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 assess the therapeutic efficacy of low-intensity focused ultrasound(LIFU)on knee arthrofibrosis in rats and explore its underlying mechanisms.Methods Fifteen male SD rats(8 weeks old,weighing 250～300 g)were randomly divided into a blank control group,a model group,and an ultrasound treatment group,with 5 animals in each group.Rat model of knee joint stiffness was established in the model and ultrasound treatment group.The rats in the ultrasound group received LIFU intervention(frequency:1 MHz,power:1.5 W,20 min per session,5 times/week)for 4 weeks.The knee ranges of motion(ROM,flexion and extension)were measured in all 3 groups at 0,14 and 28 d after intervention.Histological analysis was conducted for the morphological changes in the posterior capsular area of the knee.After the synovial fibroblasts were primary isolated from rat knee joints,the cells were divided into blank control,LIFU,TGF-β(10 ng/mL),and TGF-β+LIFU groups.Changes in fibrosis-related indicators and the TGF-β/Smad signaling pathway were assessed in each group.Results In the animal experiments,LIFU intervention for 14 d resulted in significantly improved flexion-extension ROM in knee joints when compared with the rats in the model group(P<0.05),and the improvement was more obvious at 28 d after intervention(P<0.05).After 28 d of LIFU intervention,the fibrosis of the posterior capsule of the knee joint was notably improved in the ultrasound group than the model group,and the expression levels of fibrosis-related indicators(α-SMA,TGF-β)were decreased(P<0.05).In the cellular experiments,the TGF-β group exhibited remarkable up-regulation of fibrosis-related molecules(α-SMA,COL1A1,COL3A1)at both protein and mRNA levels(P<0.05),and activation of the TGF-β/Smad signaling pathway when compared to the blank control group.While LIFU intervention inhibited the expression of TGF-β-induced upregulation of fibrotic indicators(α-SMA,COL1A1,COL3A1)and the activation of TGF-β/Smad signaling pathway(P<0.05).Conclusion LIFU can effectively improve knee arthrofibrosis in rats,which potentially through the inhibition of fibroblast activation and modulation of the TGF-β/Smad signaling pathway.

Objective: To understand the current status, international cooperation, research hotspots, and development trends of nutritional studies on patients with head and neck cancer from 2014 to 2024, and to predict future research trends. Methods: The Web of Science Core Collection database was searched to retrieve nutritional studies on patients with head and neck cancer from January 2014 to March 2024. The type of studies were “articles,” the language was English, CiteSpace 6.1 R6 software was used to conduct the bibliometric analysis, and the results were visualized to form a scientific knowledge map. Results: A total of 1 528 documents were retrieved, with a linear increase in the number of annual publications. The country with the highest number of publications was the United States, and the institution with the highest number of publications was the University of Queensland, with closer collaboration between authors and institutions. The most frequently cited publication was a set of nutrition guidelines, and the highest-impact articles were mainly concerned with performing percutaneous endoscopic gastrostomy. Keyword analysis showed that quality of life, radiotherapy, and weight loss were the keywords of highest interest. The keyword cluster analysis resulted in 17 clusters, which were divided into five main categories: head and neck cancer, treatment, outcome results, intervention modalities, and rehabilitation. Body composition, enteral nutrition, and accelerated postoperative rehabilitation were persistent research hotspots. Keyword highlighting revealed that “enhanced recovery after surgery” has been the focus of research in the last two years, with “index” and “model” emerging as theme words. Conclusion The number of publications in the literature related to nutrition for patients with head and neck cancer has increased annually over the past 10 years. The research hotspots mainly focus on the quality of life and weight loss during radiotherapy, the content and application prospect of body composition assessment, different modes of nutritional support interventions and enteral nutritional tube feeding routes, and perioperative nutritional management in enhanced recovery after surgery. The potential clinical value of preoperative nutritional intervention under the concept of enhanced recovery and the construction of new types of nutritional index are the trends of future research.

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.

Toxic Chinese herbal medicines(TCHMs)both represent a unique class of therapeutic agents that exhibit both potent efficacy("using toxins to combat pathogens and often curing critical con-ditions")and pose safety concerns("potentially causing severe harm").Balancing clinical effectiveness with safe applications remains a priority of research for these substances.This review summarizes the hepatotoxic mechanisms,research progress,detoxification strategies and clinical challenges associated with TCHMs documented in the 2025 Pharmacopoeia of the People's Republic of China(Volume Ⅰ)in the hope of providing evidence-based insights into the safe and rational clinical use of these hepatotoxic herbs.

Toxic Chinese herbal medicines(TCHMs)both represent a unique class of therapeutic agents that exhibit both potent efficacy("using toxins to combat pathogens and often curing critical con-ditions")and pose safety concerns("potentially causing severe harm").Balancing clinical effectiveness with safe applications remains a priority of research for these substances.This review summarizes the hepatotoxic mechanisms,research progress,detoxification strategies and clinical challenges associated with TCHMs documented in the 2025 Pharmacopoeia of the People's Republic of China(Volume Ⅰ)in the hope of providing evidence-based insights into the safe and rational clinical use of these hepatotoxic herbs.

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.

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.

Objective:To report on a case of Kabuki syndrome (KS) due to a novel variant of KMT2D gene. Methods:A child diagnosed with KS at the Fujian Children′s Hospital on July 25, 2022 was selected as the study subject. Whole exome sequencing was carried out for the child and her parents. Candidate variant was validated by Sanger sequencing and bioinformatic analysis.Results:The child, a 4-month-old female, had presented with distinctive facial features, growth retardation, cardiac malformations, horseshoe kidney, hypothyroidism, and recurrent aspiration pneumonia. Whole exome sequencing revealed that she has harbored a heterozygous c. 6285dup (p.Lys2096Ter) variant of the KMT2D gene. Sanger sequencing confirmed that neither of her parents had carried the same variant. The variant was previously unreported, and may result in a truncated protein and loss of an enzymatic activity region. The corresponding site of the variant is highly conserved. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), the variant was classified as pathogenic (PVS1+ PS2+ PM2_Supporting). Conclusion:The c. 6285 dup variant of the KMT2D gene probably underlay the KS in this child.