BACKGROUND:The self-renewal and multi-directional differentiation of pluripotent stem cells possess the potential to revolutionize people's understanding of biology,medicine,development,and disease.Stem cells play an important role in the early stage of embryonic development,and the study of them could be beneficial to understanding of the basic principles of biological development and tissue or organ formation,exploring the potential mechanisms of various diseases,studying the repair and regeneration of damaged tissues or organs,and promoting drug discovery and personalized treatment. OBJECTIVE:To review the research progress of pluripotent stem cells,summarize and categorize the fundamental types of pluripotent stem cells,and elucidate the lineage situations of various types of pluripotent stem cells in common mammals. METHODS:PubMed,Web of Science,CNKI,and WanFang databases were searched systematically,with the keywords"pluripotent stem cells;embryonic stem cells;induced pluripotent stem cells;expanded potential stem cells;livestock pluripotent stem cells"in English and Chinese.The 99 articles related to mammalian pluripotent stem cells were systematically screened according to inclusion and exclusion criteria,and then reviewed. RESULTS AND CONCLUSION:(1)According to classical theory in mouse embryonic stem cell research,the pluripotent state of stem cells is divided into two forms:na?ve and primed.Na?ve state corresponds to the inner cell mass of pre-implantation embryos before attachment to the uterine wall,while primed state corresponds to the epiblast after implantation.These two states exhibit significant differences in epigenetic features,transcriptional activity,external signal dependency,and metabolic phenotype.It is later discovered that there is an intermediate state between na?ve and primed called formative pluripotency.Therefore,the pluripotency of pluripotent stem cells is a continuous developmental process rather than a unique cell state.(2)In addition to obtaining pluripotent stem cells from the inner cell mass,there are various methods and lineages for acquiring pluripotent stem cells,including embryonic germ cells established using primitive germ cells from mouse embryos,induced pluripotent stem cells created by the dedifferentiation of adult mouse and human fibroblasts with four factors—Oct3/4,Sox2,c-Myc,and Klf4;embryonic stem cell-like cell lines cultured from somatic cell nuclear transfer,parthenogenesis,neonatal or adult testicular or ovarian tissue,very small embryonic-like stem cells derived from various adult tissues and expanded pluripotent stem cells derived from pre-implantation stages.These pluripotent stem cells all share the common characteristics of continuous self-renewal,expressing core pluripotency factors and possessing the ability to differentiate into the three primary germ layers.(3)Currently,pluripotent stem cells are being used for disease modeling to study the mechanisms of various diseases and develop new drugs.Simultaneously,scientists are attempting to use pluripotent stem cells to cultivate various tissues and organs,offering new possibilities for regenerative medicine and transplantation.However,the clinical application of pluripotent stem cells faces safety challenges,including issues of cell mutations and immune rejection.Continual improvement in the methods of generating pluripotent stem cells will make them safer and more efficient for clinical applications.(4)Based on the methods of obtaining and lineage establishment of pluripotent stem cells in mice and humans,various types of pluripotent stem cells have been established in livestock,including embryonic stem cells,induced pluripotent stem cells,germ lineages of pluripotent stem cells,and expanded potential stem cells.Research on livestock pluripotent stem cells opens up new avenues for animal reproduction,breeding,genetic engineering,disease modeling,drug screening,and the conservation of endangered wildlife.

Donors with a serum sodium concentration of >155 mmol/L are extended criteria donors for liver transplantation (LT). Elevated serum sodium of donors leads to an increased incidence of hepatic dysfunction in the early postoperative period of LT; however, the exact mechanism has not been reported. We constructed a Lewis rat model of 70% hepatic parenchymal area subjected to ischemia-reperfusion (I/R) with hypernatremia and a BRL-3A cell model of hypoxia-reoxygenation (H/R) with high-sodium (HS) culture medium precondition. To determine the degree of injury, biochemical analysis, histological analysis, and oxidative stress and apoptosis detection were performed. We applied specific inhibitors of the epithelial sodium channel (ENaC) and Na⁺/Ca²⁺ exchanger (NCX) in vivo and in vitro to verify their roles in injury. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) levels and the area of hepatic necrosis were significantly elevated in the HS+I/R group. Increased reactive oxygen species (ROS) production, myeloperoxidase (MPO)‍-positive cells, and aggravated cellular apoptosis were detected in the HS+I/R group. The HS+H/R group of BRL-3A cells showed significantly increased cellular apoptosis and ROS production compared to the H/R group. The application of amiloride (Amil), a specific inhibitor of ENaC, reduced ischemia-reperfusion injury (IRI) aggravated by HS both in vivo and in vitro, as evidenced by decreased serum transaminases, inflammatory cytokines, apoptosis, and oxidative stress. SN-6, a specific inhibitor of NCX, had a similar effect to Amil. In summary, hypernatremia aggravates hepatic IRI, which can be attenuated by pharmacological inhibition of ENaC or NCX.
Animals ; Reperfusion Injury/drug therapy* ; Hypernatremia/complications* ; Rats ; Liver/metabolism* ; Rats, Inbred Lew ; Male ; Apoptosis ; Sodium-Calcium Exchanger/antagonists & inhibitors* ; Reactive Oxygen Species/metabolism* ; Oxidative Stress ; Epithelial Sodium Channel Blockers/pharmacology* ; Epithelial Sodium Channels ; Cell Line ; Liver Transplantation

Objective: To explore the current status of hyperopic reserve and its related factors among non-myopia preschool and primary school students aged 5 to 12 years in Guangdong Province, so as to provide a basis for formulating intervention strategies for the pre myopia stage of children. Methods: From October to December 2023, by using stratified cluster random sampling method, a survey on hyperopic reserve among preschool children and primary school students in Guangdong were conducted. And a total of 10 567 children from the senior class of kindergarten to the sixth grade of primary school who completed autorefraction measurements with and without cycloplegia and the questionnaire survey were included in the study. The prevalence characteristics of low hyperopic reserve among non-myopia children were analyzed, and multivariable Logistic regression was used to analyze the related factors. Results: The prevalence rate of low hyperopic reserve among 8 790 non-myopia children was 62.4%. The average spherical equivalent (SE) for children aged 5 to 12 years was 0.88 (0.25, 1.25)D, decreasing from 1.13 ( 0.75 , 1.50)D in senior kindergarten to -1.00 (-2.50, 0.38)D in sixth grade, with the difference was statistically significant ( H=2 475.3, P <0.01). Multivariable Logistic regression analysis, after adjusting for confounders including gender, urban and rural, and grade, revealed that parental myopia was a risk factor for low hyperopic reserve in the preschool stage (one parent with myopia: OR=1.62, 95%CI =1.35-1.93; both parents with myopia: OR=2.05, 95%CI = 1.66 -2.55); in the lower primary school stage, parental myopia (one parent with myopia: OR=1.46, 95%CI =1.27-1.68; both parents with myopia: OR=1.58, 95%CI =1.33-1.89), frequently or always reading or using electronic screens while lying down or on one s stomach ( OR=1.43, 95%CI =1.13-1.81), and never or occasionally maintaining a viewing distance of over 3 meters when watching TV/playing video games ( OR=1.34, 95%CI =1.04-1.72) were risk factors; in the higher primary school stage, failing to take a break every hour during near work ( OR=1.79, 95%CI =1.16-2.75) was a risk factor (all P <0.05). Conclusions The emmetropization of children aged 5-12 years in Guangdong Province is accelerated, and non-myopia children generally exhibit insufficient hyperopic reserve. The contributing factors for insufficient hyperopia reserve in non-myopia children vary across different educational stages, necessitating targeted precision interventions.

Objective To explore the characteristics of coagulation and immune function and their clinical significance in children with severe adenovirus pneumonia(SAP).Methods A total of 122 children with SAP and 120 children with non-severe adenovirus pneumonia(NSAP)were enrolled and assigned to severe group and non-severe group.The severe group was further subdivided into good prognosis subgroup(n=105)and poor prognosis subgroup(n=17)according to prognosis.Addition-ally,120 healthy children undergoing physical examination during the same period were included as control group.Coagulation function indicators,including prothrombin time(PT),activated partial thromboplastin time(APTT),fibrinogen(FIB),and thrombin time(TT)were measured.Levels of immunoglobulin A(IgA),immunoglobulin G(IgG),and immunoglobulin M(IgM)were determined using the nephelometric immunoassay.Multivariate Cox regression analysis was conducted to explore the influencing factors of poor prognosis.Results Compared with the control group,children in both the non-severe and severe groups exhibited increased levels of white blood cells(WBC),neutrophils(N),C-reactive protein(CRP),erythrocyte sedimentation rate(ESR),interleukin-6(IL-6),procalci-tonin(PCT),FIB,and IgG,as well as decreased levels of B lymphocytes,natural killer(NK)cells,PT,APTT,IgA,and IgM(P＜0.05).Compared with the non-severe group,children in the severe group showed increased levels of WBC,N,CRP,ESR,IL-6,PCT,FIB,and IgG,as well as decreased levels of B lymphocytes,NK cells,PT,APTT,IgA,and IgM(P＜0.05).Compared with the good prognosis subgroup,the poor prognosis subgroup exhibited increased levels of CRP,IL-6,PCT,and IgG,as well as decreased levels of APTT,IgM,and IgA(P＜0.05).The results of multivariate Cox regression analysis showed that PCT,APTT,and IgM were influencing factors of poor prognosis in children with SAP(P＜0.05).Conclusion Children with SAP have decreased levels of PT,APTT,IgA,and IgM,as well as increased levels of FIB and IgG.Coagulation and im-mune function indicators are correlated with the prognosis of SAP.

Objective:To compare the dosimetric differences between active breathing coordinator (ABC) and Catalyst for respiratory gating after breast conserving surgery for left breast cancer.Methods:Data of 48 female patients with left breast cancer after breast conserving surgery admitted to the Radiotherapy Department of Shenzhen People′s Hospital from November 2020 to August 2021 were retrospectively selected. They were randomized to receive dynamic intensity modulated radiotherapy (IMRT) plans with ABC or Catalyst. The dosimetric differences in targets and organs at risk between the two groups were analyzed.Results:Comparison of the two respiratory gating IMRT plans revealed no statistically significant differences ( P > 0.05) in D90%, D98%, Dmax, Dmean, conformity index (CI), homogeneity index (HI), and monitor unit parameters in the target volume, (i.e., chest wall), as well as the ipsilateral lung and heart under the deep inhalation breath hold (DIBH) mode. The Dmean, Dmax, and D2% of the left anterior descending coronary artery (LAD) in the Catalyst group were better than those in the ABC group [(1 047.72 ± 1 401.84) vs. (454.48 ± 206.26), (1 619.28 ± 809.05) vs.(1 068.53 ± 419.63), (1 405.85 ± 798.30) vs. (1 016.54 ± 592.00) cGy], with statistically significant differences ( t= -2.07, -3.18, -2.07, P<0.05). Conclusions:Both ABC and Catalyst respiratory gating systems meet the requirements for clinical treatment, with the latter more effective in reducing the exposure dose of LAD.

Objective:To compare translational and rotational setup errors between immobilization with open masks combined with positioning with the optical surface monitoring system (OSMS) and immobilization with full masks combined with positioning with laser lights and mask markers, find the advantages of open masks combined with OSMS in hypofractionated stereotactic radiotherapy (HSRT) for brain metastases, and calculate planning target volume (PTV) expansions with different immobilization and positioning method for patients with brain metastases.Methods:The setup data of 55 patients with brain metastases who received HSRT were analyzed retrospectively. According to immobilization and positioning method, the patients were divided into group A (OSMS + open masks), group B1 (full head-neck-shoulders masks + polyurethane foam cushions), and group B2 (full head-neck-shoulders masks + standard headrests). Positioning was directed by automatic couch motion in OSMS in group A and by laser lights and mask markers in groups B1 and B2. Cone beam computed tomography (CBCT) scans were registered using the bone registration method to obtain setup errors in six directions ( x, y, z, roll, pitch, yaw). PTV expansions were calculated according to the van Herk formula. Results:A total of 288 sets of CBCT registration data were acquired. Among three groups, group A showed the smallest mean setup errors and 3D vector error, which were (0.47±0.33) mm, (0.49±0.31) mm, (0.44±0.31) mm, (0.42±0.32)°, (0.48±0.31)°, (0.42±0.22)°, and (0.90±0.39) mm, respectively. Group A differed significantly from group B1 and group B2 in the errors at all directions ( P < 0.05) except for the yaw direction compared with group B1 ( P > 0.05). Group A had no setup error ≥2 mm in translational directions or ≥2° in rotational directions. Group B1 showed significantly smaller setup errors in the y, z, and yaw directions and 3D vector error than group B2 ( P < 0.05). In group A, PTV expansions in three directions ( x, y, and z) were 1.32, 1.19, and 1.22 mm, respectively, which were smaller than those of the other two groups. Conclusions:In HSRT for patient with brain metastases, compared with full head-neck-shoulders masks combined with laser lights and mask markers, open masks combined with OSMS can significantly improve setup precision in six directions and reduce repeated setup and PTV expansions, which shows promise for clinical application.

Objective To establish a novel clinical application process of the optical surface monitoring system(OSMS)guided volumetric modulated arc therapy(VMAT)for total body irradiation(TBI),and to assess the accuracy and effectiveness of OSMS in inter-fractional auxiliary positioning before radiotherapy and real-time monitoring of intra-fractional motion during radiotherapy.Methods A retrospective analysis was conducted on 15 leukemia patients who underwent OSMS-guided VMAT-TBI before hematopoietic stem cell transplantation.CT simulation positioning was performed,and the whole-body image data which were collected in head-first supine position(HFS)and feet-first supine position(FFS)were transmitted to the treatment planning system for image registration,multicenter VMAT planning and dose verification.The prescription dose was 800 cGy in 4 fractions twice daily.OSMS was used to assist positioning before delivery,and CBCT was used for position verification.During treatment,OSMS was used for monitoring.The intra-fractional error monitored by OSMS in real time was obtained by analyzing the offline log files.Results The mean dose and coverage of the target area in HFS plan were(905.4±19.0)cGy and 93.0%±2.8%.The mean doses to lung and kidney were(603.7±55.7)cGy and(600.4±49.6)cGy,respectively,and the maximum dose to the lens was(393.9±58.9)cGy.The mean dose and coverage of the target area in FFS plan were(888.5±58.9)cGy and 94.0%±3.2%;and the maximum dose at the junction was(1148.9±72.9)cGy.Fractional treatment delivery time was(75.1±15.1)min.OSMS-assisted positioning was carried out before delivery,and the total deviations of CBCT three-dimensional vector in translational and rotation directions were(2.71±1.96)mm and 0.91°±0.90°,respectively.The three-dimensional vector deviation of the intra-fractional motion amplitude in translational direction monitored by OSMS during the treatment was(1.95±1.88)mm,of which the deviation within 1 mm accounted for 57.5%,79.7%and 62.1%in longitudinal,lateral and vertical directions,respectively.The three-dimensional vector deviation in rotation direction was 0.76°±0.72°,of which the deviation within 1°accounted for 93.1%,85.7%and 94.3%in rotation,pitch and roll directions,respectively.Conclusion VMAT simplifies TBI process,while improving target coverage and organs-at-risk sparing.The use of OSMS can reduce positioning errors,especially rotation errors.In order to ensure the accurate implementation of TBI and the safety of patients,it is necessary to use OSMS for auxiliary positioning and intra-fractional position monitoring.

Objective To study the application of serum microRNA(miR)-338-3p and miR-495-3p levels in the diagnosis and disease evaluation of severe adenovirus pneumonia in children.Methods A total of 130 chil-dren with adenovirus pneumonia who were treated in Cangzhou Central Hospital from November 2020 to No-vember 2022 were enrolled as an observation group.According to the severity of the disease,the children were divided into a mild pneumonia group with 90 children and a severe pneumonia group with 40 children.A total of 130 healthy children who were examined in Cangzhou Central Hospital during the same period were en-rolled as the control group.The observation and control groups and the children with different disease severity were compared in terms of the serum levels of miR-338-3p and miR-495-3p.Receiver operating characteristic(ROC)curve was used to analyze the diagnostic value of serum miR-338-3p and miR-495-3p for severe adeno-virus pneumonia.Multivariate Logistic regression was used to analyze the influencing factors of severe adeno-virus pneumonia.Results The observation group had a significantly lower serum level of miR-338-3p and a significantly higher serum level of miR-495-3p than the control group(P＜0.05).There were significant differences in electrolyte disturbance,circulatory system complications incidence,miR-338-3p level,miR-495-3p level,sequential organ failure score and Murray lung injury score between the mild pneumonia group and the severe pneumonia group(P＜0.05).ROC curve analysis showed that the area under the curve(AUC)of serum miR-338-3p and miR-495-3p in the auxiliary diagnosis of severe adenovirus pneumonia were 0.745(95％CI 0.662-0.828)and 0.774(95％CI 0.685-0.863),respectively.And the AUC of the combination of the two was 0.884(95％CI 0.821-0.946),which was better than that of each index alone(Z=2.593,1.963,P＜0.05).Conclusion The level of serum miR-338-3p is decreased and the level of serum miR-495-3p is increased in children with severe adenovirus pneumonia.The combined detection of miR-338-3p and miR-495-3p has a certain value in the diagnosis of severe adenovirus pneumonia and can be used as a serum indica-tor to evaluate the severity of severe adenovirus pneumonia.

Objective:To investigate the evaluation efficacy and predictive prognostic value of alpha-fetoprotein (AFP) response in tyrosine kinase inhibitors (TKIs) in combination with PD-1 inhibitors (α-PD-1) for intermediate-to-advanced hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 205 patients with intermediate-to-advanced HCC who were admitted to 9 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from March 2020 to July 2022 were collected. There were 178 males and 27 females, aged (52±12)years. Based on AFP response at 6-8 weeks after treatment, patients were divided into the AFP response group (AFP level decreased by ≥50% compared to baseline) and the AFP no response group (AFP level decreased by <50% compared to baseline). Observation indicators: (1) AFP response evaluation of anti-tumor efficacy; (2) comparison of patient prognosis; (3) analysis of factors affecting patient prognosis. Measurement data with normal distrubution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range) and M( Q1, Q3). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and the Log-Rank test was used for survival analysis. The COX proportional risk model was used for univariate analysis and the COX stepwise regression model was used for multivariate analysis. Results:(1) AFP response evaluation of anti-tumor efficacy. Before treatment, all 205 patients were positive of AFP, with a baseline AFP level of 1 560(219,3 400)μg/L. All 205 patients were treated with TKIs in combination with α-PD-1, and the AFP level was 776(66,2 000)μg/L after 6 to 8 weeks of treatment. Of the 205 patients, 88 cases were classified as AFP response and 117 cases were classified as AFP no response. According to the response evaluation criteria in solid tumors version 1.1, the objective response rate (ORR) and disease control rate (DCR) were 42.05%(37/88) and 94.32%(83/88) in patients of the AFP response group and 16.24% (19/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=16.846, 25.950, P<0.05). According to the modified response evaluation criteria in solid tumors, the ORR and DCR were 69.32% (61/88) and 94.32% (83/88) in patients of the AFP response group and 33.33% (39/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=26.030, 25.950, P<0.05). (2) Comparison of patient prognosis. All 205 patients were followed up for 12.4(range, 2.4-34.0)months after treatment. The median progression free survival time and total survival time were 5.5 months and 17.8 months, respectively. The 1-year, 2-year progression free survival rates were 20.8% and 7.2%, and the 1-year, 2-year overall survival rates were 68.7% and 31.5%, respectively. The median progression free survival time, 1-year and 2-year progression free survival rates were 9.7 months, 39.6% and 14.2% in patients of the AFP response group and 3.7 months, 7.8% and 2.0% in patients of the AFP no response group, showing a significant difference in progression free survival between them ( χ2=43.154, P<0.05). The median overall survival time, 1-year and 2-year overall survival rates were not reached, 85.2% and 56.3% in patients of the AFP response group and 14.6 months, 56.3% and 14.5% in patients of the AFP no response group, showing a significant difference in overall survival between them ( χ2=33.899, P<0.05). (3) Analysis of factors affecting patient prognosis. Results of multivariate analysis showed that invasion of large blood vessels, extrahepatic metastasis, combined hepatic artery intervention therapy, and AFP response were independent factors influencing progression free survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio=1.474, 1.584, 0.631, 0.367, 95% confidence interval as 1.069-2.033, 1.159-2.167, 0.446-0.893, 0.261-0.516, P<0.05), and Eastern Cooperative Oncology Group score, invasion of large blood vessels, extrahepatic metastasis, and AFP response were independent factors influencing overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio= 1.347, 1.914, 1.673, 0.312, 95% confidence interval as 1.041-1.742, 1.293-2.833, 1.141-2.454, 0.197-0.492, P<0.05). Conclusions:AFP response at 6-8 weeks after treatment can effectively evaluate anti-tumor efficacy of TKIs in combination with α-PD-1 for intermediate-to-advanced HCC. AFP response is the independent factor influencing progression free survival and overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1.

Based on the theory of "one qi circulation" founded by HUANG Yuanyu， the core disease mechanism of colorectal cancer is the innate spleen deficiency and stomach qi failing to bear downward， which leads to the turbidity assemble in large intestine， forming the carcinoma toxin， and ultimately transforms into colorectal cancer. The treatment should base on recovering the circulation of qi， Huangya Decoction （黄芽汤） as the basic formula， the circulation of qi ascending and descending as the base， adjusting ascending and descending together with Xiaqi Decoction （下气汤）， and differentiating the syndrome on yin-yang excess-deficiency； for spleen-kidney yang deficiency syndrome， treated with Tianhun Decoction （天魂汤） to supplement liver， kidney and assist yang； for liver-kidney yin deficiency syndrome， treated wtih Dipo Decoction （地魄汤） to supplement lung， kidney， and assist yang. They jointly prompt one qi circulation to provide the thoughts for the treatment of colorectal cancer by traditional Chinese medicine.