Esophageal cancer is one of the malignant tumors that poses a threat to human health, with both high incidence and malignancy. Currently, surgery following neoadjuvant chemoradiotherapy is the standard treatment for locally advanced esophageal cancer; however, the long-term prognosis remains unsatisfactory. In recent years, inhibitors of programmed death protein-1 (PD-1) and its ligand (programmed death ligand-1, PD-L1) have achieved breakthrough progress in other solid tumors, and research on esophageal cancer is gradually being conducted. With the demonstration of good efficacy of PD-1/PD-L1 inhibitors in the first-line and second-line treatment of advanced unresectable esophageal cancer, their incorporation into neoadjuvant treatment regimens has become a hot topic. Therefore, this article reviews the mechanism of action of PD-1/PD-L1 inhibitors and their application in the neoadjuvant treatment of esophageal cancer.

Objective To investigate whether miR-15b-5p can alleviate airway inflammation in asthma by negatively regulating ubiquitin specific peptidase 9X (USP9X) to down-regulate the expression of phosphatidylinositol 4, 5-diphosphate 3-kinase catalytic subunit α/AKT serine/threonine kinase 1 (PIK3CA/AKT1) pathway. Methods USP9X was predicted to be a direct target of miR-15b-5p by using an online database (miRWalk), and the luciferase reporter gene assay was performed to verify it. Co-immunoprecipitation (CO-IP) was used to verify the direct binding between USP9X and PIK3CA and the role of USP9X and its small molecule inhibitor WP1130 in the deubiquitination of PIK3CA. C57 mice were randomly divided into Control group, OVA group, OVA combined with NC group and miR-15b-5p agomir group, with 10 mice in each group. BEAS-2B cells were induced with interleukin 13 (IL-13) and treated with miR-15b-5p mimic. HE, Masson, PAS, immunohistochemistry, immunofluorescence staining, flow cytometry, Western blot and quantitative real-time PCR(qRT-PCR) were performed. Results It was found that the administration of miR-15b-5p agomir and mimic could reduce peribronchial inflammatory cells and improve airway inflammation, and miR-15b-5p could target negative regulation of USP9X. USP9X could directly bind to PIK3CA and regulate PIK3CA level in a proteasome-dependent manner, and USP9X could deubiquitinate K29-linked PIK3CA protein. Down-regulation of USP9X could increase PIK3CA ubiquitination level. WP1130, a small molecule inhibitor of USP9X, has the same effect as knockdown of USP9X, both of which could increase the ubiquitination level of PIK3CA and reduce the protein level of PIK3CA. Conclusion The miR-15b-5p/USP9X/PIK3CA/AKT1 signaling pathway may provide potential therapeutic targets for asthma.
Animals ; MicroRNAs/metabolism* ; Asthma/pathology* ; Class I Phosphatidylinositol 3-Kinases/genetics* ; Ubiquitin Thiolesterase/metabolism* ; Proto-Oncogene Proteins c-akt/genetics* ; Mice ; Signal Transduction ; Mice, Inbred C57BL ; Humans ; Inflammation/genetics* ; Cell Line ; Female ; Male

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

Dental treatments for children and adolescents have unique clinical characteristics that differ from dental care for adults in terms of children's physiology, psychology, and behavior. These differences impose specific requirements on the application of local anesthesia in pediatric dental procedures. This article presents expert consensus on the principles of local anesthesia techniques in pediatric dental therapies, including the use of common anesthetic drugs and dosage control, safety and efficacy evaluation, and prevention and management of complications. The aim is to improve the safety and quality of pediatric dental treatments and offer guidance for clinical application by dentists.
Humans ; Child ; Anesthesia, Local/methods* ; Consensus ; Anesthesia, Dental/methods* ; Adolescent ; Anesthetics, Local/administration & dosage* ; Dental Care for Children

Outpatient humanistic care refered to providing a full process of caring medical services to outpatients. In order to standardize the human caring services for outpatients in medical institutions, promote the comprehensive service level of outpatient services, and improve the patient′s medical experience, Chinese Association for Life Care issued the group standard of Management Norms for Human caring of Outpatients in April 2023. This standard clarified the relevant terms and definitions of human caring for outpatients, specified the basic requirements for human caring, the humanistic quality and care responsibilities of outpatient staff, the outpatient care environment and facilities, the outpatient care process and measures, and quality management. It designed standardized and personalized full process care service norms, providing references for medical institutions at all levels to promote the development of human caring for outpatients.

Objective:To explore the risk factors for complications related to internal fixation after Inter-Tan intramedullary nail fixation in the treatment of intertrochanteric fractures in elderly patients.Methods:A retrospective cohort study was conducted to analyze the clinical data of 314 elderly patients with intertrochanteric fractures admitted to the Seventh Medical Center of the Chinese PLA General Hospital from January 2016 to December 2020, including 100 males and 214 females, aged 60-98 years [(80.2±8.2)years]. All the patients underwent Inter-Tan intramedullary nail fixation. According to the 2018 AO/OTA classification, 103 patients were with stable fractures and 211 with unstable fractures. The patients were further divided into complication groups and non-complication groups according to the presence of the complications during the follow-up. Six patients (5.8%) with stable fractures had the complications including nonunion in 4 and cut-out in 2. Twenty-eight patients (13.3%) with unstable fractures developed the complications, including nonunion in 5, cut-out in 20, cut-through in 1, and broken nails in 2. With the internal fixation-related complications after surgery as dependent variables, and gender, age, complications [hypertension, coronary heart disease, arrhythmia, pulmonary infection, chronic obstructive pulmonary disease (COPD), renal insufficiency, diabetes], bone density, waiting time for surgery, anesthesia method, reduction method, reduction quality, tip-apex distance, head screw displacement and other influencing factors as independent variables, univariate and multivariate Logistic regression analyses were conducted on the patients with stable fractures and unstable fractures separately to screen the independent risk factors of internal fixation-related complications.Results:For the patients with stable fractures, the univariate analysis indicated significant differences in bone density and reduction quality between the complication group and non-complication group ( P<0.05 or 0.01); the multivariate Logistic regression analysis showed that bone density T value ≤-3.0 SD ( OR=33.17, 95% CI 2.40, 457.82, P<0.01) and poor reduction quality ( OR=71.38, 95% CI 3.58, 1 422.02, P<0.01) were significantly correlated with the incidence of the postoperative complications. For the patients with unstable fractures, the univariate analysis indicated significant differences in age, reduction quality, bone density, tip-apex distance, and screw displacement between the complication group and non-complication group ( P<0.05 or 0.01); the multivariate Logistic regression analysis showed that age >80 years ( OR=2.82, 95% CI 1.01, 7.93, P<0.05), bone density T value ≤-3.0 SD ( OR=6.10, 95% CI 2.06, 17.51, P<0.01), poor reduction quality ( OR=12.25, 95% CI 2.90, 51.79, P<0.01), tip-apex distance ≥25 mm ( OR=3.65, 95% CI 1.20, 11.08, P<0.05), and head screw displacement <4 mm ( OR=7.26, 95% CI 2.54, 20.81, P<0.01) were significantly correlated with the postoperative complications. Conclusion:For Inter-Tan intramedullary nail fixation of intertrochanteric fractures in elderly patients, low bone density and poor reduction quality are independent risk factors for the postoperative complications in patients with stable intertrochanteric fractures; old age, low bone density, poor reduction quality, tip-apex distance, and head screw displacement are independent risk factors for the postoperative complications in patients with unstable fractures.

Objective:To compare the failure risks between restricted and unrestricted cephalomedullary nail sliding during InterTAN intramedullary nail fixation for intertrochanteric fractures in the elderly patients.Methods:A retrospective study was conducted to analyze the data of 192 elderly patients with intertrochanteric fracture who had been admitted to Department of Orthopaedics, The Seventh Medical Center, General Hospital of the People's Liberation Army from January 2021 to December 2022. The patients were divided into 2 groups based on whether the set screws were tightened or not during surgery. In the observation group of 78 cases, there were 31 males and 47 females with an age of (80.2±7.7) years, and 23 cases of type 31-A1 and 55 cases of type 31-A2 by the AO classification. Their set screws were not tightened during surgery to allow the cephalomedullary nail sliding. In the control group of 114 cases, there were 40 males and 74 females with an age of (81.6±7.8) years, and 42 cases of type 31-A1 and 72 cases of type 31-A2. Their set screws were tightened during surgery to restrict the cephalomedullary nail sliding. The incidence of postoperative fixation complications and sliding distances of the cephalomedullary nail within 1 year after surgery were compared between the 2 groups in the total fractures and in the stable and unstable fractures as well.Results:There was no statistically significant difference in the preoperative general data between the 2 groups of patients, indicating comparability ( P>0.05). The incidence of fixation complications within 1 year after surgery was 5.1% (4/78) for the observation group and 12.3% (14/114) for the control group, showing no statistically significant difference between the 2 groups ( P>0.05). The sliding distance of the cephalomedullary nail in the observation group [7.05 (6.00, 8.25) mm] was significantly larger than that in the control group [5.65 (3.55, 7.00) mm] ( P<0.05). For stable fractures, the incidence of fixation complications within 1 year after surgery was 7.1% (2/28) for the observation group and 7.0% (3/43) for the control group, showing no statistically significant difference ( P>0.05), and the sliding distance of the cephalomedullary nail in the observation group [6.00 (5.25, 7.00) mm] was significantly greater than that in the control group [3.05 (2.00, 5.00) mm] ( P<0.05). For unstable fractures, the incidence of fixation complications within 1 year after surgery for the observation group patients [4.0% (2/50)] was significantly lower than that for the control group patients [15.5% (11/71)], and the sliding distance of the cephalomedullary nail in the observation group [8.00 (6.70, 10.00) mm] was significantly greater than that in the control group [6.00 (4.87, 7.57) mm] ( P<0.05). Conclusions:In the InterTAN intramedullary nail fixation for intertrochanteric fractures in the elderly patients, tightening of set screws is crucial because it not only increases the stability but also limits compression at the fracture site. It is recommended not to tighten the set screws for unstable fractures, but further observation is needed before it can be determined whether the set screws should be tightened or not for stable fractures.

Objective:To analyze the factors affecting delayed chemotherapy in children with Burkitt lymphoma (BL) and their influence on prognosis.Methods:Retrospective cohort study. Clinical data of 591 children aged ≤18 years with BL from May 2017 to December 2022 in China Net Childhood Lymphoma (CNCL) was collected. The patients were treated according to the protocol CNCL-BL-2017. According to the clinical characteristics, therapeutic regimen was divided into group A, group B and group C .Based on whether the total chemotherapy time was delayed, patients were divided into two groups: the delayed chemotherapy group and the non-delayed chemotherapy group. Based on the total delayed time of chemotherapy, patients in group C were divided into non-delayed chemotherapy group, 1-7 days delayed group and more than 7 days delayed group. Relationships between delayed chemotherapy and gender, age, tumor lysis syndrome before chemotherapy, bone marrow involvement, disease group (B/C group), serum lactate dehydrogenase (LDH) > 4 times than normal, grade Ⅲ-Ⅳ myelosuppression after chemotherapy, minimal residual disease in the interim assessment, and severe infection (including severe pneumonia, sepsis, meningitis, chickenpox, etc.) were analyzed. Logistic analysis was used to identify the relevant factors. Kaplan-Meier method was used to analyze the patients' survival information. Log-Rank was used for comparison between groups.Results:Among 591 patients, 504 were males and 87 were females, the follow-up time was 34.8 (18.6,50.1) months. The 3-year overall survival (OS) rate was (92.5±1.1)%,and the 3-year event-free survival (EFS) rate was (90.5±1.2)%. Seventy-three (12.4%) patients were in delayed chemotherapy group and 518 (87.6%) patients were in non-delayed chemotherapy group. The reasons for chemotherapy delay included 72 cases (98.6%) of severe infection, 65 cases (89.0%) of bone marrow suppression, 35 cases (47.9%) of organ dysfunction, 22 cases (30.1%) of tumor lysis syndrome,etc. There were 7 cases of chemotherapy delay in group B, which were seen in COPADM (vincristine+cyclophosphamide+prednisone+daunorubicin+methotrexate+intrathecal injection,4 cases) and CYM (methotrexate+cytarabine+intrathecal injection,3 cases) stages. There were 66 cases of chemotherapy delay in group C, which were common in COPADM (28 cases) and CYVE 1 (low dose cytarabine+high dose cytarabine+etoposide+methotrexate, 12 cases) stages. Multinomial Logistic regression analysis showed that the age over 10 years old ( OR=0.54,95% CI 0.30-0.93), tumor lysis syndrome before chemotherapy ( OR=0.48,95% CI 0.27-0.84) and grade Ⅲ-Ⅳ myelosuppression after chemotherapy ( OR=0.55,95% CI 0.33-0.91)were independent risk factors for chemotherapy delay.The 3-year OS rate and the 3-year EFS rate of children with Burkitt lymphoma in the delayed chemotherapy group were lower than those in the non-delayed chemotherapy group ((79.4±4.9)% vs. (94.2±1.1)%, (80.2±4.8)% vs. (92.0±1.2)%,both P<0.05). The 3-year OS rate of the group C with chemotherapy delay >7 days (42 cases) was lower than that of the group with chemotherapy delay of 1-7 days (22 cases) and the non-delay group (399 cases) ((76.7±6.9)% vs. (81.8±8.2)% vs. (92.7±1.3)%, P=0.002).The 3-year OS rate of the chemotherapy delay group (9 cases) in the COP (vincristine+cyclophosphamide+prednisone) phase was lower than that of the non-chemotherapy delay group (454 cases) ((66.7±15.7)% vs. (91.3±1.4)%, P=0.005). Similarly, the 3-year OS rate of the chemotherapy delay group (11 cases) in the COPADM1 phase was lower than that of the non-chemotherapy delay group (452 cases) ((63.6±14.5)% vs. (91.5±1.3)%, P=0.001). Conclusions:The delayed chemotherapy was related to the age over 10 years old, tumor lysis syndrome before chemotherapy and grade Ⅲ-Ⅳ myelosuppression after chemotherapy in pediatric BL. There is a significant relationship between delayed chemotherapy and prognosis of BL in children.

Objective:To summarize the clinical phenotype and genetic characteristics of deficiency in ELF4 gene X-linked (DEX).Methods:A case series study was conducted to retrospectively analyze the clinical data and genetic testing results of 2 cases of DEX treated at Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and the First Hospital of Jilin University from January 2023 to April 2024. And literature up to April 2024 was searched from the PubMed database, as well as CNKI and Wanfang databases, using keywords such as "ELF4 deficiency" "deficiency in ELF4, X-linked""ELF4 gene". The main clinical manifestations and genotypes of DEX were summarized.Results:Both patients were male, with onset ages of 3 months and 3 years, respectively. Both patients presented with recurrent oral ulcers and abdominal pain. And the laboratory examination showed a significant increase in inflammatory markers. Intestinal examinations showed multiple intestinal ulcers, and both patients developed intestinal fistulas. Whole exome sequencing found ELF4 c.799C>T, p Arg267Trp and ELF4 c. 248-7G>A, both maternal variants. Based on clinical and genetic results, DEX were diagnosed. In terms of treatment, both patients underwent surgical treatment during the acute phase of the disease and received anti-tumor necrosis factor α therapy, but recurrent gastrointestinal symptoms were still observed in Patient 1, while the clinical effect in Patient 2 was still acceptable. However, the inflammatory markers in both patients were not normal even after treatment. Literature review found 18 patients including 2 patients in this study, reported in 5 English articles and no Chinese reports. Thirteen patients had disease onset age before 5. The main clinical manifestations were fever (12/17), oral ulcers (14/18), abdominal pain (8/18), diarrhea (6/18), perianal ulcers (5/17), ileum ulcers (6/16), colon ulcers (7/16), skin involvement (7/17) and recurrent infections (7/18); laboratory examinations found increased erythrocyte sedimentation rate (13/15) as well as C-reactive protein (9/9), and anemia (13/15); in terms of immunological function, there is a decrease in natural killer cells (9/15) as well as a decrease in class switching memory B cells (8/9). The main types of gene variantions were missense variantions (6/18), nonsense variantions (4/18) or frameshift variantions (3/18).Conclusions:DEX should be considered when an early-onset male patient manifested with recurrent fever, oral ulcers or mucosal ulcers, with elevated inflammatory markers, with or without recurrent infection. It is recommended to perform lymphocyte subsets analysis, gastrointestinal endoscopy and genetic testing to support the diagnosis.