The immunomodulatory， repair， and regeneration-promoting functions of mesenchymal stem cells make them one of the potential treatment methods for liver diseases. At present， viral and non-viral delivery methods have been developed to genetically modify mesenchymal stem cells， and gene modification can promote the survival， homing， and cytokine secretion of mesenchymal stem cells， thereby enhancing the ability of mesenchymal stem cells to treat liver diseases. This article mainly summarizes the research advances in gene-modified mesenchymal stem cells in the treatment of liver diseases， in order to provide new insights and strategies for the clinical treatment of liver diseases.

ObjectiveTo study the effect of Bufei Tongbi decoction on pulmonary fibrosis in diabetic rats via the transforming growth factor-β₁ （TGF-β₁）/phosphorylated Smad family member 3 （p-Smad3） signaling pathway. MethodsStreptozotocin （60 mg·kg^-1） and bleomycin （24.80 U·kg^-1） were used to prepare the rat model of diabetes with pulmonary fibrosis by intratracheal injection. Sixty rats were randomly assigned into blank， model， low-， medium-， and high-dose （3.98， 7.95， and 15.90 g·kg^-1， respectively） Bufei Tongbi decoction， and pirfenidone （0.36 mg·kg^-1） groups （n=10）. The successfully modeled rats in each group were administrated with corresponding agents once per day for four consecutive weeks. After drug administration， fasting blood glucose and lung function indicators were measured. Chemical immunoassay was employed to determine the serum levels of hydroxyproline （Hyp）， hyaluronic acid （HA）， and laminin （LN）. The lung index was determined by the wet and dry methods. The pathological changes in the lung tissue were observed by hematoxylin-eosin （HE） staining， and the degree of fibrosis was detected by Masson staining. The mRNA and protein levels of TGF-β₁， p-Smad3， Smad3， α-smooth muscle actin （α-SMA）， collagen type Ⅰ alpha 1 （Col1A1）， and fibronectin were determined by PCR and Western blotting， respectively. ResultsCompared with the blank group， the model group showed alveolar septa thickening， obvious thickening of the basement membrane of pulmonary blood vessels， severe destruction of the alveolar structure， structural disarrangement of the lung parenchyma， and an increase in the proportion of inflammatory cell infiltration in the lung tissue， together with a large amount of blue collagen deposition and a large amount of collagen fibroplasia in the bronchial wall， vessel wall， interstitium， and alveolar wall， which indicated severe fibrosis. Bufei Tongbi decoction groups and the pirfenidone group showed lower fasting blood glucose level （P<0.05） and higher forced vital capacity （FVC）， cytoplasmic dynein （Cydn）， FEV_0.3/FEV ratio， and lung index （P<0.05） than the model group. Moreover， these groups demonstrated alleviated lung fibrosis， elevated Hyp， HA， and LN levels， down-regulated mRNA levels of α-SMA， Col1A1， and fibronectin， and down-regulated protein levels of TGF-β₁， Smad3， p-Smad3， α-SMA， Col1A1， and fibronectin （P<0.05）. ConclusionBufei Tongbi decoction can inhibit pulmonary fibrosis in diabetic rats by inhibiting the TGF-β₁/p-Smad3 signaling pathway.

Objective Advances in synthetic DNA technology have made it much easier to fake human DNA samples.There are literature reports that fake human DNA can be synthesized by different methods and implanted in the field to confuse the investigation or mislead the trial.Therefore,distinguishing authentic human DNA from synthetic DNA and performing individual identification has become a critical scientific challenge.Methods We define a novel composite genetic marker(methylation-microhaplotype)by combining CpG sites stably hypermethylated or hypomethylated in natural human DNA and nearby immediately adjacent microhaplotype sites.A total of 19 locis were obtained according to the screening criteria,and a composite detection system for methylation-microhaplotypes was established using MPS technology.Random volunteer DNA samples were extracted and synthetic DNA samples were prepared based on whole genome amplification techniques.Population DNA samples were analyzed to evaluate forensic parameters and methylation variability of the methylation-microhaplotype markers.Comparative analyses of human and synthetic DNA were conducted to assess the markers'ability to discriminate between the two and to detect/type both components in mixed mixed samples.Results The composite detection system composed of 19 locis demonstrated high individual identification ability,achieving a cumulative individual identification probability of 0.999 999 999 996 86.12 hypermethylated locis and 7 hypomethylated locis had relatively stable methylation levels in 57 human DNA samples.According to the allele methylation rate(Ram)value,the system can effectively identify natural and synthetic DNA samples.Meanwhile,for mixed DNA samples,the presence of human and synthetic DNA samples can be found and genotyped.Conclusion Methylation-microhaplotype genetic markers,which can discover human DNA and synthetic DNA and can detect the presence and genotyping of them from mixed samples,is a potential useful tool for forensic DNA analysis.

Objective Melatonin has been shown to have neuroprotective effects.This study is aimed at observing the effects of copper deposition on cognitive function in a toxic milk(TX)mouse model of Wilson disease(WD),and investigating the effects and mechanisms of action of Gandou Bushen Decoction(GDBSD)on melatonin synthesis and pineal function in the WD model mice.Methods A total of 30 homozygous TX mice were randomly assigned to 3 groups(n=10 in each group),including a WD group,a GDBSD group,and a dimercaptosuccinic acid(DMSA)group.A total of 10 DL mice were included in the normal control(NC)group.The structure and copper content of pineal gland tissues,oxidative stress and apoptosis-related markers,and serum melatonin levels were evaluated using hematoxylin-eosin(HE)staining,enzyme-linked immunosorbent assay(ELISA),flow cytometry,and Western blot.Results Compared with the NC group,the WD group exhibited decreased learning and cognitive abilities(P＜0.05),damaged pineal gland structure,increased copper content,reactive oxygen species(ROS)levels,and mitochondrial damage rate in the pineal gland(P＜0.01),altered levels of melatonin and oxidative stress-related markers(P＜0.05),upregulated expression levels of pro-apoptotic proteins Bax and Caspase-3,and decreased expression of the anti-apoptotic protein Bcl-2(P＜0.01).After treatment with GDBSD and DMSA,the SIRT3/FOXO3α signaling pathway was activated,the copper content in the pineal gland was reduced,and oxidative stress and apoptosis-related damages were improved,leading to an improvement in learning and memory abilities(P＜0.05).Conclusion GDBSD can alleviate cognitive impairments in WD mice caused by pineal gland copper deposition by inhibiting oxidative stress and apoptosis in the pineal gland.The underlying molecular mechanism is associated with the regulation of the SIRT3/FOXO3α signaling pathway.

Objective To explore the correlation between the rs7296288 single nucleotide polymorphism(SNP)of the DHH gene and the onset of depression.Methods From March 2018 to December 2019,480 patients with depression in Sichuan Provincial People's Hospital,Jining Mental Hospital,Yunnan Mental Health Center were collected as the case group,and 329 patients without depression were collected as the control group.Peripheral blood samples were collected and DNA was extracted.After multiple amplification and high-throughput sequencing,statistical software was used to analyze the relevant data.Results The rs7296288 polymorphism of the DHH gene,the AA genotype was 32.9％in the control group and 36.7％in the case group,with no statistical difference;the AC genotype was 52.8％in the control group and 47.7％in the case group,with no statistical difference;the CC genotype was 14.3％in the control group and 15.6％in the case group,with no statistical difference.The co-dominant,dominant,and recessive statistical models were not statistically significant.Subgroup analysis of the degree of depressive episodes,suicide attempts,and first-episode patients did not find an association between the rs7296288 SNP locus of the DHH gene and the clinical features of depression,that is,the SNP rs7296288 of the DHH gene had no significant correlation with depression.Conclusion The rs7296288 polymorphism of DHH gene is not correlated with the pathogenesis of depression.

Objective To explore the prognostic value of quantitative parameters of intra-voxel incoherent motion-diffusion weighted imaging(IVIM-DWI)in predicting the prognosis of patients with Kirsten rats arcomaviral oncogene homolog(KRAS)mutation non-small cell lung cancer(NSCLC)undergoing first-line concurrent chemoradiotherapy.Methods A total of 139 patients with KRAS-mutated NSCLC were selected as the research subjects,and all of them received first-line concurrent chemoradiotherapy.Based on follow-up results(with all-cause mortality within one year defined as the endpoint event),patients were divided into favorable prognosis group and poor prognosis group.General data and IVIM-DWI quantitative parameters[apparent diffusion coefficient(ADC),diffusion coefficient(D),pseudo-diffusion coefficient(D*)and perfusion fraction(f)]were compared be-tween the two groups.Cox regression analysis was employed to identify factors influencing poor prognosis in patients with KRAS-mutated NSCLC.Receiver operating characteristic(ROC)curves were plotted to evaluate the prognostic predictive value of IVIM-DWI quantitative parameters.Kaplan-Meier(K-M)survival curves and the Log-rank test were used to analyze the relationships between IVIM-DWI quantitative parameters and prognosis in patients with KRAS-mutated NSCLC.Results Among the 139 patients,four were lost during follow-up,resulting in a survival rate of 69.63％(94/135).The favorable prognosis group comprised 94 patients,while the poor prognosis group included 41 pa-tients.There were statistically significant differences in the types of KRAS mutations,the best thera-peutic effect after treatment,and smoking history between the two groups(P＜0.05).After adjus-ting for confounding factors,ADC,D,D* and f values were identified as influencing factors for poor prognosis in patients with KRAS-mutated NSCLC(P＜0.05).The area under the curve(AUC)for the combined prediction of prognosis using ADC,D,D* and f values was 0.933,which was higher than the AUC for each parameter alone.Patients with low ADC,D,D* and f values exhibited sig-nificantly lower survival rates compared to those with high values(P＜0.05).Conclusion IVIM-DWI quantitative parameters,including ADC,D,D* and f values,are influencing factors for the prognosis of first-line concurrent chemoradiotherapy in patients with KRAS-mutated NSCLC.The combined predictive performance of these parameters is high,offering guidance for clinical diagnosis and treatment and potentially improving disease prognosis.

Bovine rotavirus(BRV)is an important pathogen causing diarrhea in calves.To understand the genomic charac-teristics and genetic variations in bovine rotavirus,and to further enrich data on the biological characteristics of rotavirus,we aimed to amplify 11 gene segments of the isolated and cultured G6P[1]bovine rotavirus BLL strain,perform whole genome se-quencing,and analyze the molecular characteristics.MEGA7.0 and DNAMAN software were used for homology and typing a-nalysis,and the whole genome phylogenetic tree was constructed to analyze genetic evolution relationships.The complete geno-type of the BLL strain was G6-P[1]-I2-R2-C2-M2-A3-N2-T6-E2-H3.Phylogenetic analysis of the VP7 and VP4 genes of the BLL strain showed that the VP7 gene had the highest homology with RVA/Cow-wt/HB01/China/2021,and the VP4 gene of the BLL strain was in the same branch as RVA/Human-tc/ISR/Ro8059/1995.From the sequence alignment of VP8*amino acids,the sialic acid domain of the BLL strain was found to be similar to that in other P[1]strains,but different from those in other types of strains,except for residue 189,which was the same as that in Ro8059 but different from that in other strains.The results suggested that the BLL strain might potentially infect humans.Therefore,continued monitoring and study of the biological characteristics of this strain are necessary to provide more information and evidence supporting further research on the cross-species transmission of group A rotavirus in China.

Objective To explore the effect of hyperbaric oxygen combined with synchronous brain bionic electrical stimulation on patients with stroke-related sleep disorders.Methods From November,2023 to November,2024,a total of 68 stroke patients with stroke-related sleep disorders ad-mitted to Huashan Hospital,Fudan University were selected.They were randomly divided into control group(n=34)and experimental group(n=34).The control group received routine hyperbaric oxygen therapy,while the ex-perimental group received routine hyperbaric oxygen therapy combined with synchronous brain bionic electrical stimulation inside the chamber,for four weeks.Pittsburgh Sleep Quality Index(PSQI),sleep-monitoring wrist-bands,Self-rating Anxiety Scale(SAS)and Self-rating Depression Scale(SDS)were used to assess the outcomes before and after treatment..Results Four patients in the control group and one in the experimental group dropped out.After treatment,the scores of each factors of PSQI decreased in both groups(t>2.693,P<0.05),and were lower in the experimental group than in the control group(t>2.699,P<0.01),expect hypnotic drug use(P>0.05);the total sleep time,deep sleep time and rapid eye movement sleep time became longer in both groups(|t|>7.270,P<0.001),and they were longer in the experimental group than in the control group(|t|>5.712,P<0.001);the scores of SAS and SDS decreased in both groups(t>9.530,P<0.001),and they were less in the experimental group than in the control group(t>4.740,P<0.001).Conclusion Synchronous brain bionic electrical stimulation in hyperbaric oxygen chamber could effectively prolong the total sleep time,deep sleep time and rapid eye movement time of patients with stroke-related sleep disorders,re-lieve anxiety and depression after stroke,and improve sleep quality.

Objective:To investigate the relationship between blood pressure trajectories and blood pressure variability with the risk of target organ damage in Chinese population from childhood to middle age.Methods:This study is a population-based, long-term follow-up cohort study. Participants who had their blood pressure measured at least 5 times in the Hanzhong Adolescent hypertension cohort from 1987 to 2023 were included in this study. Group-based trajectory modeling was used to identify different systolic and diastolic blood pressure trajectories, and the subjects were divided into low-increasing group, moderate-increasing group and high-increasing group according to blood pressure trajectories. Blood pressure variability was assessed using standard deviation (SD), variability independent of the mean (VIM), and average real variability (ARV). Target organ damage was evaluated during the final follow-up in 2023 (middle age). Logistic regression models were used to analyze the relationship between blood pressure trajectories and blood pressure variability with the risk of target organ damage.Results:A total of 2 447 subjects were included, with a median age of 48 years, of whom 1 373 were male (56.1%). Based on systolic blood pressure, 868 were in the low-increasing group, 1 238 in the moderate-increasing group, and 341 in the high-increasing group. For diastolic blood pressure, the distribution was 894, 1 263 and 290, respectively. Compared with the low-increasing group of systolic blood pressure, the moderate-increasing group (arteriosclerosis: OR=4.14, 95% CI 2.96-5.79; proteinuria: OR=2.06, 95% CI 1.38-3.07; left ventricular hypertrophy: OR=1.68, 95% CI 1.00-2.82) and high-increasing group (arterial stiffness: OR=15.44, 95% CI 10.14-23.50; proteinuria: OR=5.80, 95% CI 3.63-9.29; left ventricular hypertrophy: OR=2.93, 95% CI 1.55-5.53) had a higher risk of target organ damage (all P<0.005). The moderate-increasing group of diastolic blood pressure had a higher incidence of arterial stiffness ( OR=3.72, 95% CI 2.69-5.12) and proteinuria ( OR=1.67, 95% CI 1.15-2.42) than the low-increasing group (all P<0.005), while the high-increasing group had a significantly higher risk of all type of target organ damage compared to the low-increasing group (arterial stiffness: OR=10.84, 95% CI 7.08-16.61; proteinuria: OR=3.72, 95% CI 2.31-5.99; left ventricular hypertrophy: OR=2.38, 95% CI 1.23-4.59; all P<0.005). Additionally, higher systolic blood pressure variability was associated with an increased incidence of arterial stiffness (SD: OR=2.25, 95% CI 1.96-2.57; VIM: OR=1.64, 95% CI 1.45-1.86; ARV: OR=1.70, 95% CI 1.50-1.93) and proteinuria (SD: OR=1.65, 95% CI 1.44-1.89; VIM: OR=1.41, 95% CI 1.22-1.63; ARV: OR=1.45, 95% CI 1.26-1.67; all P<0.005). The results for diastolic blood pressure variability indicators were similar to those for systolic blood pressure. Conclusion:Early-life blood pressure trajectories are predictive of target organ damage risk in middle age. Higher blood pressure variability is related to an increased risk of arterial stiffness and proteinuria, but was less associated with left ventricular hypertrophy. Focusing on the risk of high blood pressure early in life can help prevent the occurrence of target organ damage in middle age.

Due to advances in treatment methods, the survival rate and quality of life of cancer patients have been improved. Radiation-induced vascular injury (RIVI) is a common adverse reaction following radiotherapy, mainly manifested as capillary injury and atherosclerosis in the irradiated area. Radiotherapy induces RIVI in the cerebral vessels, carotid arteries, coronary arteries, and large arteries through mechanisms such as endothelial cell injury and senescence, oxidative stress and inflammatory responses, angiogenesis, and vascular remodeling. In this review research progress in the pathological features, pathophysiological mechanisms, clinical manifestations, prevention and treatment strategies of RIVI was summarized, aiming to provide insights for future research on RIVI.