rate， plasma content of aldosterone， the expression of AQP3 in gastric tissue were decreased， most of the above differences were statistically significant （P＜0.05 or P＜0.01）. The pathological and morphological changes in the gastric and small intestine tissues of rats had been improved to varying degrees. CONCLUSIONS HMF of Fructus Aurantii with dry property HMF could improve the symptoms of rats with damp blockage of middle energizer， the mechanism of which may be associated with reducing the content of plasma aldosterone and down-regulating the expression of gastric AQP3.

ObjectiveTo explore the protective effects of Dahuang Tangluo pills on early diabetic kidkdey disease （DKD） in db/db mice. MethodEight db/m mice were selected as the control group. Forty male db/db mice were selected and blood samples were collected via tail vein to measure fasting blood glucose （FBG）. Mice with FBG ≥ 16.7 mmol·L^-1， increased urine output， and persistent albuminuria were considered successful in model establishment. After successful modeling， they were randomly divided into a model group， a dapagliflozin group （1.5 mg·kg^-1·d^-1）， and high， medium， and low dose groups of Dahuang Tangluo pills （3.6， 1.8， 0.9 g·kg^-1·d^-1， respectively）， with eight mice in each group. All medication groups were administered orally， while the control and model groups were given an equal amount of distilled water by gavage daily. After continuous administration for 10 weeks， the survival status of the mice was observed， and their body weight， FBG， and kidney function-related indicators were measured. Inflammatory indicators in renal tissues were determined by enzyme-linked immunosorbent assay （ELISA）. Hematoxylin-eosin （HE） staining， Masson staining， and electron microscopy were used to observe the pathological changes in renal tissues in each group. Immunofluorescence was employed to examine the expression of advanced glycation end products （AGEs） and receptors for advanced glycation end products （RAGE） proteins. Real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot were utilized to detect the gene and protein expression levels of AGEs， RAGE， inhibitor of nuclear factor-κB （NF-κB） kinase （IKK）， and NF-κB in the renal tissues of mice in each group. ResultCompared with control group， the model group showed a significant increase in body weight， FBG， serum creatinine （SCr）， urinary microalbumin/urine creatinine ratio （ACR）， total cholesterol （TC）， and triglycerides （TG） （P<0.05）. The levels of intercellular adhesion molecule-1 （ICAM-1）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α） in renal tissues were significantly elevated （P<0.05）. Renal histopathological staining and electron microscopy revealed loose arrangement， gaps， structural disarray， mesangial proliferation， and significant fibrosis in renal tissues. Real-time PCR results showed a significant increase in the expression of RAGE， IKK， and NF-κB genes in renal tissues （P<0.05）. Immunofluorescence results demonstrated a significant increase in the expression of AGEs and RAGE proteins in renal tissues （P<0.05）. Western blot results showed a significant increase in the expression of AGEs， RAGE， IKK， and NF-κB proteins in renal tissues （P<0.05）. After drug intervention， compared with model group， the dapagliflozin group and the high-dose Dahuang Tangluo pills group showed significant reductions in body weight， FBG， SCr， and ACR （P<0.05）， and a significant decrease in TC in mouse serum （P<0.05）， while the high-dose Dahuang Tangluo pills group showed a significant decrease in TG in mouse serum （P<0.05）. All treatment groups showed a significant reduction in ICAM-1， IL-6， and TNF-α in renal tissues （P<0.05）. Renal histopathological staining and electron microscopy showed improved kidney injury， decreased collagen fiber deposition， and reduced mesangial proliferation in all treatment groups. Real-time PCR results showed a significant decrease in the expression of RAGE， IKK， and NF-κB genes in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Immunofluorescence results demonstrated a significant decrease in the expression of AGEs and RAGE proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. Western blot results showed a significant decrease in the expression of AGEs， RAGE， IKK， and NF-κB proteins in the dapagliflozin group and the high- and medium-dose Dahuang Tangluo pills groups （P<0.05）. ConclusionDahuang Tangluo pills can improve the pathological structure of the kidneys and reduce renal inflammation in DKD mice， possibly through inhibiting the AGEs/RAGE/IKK/NF-κB pathway.

OBJECTIVE To compare the changes of chemical components of Morus alba leaves， screen differential markers， and determine their contents， so as to provide reference for quality control of M. alba leaves before and after baked with honey. METHODS The fingerprints of M. alba leaves before and after baked with honey were established by high-performance liquid chromatography （HPLC）. The common peaks of the fingerprints were identified and the similarity was evaluated. The differential markers of M. alba leaves before and after baked with honey were screened by principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis （OPLS-DA） using common peak are of raw material and product baked with honey of M. alba leaves as index. The quantitative analysis was carried out. RESULTS Twenty-three and twenty-four common peaks were identified from the HPLC fingerprint spectra of ten batches of raw material and ten batches of product baked with honey of M. alba leaves， respectively. The similarities of HPLC fingerprints for raw material and product baked with honey of M. alba leaves were all greater than 0.97. The results of PCA showed that raw material and product baked with honey of M. alba leaves could be divided into two categories. The results of OPLS-DA showed that the variable importance in projection of peak 2， peak H （5- hydroxymethylfurfural）， peak 1， peak 17 （isochlorogenic acid C） and peak 16 were all greater than 1. The average contents of differential marker of isochlorogenic acid C in raw material and product baked with honey of M. alba leaves were 0.093 6 and 0.127 8 mg/g， respectively； there was statistical significance （P＜0.05）. CONCLUSIONS Five differential markers such as isochlorogenic acid C are obtained. The content of isochlorogenic acid C in M. alba leaves is significantly increased after baked with honey.

Objective To investigate the effect of early warning score system combined with(situation,background,ssessment,recommendation,SBAR)communication model in early warning of high-risk neonates,therefore to provide an effective communication method for an effective communication method to assess the changes of condition in neonates.Methods A before-after study model was adopted in the study.A total of 270 high-risk neonates admitted to the ward of the Department of Neonatology in a tertiary hospital between August and September 2022 were selected as research subjects.The high-risk neonates admitted in hospital in August were assigned in a control group,and those admitted in September were assigned in an trial group,with 135 neonates per group.Routine care was carried out in the control group,while early warning scoring combined with SBAR communication model were applied in the trial group on top of the cares offered to the control group.The occurrence of early warning events,concordance rate of nurse warning event and doctor handling events,and the satisfaction rate of doctors with the nursing performance were compared between the two groups.Results A total of 63.6%of early warning events were triggered by nurses in the control group,while it was 92.6%in the trial group,with a statistically significant difference between the groups(χ2=16.622,P<0.001).The consistency of handling of early warning events between the nurses and doctors in the trial group(Kappa coefficient=0.926)was higher than that in the control group(Kappa coefficient=0.641).The satisfaction rates of the doctors with the nurses about specialist knowledge,ability in emergency events,mastery of disease,timely observation of disease progress,collaboration between doctors and nurses,working enthusiasm,communication capability and the psychological quality in the trial group were all significantly higher than those in the control group[80.0%-95.0%vs.30.0%-55.0%,all P<0.01].Conclusions The Early Warning Score system combined with SBAR communication model can help nurses to accurately evaluate the changes of disease in neonates,complete the communication with doctors timely and effectively.It improves the observation,communication and handling capability among the nurses as well as the satisfaction rate of doctors with nursing work.

Objective To investigate the relationship between polymorphism of resistin(RETN)gene and metabolic associated fatty liver disease(MAFLD)in type 2 diabetes mellitus(T2DM)patients in middle and high altitude areas.Methods A total of 400 patients with T2DM in Qinghai area were recruited and divided into simple T2DM group(T2DM,n=200)and T2DM combined with MAFLD group(T2DM+ MAFLD,n=200)according to liver ultrasonography.Healthy individuals confirmed by physical examination were selected as the normal control group(NC,n=180).Plasma resistin levels were measured by ELISA.The polymorphism of RETN-420C/G and +299G/A genes were detected by PCR sequencing.Results By comparing the polymorphism of RETN-420C/G gene in each group,it was found that the frequencies of G/G genotype and G allele frequency in T2DM+MAFLD group were higher than those in NC group and T2DM group(P<0.05),while the frequencies of C/C genotype and C allele frequency were lower than those in NC group and T2DM group(P<0.05).The risk of MAFLD increased by 1.571,2.126 and 1.537 times respectively in T2DM patients with C/G,G/G genotype and G allele.Logistic regression analysis showed that G/G genotype was a risk factor for MAFLD in T2DM patients.By comparing the polymorphism of RETN+299G/A gene in each group,it was found that A allele frequency in T2DM+MAFLD group was higher than that in NC group and T2DM group,while G allele frequency was lower than that in NC group and T2DM group(P<0.05).The allele A increased the risk of MAFLD in T2DM patients by 1.432 times compared to allele G.Conclusion RETN gene-420C/G locus G/G genotype increases the risk of T2DM combined with MAFLD in middle and high altitudeareas.