Background::Growth retardation is a common complication of chronic kidney disease in children, which can be partially relieved after renal transplantation. This study aimed to develop and validate a predictive model for growth patterns of children with end-stage renal disease (ESRD) after kidney transplantation using machine learning algorithms based on genomic and clinical variables.Methods::A retrospective cohort of 110 children who received kidney transplants between May 2013 and September 2021 at the First Affiliated Hospital of Zhengzhou University were recruited for whole-exome sequencing (WES), and another 39 children who underwent transplant from October 2021 to March 2022 were enrolled for external validation. Based on previous studies, we comprehensively collected 729 height-related single-nucleotide polymorphisms (SNPs) in exon regions. Seven machine learning algorithms and 10-fold cross-validation analysis were employed for model construction.Results::The 110 children were divided into two groups according to change in height-for-age Z-score. After univariate analysis, age and 19 SNPs were incorporated into the model and validated. The random forest model showed the best prediction efficacy with an accuracy of 0.8125 and an area under curve (AUC) of 0.924, and also performed well in the external validation cohort (accuracy, 0.7949; AUC, 0.796). Conclusions::A model with good performance for predicting post-transplant growth patterns in children based on SNPs and clinical variables was constructed and validated using machine learning algorithms. The model is expected to guide clinicians in the management of children after renal transplantation, including the use of growth hormone, glucocorticoid withdrawal, and nutritional supplementation, to alleviate growth retardation in children with ESRD.

BACKGROUND: The derivation of salivary gland (SG) progenitors from pluripotent stem cells (PSCs) presents significant potential for developmental biology and regenerative medicine. However, the existing protocols for inducing SG include limited factors, making it challenging to mimic the in vivo microenvironment of embryonic SGs. METHODS: We reported a cocktail factor approach to promote the differentiation of mouse embryonic stem cell (mESC)-derived oral epithelium (OE) into SG progenitors through a three-dimensional co-culture method. Upon confirming that the embryonic SG can promote the differentiation of mESC-derived OE, we performed RNA sequence analysis to identify factors involved in the differentiation of SG progenitors. RESULTS: Our findings highlight several efficient pathways related to SG development, with frequent appearances of four factors: IFN-c, TGF-b2, EGF, and IGF-1. The combined treatment using these cocktail factors increased the expression of key SG progenitor markers, including Sox9, Sox10, Krt5, and Krt14. However, absence of any one of these cocktail factors did not facilitate differentiation. Notably, aggregates treated with the cocktail factor formed SG epitheliallike structures and pre-bud-like structures on the surface. CONCLUSION In conclusion, this study offers a novel approach to developing a differentiation protocol that closely mimics the in vivo microenvironment of embryonic SGs. This provides a foundation for generating PSC-derived organoids with near-physiological cell behaviors and structures.

Enterotoxigenic Escherichia coli（ETEC）infection can induce watery diarrhea，leading to dehydration，electrolyte disturbance，and even death in severe cases. Recombinant B subunit/inactivated whole-cell cholera（rBS/WC）vaccine is effective in preventing ETEC infectious diarrhea. On the basis of the latest evidence on etiology and epidemiology of ETEC，as well as the effectiveness，safety，and health economics of rBS/WC vaccine，National Clinical Research Center for Child Health（The Children’s Hospital，Zhejiang University School of Medicine）and Zhejiang Provincial Center for Disease Control and Prevention invited experts to develop expert consensus on rBS/WC vaccine in prevention of ETEC infectious diarrhea. It aims to provide the clinicians and vaccination professionals with guidelines on using rBS/WC vaccine to reduce the incidence of ETEC infectious diarrhea.

The differentiation of pluripotent stem cells has been used to study disease mechanisms and development. We previously described a method for differentiating human pluripotent stem cells (hPSCs) into salivary gland epithelial progenitors (SGEPs). Here, cystic fibrosis transmembrane conductance regulator (CFTR) knockout hPSCs were differentiated into SGEPs derived from CFTR knockout hESCs (CF-SGEPs) using the same protocol to investigate whether the hPSC-derived SGEPs can model the characteristics of CF. CF—a disease that affects salivary gland (SG) function—is caused by mutations of the CFTR gene. Firstly, we successfully generated CFTR knockout hPSCs with reduced CFTR protein expression using the CRISPR-Cas9 system. After 16 days of differentiation, the protein expression of CFTR decreased in SGEPs derived from CFTR knockout hESCs (CF-SGEPs). RNA-Seq revealed that multiple genes modulating SG development and function were down-regulated, and positive regulators of inflammation were up-regulated in CF-SGEPs, correlating with the salivary phenotype of CF patients. These results demonstrated that CFTR suppression disrupted the differentiation of hPSC-derived SGEPs, which modeled the SG development of CF patients. In summary, this study not only proved that the hPSC-derived SGEPs could serve as manipulable and readily accessible cell models for the study of SG developmental diseases but also opened up new avenues for the study of the CF mechanism.

Objective:To investigate the epidemic trend and risk change of acquired immunodeficiency syndrome (AIDS) complicated with malignant tumors after combination antiretroviral therapy (cART).Methods:The types of malignant tumors in patients with AIDS at different stages of cART were analyzed among anti-human immunodeficiency virus (HIV)-positive population in Hubei Province screened in National AIDS/HIV prevention and control information system from 1st January, 2004 to 31st December, 2018. The standardized incidence ratios(SIR) of malignant tumors in AIDS patients was analyzed based on the incidence of malignant tumors in the general population in Hubei Province or China in 2013. The changes in risks for development of malignant tumors in AIDS patients at different cART stages from 2004 to 2013 and 2014 to 2018 were compared.Chi-square test was used for statistical analysis.Results:Three hundred and twenty-three out of 22 994 AIDS patients were diagnosed with malignant tumors. Non-Hodgkin lymphoma(NHL) and cervical cancer were most common types in acquired immunodeficiency syndrome-defining cancers (ADC), while liver cancers and lung cancers were the most common types in non-acquired immunodeficiency syndrome-defining cancers (NADC). The overall risk of malignancy in AIDS patients was similar to that in the general population (SIR=1.06, χ2=0.62, P=0.426). However, the risks of Kaposi sarcoma, NHL, Hodgkin lymphoma, cervical cancer, and head and face cancers (excepting nasopharyngeal cancer) in AIDS patients were significantly higher than those in the general population (SIR=834.09, 9.65, 13.33, 5.22 and 2.94, respectively, χ2=11 747.27, 625.54, 56.65, 184.21 and 13.66, respectively, all P<0.01). The risks of lung cancer, colorectal anal cancer, stomach cancer and breast cancer in AIDS patients were significantly lower than those in the general population (SIR=0.33, 0.36, 0.43 and 0.45, respectively, χ2=33.43, 12.84, 9.01 and 7.21, respectively, all P<0.05). The SIR of cervical cancer, liver cancer and colorectal anal cancer from 2014 to 2018 were 4.06, 0.43 and 0.10, respectively, which were significantly lower than those from 2004 to 2013 (7.42, 1.96 and 0.84, respectively). The differences were all statistically significant ( χ2=5.39, 19.52 and 10.86, respectively, all P<0.05). Conclusions:At present, there are no significant differences of the incidences of malignant tumors between AIDS patients and general population, but the tumor types are different. The most common malignant tumors in this region are NHL and cervical cancer, which should be noted that HIV screening among patients with such tumors is conducive to comprehensive treatment to improve the efficacy.

Objective:To analyze the incidence and epidemiological characteristics of traumatic spinal cord injury in China in 2018.Methods:Multi-stage stratified cluster sampling was used to randomly select hospitals capable of treating patients with spinal cord injury from 3 regions，9 provinces and 27 cities in China to retrospectively investigate eligible patients with traumatic spinal cord injury admitted in 2018. National and regional incidence rates were calculated. The data of cause of injury，injury level，severity of injury，segment and type of fracture，complications，death and other data were collected by medical record questionnaire，and analyzed according to geographical region，age and gender.Results:Medical records of 4，134 patients were included in this study，with a male-to-female ratio of 2.99∶1. The incidence of traumatic spinal cord injury in China in 2018 was 50.484 / 1 million （95% CI 50.122-50.846）. The highest incidence in the Eastern region was 53.791 / 1 million （95% CI 53.217-54.365）. In the whole country，the main causes of injury were high falls （29.58%），as well as in the Western region （40.68%），while the main causes of injury in the Eastern and Central regions were traffic injuries （31.22%，30.10%）. The main injury level was cervical spinal cord in the whole country （64.49%），and the proportion of cervical spinal cord injury in the Central region was the highest （74.68%），and the proportion of lumbosacral spinal cord injury in the Western region was the highest （32.30%）. The highest proportion of degree of injury was incomplete quadriplegia （55.20%），and the distribution pattern was the same in each region. A total of 65.87% of the patients were complicated with fracture or dislocation，77.95% in the Western region and only 54.77% in the Central region. In the whole country，the head was the main combined injury （37.87%），as well as in the Eastern and Central regions，while the proportion of chest combined injury in the Western region was the highest （38.57%）. A total of 32.90% of the patients were complicated with respiratory complications. There were 23 patients （0.56%） died in hospital，of which 17（73.91%） died of respiratory dysfunction. Conclusions:The Eastern region of China has a high incidence of traumatic spinal cord injury. Other epidemiological features include high fall as the main cause of injury cervical spinal cord injury as the main injury level，incomplete quadriplegia as the main degree of injury，head as the main combined injury，and respiratory complications as the main complication.

Objective:To investigate the relationship between positive rate and titer of hepatitis B surface antibody (anti-HBs) and CD4 + T lymphocyte count level in human immunodeficiency virus (HIV) infected patients after hepatitis B virus (HBV) exposure. Methods:A total of 4 893 HIV-infected patients were admitted to Zhongnan Hospital of Wuhan University from January 2010 to December 2018. The demographic data, HIV-related diagnosis, treatment information, CD4 + T lymphocyte count and serum markers of HBV infection of HIV infected patients were retrospectively analyzed. The patients were grouped according to the CD4 + T lymphocyte count and serum markers of HBV infection, and the differences of anti-HBs positive rate and HBV exposure rate in patients with different CD4 + T lymphocyte counts were compared.The differences of CD4 + T lymphocyte count in patients with different titer of anti-HBs were compared. Statistical analysis was performed using chi-square test, analysis of variance or t test. Results:Patients with HIV infection were divided into CD4 + T lymphocyte count<200/μL group (3 293 cases), 200-500/μL group (1 200 cases) and CD4 + T lymphocyte count>500/μL group (400 cases). The HBV exposure rates in the three groups were 78.0%(2 569/3 293), 77.0%(924/1 200) and 76.2%(305/400), respectively. The anti-HBs positive rates were 38.2%(1 258/3 293), 53.8%(645/1 200) and 62.5%(250/400), respectively. The anti-HBs titers were (120.00±36.45) IU/L, (148.00±26.40) IU/L and (212.00±92.08) IU/L, respectively. The exposure rates of HBV in the three groups were similar ( χ2=0.992, P=0.609), but the positive rates and titers of anti-HBs were significantly different ( χ2=146.779 and F=45.362, respectively, both P<0.01). When the patients were grouped by anti-HBs titer, 2 740 cases were divided into anti-HBs negative group (<10 IU/L), 1 220 cases in low anti-HBs group (10-99 IU/L), 693 cases in medium anti-HBs group (100-499 IU/L) and 240 cases in high anti-HBs group (≥500 IU/L). The CD4 + T lymphocyte count levels of the four groups were (150.00±8.42)/μL, (185.00±7.08)/μL, (243.00±12.07)/μL and (308.00±22.60)/μL, respectively. The overall CD4 + T lymphocyte count levels among the four groups were significantly different ( F=68.479, P<0.01). Among the 90 HIV infected patients who received anti-retroviral therapy (ART), the anti-HBs titer increased from (91.96±21.87) IU/L to (200.76±56.43) IU/L after treatment, and the anti-HBs level before and after treatment was significantly different ( t=-2.542, P=0.035). Among 208 patients with negative HBV markers, no patients had hepatitis B surface antigen switched to positive when monitored for an interval time of (26.2±5.3) months. Conclusions:The risk of HBV exposure in patients with HIV infection is not significantly related to the disease stage, but the positive rate and titer of anti-HBs are significantly positively correlated with CD4 + T lymphocyte count level. The monitoring of anti-HBs and the serum markers of HBV infection in the same individual is conducive to the in-depth understanding of the protective effect of anti-HBs and the scientific evaluation of the risk of infection after HBV exposure.

The data of patients with HIV/AIDS from Hubei Province during 2004 to 2018 were obtained from the National AIDS Comprehensive Prevention and Control Information System. A total of 22 980 HIV-positive or AIDS patients were followed up for 113 164 person-years and 323 malignant tumors were diagnosed. Non-Hodgkin′s lymphoma (NHL), cervical cancer, liver cancer, lung cancer, and Kaposi sarcoma (KS) accounted for 70.0% (226/323) of all malignant tumors in this population. The average crude incidence and mortality of malignant tumors in HIV-infected patients were 285.43/100 000(269.11/100 000 in males and 325.87/100 000 in females), and 169.67/100 000(184.78/100 000 in males and 132.19/100 000 in females), respectively. The result indicates that the overall cancer incidence and mortality in HIV/AIDS population under widely implementation of combination anti-retroviral therapy (cART) are similar to those in the general population of the region. But the incidence and mortality of AIDS-related tumors such as KS, NHL, HD and cervical cancer are higher than those in general population, and attention should be given to screening of these malignancies in HIV/AIDS population.

Objective: To understand current situation and relations of childhood abuse and psychological capital, providing scientific basis for adolescent mental health promotion. Methods: Stratified cluster sampling method was used to select 1 894 students from junior high schools and senior high schools in Harbin. Questionnaire survey was conducted by using Childhood Trauma QuestionnaireShort Form (CTQ-SF) and Positive Psychological Capital (PPQ). Results: The total rate of childhood abuse among adolescents in the region was 98.3%. In addition to emotional abuse, scores of other dimensions of childhood abuse were higher for boys than for girls(P<0.01). Childhood abuse in rural area was higher than those in urban area except physical abuse(P<0.05). High psychological capital was observed among participants with boys higher in selfefficacy and resilience than that of girls(P<0.05). Psychological capital in urban students was higher than rural students(P<0.05). Except for the negative correlation between sexual abuse and resilience, all other dimensions of childhood abuse were negatively correlated with four dimensions of psychological capital. Stepwise regression analysis showed that emotional abuse, emotional neglect and physical neglect was negatively correlated with all dimensions of psychological capital(P<0.01); Sexual abuse showed negative association with selfefficacy and optimism(P<0.01). Conclusion Childhood abuse is closely related to psychological capital among adolescents in Harbin, suggesting exposure to childhood abuse might confer detrimental effects on psychological capital development.

BACKGROUND: Bone tissue engineering based on pluripotent stem cells (PSCs) is a new approach to deal with bone defects. Protocols have been developed to generate osteoblasts from PSCs. However, the low efficiency of this process is still an important issue that needs to be resolved. Many studies have aimed to improve efficiency, but developing accurate methods to determine efficacy is also critical. Studies using pluripotency to estimate efficacy are rare. Telomerase is highly associated with pluripotency. METHODS: We have described a quantitative method to measure telomerase activity, telomeric repeat elongation assay based on quartz crystal microbalance (QCM). To investigate whether this method could be used to determine the efficiency of in vitro osteogenic differentiation based on pluripotency, we measured the pluripotency pattern of cultures through stemness gene expression, proliferation ability and telomerase activity, measured by QCM. RESULTS: We showed that the pluripotency pattern determined by QCM was similar to the patterns of proliferation ability and gene expression, which showed a slight upregulation at the late stages, within the context of the general downregulation tendency during differentiation. Additionally, a comprehensive gene expression pattern covering nearly every stage of differentiation was identified. CONCLUSION: Therefore, this assay may be powerful tools for determining the efficiency of differentiation systems based on pluripotency. In this study, we not only introduce a new method for determining efficiency based on pluripotency, but also provide more information about the characteristics of osteogenic differentiation which help facilitate future development of more efficient protocols.
Bone and Bones ; Down-Regulation ; Gene Expression ; In Vitro Techniques ; Methods ; Mouse Embryonic Stem Cells ; Osteoblasts ; Pluripotent Stem Cells* ; Quartz Crystal Microbalance Techniques ; Telomerase* ; Up-Regulation