Discussion of the classification of pediatric drug clinical trials in children's hospitals in China.

Objectives: This study aimed to gain insights into pediatric clinical trials conducted in children's hospitals in China and provide valuable references for the development of children's hospitals and the research and development of pediatric drugs. Methods: A comprehensive search was performed on the Chinese Clinical Trial Registry (Chi CTR) and ChinaDrugTrials.org.cn to collect information on all clinical trials involving subjects under 18 years, including those conducted in children's hospitals. The retrieval period was extended until 31 December 2022. Results: A total of 459 pediatric clinical trials were collected, comprising 299 from Chi CTR and 160 from the Drug Clinical Trial Registration and Information Publicity Platform (Information Platform). Post-marketing drug studies and phase III clinical trials accounted for the majority of research stages. These trials covered a wide range of diseases/systems, with a particular focus on respiratory system disorders, tumors, endocrine disorders, and nutritional or metabolic diseases. Chemical drugs constituted the most extensively studied category, while traditional Chinese medicine/natural drugs received comparatively less attention. Clinical trial activities were primarily geographically focused on the eastern coastal regions of China, with multicenter trials being the most predominant. Ethics committee approval was obtained for 427 studies. Conclusion: The pediatric clinical trials conducted by children's hospitals in China have shown an overall upward trend; however, there is limited research focusing on traditional Chinese medicine, along with significant regional and institutional imbalances. Furthermore, there is still room for improvement regarding ethical review processes. It is recommended that children's hospitals enhance their scientific research capabilities while optimizing resource allocation to meet medical service demands effectively. Additionally, fostering more research-focused children's hospitals will contribute to the high-quality development of children's health in China.

TRPV1+ neurons alter Staphylococcus aureus skin infection outcomes by affecting macrophage polarization and neutrophil recruitment.

BACKGROUND: The interaction between the nervous system and the immune system can affect the outcome of a bacterial infection. Staphylococcus aureus skin infection is a common infectious disease, and elucidating the relationship between the nervous system and immune system may help to improve treatment strategies. RESULTS: In this study, we found that the local release of calcitonin gene-related peptide (CGRP) increased during S. aureus skin infection, and S. aureus could promote the release of CGRP from transient receptor potential cation channel subfamily V member 1 (TRPV1+) neurons in vitro. The existence of TRPV1+ neurons inhibited the recruitment of neutrophils to the infected region and regulated the polarization of macrophages toward M2 while inhibiting polarization toward M1. This reduces the level of inflammation in the infected area, which aggravates the local infection. Furthermore, this study demonstrates that TRPV1 may be a target for the treatment of S. aureus skin infections and that botulinum neurotoxin A (BoNT/A) and BIBN4096 may reverse the inhibited inflammatory effect of CGRP, making them potential therapeutics for the treatment of skin infection in S. aureus. CONCLUSIONS: In S. aureus skin infection, TRPV1+ neurons inhibit neutrophil recruitment and regulate macrophage polarization by releasing CGRP. BoNT/A and BIBN4096 may be potential therapeutic agents for S. aureus skin infection.

Cost-effectiveness of camrelizumab plus chemotherapy vs. chemotherapy in the first-line treatment of non-squamous NSCLC: Evidence from China.

Objective: We aimed to evaluate the cost-effectiveness of camrelizumab plus chemotherapy compared with chemotherapy alone as the first-line treatment for patients with metastatic or advanced non-squamous non-small cell lung cancer (NSCLC) without targetable epidermal growth factor receptor or anaplastic lymphoma kinase genetic aberrations in patients in China. Methods: A partitioned survival model was constructed to estimate the cost-effectiveness of camrelizumab plus chemotherapy vs. chemotherapy in the first-line treatment of non-squamous NSCLC from a Chinese healthcare perspective. Survival analysis was performed to calculate the proportion of patients in each state using data from trial NCT03134872. The cost of drugs was obtained from Menet, and the cost of disease management was obtained from local hospitals. Health state data were obtained from published literature. Both deterministic sensitivity analyses (DSA) and probabilistic sensitivity analysis (PSA) were adopted to verify the robustness of the results. Results: Compared with chemotherapy alone, camrelizumab plus chemotherapy provided 0.41 incremental quality-adjusted life years (QALYs) at an incremental cost of $10,482.12. Therefore, the incremental cost-effectiveness ratio of camrelizumab plus chemotherapy was $25,375.96/QALY from the Chinese healthcare perspective, much lower than three times the GDP per capita of China in 2021 ($35,936.09) as the willingness-to-pay threshold. The DSA indicated that the incremental cost-effectiveness ratio was most sensitive to the utility value of progression-free survival, followed by the cost of camrelizumab. The PSA illustrated that camrelizumab had 80% probability of being cost-effective at the threshold of $35,936.09 per QALY gained. Conclusion: The results suggest that camrelizumab plus chemotherapy is a cost-effective choice in the first-line treatment for patients with non-squamous NSCLC in China. Although this study has limitations such as short time of use of camrelizumab, no adjustment of Kaplan-Meier curves and the median overall survival that has not been reached, the difference in results caused by these factors is relatively small.

The Consistency Between the Chinese Essential Medicines List and Treatment Guidelines-Taking Oncology Medicines as an Example.

The concepts of "essential medicine" and "national medicine policy" were first put forward for the first time at the World Health Assembly in 1975 in an effort to alleviate the problem of medicine unavailability in developing and poor countries. The essential medicine system in China has experienced three development stages since 1979, when the concept of essential medicines was first introduced, to actively respond to the call of the World Health Organization. Currently, the essential medicines list published in China is the national essential medicines list (2018 Edition). In this study, we examined the consistency between the essential medicines for treating seven cancers (liver cancer, breast cancer, esophageal cancer, lung cancer, colorectal cancer, gastric cancer, and leukemia) and the recommended medicines by cancer treatment guidelines to determine whether the essential medicines are of high quality for clinical needs. The results indicated that the degree of similarity between oncology medicines on the essential medicines list and oncology medicines recommended by guidelines was low, with the majority falling between 30 and 60%. Therefore, to improve the quality of essential medicines, it is necessary to further improve the matching degree. In addition, to further improve the consistency between the essential medicines list and treatment guidelines, the following suggestions are put forward in this paper: (1). Formulate universal treatment guidelines; (2). When selecting essential medicines, greater consideration should be given to those recommended in the guidelines; (3). The essential medicines list and treatment guidelines should be concurrently updated; (4). The cycle for updating the essential medicines list and treatment guidelines should be shortened.

Current development and prospects of deep learning in spine image analysis: a literature review.

Background and Objective: As the spine is pivotal in the support and protection of human bodies, much attention is given to the understanding of spinal diseases. Quick, accurate, and automatic analysis of a spine image greatly enhances the efficiency with which spine conditions can be diagnosed. Deep learning (DL) is a representative artificial intelligence technology that has made encouraging progress in the last 6 years. However, it is still difficult for clinicians and technicians to fully understand this rapidly evolving field due to the diversity of applications, network structures, and evaluation criteria. This study aimed to provide clinicians and technicians with a comprehensive understanding of the development and prospects of DL spine image analysis by reviewing published literature. Methods: A systematic literature search was conducted in the PubMed and Web of Science databases using the keywords "deep learning" and "spine". Date ranges used to conduct the search were from 1 January, 2015 to 20 March, 2021. A total of 79 English articles were reviewed. Key Content and Findings: The DL technology has been applied extensively to the segmentation, detection, diagnosis, and quantitative evaluation of spine images. It uses static or dynamic image information, as well as local or non-local information. The high accuracy of analysis is comparable to that achieved manually by doctors. However, further exploration is needed in terms of data sharing, functional information, and network interpretability. Conclusions: The DL technique is a powerful method for spine image analysis. We believe that, with the joint efforts of researchers and clinicians, intelligent, interpretable, and reliable DL spine analysis methods will be widely applied in clinical practice in the future.

Clinical Outcomes of Culture-Negative and Culture-Positive Periprosthetic Joint Infection: Similar Success Rate, Different Incidence of Complications.

OBJECTIVE: To compare the clinical outcomes of culture-negative periprosthetic joint infection (CN PJI) with those of culture-positive periprosthetic joint infection (CP PJI). METHODS: This study retrospectively examined data from 77 patients who underwent revision surgery due to periprosthetic joint infection (PJI) after hip and knee arthroplasty at our center from January 2012 to June 2017. There were 37 males and 40 females, with an average age of 63.6 year. All patients were classified by Tsukayama type, according to the bacterial culture results of synovial fluid and pre- and intraoperative tissues, 24 cases were included in the CN PJI group, and 53 cases were included in the CP PJI group. All patients underwent routine blood tests, liver, renal function tests, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) measurements. The remission rates of CN PJI and CP PJI were compared. The effects of the culture results on the curative effect were further compared by survival analysis. RESULTS: The patients were followed regularly with an average of 29.2 months (range, 12-76 months). In total, there were 24 cases of CN PJI, with an incidence of 29.63%. The overall success rate of CN PJI group was 86.4% (19/22), and overall success rate of CP PJI group was 87.5% (42/48). The relative efficacy of various surgical options was: one-stage revision 100% (7/7), two-stage revision 96.3% (26/27), debridement and implant retention 64.3% (9/14), respectively. There was no significant difference in the success rate between the CN PJI group and the CP PJI group. The incidence of antibiotic-related complications for the CN PJI group was significantly higher than that of the CP PJI group, with 58.3% for CN PJI and 11.3% for CP PJI, respectively. CONCLUSION: When CN PJI was treated according to the strict standards for the diagnosis and treatment, the success rate of treatment for the CN PJI group was similar to that for the CP PJI group. The incidence of antibiotic-related complications from the CN PJI group was higher than that from the CP PJI group.

The role of circRNA derived from RUNX2 in the serum of osteoarthritis and its clinical value.

BACKGROUND: Circular RNA (circRNA) has been shown to affect the pathological process of osteoarthritis (OA) and is expected to become a potential marker for disease diagnosis. This study aimed to investigate the association between circRNA derived from the gene of runt-related transcription factor 2 (RUNX2) and OA risk. METHODS: The expression profile of RUNX2-derived circRNAs in serum of OA patients was detected. Then, the cytological localization of screened differential circRNAs was studied. Luciferase (LUC) reporter assay was used to identify the microRNA (miRNA) sponge capacity of the circRNAs. Bioinformatics analysis was used to construct the functional pathway of this circRNA-miRNAs network. And then, the diagnostic value of RUNX2-derived circRNAs in OA was evaluated. RESULTS: RUNX2-derived hsa_circ_0005526 (circ_RUNX2) is significantly highly expressed in OA serum and mainly located in the cytoplasm within the cartilage cell by sponging multiple miRNAs (miR-498, miR-924, miR-361-3p, and miR-665). Bioinformatics analysis showed ECM-receptor interaction pathway ranked the most significant pathway of circ_RUNX2-miRNAs regulatory network in KEGG database. The ROC curve showed that there may be good diagnostic value of serum circ_RUNX2 in OA. CONCLUSION: RUNX2-derived circ_RUNX2 may be involved in OA development via ECM-receptor interaction pathways and may be used as potential clinical indicator of OA.

Histological subtype remains a prognostic factor for survival in nasopharyngeal carcinoma patients.

OBJECTIVES: There is currently no consensus on the prognostic significance of the histological subtype of nasopharyngeal carcinoma (NPC). The aim of the current study was to evaluate the impact of histological subtype on survival in NPC patients based on the Surveillance, Epidemiology, and End Results (SEER) Program. METHODS: Patients with NPC were identified within the SEER database (2004-2015). The effects of histological subtype on cause-specific survival (CSS) in NPC patients were evaluated using univariate and multivariate Cox regression analyses. Subgroup analysis according to histological subtype in NPC patients was carried out by 1:1 propensity score matching (PSM). RESULTS: A total of 4085 NPC patients were selected from the SEER database, including 1929 with keratinizing squamous cell carcinoma (KSCC), 2203 with nonkeratinizing carcinoma (NKC), and 53 with basaloid squamous cell carcinoma (BSCC). The 3-year and 5-year CSS rates were 61.76% and 55.07% for KSCC patients, 79.57% and 72.09% for NKC patients, and 77.55% and 74.03% for BSCC patients, respectively. Multivariate analysis identified sex, age, marital status, race, T stage, N stage, M stage, radiotherapy, chemotherapy, and histological subtype as significant prognostic factors for CSS in NPC patients. KSCC was found to be associated with worse CSS than NKC on Kaplan-Meier analysis and subgroup analysis after 1:1 PSM. CONCLUSIONS: Histological subtype determines the long-term survival outcomes of patients with NPC. Moreover, the NKC subtype has the best prognosis, while the KSCC subtype has the worst prognosis. LEVEL OF EVIDENCE: NA Laryngoscope, 130:E83-E88, 2020.

Nomogram for predicting the overall survival of patients with inflammatory breast cancer: A SEER-based study.

OBJECTIVES: Inflammatory breast cancer (IBC) is a rare malignancy that is a unique biologic subtype of breast cancer. A nomogram to predict the overall survival (OS) of IBC patients is lacking. The aim of the study was to construct and validate a nomogram to predict the OS of IBC patients based on the Surveillance, Epidemiology, and End Results (SEER) Program. METHODS: Patients diagnosed with IBC between 2010 and 2016 were selected from the SEER database. Univariate and multivariate Cox regression analyses were used to identify independent prognostic factors. A nomogram was constructed to predict the 1-, 3- and 5-year OS of these patients. The nomogram was internally and externally validated by Harrell's C-indexes and calibration plots. RESULTS: Patients were randomly divided into a training set (n = 2464) and a validation set (n = 1052). The training set was used to establish a nomogram. Multivariate analysis identified that race, age at diagnosis, breast cancer subtype, grade, N stage, M stage, radiation, chemotherapy, and surgery were significant prognostic factors for the OS. The internally and externally validated Harrell's C-indexes were 0.763 and 0.786, respectively. The calibration plots for predictions of the 1-, 3-, and 5-year OS were in excellent agreement. CONCLUSIONS: A nomogram was constructed to predict the OS for IBC patients based on the SEER database and to provide accurate and individualised survival predictions.

A simplified T classification based on the 8th edition of the UICC/AJCC staging system for nasopharyngeal carcinoma.

Objective: This study aimed to establish a simplified T classification based on the 8th edition of the Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system for nasopharyngeal carcinoma (NPC). Methods: In total, 325 patients with NPC were included in this study. All patients underwent magnetic resonance imaging, and the staging criteria were recorded. These patients were subjected to staging with the 8th edition of the UICC/AJCC staging system for NPC. Results:  Involvement of the oropharynx, nasal cavity, adjacent soft tissue (medial pterygoid, lateral pterygoid, and prevertebral muscles), cervical vertebra, orbit, and hypopharynx were always accompanied by other equivalently or more advanced T-stage classifications. All cases with involvement of the paranasal sinuses showed skull base erosion. The majority of cases with involvement of the pterygoid structure showed skull base erosion. Conclusion: According to the simplification principle, the following new T classification based on the 8th edition of the UICC/AJCC staging system was established: T1, tumor confined to nasopharynx, or beyond the nasopharynx without parapharyngeal involvement; T2, tumor with extension to the parapharyngeal space; T3, tumor with infiltration to bony structures at the skull base; T4, tumor with intracranial extension, involvement of the cranial nerves or parotid gland, and/or extensive soft tissue infiltration beyond the lateral surface of the lateral pterygoid muscle. Validation with a large series of patients is needed.

Safety and efficacy of nimotuzumab combined with chemoradiotherapy in Chinese patients with locally advanced cervical cancer.

OBJECTIVE: To evaluate efficacy and safety of nimotuzumab combined with chemotherapy and radiotherapy in women with locally advanced cervical cancer. MATERIALS AND METHODS: Women with locally advanced cervical cancer (stage IIB, III, or IVA) who experienced relapse after first-line chemoradiotherapy and one or more lines of palliative chemotherapy were enrolled. All patients received nimotuzumab weekly at 200 mg/m2 as single agent for 4 weeks (induction phase), then concurrent with 6 cycles (21-day per cycle) of gemcitabine (800 mg/m2) or cisplatin (50 mg/m2) for 18 weeks (concurrent phase) and then once every 2 weeks (maintenance phase). Overall response rate (ORR) was assessed after 4 weeks of induction therapy and then every 3 months according to response evaluation criteria in solid tumors version 1.1 (primary end point). Secondary end points include progression-free survival (PFS), overall survival (OS), and drug toxicity. Descriptive statistics was used for ORR, and Kaplan-Meier curves were generated for OS and PFS. RESULTS: A total of 80 women with locally advanced cervical cancer were enrolled and evaluated for safety and efficacy. Our results demonstrated that none of the patients had a complete response (0%), 11 patients had a partial response (14%), and 10 patients had progressive disease (13%), giving a tumor response rate of 14%. A total of 59 patients had stable disease (74%), giving a disease control rate of 88% (70/80). Median PFS was 8.21 months (95% confidence interval [CI]: 5.09-12.45). Median OS was 11.96 months (95% CI: 8.11-23.95). The most common adverse events were mucositis, myelosuppression, and gastrointestinal disturbance. CONCLUSION: Our study results suggested that nimotuzumab in combination with chemotherapy and radiotherapy is well tolerated, and could be a better treatment alternative in patients with locally advanced cervical cancer.