Objective:To investigate the therapeutic effectiveness of endoscopic retrograde cholangiopancreatography (ERCP) and stent implantation in the treatment of pancreaticobiliary injuries in children.Methods:A retrospective analysis was conducted on the clinical data of children diagnosed with pancreaticobiliary injury and undergoing ERCP and stent implantation at Beijing Children′s Hospital, Capital Medical University from January 2021 to December 2022. Demographic information, clinical data, endoscopic treatment methods, postoperative complications and clinical prognosis of the children were collected. The etiology, location of pancreaticobiliary injury, occurrence of complications after endoscopic treatment, and the time for improvement and recovery after endoscopic treatment were analyzed. The patients were divided into five groups according to the etiologies of pancreaticobiliary duct injuries: post-surgical, pancreatic trauma, acute pancreatitis, chronic pancreatitis, and systemic lupus erythematosus groups. They were also classified into four groups according to the sites of pancreaticobiliary duct injuries: common bile duct, pancreatic head, pancreatic body, and pancreatic tail groups. Multi-factor analysis of variance was used for comparing the time of improvement and recovery among different groups.Results:Among 22 patients, there were 8 males and 14 females, and the age was 7.5 (3.3,10.8) years. There were 19 cases of pancreatic or bile duct fistula, and 3 cases of pancreatic or bile duct stenosis. A total of 33 endoscopic procedures were performed on the 22 patients, out of which, 3 duct stenosis were failed to insert the stent because the catheter failed to pass through the stenosis site. The success rate was 91% (30/33). The pancreatic duct or bile duct stent was inserted, with the stent located at pancreatic or bile duct fistula. Postoperative complications included pancreatitis in 3 cases (9%, 3/33), hyperamylasemia in 5 cases (15%, 5/33), and postoperative infection in 4 cases (12%, 4/33). All patients were followed up for more than 1 year. Significant improvement was observed in external drainage and imaging monitoring among patients with successfully placed stents. There was no significant difference in the improvement time of ERCP in the treatment of pancreaticobile duct injury caused by different etiology ( F=0.65, P=0.637). However, there were significant differences in healing time ( F=6.46, P=0.004), among which the healing time of injuries caused by systemic lupus erythematosus was significantly different from that after surgery, trauma, acute pancreatitis and chronic pancreatitis (all P<0.05). There was no significant difference in the improvement and healing time among different injury sites (all P>0.05). Conclusions:ERCP and stent implantation can safely and effectively improve the clinical symptoms of children with pancreaticobiliary injury. Early intervention can improve long-term prognosis.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

Objective: QL1604 is a highly selective, humanized monoclonal antibody against programmed death protein 1. We assessed the efficacy and safety of QL1604 plus chemotherapy as first-line treatment in patients with advanced cervical cancer. Methods: This was a multicenter, open-label, single-arm, phase II study. Patients with advanced cervical cancer and not previously treated with systemic chemotherapy were enrolled to receive QL1604 plus paclitaxel and cisplatin/carboplatin on day 1 of each 21-day cycle for up to 6 cycles, followed by QL1604 maintenance treatment. Results: Forty-six patients were enrolled and the median follow-up duration was 16.5 months. An 84.8% of patients had recurrent disease and 13.0% had stage IVB disease. The objective response rate (ORR) per Response Evaluation Criteria in Advanced Solid Tumors (RECIST) v1.1 was 58.7% (27/46). The immune ORR per immune RECIST was 60.9% (28/46).The median duration of response was 9.6 months (95% confidence interval [CI]=5.5–not estimable). The median progression-free survival was 8.1 months (95% CI=5.7–14.0). Fortyfive (97.8%) patients experienced treatment-related adverse events (TRAEs). The most common grade≥3 TRAEs (>30%) were neutrophil count decrease (50.0%), anemia (32.6%), and white blood cell count decrease (30.4%). Conclusion QL1604 plus paclitaxel-cisplatin/carboplatin showed promising antitumor activity and manageable safety profile as first-line treatment in patients with advanced cervical cancer. Programmed cell death protein 1 inhibitor plus chemotherapy may be a potential treatment option for the patient population who have contraindications or can’t tolerate bevacizumab, which needs to be further verified in phase III confirmatory study.

The orphan nuclear receptor Nur77 is emerging as an attractive target for cancer therapy, and activating Nur77's non-genotypic anticancer function has demonstrated strong therapeutic potential. However, few Nur77 site B ligands have been identified as excellent anticancer compounds. There are no co-crystal structures of effective anticancer agents at Nur77 site B, which greatly limits the development of novel Nur77 site B ligands. Moreover, the lack of pharmaceutical ligands restricts Nur77's therapeutic proof of concept. Herein, we developed a first-in-class Nur77 site B ligand (NB1) that significantly inhibited cancer cells by mediating the Nur77/Bcl-2-related apoptotic effect at mitochondria. The X-ray crystallography suggests that NB1 is bound to the Nur77 site B with a distinct binding mode. Importantly, NB1 showed favorable pharmacokinetic profiles and safety, as evidenced by its good oral bioavailability in rats and lack of mortality, bodyweight loss, and pathological damage at the 512.0 mg/kg dose in mice. Furthermore, oral administration of NB1 demonstrated remarkable in vivo anticancer efficacy in an MDA-MB-231 xenograft model. Together, our work discovers NB1 as a new generation Nur77 ligand that activates the Nur77/Bcl-2 apoptotic pathway with a safe and effective cancer therapeutic potency.

Objective Viral myocarditis(VMC)is an inflammatory cardiovascular disease caused by Coxsackievirus,glandular virus,orphan virus and other viral infections.However,the pathogenesis of VMC is still unclear,so itis important to replicate a new animal model to study its mechanism.Methods So FAR,THE domestic and foreign literatures related to animal models of viral myocarditis were reviewed,and the modeling methods,types of animals,modeling mechanism,advantages and disadvantages,and clinical anastomosis of the included animal models were summarized and evaluated according to the characteristics of clinical symptoms of Chinese and western medicine.Results According to the statistics of the included models,it was found that the animal model of VMC induced by CVB3 was the most common.The model replication of viral myocarditis was mainly based on western medicine indicators,and the coincidence with traditional Chinese medicine syndrome type was low.In addition,there is no recognized model replication method with TCM syndrome types,and the model making process lacks TCM syndrome differentiation thinking,so it will cause certain limitations to the research of TCM.Conclusion Therefore,this article puts forward the improved method of animal model of viral myocarditis,and perfect the evaluation for animal model system,make the animal model of viral myocarditis build closer to clinical,for viral myocarditis curative effect of traditional Chinese medicines to judge and the discussion of pharmacological effects,provides a theoretical basis for the follow-up study of viral myocarditis provide theoretical basis for the prevention and control measures,the pathogenesis,in order to establish a combination model of viral myocarditis highly consistent with the clinical characteristics of traditional Chinese and Western medicine,so as to standardize the evaluation criteria of animal models of VMC,is the focus of future research on animal models of viral myocarditis.

Objective:To investigate the expression and clinical significance of vitamin D receptor (VDR) and human β-defensin-2(HBD2) in children with Helicobacter pylori (Hp) infection and gastritis.Methods:Eighty-one children who were hospitalized in the Department of Gastroenterology at Beijing Children′s Hospital from January 2021 to June 2023 and underwent endoscopic examination were collected.They were divided into Hp infection group and non-Hp infection group according to whether they were infected with Hp.The expression levels of VDR and HBD2 between two groups, and the correlation between VDR, HBD2 expression levels and gastritis were compared and analyzed.Results:Among 81 cases, 48 cases were Hp positive, including 24 males and 24 females, with an average age of (11.4±2.7) years; 33 cases were Hp negative, including 14 males and 19 females, with an average age of (11.3±2.6) years.There were no significant differences in sex and age between two groups ( P>0.05). The positive rates of VDR and HBD2 expression in gastric mucosa of children with Hp infection were higher than those of children without Hp infection, and the differences were statistically significant (87.5% vs.39.4%, 79.2% vs.63.6%, all P<0.05). The expressions of VDR and HBD2 had no correlation with age and sex ( P>0.05). The expressions of VDR and HBD2 were positively correlated with granular degeneration of gastric mucosa ( r=0.384, P<0.001; r=0.258, P=0.020). The expression of VDR was positively correlated with the degree of gastric inflammation ( r=0.365, P=0.001), while the expression of HBD2 was not correlated with the degree of gastric inflammation ( P>0.05). Conclusion:The expression levels of VDR and HBD2 in gastric mucosa of children infected with Hp are increased.The expression level of VDR is correlated with the degree of gastritis and the granular degeneration of gastric mucosa.The expression level of HBD2 is correlated with the granular degeneration of gastric mucosa.But there is no correlation between the level of HBD2 expression and the degree of gastritis.

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 and genetic characteristics of a child with frontometaphyseal dysplasia 1 (FMD1) due to variant of FLNA gene. METHODS: Clinical phenotype of the patient was analyzed. Whole exome sequencing (WES) was carried out to detect pathogenic genetic variants. Sanger sequencing was used to verify the result in his parents. RESULTS: The 2-year-and-9-month-old boy presented with facial dysmorphism (supraorbital hyperostosis, down-slanting palpebral fissure and ocular hypertelorism), skeletal deformities (bowed lower limbs, right genu valgum, left genu varus, slight deformity of index and middle fingers, and flexion contracture of little fingers). He also had limited left elbow movement. High-throughput sequencing revealed that he has carried a de novo heterogeneous c.3527G>A (p.Gly1176Glu) missense variant of the FLNA gene. The same variant was found in neither parent. CONCLUSION The clinical manifestations of FMD1 such as joint contracture and bone dysplasia can occur in infancy and deteriorate with age, and require long-term follow-up and treatment. Above finding has expanded the spectrum of FLNA gene variants.
Child ; Filamins/genetics* ; Forehead/abnormalities* ; Humans ; Infant ; Male ; Osteochondrodysplasias/genetics* ; Phenotype ; Whole Exome Sequencing

BACKGROUND: Most Chinese migrants have been faced with obstacles to getting access to local public health services. Young migrants among internal migrants make a major contribution to the economy. However, the establishment of their health records has been ignored. This research was aimed at exploring the status and associated factors of the establishment of health records among young Chinese migrants. METHODS: Data were obtained from the 2017 China Migrants Dynamic Survey (CMDS). Chi-square test and binary logistic regression were performed to investigate the associated factors of the establishment of health records among young Chinese migrants. RESULTS: Approximately 30.2% of young migrants had their health records established in inflow communities. Urban residence, medical insurance (insured), and lower average monthly household income were attributed to the establishment of more health records. Young migrants who were in northeast China and across provinces and immigrated for working or engaging in trade were less likely to have health records established. Young migrants who participated in social activities and public affairs activities and took type of people in touch as natives in the inflow area showed a higher possibility of establishing health records. Meanwhile, receiving health education and hearing about national basic public health services (BPHSs) were beneficial for establishing the health records of more young migrants. CONCLUSION This study showed that the health records of young migrants had a relatively low establishment rate. Sociodemographic and migration characteristics, health status, public health services, and social integration factors were all related to the health record establishment of young Chinese migrants.
Adolescent ; Adult ; China ; Female ; Health Records, Personal ; Humans ; Male ; Transients and Migrants/statistics & numerical data* ; Young Adult