Thyroid cancer(TC)is a common malignant tumor of the endocrine system,with differentiated TC(DTC)accounting for more than 90%.Most patients usually have a good overall prognosis after receiving radioactive iodine(RAI)treatment,however some patients'lesions gradually lose the ability to take up iodine during treatment and become RAI-refractory DTC(RAIR-DTC),with a poor prognosis.For RAIR-DTC recurrence lesions or distant metastases that cannot be surgically removed,it was previously believed that there were limited treatment options.With a deeper understanding of the pathogenesis of RAIR-DTC and its changes at the biomolecular level,targeted therapy,immunotherapy and combined targeted and immune therapy have shown broad application prospects.Their effectiveness and safety have also been confirmed in human studies,bringing new hope for the treatment of RAIR-DTC.This article summarized the pathogenesis and development mechanism of RAIR-DTC,the current status of clinical research on targeted therapy and immunotherapy,and their main conclusions,in order to provide direction for future research.Multi-kinase inhibitors(MKIs)are the first-line therapy for advanced metastatic RAIR-DTC.Currently,Food and Drug Administration(FDA)of the United States has approved the following drugs for the treatment of RAIR-DTC:sorafenib,lenvatinib and cabozantinib.The first two of these have been approved by China National Medical Products Administration for RAIR-DTC treatment.In China,anlotinib and donafenib have also been approved for RAIR-DTC treatment.The efficacy and safety of these targeted therapies have been verified.Apatinib,an anti-angiogenesis inhibitor independently developed in China,is expected to be an effective salvage therapy for sorafenib-resistant lesions.Selective single-target inhibitors,with their more specific action targets,generally cause fewer side effects.For certain RAIR-DTC patients with specific mutation types,selective single-target inhibitors may be more effective.TC is generally considered to have a low tumor mutational burden(TMB),and its response to immunotherapy was once thought to be limited.Immune checkpoint inhibitors(ICIs),including pembrolizumab,durvalumab,atezolizumab and ipilimumab,have shown limited efficacy when used alone.However,when combined with targeted therapy,pembrolizumab can enhance the efficacy of targeted drugs,serving as a viable salvage therapy,potentially due to the"synergistic effect"of the combination therapy.It is crucial to determine the individual contributions of each therapy to tumor suppression and survival extension,especially when the sample size is limited.The design of reasonable controls becomes the key in these studies.Previous studies were obstructed by the unclear definition of RAIR-DTC,limited sample sizes and high heterogeneity.Therefore,prospective,multi-center,large-scale clinical trials are needed in the future.Additionally,it is essential to consider whether prolonged progression-free survival(PFS)after treatment can be translated into long-term survival benefits,and whether it improves the quality of life for patients.In conclusion,the treatment of RAIR-DTC still faces many challenges,we must continue to explore and address these issues in the future.

Objective:To investigate the association of regulatory T cell (Treg) levels in peripheral blood with bronchopulmonary dysplasia (BPD) in preterm infants and its predictive value for BPD.Methods:In this case-control study, a total of 102 infants with gestational age ≤32 weeks who were hospitalized in the Neonatal Intensive Care Unit of the First Affiliated Hospital of Xinxiang Medical University from April 2022 to April 2024 were included.They were divided into a BPD group (31 cases) and a non-BPD group (71 cases) based on the diagnostic criteria of BPD.Peripheral blood samples were collected on 0 day, 7 days, 14 days, 21 days and 28 days after birth.Differences in Treg levels between the 2 groups and the relationship between Treg levels and BPD were analyzed.The independent sample t test or χ2 test was used to analyze differences between the 2 groups.One-Way ANOVA was used to compare data between groups.Multivariate Logistic regression was used to analyze the risk factors of BPD.The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of Treg levels on 7 days after birth for early diagnosis of BPD. Results:Gestational age[(28.1±1.4) weeks vs.(30.9±1.0) weeks], birth weight[(1 024±243) g vs.(1 301±188) g], Apgar score at 1 minute after birth[(4.3±1.9) points vs.(7.8±1.9) points], Apgar score at 5 minutes after birth[(7.2±1.7) points vs.(9.1±1.3) points], proportion of invasive mechanical ventilation time ≥7 days [87.1%(27/31) vs.45.1%(32/71)] and oxygen inhalation time[(45.1±11.7) days vs.(19.7±7.3) days] were statistically significantly different between BPD and non-BPD groups (all P<0.05).The Treg level in the peripheral blood of preterm infants increased first and then decreased after birth, with the peak observed on 7 days after birth.On 7 days after birth, the BPD group had a significantly higher Treg level than the non-BPD group[(10.4±1.2)% vs.(8.7±1.7)%] ( P<0.05).The multivariate Logistic regression analysis showed increased Treg levels in peripheral blood on 7 days after birth ( OR=3.320, 95% CI: 1.057-10.427, P=0.040), gestational age ( OR=0.040, 95% CI: 0.003-0.446, P=0.009), invasive mechanical ventilation time ≥7 days ( OR=4.126, 95% CI: 1.301-14.125, P=0.002), and oxygen inhalation time ( OR=1.716, 95% CI: 1.317-3.933, P=0.041) were risk factors of BPD in preterm infants.The ROC curve analysis showed that the area under the curve of Treg levels on 7 days after birth for BPD prediction was 0.794, the best cut-off value was 9.35%, the sensitivity was 90.3%, and the specificity was 66.2%. Conclusions:Treg levels in the peripheral blood of preterm infants increase first and then decrease in the early stage after birth, peaking at 7 days after birth.Elevated Treg levels at 7 days after birth may have early predictive value for the occurrence of BPD in preterm infants.

Objective:To construct the user personas of the patients who practice self-management home rehabilitation after lower limb bone transport by exploring their self-management experiences and needs in rehabilitation at home so as to provide targeted countermeasures for related medical staff.Methods:A purposive sampling method was employed to select the 21 patients who had undergone home rehabilitation after lower limb bone transport at Department of Orthopedic Trauma, Nanfang Hospital from September to December 2024. The cohort included 12 males and 9 females, with an age of (39.8±15.1) years. The phenomenological research method was used to conduct semi-structured interviews with this cohort. After the data from interviews were explored by the Colaizzi 7-step analysis to extract the factual labels, role dimension models were built, covering 3 dimensions: description, characteristics (basic, cognitive, behavioral, social support, and psychological adjustment characteristics) and needs.Results:All patients were interviewed. Four user personas were constructed, including self-awareness growth type (5 cases), emotional dependency-driven type (4 cases), risk-aversion procrastination type (7 cases), and management motivation-impaired type (5 cases). The patients of self-awareness growth type were 21 to 36 years old and received high school or university education, characterized by high self-efficacy, active measures to improve and maintain their state of rehabilitation, good management of negative emotions, and a low sense of stigma. The patients of emotional low-driven type were 42 to 74 years old and received their education in a primary school or junior high school, characterized by lack of independence, dependence on others for rehabilitation management, common management of negative emotions, low self-efficacy, and a strong sense of stigma. The patients of risk-aversion procrastination type were 33 to 56 years old and received their education in a junior or senior high school, characterized by a willingness to cooperate but insufficient motivation for rehabilitation management, an awareness of rehabilitation which was vulnerable to external factors, common management of negative emotions, low self-efficacy, and a strong sense of stigma. The patients of management motivation-impaired type were 51 to 61 years old, received primary school education or lower, characterized by insufficient knowledge and poor self-management behavior, constant failure to follow the prescribed rehabilitation exercises, poor management of negative emotions, low self-efficacy, and a low sense of stigma.Conclusion:The user personas we have constructed for the patients who practice self-management home rehabilitation after lower limb bone transport can help healthcare professionals with specific targeted interventions to enhance self-management efficacy to facilitate the rehabilitation process for the patients.

Objective:To investigate the causal relationship between type 2 diabetes mellitus (T2DM), type 1 diabetes mellitus (T1DM), body mass index (BMI) and papillary thyroid cancer using Mendelian randomization(MR) study.Methods:Publicly available genome-wide association studies (GWAS) were used as the data source to screen single nucleotide polymorphisms significantly associated with exposure factors (instrumental variables), and the inverse variance weighting (IVW), weighted median, MR-Egger analysis, simple mode, and weighted mode of two-sample MR were used to assess the causal association between T2DM, T1DM, BMI and papillary thyroid cancer. The reliability and stability of the results were assessed by heterogeneity analysis, multiple validity analysis and sensitivity analysis.Results:A total of 118 strong instrumental variables for T2DM, 76 for T1DM, and 486 for BMI were screened respectively to conduct two-sample MR analysis. Among the 5 MR analysis methods, the results of the IVW method showed that T2DM was significantly associated with papillary thyroid cancer (odds ratio ( OR)=1.147, 95% CI: 1.026-1.282; P=0.016), and the genetic effect values ( β values) of the other 4 analysis methods and IVW method were in the same direction; the results of heterogeneity analysis, multiplicity analysis and sensitivity analysis showed all P>0.05. T1DM (IVW method: OR=1.000, 95% CI: 0.952-1.051; P=0.994) and papillary thyroid cancer, BMI (IVW method: OR=1.214, 95% CI: 0.923-1.598; P=0.166) and papillary thyroid cancer were not clearly causally related. Conclusions:There is a causal association between T2DM and papillary thyroid cancer, and T2DM increases the risk of papillary thyroid cancer. There is no clear causal association between T1DM, BMI and papillary thyroid cancer.

Thyroid cancer(TC)is a common malignant tumor of the endocrine system,with differentiated TC(DTC)accounting for more than 90%.Most patients usually have a good overall prognosis after receiving radioactive iodine(RAI)treatment,however some patients'lesions gradually lose the ability to take up iodine during treatment and become RAI-refractory DTC(RAIR-DTC),with a poor prognosis.For RAIR-DTC recurrence lesions or distant metastases that cannot be surgically removed,it was previously believed that there were limited treatment options.With a deeper understanding of the pathogenesis of RAIR-DTC and its changes at the biomolecular level,targeted therapy,immunotherapy and combined targeted and immune therapy have shown broad application prospects.Their effectiveness and safety have also been confirmed in human studies,bringing new hope for the treatment of RAIR-DTC.This article summarized the pathogenesis and development mechanism of RAIR-DTC,the current status of clinical research on targeted therapy and immunotherapy,and their main conclusions,in order to provide direction for future research.Multi-kinase inhibitors(MKIs)are the first-line therapy for advanced metastatic RAIR-DTC.Currently,Food and Drug Administration(FDA)of the United States has approved the following drugs for the treatment of RAIR-DTC:sorafenib,lenvatinib and cabozantinib.The first two of these have been approved by China National Medical Products Administration for RAIR-DTC treatment.In China,anlotinib and donafenib have also been approved for RAIR-DTC treatment.The efficacy and safety of these targeted therapies have been verified.Apatinib,an anti-angiogenesis inhibitor independently developed in China,is expected to be an effective salvage therapy for sorafenib-resistant lesions.Selective single-target inhibitors,with their more specific action targets,generally cause fewer side effects.For certain RAIR-DTC patients with specific mutation types,selective single-target inhibitors may be more effective.TC is generally considered to have a low tumor mutational burden(TMB),and its response to immunotherapy was once thought to be limited.Immune checkpoint inhibitors(ICIs),including pembrolizumab,durvalumab,atezolizumab and ipilimumab,have shown limited efficacy when used alone.However,when combined with targeted therapy,pembrolizumab can enhance the efficacy of targeted drugs,serving as a viable salvage therapy,potentially due to the"synergistic effect"of the combination therapy.It is crucial to determine the individual contributions of each therapy to tumor suppression and survival extension,especially when the sample size is limited.The design of reasonable controls becomes the key in these studies.Previous studies were obstructed by the unclear definition of RAIR-DTC,limited sample sizes and high heterogeneity.Therefore,prospective,multi-center,large-scale clinical trials are needed in the future.Additionally,it is essential to consider whether prolonged progression-free survival(PFS)after treatment can be translated into long-term survival benefits,and whether it improves the quality of life for patients.In conclusion,the treatment of RAIR-DTC still faces many challenges,we must continue to explore and address these issues in the future.

Objective:To investigate the association of regulatory T cell (Treg) levels in peripheral blood with bronchopulmonary dysplasia (BPD) in preterm infants and its predictive value for BPD.Methods:In this case-control study, a total of 102 infants with gestational age ≤32 weeks who were hospitalized in the Neonatal Intensive Care Unit of the First Affiliated Hospital of Xinxiang Medical University from April 2022 to April 2024 were included.They were divided into a BPD group (31 cases) and a non-BPD group (71 cases) based on the diagnostic criteria of BPD.Peripheral blood samples were collected on 0 day, 7 days, 14 days, 21 days and 28 days after birth.Differences in Treg levels between the 2 groups and the relationship between Treg levels and BPD were analyzed.The independent sample t test or χ2 test was used to analyze differences between the 2 groups.One-Way ANOVA was used to compare data between groups.Multivariate Logistic regression was used to analyze the risk factors of BPD.The receiver operating characteristic (ROC) curve was used to evaluate the predictive value of Treg levels on 7 days after birth for early diagnosis of BPD. Results:Gestational age[(28.1±1.4) weeks vs.(30.9±1.0) weeks], birth weight[(1 024±243) g vs.(1 301±188) g], Apgar score at 1 minute after birth[(4.3±1.9) points vs.(7.8±1.9) points], Apgar score at 5 minutes after birth[(7.2±1.7) points vs.(9.1±1.3) points], proportion of invasive mechanical ventilation time ≥7 days [87.1%(27/31) vs.45.1%(32/71)] and oxygen inhalation time[(45.1±11.7) days vs.(19.7±7.3) days] were statistically significantly different between BPD and non-BPD groups (all P<0.05).The Treg level in the peripheral blood of preterm infants increased first and then decreased after birth, with the peak observed on 7 days after birth.On 7 days after birth, the BPD group had a significantly higher Treg level than the non-BPD group[(10.4±1.2)% vs.(8.7±1.7)%] ( P<0.05).The multivariate Logistic regression analysis showed increased Treg levels in peripheral blood on 7 days after birth ( OR=3.320, 95% CI: 1.057-10.427, P=0.040), gestational age ( OR=0.040, 95% CI: 0.003-0.446, P=0.009), invasive mechanical ventilation time ≥7 days ( OR=4.126, 95% CI: 1.301-14.125, P=0.002), and oxygen inhalation time ( OR=1.716, 95% CI: 1.317-3.933, P=0.041) were risk factors of BPD in preterm infants.The ROC curve analysis showed that the area under the curve of Treg levels on 7 days after birth for BPD prediction was 0.794, the best cut-off value was 9.35%, the sensitivity was 90.3%, and the specificity was 66.2%. Conclusions:Treg levels in the peripheral blood of preterm infants increase first and then decrease in the early stage after birth, peaking at 7 days after birth.Elevated Treg levels at 7 days after birth may have early predictive value for the occurrence of BPD in preterm infants.

Objective:To investigate the causal relationship between type 2 diabetes mellitus (T2DM), type 1 diabetes mellitus (T1DM), body mass index (BMI) and papillary thyroid cancer using Mendelian randomization(MR) study.Methods:Publicly available genome-wide association studies (GWAS) were used as the data source to screen single nucleotide polymorphisms significantly associated with exposure factors (instrumental variables), and the inverse variance weighting (IVW), weighted median, MR-Egger analysis, simple mode, and weighted mode of two-sample MR were used to assess the causal association between T2DM, T1DM, BMI and papillary thyroid cancer. The reliability and stability of the results were assessed by heterogeneity analysis, multiple validity analysis and sensitivity analysis.Results:A total of 118 strong instrumental variables for T2DM, 76 for T1DM, and 486 for BMI were screened respectively to conduct two-sample MR analysis. Among the 5 MR analysis methods, the results of the IVW method showed that T2DM was significantly associated with papillary thyroid cancer (odds ratio ( OR)=1.147, 95% CI: 1.026-1.282; P=0.016), and the genetic effect values ( β values) of the other 4 analysis methods and IVW method were in the same direction; the results of heterogeneity analysis, multiplicity analysis and sensitivity analysis showed all P>0.05. T1DM (IVW method: OR=1.000, 95% CI: 0.952-1.051; P=0.994) and papillary thyroid cancer, BMI (IVW method: OR=1.214, 95% CI: 0.923-1.598; P=0.166) and papillary thyroid cancer were not clearly causally related. Conclusions:There is a causal association between T2DM and papillary thyroid cancer, and T2DM increases the risk of papillary thyroid cancer. There is no clear causal association between T1DM, BMI and papillary thyroid cancer.

Objective:To construct the user personas of the patients who practice self-management home rehabilitation after lower limb bone transport by exploring their self-management experiences and needs in rehabilitation at home so as to provide targeted countermeasures for related medical staff.Methods:A purposive sampling method was employed to select the 21 patients who had undergone home rehabilitation after lower limb bone transport at Department of Orthopedic Trauma, Nanfang Hospital from September to December 2024. The cohort included 12 males and 9 females, with an age of (39.8±15.1) years. The phenomenological research method was used to conduct semi-structured interviews with this cohort. After the data from interviews were explored by the Colaizzi 7-step analysis to extract the factual labels, role dimension models were built, covering 3 dimensions: description, characteristics (basic, cognitive, behavioral, social support, and psychological adjustment characteristics) and needs.Results:All patients were interviewed. Four user personas were constructed, including self-awareness growth type (5 cases), emotional dependency-driven type (4 cases), risk-aversion procrastination type (7 cases), and management motivation-impaired type (5 cases). The patients of self-awareness growth type were 21 to 36 years old and received high school or university education, characterized by high self-efficacy, active measures to improve and maintain their state of rehabilitation, good management of negative emotions, and a low sense of stigma. The patients of emotional low-driven type were 42 to 74 years old and received their education in a primary school or junior high school, characterized by lack of independence, dependence on others for rehabilitation management, common management of negative emotions, low self-efficacy, and a strong sense of stigma. The patients of risk-aversion procrastination type were 33 to 56 years old and received their education in a junior or senior high school, characterized by a willingness to cooperate but insufficient motivation for rehabilitation management, an awareness of rehabilitation which was vulnerable to external factors, common management of negative emotions, low self-efficacy, and a strong sense of stigma. The patients of management motivation-impaired type were 51 to 61 years old, received primary school education or lower, characterized by insufficient knowledge and poor self-management behavior, constant failure to follow the prescribed rehabilitation exercises, poor management of negative emotions, low self-efficacy, and a low sense of stigma.Conclusion:The user personas we have constructed for the patients who practice self-management home rehabilitation after lower limb bone transport can help healthcare professionals with specific targeted interventions to enhance self-management efficacy to facilitate the rehabilitation process for the patients.

With good prognosis of differentiated thyroid cancer (DTC), the 10-year survival rate of DTC patients is more than 90%. As a kind of radiation exposure, radioactive iodine (RAI) treatment has the potential to induce malignancies. Based on this view, whether RAI treatment will increase the risk of secondary primary malignancy (SPM) still has a lot of controversy. This review summarizes current situation of related researches, and also summarizes the limitations of the current researches and the problems to be solved in the future research. In this review, it is believed that RAI treatment does not increase the overall risk of SPM in postoperative-DTC patients.

Infectious bone defect is bone defect with infection or as a result of treatment of bone infection. It requires surgical intervention, and the treatment processes are complex and long, which include bone infection control,bone defect repair and even complex soft tissue reconstructions in some cases. Failure to achieve the goals in any step may lead to the failure of the overall treatment. Therefore, infectious bone defect has been a worldwide challenge in the field of orthopedics. Conventionally, sequestrectomy, bone grafting, bone transport, and systemic/local antibiotic treatment are standard therapies. Radical debridement remains one of the cornerstones for the management of bone infection. However, the scale of debridement and the timing and method of bone defect reconstruction remain controversial. With the clinical application of induced membrane technique, effective infection control and rapid bone reconstruction have been achieved in the management of infectious bone defect. The induced membrane technique has attracted more interests and attention, but the lack of understanding the basic principles of infection control and technical details may hamper the clinical outcomes of induced membrane technique and complications can possibly occur. Therefore, the Chinese Orthopedic Association organized domestic orthopedic experts to formulate An evidence-based clinical guideline for the treatment of infectious bone defect with induced membrane technique ( version 2023) according to the evidence-based method and put forward recommendations on infectious bone defect from the aspects of precise diagnosis, preoperative evaluation, operation procedure, postoperative management and rehabilitation, so as to provide useful references for the treatment of infectious bone defect with induced membrane technique.