This study aimed to investigate the effect of saltwater stir-fried Plantaginis Semen(SPS) on renal fibrosis in rats and decipher the underlying mechanism. Thirty-six Sprague-Dawley rats were randomly assigned into control, model, losartan potassium, and low-, medium-, and high-dose(15, 30, and 60 g·kg~(-1), respectively) SPS groups. Rats in other groups except the control group were subjected to unilateral ureteral obstruction(UUO) to induce renal fibrosis, and the modeling and gavage lasted for 14 days. After 14 consecutive days of treatment, the levels of serum creatinine(Scr) and blood urea nitrogen(BUN) in rats of each group were determined by an automatic biochemical analyzer. Hematoxylin-eosin(HE) and Masson staining were used to evaluate pathological changes in the renal tissue. Western blot and immunofluorescence assay were conducted to determine the protein levels of fibronectin(FN), collagen Ⅰ, vimentin, and α-smooth muscle actin(α-SMA) in the renal tissue. The mRNA levels of epithelial-mesenchymal transition(EMT)-associated transcription factors including twist family bHLH transcription factor 1(TWIST1), snail family transcriptional repressor 1(SNAI1), and zinc finger E-box binding homeobox 1(ZEB1), as well as inflammatory cytokines such as interleukin-1β(IL-1β), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α), were determined by RT-qPCR. Human renal proximal tubular epithelial(HK2) cells exposed to transforming growth factor-β(TGF-β) for the modeling of renal fibrosis were used to investigate the inhibitory effect of SPS on EMT. Network pharmacology and Western blot were employed to explore the molecular mechanism of SPS in alleviating renal fibrosis. The results showed that SPS significantly reduced Scr and BUN levels and alleviated renal injury and collagen deposition in UUO rats. Moreover, SPS notably down-regulated the protein levels of FN, collagen Ⅰ, vimentin, and α-SMA as well as the mRNA levels of SNAI1, ZEB1, TWIST1, IL-1β, IL-6, and TNF-α in the kidneys of UUO rats and TGF-β-treated HK-2 cells. In addition, compared with Plantaginis Semen without stir-frying with saltwater, SPS showed increased content of specific compounds, which were mainly enriched in the mitogen-activated protein kinase(MAPK) signaling pathway. SPS significantly inhibited the phosphorylation of extracellular signal-regulated kinase(ERK) and p38 MAPK in the kidneys of UUO rats and TGF-β-treated HK2 cells. In conclusion, SPS can alleviate renal fibrosis by attenuating EMT through inhibition of the MAPK signaling pathway.
Animals ; Epithelial-Mesenchymal Transition/drug effects* ; Rats, Sprague-Dawley ; Male ; Rats ; Fibrosis/genetics* ; Drugs, Chinese Herbal/administration & dosage* ; Kidney Diseases/pathology* ; Kidney Tubules/pathology* ; Humans

The structure of intestinal tissue is complex. In vitro simulation of intestinal structure and function is important for studying intestinal development and diseases. Recently, organoids have been successfully constructed and they have come to play an important role in biomedical research. Organoids are miniaturized three-dimensional (3D) organs, derived from stem cells, which mimic the structure, cell types, and physiological functions of an organ, making them robust models for biomedical research. Intestinal organoids are 3D micro-organs derived from intestinal stem cells or pluripotent stem cells that can successfully simulate the complex structure and function of the intestine, thereby providing a valuable platform for intestinal development and disease research. In this article, we review the latest progress in the construction and application of intestinal organoids.
Organoids/cytology* ; Intestines/physiology* ; Humans ; Animals ; Pluripotent Stem Cells

Objective:To evaluate the application of a two-stage sequential nutritional therapy combined with functional exercise in the preoperative prehabilitation of patients with high-output intestinal fistula(HIF).Methods:A total of 164 HIF patients scheduled for definitive fistula resection in the Department of General Surgery,Eastern Theater Command General Hospital from March 2023 to March 2025 were prospectively enrolled.They were randomly assigned to a control group or an intervention group at a 1:1 ratio,with 82 patients in each group.The control group received conventional nutritional support and basic functional exercise,while the intervention group underwent a two-stage sequential nutritional therapy combined with graded functional exercise.Nutritional indicators,inflammatory markers,functional status,and postoperative recovery were compared between the two groups at 28 days before surgery,1 day before surgery,and 1,3,and 7 days after surgery.Results:On the day before surgery,the nutritional indicators in the intervention group,including albumin[(36.8±4.1)g/L],prealbumin[(213.5±42.1)mg/L],and total protein[(69.3±6.1)g/L],were all significantly higher than those in the control group[albumin(33.1±3.9)g/L,prealbumin(163.2±37.6)mg/L,total protein(63.7±5.9)g/L],with P<0.001.The energy compliance rates on the 21st day before surgery and the day before surgery in the intervention group(85.2%,92.8%)were significantly higher than those in the control group(62.5%,72.4%),with P<0.001.The 6-minute walk distance(6MWD)in the intervention group on the day before surgery and on the 7th day after surgery[(385.1±55.2)m,(346.3±48.4)m]was significantly greater than that in the control group[(315.3±60.7)m,(298.3±51.1)m],with P<0.001.On the 1st day after surgery,the inflammatory markers in the intervention group[CRP(98.7±35.2)mg/L,IL-6(45.3±12.5)pg/mL,PCT(1.2±0.5)ng/mL]were all significantly lower than those in the control group[CRP(152.4±48.6)mg/L,IL-6(89.6±25.4)pg/mL,PCT(2.8±0.9)ng/mL],with P<0.001.Additionally,the time to first ambulation after surgery[(16.8±4.2)h],time to first flatus[(52.4±14.5)h],and ICU stay duration[(3.1±1.6)d]in the intervention group were all significantly shorter than those in the control group,with P<0.001 Conclusion:The two-stage sequential nutritional therapy combined with functional exercise significantly improves the attainment of nutritional targets,suppresses systemic inflammatory response,enhances muscle reserve and exercise tolerance,and effectively shortens the postoperative recovery period in HIF patients.These findings support the use of this combined approach as a targeted and feasible model for preoperative prehabilitation,demonstrating substantial clinical application value.

Plutonium isotopes(238Pu,239Pu,240Pu and 241Pu)in the environment are important"fingerprint"nuclides in the study of nuclear activity traceability.The content of plutonium isotopes in the environmental metrics is usually very low,and the measurement of these isotopes,especially 238Pu,using mass spectrometry is seriously interfered with by the coexisting 238U.The analysis of several plutonium isotopes in soil usually requires combination of multiple measurement techniques,which leads to a long analysis time and large uncertainty in the isotope ratio.In this work,the hydrous titanium oxide(HTiO)precipitated by the hydrolysis of titanium oxydichloride(TiOCl2)under near-neutral condition was used to preconcentrate plutonium from the soil digestion solution,and the highly efficient decontamination of 238U in the sample was achieved by TK200 resin column chromatography with a decontamination factor of 108.Simulation resuts of density functional theory(DFT)showed that NH3 was considered as a promising reaction gas to eliminate the interference of 238U from 238Pu measurement using mass spectrometry due to the significant discrepancy of the chemical reactivity of U+and Pu+with the reactive gas NH3.Experiments confirmed that by optimizing the flow rates of collision gas(He)and reaction gas(NH3),the interference of 238U could be effectively suppressed,and the decontamination factor of 238U was 104.Combined with chemical separation,the overall decontamination factor of 238U could reach 1012 by using the developed method.By combining chemical separation and tandem quadrupole inductively coupled plasmon-mass spectrometry(ICP-MS/MS)measurement,the simultaneous determination of four ultra-trace plutonium isotopes in soil was realized,and the detection limit of plutonium isotopes was at the femtogram level.Analysis of the international standard reference materials(NIST-SRM-4357 and IAEA-384)showed that the established method could be successfully used for the accurate analysis of ultra-trace four plutonium isotopes(238Pu,239Pu,240Pu and 241Pu)in soil samples.

Objective To investigate the effect of total paeony glycoside(TPG)on airway remodeling in bronchial asthma mice and its underlying mechanisms.Methods Forty-eight BALB/c mice were randomly divided into control group,model group,ovalbumin+budesonide group(OVA+BUD group),and OVA+TPG group,with 12 mice in each group.Except the control group,mice in other groups were sensitized by intraperitoneal injection of 10%OVA aluminum hydroxide suspension,and then stimulated by atomized inhalation of 1%OVA to establish mouse asthma model.One hour before each inhalation of OVA,mice in OVA+BUD group were atomized with 2 ml BUD suspension,and mice in OVA+TPG group were given 5 g/kg TPG by intragastric administration.Lung tissues and bronchoalveolar lavage fluid(BALF)of mice from each group were collected,and the pathological morphology of the lung tissues was detected by hematoxylin-eosin(HE)and periodic acid schiff(PAS)staining.Inflammatory cell counts[white blood cell(WBC),neutrophil(NEU),eosinophils(EOS),and leukomonocyte(LYM)]in BALF were detected by Wright-giemsa staining.The contents of inflammatory factors including tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)and IL-6 in BALF were determined by ELISA.Airway remodeling proteins[fibronectin,α-smooth muscle actin(α-SMA),collagen Ⅰ]and NOD-like receptor protein 3(NLRP3)inflammasome-related proteins[NLRP3,cleaved caspase-1,apoptosis-associated speck-like protein(ASC)]levels were detected by Western blotting.Human bronchial smooth muscle cells(HBSMCs)were divided into control group(normal culture),transforming growth factor(TGF)-β1 group(culture medium containing 10 ng/ml TGF-β1),and TGF-β1+TPG group(culture medium containing 10 ng/ml TGF-β1 and 50 μg/ml TPG).Cell proliferation was detected by CCK-8 method,and Western blotting was used to detect the expression of airway remodeling proteins and NLRP3 inflammasome-related proteins.Results Compared with control group,model group exhibited increased infiltration of inflammatory cell in lung tissues,mucosal epithelium hyperplasia,narrowed bronchial lumen narrowed,tube wall thickened,increased cup cells and mucus secretion,and an elevated pathological score of lung injury(P<0.05);the number of inflammatory cells(WBC,NEU,EOS,and LYM)and the levels of inflammatory factors(TNF-α,IL-1β,and IL-6)in BALF were increased(P<0.05),and the expressions of fibronectin,α-SMA,collagen Ⅰ,NLRP3,cleaved caspase-1 and ASC were elevated(P<0.05).Compared with model group,BUD or TPG treatment effectively reduced asthma symptoms,improved lung histopathology injury,inhibited bronchial wall thickening,significantly reduced the number of inflammatory cells(WBC,NEU,EOS,and LYM)and the content of inflammatory factors(TNF-α,IL-1β,and IL-6)in BALF,and inhibited expression of fibronectin,α-SMA,collagen Ⅰ,NLRP3,cleaved caspase-1 and ASC(P<0.05).Compared with control group,the proliferation rate of HBSMCs was increased,and the protein expression levels of fibronectin,α-SMA,collagen Ⅰ,NLRP3,cleaved caspase-1 and ASC were increased in TGF-β1 group(P<0.05).Compared with TGF-β1 group,TPG treatment decreased cell proliferation and inhibited the protein expression of fibronectin,α-SMA,collagen Ⅰ,NLRP3,cleaved caspase-1 and ASC(P<0.05).Conclusion TPG may alleviate airway remodeling and asthma symptoms by decreasing the expression of airway remodeling-related proteins,inhibiting NLRP3 inflammasome activation,and reducing the inflammatory response.

Objective To investigate the origin of Biomphalaria straminea in China, so as to provide insights into assessment of schistosomiasis mansoni transmission risk and B. straminea control. Methods Guanlan River, Dasha River, Shenzhen Reservoir, upper and lower reaches of Kuiyong River, and Xinzhen River in Shenzhen, China, were selected as sampling sites. Ten Biomphalaria samples were collected from each site, and genomic DNA was extracted from Biomphalaria samples. DNA samples were obtained from 15 B. straminea sampled from 5 sampling sites in Minas Gerais State, Pará State, Federal District, Pernambuco State, and Sao Paulo State in Brazil, South America. Cytochrome c oxidase I (COI) and mitochondrial 16S ribosomal RNA (16S rRNA) genes were sampled using the above DNA templates, and the amplified products were sequenced. The COI and 16S rRNA gene sequences were downloaded from GenBank, and the sampling sites were acquired. All COI and 16S rRNA gene sequences were aligned and evolutionary trees of B. straminea were created based on COI and 16S rRNA gene sequences to identify the genetic similarity and evolutionary relationship between B. straminea samples from China and South America. Results A total of 60 COI gene sequences with a length of 529 bp and 3 haplotypes were obtained from B. straminea sampled from China. There were 165 COI gene sequences of B. straminea retrieved from GenBank, and following alignment with the above 60 gene sequences, a total of 33 haplotypes were obtained. Phylogenetic analysis showed that the three haplotypes of B. straminea from China were clustered into one clade, among which the haplotype China11 and three B. straminea samples from Brazil retrieved from GenBank belonged to the same haplotype. Geographical evolution analysis showed that the B. straminea samples from three sampling sites along eastern coasts of Brazil had the same haplotype with China11, and B. straminea samples from other two sampling sites were closely, genetically related to China11. A total of 60 16S rDNA gene sequences with approximately 322 bp in length were amplified from B. straminea in China, with 2 haplotypes identified. A total of 70 16S rDNA gene sequences of B. straminea were captured from GenBank. Phylogenetic analysis showed that Biomphalaria snails collected from China were clustered into a clade, and the haplotype China64 and the haplotype 229BS from Brazil shared the same haplotype. The 49 16S rDNA gene sequences of B. straminea from 25 sampling sites in southern Brazil, which were captured from GenBank, were included in the present analysis, and the B. straminea from 3 sampling sites shared the same haplotype with China64 in China. Geographical evolution analysis based on COI and 16S rRNA gene sequences showed that B. straminea sampled from eastern coastal areas of Brazil shared the same haplotypes in two gene fragment sequences with Biomphalaria snails collected from China. Conclusions The Biomphalaria snails in China are characterized as B. straminea, which have a low genetic diversity. The Biomphalaria snails in China have a high genetic similarity with B. straminea sampled from eastern coastal areas of Brazil, which may have originated from the eastern coastal areas of Brazil.

Based on the literature review and the analysis of specific cases of postpartum frequent micturition,pediatric enuresis,elderly uremia complicated with bradyarrhythmia in clinic,the clinical application of the action of Ephedrae Herba in stimulating yang qi is discussed.Ephedrae Herba has the meridian tropism of the lung and bladder meridians,and is pungent,warm and dispersing,which is the most important medicine for the treatment of external contraction.Ephedrae Herba has the actions of inducing diaphoresis,calming asthma and inducing diuresis,and is widely used for the treatment of external contraction,coughing and asthma,and edema.For the patients with deficiency of both kidney yin and kidney yang without obvious bias of yin-yang consumption which result from the postpartum impairment of qi and blood,deficient innate endowment,and gradually exhaustion of essence in the kidney in the elderly or during chronic illness,a small dosage of Ephedrae Herba can stimulate yang qi during the treatment of warming kidney yang,which is helpful for promoting the drug arriving at the back shu-points of the internal organs distributed along the bladder meridian and enhancing the recovery of zang-fu organ function.Ephedrae Herba is strong in inducing diaphoresis with an intense action.When Ephedrae Herba is used to stimulate yang,the dosage of 3～9 g is appropriate,and medicines for warming yang are needs to be used together.The course of treatment with Ephedrae Herba should be avoided to be too long,in order to prevent the vital energy from the damage by its large cumulative dose.

Objective:To investigate the value of CT radiomic model based on analysis of primary gastric cancer and the adipose tissue outside the gastric wall beside cancer in differentiating stage T1-2 from stage T3-4 gastric cancer.Methods:This study was a case-control study. Totally 465 patients with gastric cancer treated in Affiliated People′s Hospital of Jiangsu University from December 2011 to December 2019 were retrospectively collected. According to postoperative pathology, they were divided into 2 groups, one with 150 cases of T1-2 tumors and another with 315 cases of T3-4 tumors. The cases were divided into a training set (326 cases) and a test set (139 cases) by stratified sampling method at 7∶3. There were 104 cases of T1-2 stage and 222 cases of T3-4 stage in the training set, 46 cases of T1-2 stage and 93 cases of T3-4 stage in the test set. The axial CT images in the venous phase during one week before surgery were selected to delineate the region of interest (ROI) at the primary lesion and the extramural gastric adipose tissue adjacent to the cancer areas. The radiomic features of the ROIs were extracted by Pyradiomics software. The least absolute shrinkage and selection operator was used to screen features related to T stage to establish the radiomic models of primary gastric cancer and the adipose tissue outside the gastric wall beside cancer. Independent sample t test or χ2 test were used to compare the differences in clinical features between T1-2 and T3-4 patients in the training set, and the features with statistical significance were combined to establish a clinical model. Two radiomic signatures and clinical features were combined to construct a clinical-radiomics model and generate a nomogram. The area under the receiver operating characteristic curve (AUC) was used to evaluate the efficacy of each model in differentiating stage T1-2 from stage T3-4 gastric cancer. The calibration curve was used to evaluate the consistency between the T stage predicted by the nomogram and the actual T stage of gastric cancer. And the decision curve analysis was used to evaluate the clinical net benefit of treatment guided by the nomogram and by the clinical model. Results:There were significant differences in CT-T stage and CT-N stage between T1-2 and T3-4 patients in the training set ( χ2=10.59, 15.92, P=0.014, 0.001) and the clinical model was established. After screening and dimensionality reduction, the 5 features from primary gastric cancer and the 6 features from the adipose tissue outside the gastric wall beside cancer established the radiomic models respectively. In the training set and the test set, the AUC values of the primary gastric cancer radiomic model were 0.864 (95% CI 0.820-0.908) and 0.836 (95% CI 0.762-0.910), and the adipose tissue outside the gastric wall beside cancer radiomic model were 0.782 (95% CI 0.731-0.833) and 0.784 (95% CI 0.702-0.866). The AUC values of the clinical model were 0.761 (95% CI 0.705-0.817) and 0.758 (95% CI 0.671-0.845), and the nomogram were 0.876 (95% CI 0.835-0.917) and 0.851 (95% CI 0.781-0.921). The calibration curve reflected that there was a high consistency between the T stage predicted by the nomogram and the actual T stage in the training set ( χ2=1.70, P=0.989). And the decision curve showed that at the risk threshold 0.01-0.74, a higher clinical net benefit could be obtained by using a nomogram to guide treatment. Conclusions:The CT radiomics features of primary gastric cancer lesions and the adipose tissue outside the gastric wall beside cancer can effectively distinguish T1-2 from T3-4 gastric cancer, and the combination of CT radiomic features and clinical features can further improve the prediction accuracy.

ObjectiveTo prepare oral nanoemulsions encapsulating essential oil from Alpinia zerumbet fructus（EOFAZ） and to investigate its pro-absorption effect in vitro and distribution in vivo. MethodThe proteoglycan conjugate polysaccharides of vinegar-processed Bupleuri Radix-bovine serum albumin（VBCP-BSA） was prepared by Maillard reaction of VBCP and BSA. Taking VBCP-BSA as emulsifier， vitamin B₁₂（VB₁₂） as absorption enhancer， and medium chain triglycerides mixed with EOFAZ as oil phase， the nanoemulsions loaded with EOFAZ was prepared by high energy emulsification method. The particle size， particle size distribution， surface Zeta potential， EOFAZ content and appearance and morphology of the nanoemulsions were characterized， and fluorescein tracer method was used to investigate the absorption effect of fluorescein-labeled EOFAZ nanoemulsions in vitro and their distribution in vivo. ResultVBCP-BSA was formed by Maillard reaction for 48 h with high grafting rate. Using VBCP-BSA as emulsifier， the homogeneous pink nanoemulsions was prepared and denoted as EOFAZ@VBCP-BSA/VB₁₂. The particle size of the nanoemulsions was less than 100 nm and the particle size distribution was uniform. The surface of the nanoemulsions was a weak negative charge， and the shape was spherical. The encapsulation rate of the nanoemulsions for EOFAZ was greater than 80%， which had a good absorption effect in vitro and could enhance liver accumulation after oral administration. ConclusionThe designed proteoglycan nanoemulsions can effectively load EOFAZ， promote oral absorption and enhance liver distribution， which can provide experimental basis for the development of oral EOFAZ liver protection preparations.

Objective To investigate the prevalence of tension-type headache(TTH)in children and adolescents aged 0-19 years globally in 1990-2021,and to provide a basis for the prevention and treatment of TTH.Methods Based on the Global Burden of Disease Study data,the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years,with different sexes,age groups,sociodemographic index(SDI)regions and countries/territories.Results The age-standardized prevalence rate(ASPR)of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000,which was increased by 1.73%since 1990.The ASPR in females was slightly higher than that in males(1990:17 707.65/100 000 vs 16 403.78/100 000;2021:17 946.29/100 000 vs 16 763.09/100 000).The ASPR in adolescence was significantly higher than that in school-aged and preschool periods(1990:27 672.04/100 000 vs 10 134.16/100 000;2021:28 239.04/100 000 vs 10 059.39/100 000).Regions with high SDI exhibited a higher ASPR than the other regions,with significant differences in prevalence rates across different countries.From 1990 to 2021,there was a slight increase in global ASPR,with an average annual percentage change(AAPC)of 0.06%.Females experienced a smaller increase than males based on AAPC(0.04%vs 0.07%).There was reduction in ASPR in preschool and school-aged groups,with an AAPC of-0.02%,while there was a significant increase in ASPR in adolescence,with an AAPC of 0.07%.ASPR decreased in regions with low-middle and low levels of SDI,with an AAPC of-0.02%and-0.04%,respectively,while it increased in regions with middle SDI,with an AAPC of 0.24%.Conclusions There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally,with significant differences across sexes,age groups,SDI regions and countries/territories.