Objective To explore the feasibility and reference value of allogeneic lung transplantation and postoperative monitoring in miniature pigs for lung transplantation research. Methods Two miniature pigs (R1 and R2) underwent left lung allogeneic transplantation. Complement-dependent cytotoxicity tests and blood cross-matching were performed before surgery. The main operative times and partial pressure of arterial oxygen (PaO₂) after opening the pulmonary artery were recorded during surgery. Postoperatively, routine blood tests, biochemical blood indicators and inflammatory factors were detected, and pathological examinations of multiple organs were conducted. Results The complement-dependent cytotoxicity test showed that the survival rate of lymphocytes between donors and recipients was 42.5%-47.3%, and no agglutination reaction occurred in the cross-matching. The first warm ischemia times of D1 and D2 were 17 min and 10 min, respectively, and the cold ischemia times were 246 min and 216 min, respectively. Ultimately, R1 and R2 survived for 1.5 h and 104 h, respectively. Postoperatively, in R1, albumin (ALB) and globulin (GLB) decreased, and alanine aminotransferase increased; in R2, ALB, GLB and aspartate aminotransferase all increased. Urea nitrogen and serum creatinine increased in both recipients. Pathological results showed that in R1, the transplanted lung had partial consolidation with inflammatory cell infiltration, and multiple organs were congested and damaged. In R2, the transplanted lung had severe necrosis with fibrosis, and multiple organs had mild to moderate damage. The expression levels of interleukin-1β and interleukin-6 increased in the transplanted lungs. Conclusions The allogeneic lung transplantation model in miniature pigs may systematically evaluate immunological compatibility, intraoperative function and postoperative organ damage. The data obtained may provide technical references for subsequent lung transplantation research.

OBJECTIVE To investigate the effects and mechanisms of Lycium ruthenicum Murr. in improving sleep. METHODS Network pharmacology was employed to identify the active components of L. ruthenicum and their associated disease targets， followed by enrichment analysis. A caffeine‑induced zebrafish model of sleep deprivation was established ， and the zebrafish were treated with L. ruthenicum Murr. extract （LRME） at concentrations of 0.1， 0.2 and 0.4 mg/mL， respectively； 24 h later， behavioral changes of zebrafish and pathological alterations in brain neurons were subsequently observed. The levels of inflammatory factors [interleukin-6 （IL-6）， IL-1β， IL-10， tumor necrosis factor-α （TNF-α）]， oxidative stress markers [superoxide dismutase （SOD）， malondialdehyde （MDA）， glutathione peroxidase （GSH-Px）， catalase （CAT）]， and neurotransmitters [5- hydroxytryptamine （5-HT）， γ-aminobutyric acid （GABA）， glutamic acid （Glu）， dopamine （DA）， and norepinephrine （NE）] were measured. The protein expression levels of protein kinase B1 （AKT1）， phosphorylated AKT1 （p-AKT1）， epidermal growth factor receptor （EGFR）， B-cell lymphoma 2 （Bcl-2）， sarcoma proto-oncogene，non-receptor tyrosine kinase （SRC）， and heat shock protein 90α family class A member 1 （HSP90AA1） in the zebrafish were also determined. RESULTS A total of 12 active components and 176 intersecting disease targets were identified through network pharmacology analysis. Among these， apigenin， naringenin and others were recognized as core active compounds， while AKT1， EGFR and others served as key targets； EGFR tyrosine kinase inhibitor resistance signaling pathway was identified as the critical pathway. The sleep improvement rates in zebrafish of LRME low-， medium-， and high-dose groups were 54.60%， 69.03% and 77.97%， 开发。E-mail：hjp_yft@163.com respectively， while the inhibition ratios of locomotor distance were 0.57， 0.83 and 0.95， respectively. Compared with the model group， the number of resting counts， resting time and resting distance were significantly increased/extended in LRME medium- and high-dose groups （P＜0.05）. Neuronal damage in the brain was alleviated. Additionally， the levels of IL-6， IL-1β， TNF-α， MDA， Glu， DA and NE， as well as the protein expression levels of AKT1， p-AKT1， EGFR， SRC and HSP90AA1， were markedly reduced （P＜0.05）， while the levels of IL-10， SOD， GSH-Px， CAT， 5-HT and GABA， as well as Bcl-2 protein expression， were significantly elevated （P＜0.05）. CONCLUSIONS L. ruthenicum Murr. demonstrates sleep-improving effects， and its specific mechanism may be related to the regulation of inflammatory responses， oxidative stress， neurotransmitter balance， and the EGFR tyrosine kinase inhibitor resistance signaling pathway.

OBJECTIVE To explore the risk factors for acute kidney injury （AKI） in children with steroid-resistant nephrotic syndrome （SRNS） during tacrolimus treatment and construct a predictive model. METHODS A retrospective selection was made of 155 children diagnosed with SRNS and treated with tacrolimus at Xuzhou Children’s Hospital from January 1， 2022， to December 31， 2023， serving as the study subjects. Various clinical data of the children were collected by reviewing the medical record system. Children who developed AKI during medication were assigned to the AKI group （n＝26）， and those who did not develop AKI were assigned to the control group （n＝129）. Univariate and multivariate Logistic regression analyses were used to screen independent risk factors. A clinical predictive model was constructed based on significant variables， and nomogram， calibration curve， receiver operator characteristic curve， and decision curve were drawn to evaluate the model’s performance. RESULTS Univariate analysis showed that blood urea nitrogen （BUN）， serum creatinine （Scr）， estimated glomerular filtration rate （eGFR）， the maximum trough concentration （cmin） of tacrolimus， CYP3A5*3/*3 genotype， concurrent infection， concurrent hypertension， and the use of non-steroidal anti-inflammatory drugs were influencing factors for AKI in children with SRNS during tacrolimus treatment （P＜0.05）. Multivariate Logistic regression analysis revealed that BUN≥9.58 mmol/L， Scr≥125 μmol/L， eGFR＜37 mL/（min·1.73 m2）， tacrolimus maximum cmin≥11.26 ng/mL，CYP3A5*3/*3 genotype， concurrent infection， and concurrent hypertension were independent risk factors for AKI in children with SRNS during tacrolimus treatment （P＜0.05）. The constructed clinical predictive model had an area under the curve of 0.747， showing good agreement between predicted and actual AKI occurrence and demonstrating favorable clinical net benefit in predicting AKI in children. CONCLUSIONS Impaired baseline renal function （elevated BUN， elevated Scr， and decreased eGFR）， elevated maximum cmin of tacrolimus， CYP3A5*3/*3 genotype， concurrent infection， and hypertension during treatment are independent risk factors for AKI in children with SRNS during tacrolimus treatment. The established clinical predictive model provides a scientific basis for implementing risk stratification management.

Objective: To investigate the efficacy of magnesium-strontium co-doped hydroxyapatite mineralized collagen (MSHA/Col) in improving the bone repair microenvironment and enhancing bone regeneration capacity, providing a strategy to address the insufficient biomimetic composition and limited bioactivity of traditional hydroxyapatite mineralized collagen (HA/Col) scaffolds. Methods: A high-molecular-weight polyacrylic acid-stabilized amorphous calcium magnesium strontium phosphate precursor (HPAA/ACMSP) was prepared. Its morphology and elemental distribution were characterized by high-resolution transmission electron microscopy (TEM) and energy-dispersive spectroscopy. Recombinant collagen sponge blocks were immersed in the HPAA/ACMSP mineralization solution. Magnesium-strontium co-doped hydroxyapatite was induced to deposit within collagen fibers (experimental group: MSHA/Col; control group: HA/Col). The morphological characteristics of MSHA/Col were observed using scanning electron microscopy (SEM). Its crystal structure and chemical composition were analyzed by X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The mineral phase content was evaluated by thermogravimetric analysis. The scaffold's porosity, ion release, and in vitro degradation performance were also determined. For cytological experiments, CCK-8 assay, live/dead cell staining, alkaline phosphatase staining, alizarin red S staining, RT-qPCR, and western blotting were used to evaluate the effects of the MSHA/Col scaffold on the proliferation, viability, early osteogenic differentiation activity, late mineralization capacity, and gene and protein expression levels of key osteogenic markers [runt-related transcription factor 2 (Runx2), collagen type Ⅰ (Col-Ⅰ), osteopontin (Opn), and osteocalcin (Ocn)] in mouse embryonic osteoblast precursor cells (MC3T3-E1). Results: HPAA/ACMSP appeared as amorphous spherical nanoparticles under TEM, with energy spectrum analysis showing uniform distribution of carbon, oxygen, calcium, phosphorus, magnesium, and strontium elements. SEM results of MSHA/Col indicated successful complete intrafibrillar mineralization. Elemental analysis showed the mass fractions of magnesium and strontium were 0.72% (matching the magnesium content in natural bone) and 2.89%, respectively. X-ray diffraction revealed characteristic peaks of hydroxyapatite crystals (25.86°, 31°-34°). Infrared spectroscopy results showed characteristic absorption peaks for both collagen and hydroxyapatite. Thermogravimetric analysis indicated a mineral phase content of 78.29% in the material. The scaffold porosity was 91.6% ± 1.1%, close to the level of natural bone tissue. Ion release curves demonstrated sustained release behavior for both magnesium and strontium ions. The in vitro degradation rate matched the ingrowth rate of new bone tissue. Cytological experiments showed that MSHA/Col significantly promoted MC3T3-E1 cell proliferation (130% increase in activity at 72 h, P < 0.001). MSHA/Col exhibited excellent efficacy in promoting osteogenic differentiation, significantly upregulating the expression of osteogenesis-related genes and proteins (Runx2, Col-Ⅰ, Opn, Ocn) (P < 0.01). Conclusion The MSHA/Col scaffold achieves dual biomimicry of natural bone in both composition and structure, and effectively promotes osteogenic differentiation at the genetic and protein levels, breaking through the functional limitations of pure hydroxyapatite mineralized collagen. This provides a new strategy for the development of functional bone repair materials

ObjectiveTo investigate the effect and mechanism of polysaccharide in water extract of Cyclocarya paliurus （CPWP） in inhibiting benign prostatic hyperplasia （BPH）. MethodsCPWP was obtained by heating reflux， aqueous extraction， alcohol precipitation， and freeze drying. The chemical composition and structural properties of CPWP were analyzed by high performance liquid chromatography with 1-pheny-3-methyl-5-pyrazolone pre-column derivatization and infrared spectroscopy. Male SD rats were randomly assigned into control， model， finasteride （ig 5 mg·kg^-1）， and low-， medium-， and high-dose （ig 50， 75， 100 mg·kg^-1） CPWP groups， with 8 rats in each group. The BPH model was established by subcutaneously injecting propionate testosterone in castrated rats. The rats in the drug intervention groups were administrated with corresponding drugs， and those in the control group were administrated with an equal volume of normal saline each day. After 30 consecutive days， the rats were sacrificed， and the prostate tissue was separated and weighed. The effects of drug interventions on the body weight， prostate wet weight， and prostate index of rats were examined. The prostate tissue was stained with hematoxylin-eosin （HE） for observation of pathological changes. Enzyme-linked immunosorbent assay was employed to measure the level of dihydrotestosterone （DHT）， and immunohistochemical staining was used to detect the expression of steroid 5 alpha-reductase 2 （SRD5A2） and Ki67 in the prostate tissue. ResultsCPWP was identified as a saccharide， with characteristic absorption peaks of saccharides. CPWP showed the total sugar content of 44.15% and molecular weight within the range of 5.5-78.8 kDa， being composed of mannose， rhamnose， galacturonic acid， glucose， galactose， xylose， and arabinose. Compared with the control group， the model group had significantly increased prostate wet weight and prostate index （P<0.01）， thick and tall prostate epithelial cells， increased internal wrinkles， papillary expansion into the cavity， an elevation in DHT level in the serum， and up-regulated expression of SRD5A2 and Ki67 in the prostate tissue （P<0.05， P<0.01）. Compared with the model group， both the finasteride and CPWP groups showed decreases in prostate wet weight and prostate index （P<0.05， P<0.01）， thinned prostate epithelial cells， with only a small portion of internal wrinkles and papillary expansion into the cavity， shortened papillary protrusions， lowered DHT level in the serum， and down-regulated expression of SRD5A2 and Ki67 in the prostate tissue （P<0.01）. Moreover， CPWP exerted effects in a dose-dependent manner. ConclusionCPWP inhibits BPH by regulating the expression of SRD5A2.

This paper comprehensively discusses on the potential neurobiological mechanisms of acupuncture in the treatment of tobacco dependence， focusing on three important aspects， including acupuncture's regulation of tobacco dependence behavior， effects of acupuncture on withdrawal syndrome， and the role of acupuncture in preventing relapse. It is found that acupuncture can inhibit drug-seeking behavior by regulating the reward pathway and related neurons， such as dopamine， thus modulating tobacco dependence behavior. It also alleviates withdrawal symptoms by improving the oral environment of smokers and reducing negative emotions after quitting. Furthermore， acupuncture can prevent relapse by decreasing brain network activity related to smoking cravings and improving cognitive brain functions like addiction memory. Currently， research on the specific neurobiological mechanism of acupuncture in treating tobacco dependence and the involved neural circuits is limited. Future research directions are proposed， including the evaluation of clinical effects， exploration of specific therapeutic mechanisms， investigation of brain pathology， and strengthening the exploration of brain functions. Additionally， combining modern technologies to clarify the neural circuits involved in acupuncture intervention will provide a basis for acupuncture treatment of tobacco addiction.

OBJECTIVE To establish a method for simultaneous determination of 7 anti-tumor drugs （irinotecan， capecitabine， paclitaxel， docetaxel， tamoxifen， letrozole and methotrexate） in human plasma and apply it to the clinic. METHODS After precipitating with a methanol-acetonitrile mixture （1∶ 1， V/V） containing 0.1% formic acid， liquid chromatography-tandem mass spectrometry （LC-MS/MS） was used to determine the plasma concentration， using deuterium isotopes of each analyte as internal standards. The chromatography was performed on the Agilent Eclipse Plus C18 column with a gradient elution of water （containing 0.1% formic acid+0.04% 5 mmol/L ammonium formate） as mobile phase A and acetonitrile （containing 0.1% formic acid） as mobile phase B. The flow rate was 0.6 mL/min， and the column temperature was set at 40 ℃ . The sample size was 10 μL， and the analysis lasted for 5.5 min. Electrospray ionization was used in positive and negative ion mode， and multiple reaction monitoring mode was used. The ion pairs used for quantitative analysis were m/z 587.1→167.1 （irinotecan）， m/z 360.1→244.1 （capecitabine）， m/z 876.4→308.0 （paclitaxel）， m/z 830.3→304.2 （docetaxel）， m/z 372.1→129.1 （tamoxifen）， m/z 284.1→242.1 （letrozole）， and m/z 455.0→ 308.0 （methotrexate）. A total of 97 patients with malignant tumors in our hospital were selected to measure the plasma concentrations of 7 anti-tumor drugs using the above method. RESULTS The linear ranges of irinotecan， capecitabine， paclitaxel， docetaxel， tamoxifen， letrozole and methotrexate were 2-1 000 ng/mL （r＝0.994 3）， 20-10 000 ng/mL （r＝0.997 5）， 2-1 000 ng/mL （r＝0.997 9）， 1-500 ng/mL （r＝0.995 8）， 1-500 ng/mL （r＝0.995 2）， 1-500 ng/mL （r＝0.996 4）， 10-5 000 （r＝0.997 7）， respectively. The quantitative lower limits were 2， 20， 2， 1， 1， 1 and 10 ng/mL； RSDs of intra-assay precision were 0.08%-14.86% （n＝6）. RSDs of inter-batch precision were 1.51%-11.55% （n＝3）， and the accuracies were 89.17%-114.93% （n＝6）. The matrix effects ranged from 89.89%-119.74% （n＝6）. RSDs of the stability tests were 1.98%-14.88% （n＝6）. The results of E-mail：hangpengzhou@163.com clinical application showed， the average plasma concentrations of irinotecan， capecitabine， paclitaxel and docetaxel were 704.09， 909.40， 36.45， 150.43 ng/mL， respectively. The values of the coefficient of variation were 25.24%， 62.65%， 122.69%， and 92.27%. CONCLUSIONS The established LC-MS/MS method is simple and rapid， and can be used for the simultaneous determination of 7 commonly used anti-tumor drugs in the plasma of patients with malignancy.

The liver is closely associated with inflammation and the redox response， and inflammation is the body's innate defense system for clearing away harmful stimuli and participating in the liver's wound-healing response.Oxidative stress is associated with the activation of inflammatory pathways， and sustained inflammation and the corresponding regenerative wound healing response can induce fibrosis， cirrhosis， progression to end-stage liver disease or hepatocellular carcinoma， and ultimately death.Some "medicine and food homology" traditional Chinese medicine has been used in clinical effect， showing the ability to protect the liver.This paper reviewed the relationship between liver and oxidative stress response and inflammation response， and sorted out 110 "medicine and food same origin" traditional Chinese medicines based on the Chinese Pharmacopoeia（2020 edition） and the Chinese materia medica.The results showed that common floweringqince fruit， licorice root， cassia seed， emblic，seabuckthorn fruit，Chinese date， honeysuckle， ginger， cape jasmine fruit， platycodon root， lotus leaf， dandelion， reed root， honey， mountain honeysuckle， milkvetch root， glossy ganoderma， Gastrodia gastrodia and eucommia leaf were recorded to have liver protection effects.The liver protection mechanism is mainly anti-inflammatory， antioxidant and lipid peroxidation inhibition. Some Chinese herbs can also play a liver protection role by inhibiting the growth of hepatitis virus and liver cancer cells and regulating bile acid metabolism.In addition， the biological mechanism of its liver protection effect through antioxidant and anti-inflammatory effects in animal experiments was analyzed， and it was found that it plays a role through multiple pathways and multiple targets， providing new ideas for the role of "medicine and food homology" traditional Chinese medicine in the treatment strategy of liver diseases.

The liver is closely associated with inflammation and the redox response， and inflammation is the body's innate defense system for clearing away harmful stimuli and participating in the liver's wound-healing response.Oxidative stress is associated with the activation of inflammatory pathways， and sustained inflammation and the corresponding regenerative wound healing response can induce fibrosis， cirrhosis， progression to end-stage liver disease or hepatocellular carcinoma， and ultimately death.Some "medicine and food homology" traditional Chinese medicine has been used in clinical effect， showing the ability to protect the liver.This paper reviewed the relationship between liver and oxidative stress response and inflammation response， and sorted out 110 "medicine and food same origin" traditional Chinese medicines based on the Chinese Pharmacopoeia（2020 edition） and the Chinese materia medica.The results showed that common floweringqince fruit， licorice root， cassia seed， emblic，seabuckthorn fruit，Chinese date， honeysuckle， ginger， cape jasmine fruit， platycodon root， lotus leaf， dandelion， reed root， honey， mountain honeysuckle， milkvetch root， glossy ganoderma， Gastrodia gastrodia and eucommia leaf were recorded to have liver protection effects.The liver protection mechanism is mainly anti-inflammatory， antioxidant and lipid peroxidation inhibition. Some Chinese herbs can also play a liver protection role by inhibiting the growth of hepatitis virus and liver cancer cells and regulating bile acid metabolism.In addition， the biological mechanism of its liver protection effect through antioxidant and anti-inflammatory effects in animal experiments was analyzed， and it was found that it plays a role through multiple pathways and multiple targets， providing new ideas for the role of "medicine and food homology" traditional Chinese medicine in the treatment strategy of liver diseases.

ObjectiveTo investigate the effect of laminin subunit α3 （LAMA3） on the epithelial-mesenchymal transition （EMT）， invasion， and metastasis abilities of pancreatic cancer （PC）. MethodsA comprehensive analysis was performed for tumor- and EMT-related databases to identify the EMT genes associated with PC， especially LAMA3. The methods of qRT-PCR and Western blot were used to measure the expression level of LAMA3 in PC tissue and cell lines； immunofluorescence assay was used to determine the localization of LAMA3 in PANC-1 cells； Transwell assay was used to investigate the effect of LAMA3 on the invasion and migration abilities of PC cells. The t-test was used for comparison of continuous data between groups. ResultsThe analysis of the TCGA database identified 3 EMT-related oncogenes for PC， i.e.， LAMA3， AREG， and SDC1. The LASSO-Cox regression model showed that LAMA3 had the most significant impact on the prognosis of PC （risk score=0.256 1×LAMA3+0.043 1×SDC1+0.071 4×AREG）. The Cox model and nomogram showed that the high expression of LAMA3 was an independent risk factor for the poor prognosis of PC （hazard ratio=1.32， 95% confidence interval： 1.07‍ ‍—‍ 1.62， P<0.01）. Experimental results showed that there was a significant increase in the expression of LAMA3 in pancreatic cancer tissue compared with the normal pancreatic tissue. Compared with the HPDE cell line， there were varying degrees of increase in the expression of LAMA3 in pancreatic cancer AsPC-1， BxPC-3， PANC-1， MIA PaCa-2， and SW1990 cell lines， with the highest expression level in PANC-1 cells. The enrichment analysis showed that LAMA3 was associated with the biological processes and signaling pathways such as EMT， collagen metabolism， extracellular matrix degradation， the TGF-β pathway， and the PI3K pathway. After the knockdown of LAMA3， there were significant reductions in the expression levels of N-Cadherin， Vimentin， and Snail， while there was a significant increase in the expression level of E-Cadherin. Transwell assay showed that there were significant reductions in the invasion and migration abilities of PANC-1 cells after the knockdown of LAMA3. ConclusionLAMA3 is highly expressed in PC and can promote the EMT， invasion， and migration of PC cells， and therefore， LAMA3 may be used as a novel diagnostic marker and a new therapeutic target for PC.