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.

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.

Objective: To analyze the correlation between refractive errors and physical development indicators among primary school students aged 6 to 9, so as to provide a scientific basis for the development of effective prevention and control measures. Methods: A stratified cluster random sampling method was used to recruit 2 833 elementary school students aged 6 to 9 from Guangdong Province for vision screening, ocular biometry, and physical examinations in Octorber, 2020. The Chi square test, t-test, and ANOVA were employed to compare myopia rates and indicator values across different groups. Multiple linear regression models were used to analyze the correlations between height, weight, and body mass index (BMI) with refractive development indicators. Results: The screening myopia rate among primary school students aged 6 to 9 was 16.7%, and the myopia rate increased with age ( χ 2= 51.58 , P <0.01). The height and weight of the myopic group [(126.96±7.41)cm, (26.59±6.45)kg] were higher than those of the non myopic group [(124.76±7.77)cm, (25.42±5.87)kg] ( t =5.84, 3.65, P <0.01). The mean values of spherical equivalent (SE), axial length (AL), anterior chamber depth (ACD), and AL/corneal curvature radius (CR) ratio for students aged 6 to 9 were (-0.17±1.04)D, (22.96±0.78)mm, (3.38±0.24)mm, and (2.95±0.08), respectively, with statistically significant differences across different age and myopia severity groups ( t =37.08, 119.20, 41.54, 133.60; 935.30, 184.10, 73.95, 498.50, P < 0.01). After adjusting for gender, age, and residence, the multiple linear regression model showed that height was positively correlated with AL and CR, weight was positively correlated with ACD, and BMI was positively correlated with AL and ACD ( β = 0.191 , 0.070, 0.035, 0.013, 0.007, P <0.05). When stratified by myopia status, results for the non-myopic group were similar to the overall results, whereas in the myopic group, the correlations between height, BMI, and AL were not statistically significant ( P > 0.05). Conclusions Among primary school students aged 6 to 9, height and BMI are positively correlated with AL in the non myopic group but no similar correlation is observed in the myopic group, indicating that factors other than physical development, such as environmental and behavioral factors, should be considered for their impact on refractive development.

Objective: The study aims to analyze the prevalence and associated factors of myopia among 4 to 9 grade students in Guangdong Province in 2022, so as to provide a scientific basis for targeted intervention measures for myopia in children and adolescents. Methods: From September to October 2022, stratified cluster random sampling was used to select 29 095 of 4 to 9 grade students from Guangzhou, Jiangmen, and Meizhou in Guangdong Province for myopia screening and questionnaire surveys. The Chisquare test was applied to compare the differences between groups, and multivariable Logistic stepwise regression analysis was used to analyze factors associated with myopia. Results: The myopia detection rate of 4 to 9 grade students was 61.7%, with detection rates of 51.5% for 4 to 6 grade primary school students and 71.95% for 7 to 9 grade junior high school students. Multivariable Logistic regression analysis showed that higher myopia rates were detected among girls (OR=1.39, 95%CI=1.30-1.49), students with one (OR=1.82, 95%CI=1.69-1.96) or both parents having myopia (OR=2.86, 95%CI=2.56-3.18), and indoor sedentary time >6 h(OR=1.28, 95%CI=1.17-1.39) in the 4 to 6 grade. Lower myopia rates were detected in the county (OR=0.92, 95%CI=0.86-0.99) and outdoors at recess activities (OR=0.88, 95%CI=0.81-0.95). Meanwhile, higher myopia rates were detected among girls (OR=1.84, 95%CI=1.69-1.99), students with one (OR=1.87, 95%CI=1.71-2.04) or both parents having myopia (OR=3.03, 95%CI=2.63-3.50), and indoor sedentary time >6 h/d (OR=1.11, 95%CI=1.01-1.23) in the 7 to 9 grade. Lower myopia rates were detected in the county (OR=0.74, 95%CI=0.68-0.80), outdoors at recess activities (OR=0.83, 95%CI=0.76-0.91), and outdoor activity time ≥2 h/d(OR=0.87, 95%CI=0.80-0.95)(P<0.05). Conclusions The detection rate of myopia among 4 to 9 grade students in Guangdong Province is relatively high. Place of recess activities, daily outdoor activity and indoor sedentary duration are associated with myopia. Therefore, targeted intervention measures should be adopted, such as appropriately increasing outdoor activity to reduce the occurrence of myopia among primary and middle school students.

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 investigate the protection of Active Breathing Coordinator(ABC)technique for heart and its substructures in radiotherapy for left breast cancer.Methods:A total of 50 patients with left breast cancer who underwent radiotherapy in our department were retrospectively selected,and treatment plans with intensity modulated radiotherapy(IMRT)were designed on the images of ABC combined with deep inspiration breath hold(ABC-DIBH)computed tomography(CT)and free-breathing(FB)CT,respectively.The dose parameters of the organ at risks(OARs)of heart and its substructures,including left ventricle(LV),left atrium(LA),right ventricle(RV),right atrium(RA),left main coronary artery(LMCA),left anterior descending coronary artery(LAD),left circumflex coronary artery(LCX)and right coronary artery(RCA),were compared between the two conditions.Results:Compared with FB,the dose of 2%volume(D2),the mean dose(Dmean),the percent volumes covered by different doses(V30,V20,V10,V5)decreased respectively 32.91%(absolute reduction of 1279.11 cGy),36.12%(195.94cGy),58.95%(2.8%),54.32%(3.58%),50.14%(5.56%)and 46.22%(9.67%)of heart under ABC-DIBH condition,and the differences were significant(t=10.28,12.81,9.16,10.28,12.82,12.24,P＜0.01),respectively.In addition,the Dmean values of LV,LA,RV,RA,LMCA,LAD,LCX and RCA decreased by 37.64%(absolute reduction was 285.92 cGy),15.38%(23.68 cGy),34.12%(118.93cGy),9.72%(12.52 cGy),22.17%(47.99 cGy),31.81%(820.63 cGy),16.51%(34.72 cGy)and 14.86%(34.11cGy)under ABC-DIBH condition,respectively,the differences were significant(t=9.50,3.71,6.20,8.65,3.18,10.92,4.26,6.71,P＜0.05).Conclusion:ABC technique can greatly reduce the received doses of heart and its substructures by extending the distance between the heart and the target region with DIBH,thus can form a very effective protection for the heart and its substructures.In addition,it can eliminate the dynamic variation of target location of breast cancer caused by respiratory,and avoid a series of problems,such as target missing,overexposure on normal tissue,and dose deviation.

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 analyze and summarize the clinical presentation of spontaneous and secondary intracranial hypotension syndrome(IHS).Methods Patients diagnosed with spontaneous or secondary IHS from September 2022 to May 2023 were retrospectively analyzed.The clinical data,imaging features,treatment methods and prognosis were collected.The correlation between intracranial pressure values and clinical characteristics of the patients was statistically analyzed.Results A total of 30 patients were enrolled,and the proportion of spontaneous and secondary IHS was 63%(19 cases)and 37%(11 cases),respectively.In terms of clinical features,orthostatic headache was the most common type(29 cases,96.7%)and most commonly involved occipital region(12 cases,40.0%),followed by frontoparietal region(9 cases,30.0%).Among the brain imaging features,dural enhancement was the most common(17 cases,56.7%).According to CT angiography of spinal cord findings,cerebrospinal fluid leakage is one of the most common location of cervical spine segments(10 cases),and on the thoracic segments(9 cases),followed by the thoracic segments(4 cases)and lumbar segments(4 cases).After conservative treatment and surgical treatment,the total effective rate was 90%.Conclusion Orthostatic headache and cranial MRI"dural enhancement"have strong indication on the definitive diagnosis of IHS.CT myelography is helpful to precisely localize the site of cerebrospinal fluid leakage.Targeted epidural blood patch therapy is an effective method to cure IHS when conservative treatment is ineffective.

Heart failure is a fatal stage of end-stage cardiovascular disease,which brings a huge medical burden to the society because of its high mortality and re-hospitalisation rates.Intestinal microecology is the largest and most com-plex microecosystem of human body.It is inhabited by tens of thousands of microorganisms in human gastrointestinal tract.In recent years,with the deepening of the study of intestinal flora,more and more studies have found that the im-balance of intestinal microecology can cause changes of metabolites in heart failure patients,which is one of the key triggers for the development of heart failure,therefore,using the intestinal microbial homeostasis as a new entry point for the treat-ment of heart failure will be a hotspot in medical research.However,the theory of Chinese medicine,"the spleen is the guardian",covers the physiological functions of the spleen,such as the spleen's main function of transporting,spleen's main function of ascending and clearing,and its main function of hiding camping,etc.,and the functions of intestinal flora and the"spleen is the guardian"are similar to a certain extent.Therefore,this paper starts from a holistic viewpoint and takes the theory of"spleen as the guardian"in Chinese medicine as an entry point to elaborate on the pathogenesis of intes-tinal microecological imbalance and heart failure,so as to provide a reference for Chinese medicine treatment or drug re-search.