ObjectiveTo explore the potential mechanism of Huoxue Xiaoyi Formula （活血消异方， HXF） in treating ovarian endometriosis （OEM） from the perspective of T follicular helper （Tfh） cells and the Janus kinase/signal transducer and activator of transcription （JAK/STAT） signaling pathway. MethodsForty-five female SD rats with normal estrous cycles were randomly divided into three groups， HXF group， model group， and normal group， with 15 rats in each group. A rat model of OEM was established by autologous endometrial tissue implantation. After successful modeling， the treatment group received HXF at 5.85 g/（kg·d） by gavage for 14 consecutive days. The model group and normal group received 1 mL/d of normal saline by gavage. RNA-sequencing data from human proliferative-phase endometriotic and normal endometrial tissues were downloaded from the GEO database. Transcriptomic sequencing was used to analyze gene expression in rat ovarian ectopic tissues and normal uterine tissues， and comparisons were made with human data to verify JAK/STAT pathway activation in proliferative-phase ectopic tissues. Immunohistochemistry was used to detect the positive expression of CXC chemokine receptor 5 （CXCR5） and interleukin-21 （IL-21） in rat ovarian ectopic and normal uterine tissues. Western Blotting was performed to detect the protein levels of IL-21， IL-21 receptor （IL-21R）， Janus kinase 1 （JAK1）， signal transducer and activator of transcription 6 （STAT6）， and B-cell lymphoma 2 （Bcl-2）. Tfh cell infiltration was analyzed using immune cell infiltration methods. ResultsGene set enrichment analysis showed that the JAK/STAT pathway was significantly activated in human proliferative-phase endometriotic tissues compared to normal endometrial tissues. Similarly， the JAK/STAT pathway was markedly activated in rat ovarian ectopic tissues in the model group compared to the normal group， but suppressed in the HXF group compared to the model group. Compared with normal uterine tissues， ovarian ectopic tissues in the model group showed increased Tfh cell infiltration scores， higher CXCR5 and IL-21 expression， and elevated levels of IL-21， IL-21R， JAK1， STAT6， and Bcl-2 proteins. Compared with the model group， HXF group showed reduced CXCR5 and IL-21 expression and decreased protein levels of IL-21， IL-21R， JAK1， STAT6， and Bcl-2. ConclusionHXF may suppress activation of the JAK/STAT signaling pathway in ovarian endometriotic tissues by inhibiting IL-21 secretion from Tfh cells.

Objective To investigatethe relationship between gastroesophageal reflux disease (GERD) symptoms and clinicopathological characteristics, p53 expression, and survival of Chinese patients with esophageal adenocarcinoma. Methods A total of 3882 patients with esophageal adenocarcinoma, 970 matched patients with esophageal squamous cell carcinoma, and 970 matched patients with gastric cardia adenocarcinoma were included to compare the incidence of GERD symptoms. Patients with esophageal adenocarcinoma were divided into two groups according to the presence and absence of GERD symptoms. The differences in clinicopathological characteristics and p53 expression between the two groups were compared by chi-square test, and the differences in survival between the two groups were compared by landmark analysis. Results The incidence of GERD symptoms increased successively in esophageal squamous cell carcinoma, esophageal adenocarcinoma, and gastric cardia adenocarcinoma. In patients with esophageal adenocarcinoma, the proportions of male, less than 65 years old, lower thoracic tumors, tumors without squamous cell carcinoma, poorly differentiation, early tumors (stage 0-I), and p53-positive tumors in the group with GERD symptoms were higher than those in the group without GERD symptoms; moreover, the long-term survival (≥15 years) was better. Conclusion GERD symptom is an important clinical sign of esophageal adenocarcinoma. It is closely related to specific clinicopathological characteristics, p53 overexpression, and good long-term prognosis.

Gastrointestinal (GI) cancers are the most common tumors of the digestive system, and their high morbidity and cancer-related mortality dramatically threaten the health of the population. With the researching progress of immunotherapy, its use in the treatment of GI cancers in the perioperative and advanced stages is becoming more and more important. Currently, immunotherapy has become the standard first-line treatment for MSI-H late-stage colorectal cancer, while in the first-line treatment of late-stage gastric cancer, immunotherapy combined with chemotherapy and HER2-targeted drugs (in HER2-positive patients) has also achieved significant efficacy and long-term survival benefits. Advances in immunotherapy in the neoadjuvant and adjuvant treatment and in the second- and later-line treatment of late-stage GI cancers have demonstrated its promising therapeutic potential. However, there is still an urgent need for future studies to explore more immunotherapy combination strategies for patients with GI cancers, especially with MSS colorectal cancers.

Gastrointestinal (GI) cancers are the most common tumors of the digestive system, and their high morbidity and cancer-related mortality dramatically threaten the health of the population. With the researching progress of immunotherapy, its use in the treatment of GI cancers in the perioperative and advanced stages is becoming more and more important. Currently, immunotherapy has become the standard first-line treatment for MSI-H late-stage colorectal cancer, while in the first-line treatment of late-stage gastric cancer, immunotherapy combined with chemotherapy and HER2-targeted drugs (in HER2-positive patients) has also achieved significant efficacy and long-term survival benefits. Advances in immunotherapy in the neoadjuvant and adjuvant treatment and in the second- and later-line treatment of late-stage GI cancers have demonstrated its promising therapeutic potential. However, there is still an urgent need for future studies to explore more immunotherapy combination strategies for patients with GI cancers, especially with MSS colorectal cancers.

Objective:To explore the characteristics of endothelial function in children with incomplete Kawasaki disease (IKD) of different ages and its relationship with coronary artery lesion (CAL).Methods:A total of 200 children with IKD admitted to the Affiliated Hospital of Jining Medical University from February 2020 to May 2022 were selected as the IKD group, and another 200 healthy children who underwent physical examinations during the same period were selected as the control group. According to the age of children with IKD, infants ( n=78) were classified as those under 1 year old, infants ( n=62) were classified as those between 1-3 years old, and preschool children ( n=60) were classified as those over 3-6 years old. The endothelial function characteristics of IKD children in different age groups and normal control group children were analyzed and compared. In addition, IKD patients were divided into CAL group ( n=110) and nCAL group ( n=90) based on whether CAL was merged. The age, carotid intima-media thickness (IMT), flow-mediated-dilation (FMD), carotid stiffness index (SI), nitroglycerin-mediated dilation (NMD), tumor necrosis factor α (TNF-α), C-reactive protein (CRP), brachial artery endothelial dependent dilation function (EDD) and other clinical data were compared between the two groups. Cox proportional hazards model was used for univariate and multivariate analysis to identify the risk factors for CAL in IKD patients. A column chart prediction model was constructed and evaluated. Results:There were statistically significant differences in FMD, NMD, SI, IMT, reactive congestion index (RHI), and EDD between IKD patients and normal control group children (all P<0.05). There were statistically significant differences in FMD, NMD, SI, IMT, RHI, and EDD among three groups of IKD children of different ages (all P<0.05). There were statistically significant differences in the proportion of children aged ≤3 years, TNF-α, CRP, SI, IMT, EDD, FMD, and NMD between the nCAL and CAL groups (all P<0.05). Age ≤3 years, elevated levels of TNF-α, CRP, SI, IMT, and EDD, as well as decreased levels of FMD and NMD, were independent risk factors for CAL in children with IKD (all P<0.05). The column chart prediction model had high discrimination, and the area under the curve for predicting CAL occurrence in children with IKD was 0.868 and 0.830, respectively. Conclusions:There are significant differences in endothelial function among children with IKD of different ages, and endothelial function is closely related to the occurrence of CAL. When endothelial function is abnormal, CAL is more likely to occur.

Corona virus disease 2019 （COVID-19） has led to more than 500 million cases， including 6.19 million deaths. Mutated strains of SARS-CoV-2 （alpha， beta， gamma， delta and omicron） have successively emerged. Currently the omicron variant is gradually replacing the delta variant， driving a surge of cases in most countries including China， posing a great challenge to the prevention and treatment of COVID-19. In the face of the severe pandemic situation， a large number of non-medical volunteers are fighting on the front lines of the war against the pandemic and are vulnerable to exposure due to lack of professional knowledge. This paper introduces the routine skills training of volunteers and emergency response， aiming to provide behavioral guidance for non-medical volunteers in designated isolation facilities.

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Objective:To characterize the histopathological subtypes and their clinicopathological parameters of gender and onset age by common, rare and sparse primary esophageal malignant tumors (PEMT).Methods:A total of 272 437 patients with PEMT were enrolled in this study, and all of the patients were received radical surgery. The clinicopathological information of the patients was obtained from the database established by the State Key Laboratory of Esophageal Cancer Prevention & Treatment from September 1973 to December 2020, which included the clinical treatment, pathological diagnosis and follow-up information of esophagus and gastric cardia cancers. All patients were diagnosed and classified by the criteria of esophageal tumor histopathological diagnosis and classification (2019) of the World Health Organization (WHO). The esophageal tumors, which were not included in the WHO classification, were analyzed separately according to the postoperative pathological diagnosis. The χ 2 test was performed by the SPSS 25.0 software on count data, and the test standard α=0.05. Results:A total of 32 histopathological types were identified in the enrolled PEMT patients, of which 10 subtypes were not included in the WHO classification. According to the frequency, PEMT were divided into common (esophageal squamous cell carcinoma, ESCC, accounting for 97.1%), rare (esophageal adenocarcinoma, EAC, accounting for 2.3%) and sparse (mainly esophageal small cell carcinoma, malignant melanoma, etc., accounting for 0.6%). All the common, rare, and sparse types occurred predominantly in male patients, and the gender difference of rare type was most significant (EAC, male∶ female, 2.67∶1), followed with common type (ESCC, male∶ female, 1.78∶1) and sparse type (male∶ female, 1.71∶1). The common type (ESCC) mainly occurred in the middle thoracic segment (65.2%), while the rare type (EAC) mainly occurred in the lower thoracic segment (56.8%). Among the sparse type, malignant melanoma and malignant fibrous histiocytoma were both predominantly located in the lower thoracic segment (51.7%, 66.7%), and the others were mainly in the middle thoracic segment.Conclusion:ESCC is the most common type among the 32 histopathological types of PEMT, followed by EAC as the rare type, and esophageal small cell carcinoma and malignant melanoma as the major sparse type, and all of which are mainly occur in male patients. The common type of ESCC mainly occur in the middle thoracic segment, while the rare type of EAC mainly in the lower thoracic segment. The mainly sparse type of malignant melanoma and malignant fibrous histiocytoma predominately occur in the lower thoracic segment, and the remaining sparse types mainly occur in the middle thoracic segment.

OBJECTIVE: To explore the clinical characteristics and prognostic values of TP53 gene variant in patients with acute leukemia(AL). METHODS: The clinical data of 44 newly diagnosed AL patients with TP53 variant detected by next generation sequencing (NGS) were analyzed retrospectively. Targeted sequencing technique containing 108 leukemia-related genes was used for variant analysis, and conventional R-banding technique was used for karyotype analysis. The clinical features, cytogenetics, gene variant, curative effect and survival of AL patients with TP53 gene variant were analyzed. RESULTS: The median age of AML patients with TP53 gene variant (46 years) was higher than that of ALL patients (17.5 years), and the median number of bone marrow blasts (40.5%) was lower than the latter (89.2%), the differences were statistically significant (P< 0.01). A total of 28 cases of abnormal karyotype were detected, of which 25 cases were complex karyotype, 16 cases were monomeric karyotype, 14 cases had -17/17p-. The detection rates of TP53 in complex karyotype, monomeric karyotype and -17/17p- were 59.5%, 38.1% and 33.3%, respectively. Subgroup analysis showed that the detection rate of TP53 gene abnormalities in AML and ALL complex karyotypes was 73.1% and 40% respectively, the difference was statistically significant. A total of 41 TP53 gene variant types were found, and the median variant frequency was 43.58%. 75.6% variant was located in the DNA binding domain. The concomitant variant genes were mainly TET2 and IKZF1. Among 18 AML and 17 ALL patients who could be evaluated the curative effect, the CR rate of one course of treatment was 22.2% and 94.12% respectively, and the difference was statistically significant. The median RFS of 4 cases of AML with CR and 16 cases of ALL with CR were 174 and 246 days respectively, the difference was statistically insignificant. The median OS of AML and ALL was 20 and 375 days respectively, the difference was statistically significant. CONCLUSION The TP53 gene variant is associated with the complex karyotype of AML, but has no significant effect on ALL. The variant site of TP53 gene was mainly distributed in the DNA binding domain. The remission rate of AML with TP53 gene variant was lower than that of ALL. The prognosis of AL patients with TP53 gene variant is poor, so allogeneic hematopoietic stem cell transplantation should be performed as soon as possible to prolong the survival of the patients.
Acute Disease ; Humans ; Leukemia, Myeloid, Acute/genetics* ; Middle Aged ; Mutation ; Retrospective Studies ; Tumor Suppressor Protein p53/genetics*

Objective:To explore the characteristics and clinical significance of clonal heterogeneity in patients with acute lymphoblastic leukemia(ALL).Methods:From January 2016 to June 2019, 170 newly diagnosed ALL patients were enrolled in the Department of Hematology, Henan Cancer Hospital, including 93 males and 77 females, with a median age of 17 (2-80) years. Fifty-two ALL-related genes were detected by high-throughput sequencing technique. The clonal heterogeneity of mutations was analyzed according to the variant allele frequency (VAF) and the results of flow cytometry. The prognostic value of mutations was also evaluated.Results:Gene mutations were detected in 121 (71.2%, 121/170) patients, of which 2 or more clones were detected in 18 (52.9%, 18/34) T-cell acute lymphoblastic leukemia patients, while only 23 (16.9%, 23/136) B-cell acute lymphoblastic leukemia patients were positive of multiple mutations ( P<0.01).Gene mutation-related clonal heterogeneity analysis showed that 2 or more clones were frequent in patients with NOTCH1 mutations (13/19 patients) ( P<0.01). Event free survival (EFS) in patients with 3 or more clones was significantly lower than other patients (χ 2=10.330, P=0.016). Child ALL patients had similar result, that multiple clones predicted lower overall survival (OS) and EFS (OS: χ 2=7.974, P=0.047; EFS: χ 2=10.860, P=0.013). Conclusion:Clonal heterogeneity in ALL patients is closely related to the different origin of lymphocyte lineages and the age of onset, which may reveal the nature of the disease and predict the clinical outcome.