OBJECTIVE To investigate the mechanism by which aloin （ALO） ameliorates atherosclerosis （AS）. METHODS Eight C57BL/6J mice were assigned to the control group （CON group） and fed a standard diet； thirty-two apolipoprotein E-knockout （APOE－/－） mice were randomly divided into model group （MOD group）， ALO low-dose and high-dose groups [ALO-L group， ALO-H group， 20， 40 mg/（kg·d）]， and atorvastatin positive control group [ATO group， 4 mg/（kg·d）]， with 8 mice in each group， establishing the AS model through feeding with a high-fat diet. The mice were administered the drug via gavage or given an equal volume of deionized water for 8 consecutive weeks. The lipid levels in the serum of mice were measured， and the pathological structural changes in their aortas were observed. The expressions of macrophage polarization markers （CD86+ ， CD206+） in the aorta were determined， along with the mRNA expressions of inducible nitric oxide synthase （iNOS）， tumor necrosis factor-α （TNF-α）， arginase-1 （Arg-1）， and interleukin-10 （IL-10）， as well as the protein expressions of iNOS and Arg- 1， and the phosphorylation levels of nuclear factor κB p65 （NF-κB p65） and signal transduction and activator of transcription 3 （STAT3） proteins. Additionally， a macrophage polarization model was established using lipopolysaccharide （LPS）-induced RAW264.7 cells， and the effect of ALO （400 μmol/L） on the cellular polarization phenotype was investigated. RESULTS Compared with the MOD group， administration groups all showed significant improvement in dyslipidemia （except for high-density lipoprotein cholesterol in the serum of ALO-L group） （P＜0.05）； aortic intimal structure improved significantly， plaque area was reduced significantly （P＜0.01）； the CD86+ relative fluorescence intensity in the aorta decreased significantly， the CD206+relative fluorescence intensity increased significantly （P＜0.01）， while the expressions of iNOS and TNF-α mRNA were down-regulated significantly （P＜0.05）； mRNA expressions of Arg-1 and IL-10， and protein expression of Arg-1 were increased significantly in ALO-H group and ATO group （P＜0.05）； the protein expressions of iNOS， and the phosphorylation levels of NF-κB p65 and STAT3 protein were decreased significantly （P＜0.05）. In vitro experiments further confirmed that ALO significantly reduced the proportion of LPS-induced M1-type macrophages but increased the proportion of M2-type macrophages （P＜0.01）. CONCLUSIONS ALO inhibits M1-type macrophage polarization and promotes M2-type polarization， ameliorates dyslipidemia and reduces arterial plaque formation in AS model mice， improve the structure of the aortic intima potentially through suppression of the NF-κB/STAT3 signaling pathway.

BACKGROUND: The epidemiological pattern and disease burden of type 2 diabetes have been shifting in China over the past decades. This analysis described the epidemiological transition of type 2 diabetes in the past three decades and projected the trend in the future three decades in China. METHODS: Age-, sex-, and year-specific incidence, prevalence, death, and disability-adjusted life years (DALYs) for people with 15 years or older and diabetes or high fasting glucose in China and related countries from 1990 to 2021 were obtained from the Global Burden of Disease. We obtained the trends of age-, sex-, and year-specific rates and absolute numbers of incidence, prevalence, deaths, and DALYs attributable to type 2 diabetes in China from 1990 to 2021. Using the Lee-Carter model, we projected the incidence, prevalence, death, and DALYs attributable to type 2 diabetes to 2050 stratified by age and sex. RESULTS: The age-standardized incidence of type 2 diabetes was 341.5 per 100,000 persons (1.6 times in 1990) and the age-standardized prevalence was 9.96% (9960.0 per 100,000 persons, 2.5 times in 1990) in China 2021. In 2021, there were 0.9 million deaths and 26.8 million DALYs due to type 2 diabetes or hyperglycemia, as 2.9 and 2.7 times the data in 1990, respectively. The age-standardized rates of type 2 diabetes and hyperglycemia were projected to raise to 449.5 per 100,000 persons for incidence, 18.17% for prevalence, 244.6 per 100,000 persons for death, and 4720.2 per 100,000 persons for DALYs by 2050. The incidence of type 2 diabetes kept growing among individuals under the age of 20 years in the past three decades (128.7 per 100,000 persons in 1990 and 439.9 per 100,000 persons in 2021) and estimating 1870.8 per 100,000 in 2050. CONCLUSIONS The incidence, prevalence, and disease burden of type 2 diabetes grew rapidly in China in the past three decades. The prevention of type 2 diabetes in young people and the care for elder adults will be the greatest challenge for the country.
Humans ; Diabetes Mellitus, Type 2/mortality* ; China/epidemiology* ; Prevalence ; Female ; Male ; Incidence ; Middle Aged ; Adult ; Aged ; Adolescent ; Young Adult ; Disability-Adjusted Life Years ; Aged, 80 and over

This article reviews the diagnosis, therapeutic approaches, and subsequent care for a patient with a complex, long-standing history of encapsulating peritoneal sclerosis (EPS). A 40-year-old male, who had been on peritoneal dialysis (PD) for 11 years, encountered refractory peritonitis, leading to the removal of PD catheter and the subsequent diagnosis of EPS. The patient was transitioned to hemodialysis (HD) and prescribed tamoxifen to mitigate peritoneal fibrosis. After 4 months on HD, the patient underwent a kidney transplant, but acute rejection episode caused the transplanted kidney to fail 3 months postoperatively, necessitating a return to HD. Over the past 7 years, the patient has been repeatedly hospitalized due to recurrent bowel obstructions and infected abdominal fluid accumulation. A multidisciplinary approach, including anti-infective therapy, gastrointestinal intervention, nutritional support, and psychological care, has been instrumental in managing symptoms, and sustaining life. This case underscores the importance of recognizing EPS in long-term PD patients with peritonitis. While discontinuing PD, switching to HD, or receiving kidney transplantation do not halt the progression of EPS, optimized comprehensive management can extend the patient's survival.

Objective:To reveal the coupling mechanism of beam temporal profile and tissue oxygen content on radical kinetics, further explain the potential biological basis of the FLASH effect, and provide a reference for beam optimization and treatment planning design of FLASH radiotherapy (FLASH-RT).Methods:TOPAS-nBio v3.0 was used to simulate the physical and chemical processes of electron beams in water, and a full-scale kinetic model was established covering the generation, diffusion, reaction, and quenching of free radicals such as hydroxyl radical (·OH) and hydrated electrons (e aq-). Under different beam temporal profiles (single pulse, multi-pulses, continuous wave irradiation) and different oxygen concentration conditions, the evolution dynamics of free radicals were systematically simulated. At the same time, the data on e aq- content were obtained by experimental measurement of laser absorption spectroscopy to verify the accuracy of the model prediction. Results:The changing trend of e aq- concentration measured in the experiment was highly consistent with the simulation result, verifying the reliability of the constructed model. The beam time structure had a significant impact on the peak value and duration of free radical concentration. The single-pulse structure can cause the free radicals to rapidly increase and then quickly quench in a short time, while the continuous or long-pulse structure can cause the radical concentration to remain at a high level for a long time. The evolution of ·OH was not sensitive to the oxygen environment, while e aq- are greatly affected by the oxygen environment. The scavenging efficiency of free radicals in a hypoxic environment was significantly decreased, leading to an enhanced accumulation of oxidative damage to biological macromolecules. The lifespan of e aq- in an oxygen-rich environment decreased rapidly. Conclusions:Radical kinetics are regulated by both the beam temporal profile and oxygen content. FLASH-RT can utilize single-pulse or multi-pulses intervals to form periodic windows, reducing normal tissue damage by efficiently scavenging free radicals through antioxidants, while free radicals in tumor tissues continuously accumulate and amplify damage, thus generating a selective protective effect.

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

Objective: To investigate the effect of receptor of activated protein kinase C 1 ( RACK1) on lipopo- lysaccharide ( LPS) -induced barrier function in rat pulmonary microvascular endothelial cells ( RPMVEC) and its interplay with the Sonic hedgehog ( SHH) signaling pathway． Methods: RPMVEC were cultured in vitro and ran- domly divided into si-NC，si-NC + LPS，si-RACK1，si-RACK1 + LPS，si-RACK1 + LPS + Vismodegib and Vis- modegib + SAG groups．The RACK1 of RPMVEC was silenced by small interfering RNA ( siRNA) technology and the cells were treated with LPS ( 10 mg / L) ，SHH signaling pathway inhibitor ( Vismodegib) ( 20 μmol / L) and SHH signaling pathway agonist ( SAG) ( 1 μmol / L) ．Following the intervention，the expressions of RACK1 and caveolin-1 in RPMVEC were detected by immunofluorescence ，while the transendothelial electrical resistance ( TEER) was evaluated using the method of Transwell，and the expression levels of RACK1，glioma-associated on- cogene homolog 1 ( Gli-1) and caveolin-1 were detected by Western blot． Results: Silencing RACK1 increased the TEER value of RPMVEC induced by LPS ( P＜0. 05) ．The expression of caveolin-1 decreased ( P＜0. 05) ，and the expression of Gli-1 increased ( P ＜0. 05) ．Inhibiting the SHH signaling pathway could reverse the increased TEER value of LPS-induced RPMVEC caused by silencing RACK1 ( P ＜0. 05) ，and the expressions of RACK1 and caveolin-1 increased ( P＜0. 05) ．Activation of the SHH signaling pathway increased the TEER value of LPS- induced RPMVEC caused by silencing RACK1 ( P ＜0. 05) ，and the expressions of RACK1 and caveolin-1 de- creased ( P＜0. 05) ． Conclusion RACK1 plays a role in LPS-induced hyperpermeability of RPMVEC，and its effect may be achieved by modulating the SHH signaling pathway and caveolin-1．

Objective:To analyze the relationship between tumor-associated immune cells and cytokines with papillary thyroid carcinoma (PTC) and explore the correlation between tumor-associated immune cells and the risk stratification of PTC recurrence.Methods:A total of 58 PTC patients diagnosed by surgical pathology from Aug. 2022 to Aug. 2023 in the General Surgery and Thyroid and Hernia Department of Tianjin Medical University General Hospital were selected. All patients underwent thyroidectomy combined with central or lateral cervical lymph node dissection. According to lymph node metastasis status, patients were divided into lymph node metastasis-negative (22 cases) and lymph node metastasis-positive groups (36 cases) based on post-operative pathological diagnosis. Flow cytometry was used to detect the levels of tumor-associated immune cells (T, B, NK cells) and cytokines (IL-10, IL-17, IL-35, IFN-γ) in T cells.Results:Compared to normal tissue located distant from the cancer, a significant increase in the proportion of NK cells was observed in cancerous tissue ( t=-2.11, P=0.032). Similarly, the proportion of CD8+ T cells was also significantly elevated ( t=-5.12, P=0.005). In lymph node tissue, the proportion of CD4+ T cells in LNM-positive tissue was significantly higher than in LNM-negative tissue ( t=-3.89, P=0.004), while the proportion of CD8+ T cells exhibited a significant decrease ( t=2.41, P=0.004). Additionally, the levels of IL-10 in cancerous tissue were significantly elevated ( t=-3.83, P=0.003), as were the levels of IL-17 ( t=-4.83, P=0.003). In lymph node tissues categorized by LNM status, although not statistically significant, the levels of IL-10 and IL-17 were generally higher in LNM-positive cases compared to LNM-negative cases. Among the 58 cases stratified by recurrence risk, 22 cases (37.9%) were classified as low-risk, while 36 cases (62.1%) were classified as intermediate-risk. The differences in the proportions of CD4+ T and CD8+ T cell subsets in the lymph nodes of PTC patients were statistically significant. Logistic regression analysis indicated that a higher proportion of CD4+ T cell subsets in the lymph nodes of PTC patients was associated with a higher recurrence risk stratification compared to those with a lower proportion ( OR=1.107, 95% CI: 1.001-1.224). Using the predicted probability as the test variable and "low and medium risk" as the state variable, a ROC curve was constructed, yielding an AUC of 0.790 with P=0.003, indicating a good predictive effect of the model on the dependent variable. Conclusions:Compared to normal tissues located distant from cancerous regions, cancer tissues exhibit a significantly elevated proportion of tumor-associated immune cells and cytokine levels, thereby creating an immunosuppressive tumor microenvironment. Additionally, patients with papillary thyroid carcinoma (PTC) who are classified as having a higher risk of recurrence demonstrate a greater proportion of CD4+ T cell subsets in their lymph nodes.

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare familial autosomal dominant genetic disease with primary hyperparathyroidism, jaw tumors, kidney tumors and uterine tumors caused by cell division cycle 73 (CDC73) germline mutations. A 42-year-old male patient was admitted for pancreatitis and further examination revealed elevated PTH at 54.00pmol/L and a history of jaw tumors. This patient was diagnosed as HPT-JT finally and underwent upper right, lower right, and upper left parathyroid glands resection and genetic testing. Postoperative pathology revealed that atypical adenomatous nodules of parathyroid glands with extensive atypia and nucleus division and parathyroid hyperplasia and whole exome sequencing suggested that the CDC73 mutation.

Objective:To analyze the relationship between tumor-associated immune cells and cytokines with papillary thyroid carcinoma (PTC) and explore the correlation between tumor-associated immune cells and the risk stratification of PTC recurrence.Methods:A total of 58 PTC patients diagnosed by surgical pathology from Aug. 2022 to Aug. 2023 in the General Surgery and Thyroid and Hernia Department of Tianjin Medical University General Hospital were selected. All patients underwent thyroidectomy combined with central or lateral cervical lymph node dissection. According to lymph node metastasis status, patients were divided into lymph node metastasis-negative (22 cases) and lymph node metastasis-positive groups (36 cases) based on post-operative pathological diagnosis. Flow cytometry was used to detect the levels of tumor-associated immune cells (T, B, NK cells) and cytokines (IL-10, IL-17, IL-35, IFN-γ) in T cells.Results:Compared to normal tissue located distant from the cancer, a significant increase in the proportion of NK cells was observed in cancerous tissue ( t=-2.11, P=0.032). Similarly, the proportion of CD8+ T cells was also significantly elevated ( t=-5.12, P=0.005). In lymph node tissue, the proportion of CD4+ T cells in LNM-positive tissue was significantly higher than in LNM-negative tissue ( t=-3.89, P=0.004), while the proportion of CD8+ T cells exhibited a significant decrease ( t=2.41, P=0.004). Additionally, the levels of IL-10 in cancerous tissue were significantly elevated ( t=-3.83, P=0.003), as were the levels of IL-17 ( t=-4.83, P=0.003). In lymph node tissues categorized by LNM status, although not statistically significant, the levels of IL-10 and IL-17 were generally higher in LNM-positive cases compared to LNM-negative cases. Among the 58 cases stratified by recurrence risk, 22 cases (37.9%) were classified as low-risk, while 36 cases (62.1%) were classified as intermediate-risk. The differences in the proportions of CD4+ T and CD8+ T cell subsets in the lymph nodes of PTC patients were statistically significant. Logistic regression analysis indicated that a higher proportion of CD4+ T cell subsets in the lymph nodes of PTC patients was associated with a higher recurrence risk stratification compared to those with a lower proportion ( OR=1.107, 95% CI: 1.001-1.224). Using the predicted probability as the test variable and "low and medium risk" as the state variable, a ROC curve was constructed, yielding an AUC of 0.790 with P=0.003, indicating a good predictive effect of the model on the dependent variable. Conclusions:Compared to normal tissues located distant from cancerous regions, cancer tissues exhibit a significantly elevated proportion of tumor-associated immune cells and cytokine levels, thereby creating an immunosuppressive tumor microenvironment. Additionally, patients with papillary thyroid carcinoma (PTC) who are classified as having a higher risk of recurrence demonstrate a greater proportion of CD4+ T cell subsets in their lymph nodes.

Hyperparathyroidism-jaw tumor syndrome (HPT-JT) is a rare familial autosomal dominant genetic disease with primary hyperparathyroidism, jaw tumors, kidney tumors and uterine tumors caused by cell division cycle 73 (CDC73) germline mutations. A 42-year-old male patient was admitted for pancreatitis and further examination revealed elevated PTH at 54.00pmol/L and a history of jaw tumors. This patient was diagnosed as HPT-JT finally and underwent upper right, lower right, and upper left parathyroid glands resection and genetic testing. Postoperative pathology revealed that atypical adenomatous nodules of parathyroid glands with extensive atypia and nucleus division and parathyroid hyperplasia and whole exome sequencing suggested that the CDC73 mutation.