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.

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 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.

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.

Objective:To analyze the imaging manifestations of 18F-fluorodeoxyglucose positron emission tomography/computed tomography(18F-FDG PET/CT)in the patients with pleural and peritoneal mesothelioma,and to enhance the diagnostic accuracy for this disease.Methods:A retrospective analysis was conducted on the 18F-FDG PET/CT imaging and immunohistochemical results of 22 patients confirmed pleural and peritoneal mesothelioma(21 malignant and 1 benign)by pathology.The imaging features and glucose metabolism characteristics were summarized.Results:The majority of the patients with malignant pleural mesothelioma presented with unilateral pleural diffuse thickening accompanied by increased radiotracer uptake,and the thicknesses were ranged from 1.0 to 10.6 cm and the average semi-quantitative maximum standard uptake value(SUVmax)was 10.1.Over half of these patients also had a small amount of pleural effusion.The patients with malignant peritoneal mesothelioma mostly showed diffuse thickening of the peritoneum,omentum,and mesentery with increased radiotracer uptake,and the thicknesses were from 1.2 to 6.6 cm and the average SUVmax was 8.4,and over half of these patients had a significant amount of abdominal ascites.Besides the primary sites,nodular,striated,and mass-like abnormal radiotracer uptakes were observed in other metastatic sites in 17 cases of malignant mesothelioma,suggesting metastasis,and the average SUVmax was 7.4,predominantly surrounding lymph node metastasis.Bone and muscle metastases were visible in the patients with malignant pleural mesothelioma,while no such metastasis were seen in those with malignant peritoneal mesothelioma.One patient with benign pleural mesothelioma presented with bilateral pleural diffuse thickening approximately 3.5 cm thick,without significant abnormal radiotracer uptake and with a minor pleural effusion.Conclusion:The 18F-FDG PET/CT imaging manifestations of pleural and peritoneal mesothelioma exhibit the distinctive characteristics.The mode and thickness of pleural and peritoneal thickening,the presence and degree of 18F-fluorodeoxyglucose uptake,can preliminarily differentiate between benign and malignant mesothelioma,thus providing valuable references for the early clinical diagnosis of mesothelioma.PET/CT based on whole-body imaging can determine whether there are other sites of metastasis,which is helpful for clinical staging.

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.

Objective:To discuss the clinical results of treatment for congenital muscular torticollis with different injection points of botulinum toxin type A and traditional conservative method, and to expound the safety and effectiveness of this way.Methods:From January 2018 to December 2018, 60 cases aged from one month to six months with congenital muscular torticollis who visited the outpatient clinic of plastic surgery in Children＇s Hospital of Quanzhou, a teaching hospital of FuJian Medical University, and there were 38 males and 22 females. The treatment groups were divided into two groups according to random number method that were treated with botulinum toxin type A: the single point group was given one point injection, and the three-point group was injected with three points, while the control group was treated with traditional conservative treatment (mainly manual stretching exercises). The number of cases in each group was 20.Results:The differences of muscle thickness and muscle length were repeatedly measured at different time points in the same group and variance analysis conducted. The results showed that there were statistical significances among the two indicators at different time points in each group ( P<0.05). Least significant difference (LSD) was further adopted for pairwise comparison between indicators at different time points in each group and the differences were statistically significant ( P<0.05). In the comparison of treatment effect of different groups after twelve months follow-up, the cure rate was 85% (17 cases) in the single point group, 95 % (19 cases) in the three-point group, and 80 % (16 cases) in the control group, there was no significant difference among three groups ( P>0.05). Conclusions:Local injection of botulinum toxin type A is a safe and effective treatment option for congenital muscular torticollis, which can achieve the same clinical effect as traditional conservative treatment.

Objective:To compare the clinical effects on new bone formation and foot-ankle function between proximal tibial bone transport and distal tibial bone transport in the treatment of massive bone defects after tibial osteomyelitis debridement.Methods:From July 2012 to July 2017, 42 patients with chronic tibial osteomyelitis received bone transport surgery at Department of Orthopaedics, Nanfang Hospital.According to the Cierny-Mader classification for chronic osteomyelitis, all of them belonged to diffusive tibial osteomyelitis (type IV).Of them, 32 were treated by proximal tibial bone transport after tibial osteomyelitis debridement.In the proximal group, there were 27 males and 5 females, aged from 17 to 65 years and involving 20 left and 12 right sides. The other 10 cases received distal tibial bone transport. In the distal group, all of them were male, aged from 25 to 63 years and involving 6 left and 4 right sides. The 2 groups were compared in terms of external fixation index (EFI) and American Orthopaedic Foot & Ankle Society(AOFAS) Ankle and Hindfoot Scale.Results:There were no significant differences between the 2 groups in the preoperative general data such as gender, age or osteomyelitis site, indicating the 2 groups were comparable ( P>0.05). Both groups obtained complete follow-up. The proximal group was followed up for 590.1 d ± 287.3 d and the distal group for 615.6 d ± 130.6 d, showing no significant difference between groups ( P>0.05). In the proximal group 2 cases developed talipes equinovalgus after bone transport while in the distal group 3 cases did, and surgical intervention was needed for them. Surgical intervention was also carried out for16 cases of non-union at the docking site in the proximal group and for 2 ones in the distal group. The EFI was 76.2 d/cm±50.0 d/cm for the proximal group and 84.3 d/cm ± 59.9 d/cm for the distal group, showing no significant difference between groups ( P>0.05). The AOFAS scores were 81.4±10.1 for the proximal group and 60.0±5.9 for the distal group, showing a significant difference ( P<0.05). Conclusion:In the treatment of massive bone defects after tibial osteomyelitis debridement, no significant difference has been observed in the effect on bone formation between proximal tibial bone transport and distal tibial bone transport, but the former transport may have a less adverse effect on foot-ankle function.

Objective To investigate the design,incisional method and clinical experiences of using the mi cro-dissected polyfoliate anterolateral thigh perforator flap to repair of complex soft tissue defect in extremities.Methods From June,2017 to September,2018,12 cases of different kinds of complex soft tissue defect in extremities were repaired by micro-dissected free polyfoliate anterolateral thigh perforator flap.Each flap was divided into two cutaneous perforators to give two separate flap with a common vascular supply.The flaps were cut from the superficial layer of the deep cervical fesciae and without fascia lata.The donor sites were treated by subcutaneous cosmetic suture.Patients were followed-up by outpatient service,telephone and WeChat video to observe and record the flap's appearance,sensory recovery,extremities function and the scars of the donor site to evaluate its clinical efficacy.Results All flaps survived without vascular crisis happened except one-leaf necrosis occurred,which healed with local flap transferring.The donor sites remained linear scars.The mean flap thickness of this group after micro-dissection was (4.5±0.5) mm.All the patients were followed-up for 5-15 months.The 2 point discrimination ranged between 0.5-2.0 cm.Sensory restoration ranking was S3-S3+.The range of montion of wrist joint was 65°-90°,and that of ankle joint was 40°-60°.Conclusion The micro-dissected polyfoliate anterolateral thigh perforator flap is an ideal method for complex and irregular multiple sites soft tissue defect in extremities as it can keep good economic benefit and minimal damage to the donor site.