Vitrification cryopreservation technology converts the liquid water in biological samples into glassy solids through ultra-rapid cooling. In this review, the core research of vitrification cryopreservation technology was mainly reviewed, such as the optimization of cryoprotectant formulations, the improvements to temperature control methods, the innovative carrier designs and the improvements to rewarming technology. The application status and issues in the fields of organ preservation, tumor research, reproductive medicine and rare cell preservation were also summarized. By combining the technical principles with glassy state detection methods, a theoretical basis was provided for optimizing the technical system and expanding application scenarios, thereby promoting its large-scale application in clinical and biological sample libraries.

OBJECTIVE To investigate the relationship of long non-coding RNA （LncRNA） metastasis-associated lung adenocarcinoma transcript 1 （MALAT1） and doxorubicin （DOX） resistance in osteosarcoma （OS） cells. METHODS MG-63 and MG-63/DOX cells were treated with different concentrations of DOX （0， 0.01， 0.05， 0.1， 1 μmol/L）， and survival rates and half maximal inhibitory concentration were determined using CCK-8 assay. The expressions of LncRNA MALAT1 in MG-63 and MG-63/ DOX cells were detected by real-time quantitative fluorescence PCR. MG-63/DOX cells were divided into Control group， knocking down LncRNA MALAT1 negative control （sh-NC） group， sh-MALAT1 group， sh-MALAT1+anti-NC group， and sh-MALAT1+ anti-miR-154-5p group. The expressions of LncRNA MALAT1， miR-154-5p and cyclin D1 （CCND1） mRNA in MG-63/DOX cells of each group were detected. The effects of knocking down LncRNA MALAT1 on the proliferation， migration， invasion， and apoptosis of MG-63/DOX cells were detected by CCK-8 assay， scratch test， Transwell experiment and flow cytometry， respectively. The expression of proliferating cell nuclear protein （PCNA） and CCND1 protein in MG-63/DOX cells was detected by Western blot assay. Interactions between LncRNA MALAT1 and miR-154-5p， miR-154-5p and CCND1 were detected by dual luciferase reporter gene experiment. RESULTS Compared with 0 μmol/L DOX， 0.01， 0.05， 0.1 and 1 μmol/L DOX could reduce the survival rates of MG-63 and MG-63/DOX cells （except for 0.01 μmol/L DOX） （P＜0.05）， IC50 were 0.07 and 0.13 μmol/L， respectively. The survival rate， cell migration number and invasion number of MG-63/DOX cells， scratch closure rate， mRNA expressions of LncRNA MALAT1， mRNA and protein expressions of CCND1， and PCNA protein expression in sh-MALAT1 group were significantly lower than sh-NC group and Control group； the apoptosis rate and miR-154-5p expression were significantly higher than sh-NC group and Control group （P＜0.05）. sh-MALAT1+anti-miR-154-5p group was able to reverse the aforementioned biological effects in sh-MALAT1 group （P＜0.05）. In MG-63/DOX cells transfected with both MALAT1-wild type （WT） and CCND1-WT， the luciferase activity in the miR-154-5p mimic group was significantly lower than mimic negative control group （P＜ 0.05）. CONCLUSIONS Knocking down LncRNA MALAT1 can inhibit the DOX resistance of OS cells， and its mechanism may be targeting the miR-154-5p/CCND1 axis.

Objective:To develop and validate a 30-day readmission risk prediction model for patients with chronic obstructive pulmonary disease (COPD) using multiple machine learning algorithms.Methods:Convenience sampling was used to select 1 450 COPD patients hospitalized at Tianjin Medical University General Hospital from January 2017 to December 2023 as study subjects. Twenty-nine variables associated with readmission were included. LASSO was used to screen for primary characteristic variables associated with 30-day readmission. The 1 450 patients were divided into a training set ( n=870) and a test set ( n=580) in a 6∶4 ratio. Ten machine learning methods, including random forest, AdaBoost, extreme radient Boosting (XGB), decision tree and so on, were used for model training and testing to identify the optimal prediction model. The optimal model and SHAP were employed to analyze key features and rank characteristic importance. Results:Among 1 450 COPD patients, the 30-day readmission rate was 24.48% (355/1 450). There were no significant differences in the general information between patients in test set and training set ( P>0.05). LASSO regression analysis identified seven variables with the highest predictive value, namely regular weekly exercise, hospital stay, mean arterial pressure, forced expiratory volume in one second/forced vital capacity (FEV1/FVC), C-reactive protein, body mass index, and medication adherence. Machine learning showed that in the training set, XGB had the highest area under the receiver operating characteristic curve ( AUC), sensitivity, and F1 score of 0.943, 0.926, and 0.930, respectively. In the test set, the AUC and accuracy of XGB were 0.882 and 0.858, respectively, and XGB's various scores showed that it had good generalization and predictive performance. XGB analysis showed that medication adherence, FEV1/FVC, and regular weekly exercise were negatively correlated with the 30-day readmission risk, while body mass index, C-reactive protein, mean arterial pressure, and hospital stay were positively correlated. The characteristics ranked in order of importance were medication adherence, body mass index, C-reactive protein, mean arterial pressure, FEV1/FVC, hospital stay and regular weekly exercise. Conclusions:The XGB model has strong predictive performance and good generalization ability, which can effectively predict the 30-day readmission risk of COPD patients, assist in clinical identification of high-risk patients, implement nursing interventions, and reduce readmission rates.

Objective:To assess the efficacy and safety profile of antaitasvir phosphate combined with yiqibuvir in the treatment of chronic hepatitis C (CHC) of various genotypes, without cirrhosis or with compensated cirrhosis.Methods:394 cases with CHC from 22 centers were collected from October 2021 to April 2023. They were randomly assigned to receive either the experimental drugs (antaitasvir phosphate 100 mg+yiqibuvir 600 mg) or placebo treatment in a 3∶1 ratio. The patients were administered drugs once a day for 12 consecutive weeks, and then followed up for 24 weeks after treatment cessation. All subjects were unblinded at the four-week follow-up following drug discontinuation, with the experimental drug group continuing to complete subsequent post-discontinuation follow-up. The placebo group was switched to receive the experimental drugs for a repeated 12-week treatment period and followed up for another 24 weeks after discontinuation of the drug (placebo delayed treatment phase).The sustained virologic response rate (SVR12) was observed for subjects in the double-blind phase and the placebo delayed-treatment phase at 12 weeks after treatment cessation.Virological resistance analysis was performed on subjects who failed treatment. The primary efficacy endpoint was SVR12. The number and percentage of subjects who achieved "HCV RNA

BACKGROUND: Over 20 million colonoscopies are performed in China annually. An automatic clinical decision support system (CDSS) with accurate semantic recognition of colonoscopy reports and guideline-based is helpful to relieve the increasing medical burden and standardize the healthcare. In this study, the CDSS was built under a hierarchical-label interpretable classification framework, trained by a state-of-the-art transformer-based model, and validated in a multi-center style. METHODS: We conducted stratified sampling on a previously established dataset containing 302,965 electronic colonoscopy reports with pathology, identified 2041 patients' records representative of overall features, and randomly divided into the training and testing sets (7:3). A total of five main labels and 22 sublabels were applied to annotate each record on a network platform, and the data were trained respectively by three pre-training models on Chinese corpus website, including bidirectional encoder representations from transformers (BERT)-base-Chinese (BC), the BERT-wwm-ext-Chinese (BWEC), and ernie-3.0-base-zh (E3BZ). The performance of trained models was subsequently compared with a randomly initialized model, and the preferred model was selected. Model fine-tuning was applied to further enhance the capacity. The system was validated in five other hospitals with 3177 consecutive colonoscopy cases. RESULTS: The E3BZ pre-trained model exhibited the best performance, with a 90.18% accuracy and a 69.14% Macro-F1 score overall. The model achieved 100% accuracy in identifying cancer cases and 99.16% for normal cases. In external validation, the model exhibited favorable consistency and good performance among five hospitals. CONCLUSIONS The novel CDSS possesses high-level semantic recognition of colonoscopy reports, provides appropriate recommendations, and holds the potential to be a powerful tool for physicians and patients. The hierarchical multi-label strategy and pre-training method should be amendable to manage more medical text in the future.
Humans ; Colonoscopy/methods* ; Deep Learning ; Decision Support Systems, Clinical ; Female ; Male

Objective:To analyze the gene mutation spectrum of children with T-acute lymphoblastic leukemia (T-ALL) using next generation sequencing technology and to evaluate the value of gene mutations in prognosis stratification.Methods:A case series analysis was made.The clinical data of newly diagnosed pediatric T-ALL patients in the First Affiliated Hospital of Zhengzhou University from January 1, 2019 to February 29, 2024 were analyzed retrospectively.T-ALL gene mutations were analyzed.The relationships of gene mutations with clinical features and induction of responses to therapy were studied.The effects of gene mutations on overall survival (OS) and event-free survival (EFS) were examined by the Kaplan-Meier method and COX regression model.Results:A total of 80 newly diagnosed pediatric T-ALL patients were enrolled in the study, with a male-to-female ratio of 3.4∶1.0 and a median age of 8 (range, 2-17) years.A total of 57 mutations were detected in 74 patients, 46.2% (37/74) of whom showed 3 or more gene mutations.The coexistence of mutated genes was obvious. PTEN mutations were more prevalent in male patients ( P=0.018).Initial leukocyte counts were higher in patients with PTEN mutations ( P=0.038) and lower in patients with JAK3 mutations ( P=0.002).Patients with NOTCH1 mutations had a higher positive rate of fusion genes ( P=0.043).Patients with PTEN mutations had a higher rate of minimal residual disease(MRD) remission after 15/19 d of treatment with induction therapy, respectively ( P=0.013).The rate of MRD remission after 33/46 d of treatment with induction therapy was higher in patients with the FBXW7 mutation ( P=0.004) and lower in patients with JAK3 mutations ( P=0.003).Multifactorial COX regression analysis showed that IL7R mutation and three or more gene mutations were independent risk factors for OS and EFS in T-ALL patients(OS: HR=3.252, 7.357, 95% CI: 1.020-10.372, 1.646-32.882; EFS: HR=3.372, 3.009, 95% CI: 1.234-9.214, 1.174-7.708; all P<0.05). Conclusions:Gene mutations are prevalent in T-ALL children and correlate with clinical manifestations and prognosis.The coexistence of mutated genes is obvious.Pediatric T-ALL patients with IL7R mutations and three or more gene mutations have a poorer prognosis.

Objective:To investigate the clinical experience and efficacy of unrelated umbilical cord blood hematopoietic stem cell transplantation (HSCT) for the treatment of congenital amegakaryocytic thrombocytopenia (CAMT).Methods:A case summary was conducted.The clinical data of 2 children with CAMT who were finally cured by unrelated umbilical cord blood HSCT in the Department of Pediatric Medicine, the First Affiliated Hospital of Zhengzhou University from March 2020 to August 2023 were retrospectively analyzed.Related studies were retrieved from databases CNKI, Wanfang and PubMed using search terms including " congenital amegakaryocytic thrombocytopenia" and " hematopoietic stem cell transplantation" from the inception to July 2024.The clinical characteristics, diagnosis and treatment processes, and prognosis of CAMT patients treated by HSCT were then summarized.Results:Both cases exhibited scattered skin haemorrhages throughout the body and carried 2 compound heterozygous mutations with pathogenicity in the MPL gene.Both patients were finally diagnosed with CAMT.Case 1 was a girl aged 3 at the time of transplantation, and case 2 was also a girl, who aged 5 at the time of transplantation.Both of them received unrelated umbilical cord blood HSCT and hematopoietic reconstruction was achieved.The time of neutrophil and platelet implantation was 21 and 40 days after transplantation in case 1, and 20 and 31 days in case 2, respectively.The chimerism rate of neutrophil implantation in both children was complete chimerism of donor cells.Implantation syndrome was detected in case 1 following transplantation.Case 2 suffered implantation syndrome, hypertensive encephalopathy, and cytomegalovirus infection following transplantation.Both children showed no graft-versus-host disease (GVHD).Both children had hematopoietic and immune reconstruction after transplantation and their primary diseases were cured.Cases 1 and 2 were followed up for more than 14 and 17 months, respectively.Both of them achieved disease-free survival during the follow up.Literature review of 26 cases with CAMT treated by HSCT, including the above-mentioned 2 cases was conducted, with an overall disease-free survival rate of 92.3%(24/26).Of 12 cases with CAMT typing, 10 were type Ⅰ and 2 were type Ⅱ.Of the 26 cases treated by HSCT, 17 had bone marrow HSCT, with an overall survival rate of 88.2%(15/17), and 2 had peripheral blood HSCT.Seven cases had umbilical cord blood HSCT (6 cases receiving unrelated umbilical cord blood HSCT and 1 case receiving related umbilical cord blood HSCT), with an overall survival rate of 100%.Unlike bone marrow and peripheral blood HSCT, unrelated umbilical cord blood HSCT did not result in 3-4 grade GVHD. Conclusions:Unrelated umbilical cord blood HSCT can achieve good therapeutic effects in CAMT patients when there is no suitable donor.Myeloablative pretreatment is conducive to CAMT patients.

Objective:To analyze the gene mutation spectrum of children with T-acute lymphoblastic leukemia (T-ALL) using next generation sequencing technology and to evaluate the value of gene mutations in prognosis stratification.Methods:A case series analysis was made.The clinical data of newly diagnosed pediatric T-ALL patients in the First Affiliated Hospital of Zhengzhou University from January 1, 2019 to February 29, 2024 were analyzed retrospectively.T-ALL gene mutations were analyzed.The relationships of gene mutations with clinical features and induction of responses to therapy were studied.The effects of gene mutations on overall survival (OS) and event-free survival (EFS) were examined by the Kaplan-Meier method and COX regression model.Results:A total of 80 newly diagnosed pediatric T-ALL patients were enrolled in the study, with a male-to-female ratio of 3.4∶1.0 and a median age of 8 (range, 2-17) years.A total of 57 mutations were detected in 74 patients, 46.2% (37/74) of whom showed 3 or more gene mutations.The coexistence of mutated genes was obvious. PTEN mutations were more prevalent in male patients ( P=0.018).Initial leukocyte counts were higher in patients with PTEN mutations ( P=0.038) and lower in patients with JAK3 mutations ( P=0.002).Patients with NOTCH1 mutations had a higher positive rate of fusion genes ( P=0.043).Patients with PTEN mutations had a higher rate of minimal residual disease(MRD) remission after 15/19 d of treatment with induction therapy, respectively ( P=0.013).The rate of MRD remission after 33/46 d of treatment with induction therapy was higher in patients with the FBXW7 mutation ( P=0.004) and lower in patients with JAK3 mutations ( P=0.003).Multifactorial COX regression analysis showed that IL7R mutation and three or more gene mutations were independent risk factors for OS and EFS in T-ALL patients(OS: HR=3.252, 7.357, 95% CI: 1.020-10.372, 1.646-32.882; EFS: HR=3.372, 3.009, 95% CI: 1.234-9.214, 1.174-7.708; all P<0.05). Conclusions:Gene mutations are prevalent in T-ALL children and correlate with clinical manifestations and prognosis.The coexistence of mutated genes is obvious.Pediatric T-ALL patients with IL7R mutations and three or more gene mutations have a poorer prognosis.

Objective:To investigate the clinical experience and efficacy of unrelated umbilical cord blood hematopoietic stem cell transplantation (HSCT) for the treatment of congenital amegakaryocytic thrombocytopenia (CAMT).Methods:A case summary was conducted.The clinical data of 2 children with CAMT who were finally cured by unrelated umbilical cord blood HSCT in the Department of Pediatric Medicine, the First Affiliated Hospital of Zhengzhou University from March 2020 to August 2023 were retrospectively analyzed.Related studies were retrieved from databases CNKI, Wanfang and PubMed using search terms including " congenital amegakaryocytic thrombocytopenia" and " hematopoietic stem cell transplantation" from the inception to July 2024.The clinical characteristics, diagnosis and treatment processes, and prognosis of CAMT patients treated by HSCT were then summarized.Results:Both cases exhibited scattered skin haemorrhages throughout the body and carried 2 compound heterozygous mutations with pathogenicity in the MPL gene.Both patients were finally diagnosed with CAMT.Case 1 was a girl aged 3 at the time of transplantation, and case 2 was also a girl, who aged 5 at the time of transplantation.Both of them received unrelated umbilical cord blood HSCT and hematopoietic reconstruction was achieved.The time of neutrophil and platelet implantation was 21 and 40 days after transplantation in case 1, and 20 and 31 days in case 2, respectively.The chimerism rate of neutrophil implantation in both children was complete chimerism of donor cells.Implantation syndrome was detected in case 1 following transplantation.Case 2 suffered implantation syndrome, hypertensive encephalopathy, and cytomegalovirus infection following transplantation.Both children showed no graft-versus-host disease (GVHD).Both children had hematopoietic and immune reconstruction after transplantation and their primary diseases were cured.Cases 1 and 2 were followed up for more than 14 and 17 months, respectively.Both of them achieved disease-free survival during the follow up.Literature review of 26 cases with CAMT treated by HSCT, including the above-mentioned 2 cases was conducted, with an overall disease-free survival rate of 92.3%(24/26).Of 12 cases with CAMT typing, 10 were type Ⅰ and 2 were type Ⅱ.Of the 26 cases treated by HSCT, 17 had bone marrow HSCT, with an overall survival rate of 88.2%(15/17), and 2 had peripheral blood HSCT.Seven cases had umbilical cord blood HSCT (6 cases receiving unrelated umbilical cord blood HSCT and 1 case receiving related umbilical cord blood HSCT), with an overall survival rate of 100%.Unlike bone marrow and peripheral blood HSCT, unrelated umbilical cord blood HSCT did not result in 3-4 grade GVHD. Conclusions:Unrelated umbilical cord blood HSCT can achieve good therapeutic effects in CAMT patients when there is no suitable donor.Myeloablative pretreatment is conducive to CAMT patients.

Objective To explore the differences and similarities in the changes of pulp repair response after direct pulp capping with iRoot BP Plus and MTA.Methods A total of 36 male SD rats were randomly divided into 3 groups,namely iRoot BP Plus group,MTA group and blank control group.Dental pulp exposure and direct pulp capping was performed on both sides of maxillary first molars of each rat.Four rats were randomly selected and sacrificed from each group at 7,14,and 28 days postoperatively,and the specimens were taken for hematoxylin-eosin(HE)staining,and then each index was observed.Results ①From the perspective of dentin tubular formation quality,at 14 d and 28 d,there were statistical differences between iRoot BP Plus group and MTA group(P＜0.05),and iRoot BP Plus was significantly better than MTA in terms of quality of restorative dentin formation.②At 14 days after operation,iRoot BP Plus had a greater area of neodontinin than that in MTA group(P＜0.05).Conclusion Both iRoot BP Plus and MTA can promote the formation of restorative dentin bridges after direct pulp capping,and the formation quality is high.The long-term effects need to be further studied.