Derived from embryonic stem cells, induced pluripotent stem cells, or adult stem cells, liver organoids not only mimic the tissue structure, gene expression patterns, and genetic characteristics of in vivo liver but also demonstrate significant potential in simulating liver diseases, drug screening, precision medicine, and regenerative medicine. This technology is particularly valuable in modeling various conditions such as malignant liver tumors, liver fibrosis, cirrhosis, viral hepatitis, and a range of genetic and metabolic liver diseases. However, challenges remain in enhancing the derivation and proliferation efficiency of organoids, constructing immune microenvironments, developing functional vascular networks, and achieving standardization and automation in the organoid preparation process. Looking forward, with continued technological advancements and innovations, these issues are expected to be resolved, paving the way for liver organoids to play a more substantial role in clinical and research applications, ultimately contributing significantly to public health. This review comprehensively explores the development and extensive applications of liver organoid technology in the field of biomedical science. The aim is to inform subsequent research.

Objective:To explore the clinical characteristics and related socio-demographic factors of schizo-phrenia patients with different ages of onset.Methods:Totally 2 016 patients with schizophrenia aged 15 to 70 were selected according to the diagnostic criteria for schizophrenia in the Diagnostic and Statistical Manual of Mental Disorders,Fifth Edition.All of the patients were interviewed by psychiatrists using the Mini International Neuropsy-chiatric Interview to diagnose schizophrenia,Clinical-Rated Dimensions of Psychosis Symptom Severity(CRDPSS)and the Positive and Negative Syndrome Scale(PANSS)to assess symptoms.The cut-off points were 18 and 25 years old for three age groups,i.e.early onset(EOS),youth onset(YOS)and adult onset(AOS).Statistical analy-ses were performed by analysis of variance Pearson correlation analysis,and multivariate linear regression.Results:The early-onset patients had the highest total PANSS score(73.8±28.0)and CRDPSS score(11.7±5.4).Fe-male gender,high education level,Han ethnicity,early onset age,and slower onset of illness were negatively corre-lated with the total and dimension score of PANSS scale and CRDPSS scale(standardized regression coefficient:0.04-0.47),and income level and smoking were negatively correlated with those score(standardized regression coefficient:-0.04--0.14).Conclusion:Early-onset schizophrenia patients have more severe symptoms,and fe-male,high education level,early-onset disease,and chronic onset are the risk factors of symptom severity in patients with schizophrenia.

Objective:To explore the flora characteristics and differences of esophageal tissues between elderly esophageal squamous cell carcinoma (ESCC) patients and young and middle-aged ESCC patients, so as to assist in studying the potential biomarkers of elderly ESCC patients.Methods:In this study, a retrospective study was adopted. 72 ESCC patients diagnosed in Taihe Hospital, Shiyan City, Hubei Province from July 2018 to July 2019 were selected, including 49 patients in the elderly group (≥ 60 years old, 40 males and 9 females), 23 patients in the young and middle-aged group (<60 years old, 21 males and 2 females). In the same period, 20 healthy persons without abnormal gastroscopy in endoscopy center were selected as the control group (aged 35-78 years old, median age 57 years old, 16 males and 4 females). The genomic DNA was extracted from the affected esophageal tissues of patients with ESCC and the middle esophageal samples of the control group. The V4 hypervariable region of bacterial 16SrRNA gene sequence was amplified. Illumina HiSeq sequencing technology was adopted. The flora characteristics of elderly, young and middle-aged ESCC patients was compared and analyzed. QIIME and Rstudio software were used to analyze the sequence data, and nonparametric Kruskal-Wallis test or Wilcoxon rank sum test were used for statistical methods.Results:Shannon index [5.17 (4.53, 5.95) vs. 4.79 (3.74, 5.97)], Simpson index [0.94 (0.91, 0.96) vs. 0.92 (0.83, 0.96)] and Chao1 index [343.55 (259.76, 570.59) vs. 329.16 (268.88, 648.00)] were similar in flora of two groups, and there was no significant difference ( Z=-0.791, -1.057, -0.380, all P>0.05). There was no significant difference in β-diversity between the elderly group and the young and middle-aged group (PC1=19.14%, PC2=6.95%, PPC1=0.67, PPC2=0.42). At the phyla level, the top 5 phyla in abundance were as follows: Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria in the young and middle-aged group, while the top 5 phyla in abundance were as follows: Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria and Actinobacteria in the elderly group; the significant difference between the two groups was Fusobacteria ( Q=0.596, P<0.05). At the genus level, the top 5 genera in the young and middle-aged group in abundance were as follows: Prevotella, Bacteroides, Streptococcus, Selenomonas and Veillonella. In the elderly group, Prevotella, Bacteroides, Streptococcus, Selenomonas and Haemophilus were the top 5 in abundance, and there were significant difference in Fusobacterium between the two groups ( Q=0.938, P<0.05). PICRUSt function prediction showed that the abundance of Aminoacyl.tRNA.biosynthesis, Nucleotide.excision.repair, RNA.polymerase, Ribosome, Clavulanic.acid.biosynthesis, Photosynthesis and Photosynthesis. proteins in the elderly group were lower than those in the young and middle-aged group (all Q=0.734, P<0.05). Conclusion:There is no significant difference in α-diversity and β-diversity between elderly ESCC patients and young and middle-aged patients, but the abundance of Fusobacterium flora increased.

Objective:To explore the flora characteristics and differences of esophageal tissues between elderly esophageal squamous cell carcinoma (ESCC) patients and young and middle-aged ESCC patients, so as to assist in studying the potential biomarkers of elderly ESCC patients.Methods:In this study, a retrospective study was adopted. 72 ESCC patients diagnosed in Taihe Hospital, Shiyan City, Hubei Province from July 2018 to July 2019 were selected, including 49 patients in the elderly group (≥ 60 years old, 40 males and 9 females), 23 patients in the young and middle-aged group (<60 years old, 21 males and 2 females). In the same period, 20 healthy persons without abnormal gastroscopy in endoscopy center were selected as the control group (aged 35-78 years old, median age 57 years old, 16 males and 4 females). The genomic DNA was extracted from the affected esophageal tissues of patients with ESCC and the middle esophageal samples of the control group. The V4 hypervariable region of bacterial 16SrRNA gene sequence was amplified. Illumina HiSeq sequencing technology was adopted. The flora characteristics of elderly, young and middle-aged ESCC patients was compared and analyzed. QIIME and Rstudio software were used to analyze the sequence data, and nonparametric Kruskal-Wallis test or Wilcoxon rank sum test were used for statistical methods.Results:Shannon index [5.17 (4.53, 5.95) vs. 4.79 (3.74, 5.97)], Simpson index [0.94 (0.91, 0.96) vs. 0.92 (0.83, 0.96)] and Chao1 index [343.55 (259.76, 570.59) vs. 329.16 (268.88, 648.00)] were similar in flora of two groups, and there was no significant difference ( Z=-0.791, -1.057, -0.380, all P>0.05). There was no significant difference in β-diversity between the elderly group and the young and middle-aged group (PC1=19.14%, PC2=6.95%, PPC1=0.67, PPC2=0.42). At the phyla level, the top 5 phyla in abundance were as follows: Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria in the young and middle-aged group, while the top 5 phyla in abundance were as follows: Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria and Actinobacteria in the elderly group; the significant difference between the two groups was Fusobacteria ( Q=0.596, P<0.05). At the genus level, the top 5 genera in the young and middle-aged group in abundance were as follows: Prevotella, Bacteroides, Streptococcus, Selenomonas and Veillonella. In the elderly group, Prevotella, Bacteroides, Streptococcus, Selenomonas and Haemophilus were the top 5 in abundance, and there were significant difference in Fusobacterium between the two groups ( Q=0.938, P<0.05). PICRUSt function prediction showed that the abundance of Aminoacyl.tRNA.biosynthesis, Nucleotide.excision.repair, RNA.polymerase, Ribosome, Clavulanic.acid.biosynthesis, Photosynthesis and Photosynthesis. proteins in the elderly group were lower than those in the young and middle-aged group (all Q=0.734, P<0.05). Conclusion:There is no significant difference in α-diversity and β-diversity between elderly ESCC patients and young and middle-aged patients, but the abundance of Fusobacterium flora increased.

Objective To explore the feasibility and effect of 3D modeling and printing technology in constructing bone fracture models and assisting clinical teaching at the department of traumatic orthope-dics. Methods CT scan images of bone fractures were reconstructed by Mimics software. The digital 3D bone fracture models were constructed and the interactive multimedia teaching videos were output. More-over, all bone fracture models were printed by using fusion deposition modeling (FDM). At the end of the teaching course, a questionnaire survey was conducted to evaluate the teaching effect. Results The digital models of common bone fractures at the department of traumatic orthopedics were established, and the in-teractive multimedia teaching videos were output. A traumatic orthopedic teaching model with a 1∶1 scale was printed out. The questionnaire survey indicated that the application of 3D modeling and printing tech-nology to build bone fracture model with PPT teaching can obviously improve students' understanding and mastery of relevant theoretical knowledge. They helped students better remember the type of bone fractures and how to choose the correct internal fixation methods. The teaching effect was satisfactory. Conclusions 3D modeling and printing technology was applied to build bone fracture models to assist clinical teaching at the department of traumatic orthopedics. It was found that the printed 3D bone fracture models can stimulate students' enthusiasm for learning and improve their learning effect. This method has good application value.

Objective To investigate the characteristics of nosocomial infection of carbapenem resistant En-terobacteriaceae ,then to study the risk factors and prognosis of patients ,as to provide evidence for effective control of CRE hospital infection .Methods A retrospective epidemiology study was conducted of CRE infec-ted patients from January 2016 to June 2017 .This was a 1∶2 matched case-control study of patients with in-fection due to carbapenem resistant Enterobacteriaceae and randomly select 218 patients with non CRE infec-tion in the same hospital as control group ,then the risk factors of CRE infection were investigate .Results A-mong the 109 cases CRE infection patients ,the most common bacteria were Klebsiella pneumoniae ,Enter-obacter cloacae and Escherichia coli .The CRE strains were more sensitive to minocycline than other common antibiotics ,the resistance rate to other antibiotics was more than 40% .Univariate analysis showed that ICU staying time more than 7 d ,using beta lactamase inhibitors and carbapenem antibiotics ,combination therapy and mechanical ventilation were the potential risk factors of CRE nosocomial infection .The non conditional multivariate Logistic regression analysis showed that Check in ICU more than 7 d (OR＝ 4 .981 ,95% CI 2 .451-10 .122 ) ,the use of containing beta lactamase inhibitor antibiotics (OR＝ 3 .718 ,95% CI 2 .162-6 .394) ,use of carbapenem antibiotics (OR＝3 .232 ,95% CI 1 .879-5 .561) ,and mechanical ventilation (OR＝5 .26 ,95% CI 2 .576-10 .742) were independent risk factors of CRE nosocomial infection .The nosocomial in- fection CRE strain was with highly antibiotic resistance rate ,and the average hospitalization time and mortality were significantly higher than those of the control group .Conclusion The carbapenem resistant Enterobacte-riaceae infection had multiple independent risk factors ,strengthening of these independent risk factor control can effectively prevent the spread of CRE isolates infection .

Objective This study aimed to find the resting state functional connectivity of posterior cingulate with other brain regions in major depressive disorder(MDD), as well as the effect and correlations with antidepressant agents. Methods Twenty-one first-episode MDD patients according to the diagnosis criteria of DSM-Ⅳ and 21 sex-, age-, and education-matched health controls were recruited. All subjects underwent brain resting state fMRI scans at baseline. Depressive patients subsequently underwent 8 weeks of escitalopram monotherapy, and took resting state fMRI at the end of the treatment. The left posterior cingulate gyrus was selected as the region of interest, and the time series of the extraction of the posterior cingulate and the whole brain were analyzed. Results Compared to controls,MDD patients showed abnormal brain functional connectivity at baseline, especially increased functional connectivity in the hippocampus and parahippocampal gyrus(Z=4.70), left middle frontal(Z=4.65,both P<0.05), but decreased functional connectivity in the right middle frontal gyrus(Z=3.98), right temporal pole(Z=3.66), bilateral inferior temporal gyrus(Z=3.80), bilateral occipital gyrus(Z=3.57,3.54;all P<0.05). The drug significantly increased the functional connectivity of posterior cingulate with right inferior frontal gyrus(Z=4.35), right precentral gyrus(Z=5.87), left middle temporal gyrus(Z=3.96), left middle occipital gyrus(Z=3.65)and insula cortex, while reduced the functional connectivity of posterior cingulate with the bilateral superior frontal gyrus(Z=5.10), bilateral precuneus(Z=5.63), right hippocampus and parahippocampal gyrus(Z=4.96), right angular gyrus(Z=3.65, all P<0.05). Conclusion There may be abnormal resting state functional connectivities of the posterior cingulate with other brain regions in MDD patients, these abnormalities could partially change after escitalopram treatment, suggesting these abnormal connectivities might be correlated with the clinical efficacy.

Objective This study aimed to find the resting state functional connectivity of posterior cingulate with other brain regions in major depressive disorder(MDD), as well as the effect and correlations with antidepressant agents. Methods Twenty-one first-episode MDD patients according to the diagnosis criteria of DSM-Ⅳ and 21 sex-, age-, and education-matched health controls were recruited. All subjects underwent brain resting state fMRI scans at baseline. Depressive patients subsequently underwent 8 weeks of escitalopram monotherapy, and took resting state fMRI at the end of the treatment. The left posterior cingulate gyrus was selected as the region of interest, and the time series of the extraction of the posterior cingulate and the whole brain were analyzed. Results Compared to controls,MDD patients showed abnormal brain functional connectivity at baseline, especially increased functional connectivity in the hippocampus and parahippocampal gyrus(Z=4.70), left middle frontal(Z=4.65,both P<0.05), but decreased functional connectivity in the right middle frontal gyrus(Z=3.98), right temporal pole(Z=3.66), bilateral inferior temporal gyrus(Z=3.80), bilateral occipital gyrus(Z=3.57,3.54;all P<0.05). The drug significantly increased the functional connectivity of posterior cingulate with right inferior frontal gyrus(Z=4.35), right precentral gyrus(Z=5.87), left middle temporal gyrus(Z=3.96), left middle occipital gyrus(Z=3.65)and insula cortex, while reduced the functional connectivity of posterior cingulate with the bilateral superior frontal gyrus(Z=5.10), bilateral precuneus(Z=5.63), right hippocampus and parahippocampal gyrus(Z=4.96), right angular gyrus(Z=3.65, all P<0.05). Conclusion There may be abnormal resting state functional connectivities of the posterior cingulate with other brain regions in MDD patients, these abnormalities could partially change after escitalopram treatment, suggesting these abnormal connectivities might be correlated with the clinical efficacy.

Objective:To explore the effect of adipose derived mesenchymal stem cells to regulate the differentiation of macrophage RAW264.7.Methods:First,we used RAW264.7 cells to simulate macrophage and induced them to M 1 macrophage with lipopolysaccharide ( LPS,1 μg/ml) .Then we cultured these RAW264.7 cells in culture mediums which were previously used to culture adipose derived mesenchymal stem cells to imitate the transplantation of ADMSC .Last,the mRNA relative expression of IL-10, IGF-1,Arg-1,TNF-α,FIZZ1,SPHK-1 was detected by real-time PCR.The protein expression of IL-12 p40,IL-27 Rα,IL-10 was detected by Western blot.Results:After been cultured in ADMSCCM and induced by LPS ,M1 markers (TNF-αmRNA,IL-12 p40;P<0.05) of the RAW264.7 cells declined while M2 markers (IGF-1 mRNA,IL-10 mRNA,IL-10;P<0.05) rose.Conclusion: ADMSC can secrete soluble cytokines to induce the RAW264.7 cell,which have been induced to the M1 macrophages,to differentiate towards M2 macrophages.

A method was developed for the simultaneous determination of 17 characteristic ingredients of plant extracts, including paeoniflorin, hydroxysafflor yellow A, calycosin_7_glucoside ferulic acid, etc. , in hair growth cosmetics using ultra high performance liquid chromatography ( UPLC ) . Different cosmetic samples were extracted by ultrasonic_assisted extraction with the solvent of methanol/water (4∶1, V/V) solution. After demulsified by the addition of appropriate amount of NaCl and high speed centrifugation, the supernatant was transferred and analyzed with UPLC. The separation was conducted on a Waters reversed phase column of ACQUITY UPLC CSH C18(50 mm×2. 1 mm, 1. 7μm), and the mobile phases were methanol and the solution of 0. 05% phosphate in water. The detection was performed with a photodiode_array ( PDA) detector. The linear range was 0 . 2-25 mg/L with correlation coefficients higher than 0 . 999 . The limits of detection were within 0. 3-1. 5 mg/kg, and the limits of quantification were from 1. 0 to 4. 0 mg/kg. The average recoveries of 17 characteristic ingredients were within 93 . 5%-105 . 0%, with the intra_and inter_day precision ( n=6 ) less than 4. 6%. This method was simple, rapid, with good_repeatability, and had been applied to the analysis of real samples.