To investigate the clinical efficacy of neoadjuvant imatinib in the treatment of rectal gastrointestinal stromal tumor (GIST).

ObjectiveTo investigate the effects of Jianpi Qinghua granules on blood glucose fluctuations in patients with newly diagnosed overweight/obese type 2 diabetes mellitus （T2DM） and Qi-Yin deficiency syndrome from the perspective of skeletal muscle mass and function， while providing new insights for the treatment of diabetes. MethodsThis study employed a randomized， double-blind， placebo-controlled design. A total of 110 newly diagnosed overweight/obese T2DM patients meeting the inclusion criteria were randomly assigned to either the traditional Chinese medicine （TCM） group （54 cases） or the control group （56 cases）. Patients in the TCM group received Jianpi Qinghua Granules， while those in the control group received a placebo. Both groups underwent dietary and exercise guidance. After 12 weeks of intervention， blood glucose fluctuations were assessed using the following parameters： time in the target blood glucose range （TIR）， mean daily blood glucose （MBG）， standard deviation of mean daily blood glucose （SDBG）， mean amplitude of glycemic excursions （MAGE）， coefficient of variation of blood glucose （CV）， glycated hemoglobin （HbA1c） achievement rate， fasting plasma glucose （FPG）， and 2 hour postprandial glucose （2 hPG）. Skeletal muscle mass was measured by dual-energy X-ray absorptiometry （DXA）， while skeletal muscle function was evaluated using a handheld dynamometer for distal muscle strength and a 5-time sit-to-stand test for lower limb function. Additionally， pancreatic islet function and TCM syndrome scores were analyzed. ResultsNo significant differences were observed in baseline data between the two groups before intervention， ensuring comparability. After treatment， compared to the control group， the TCM group showed a significant increase in TIR （P<0.01）. While the SDBG and CV decreased， and MBG and MAGE increased in the TCM group， these differences were not statistically significant. Notably， the TCM group exhibited significant reductions in 2 hPG （P<0.01） and HbA1c （P<0.05）， though the decrease in FPG was not statistically significant. The HbA1c achievement rate in the TCM group was significantly higher than that in the control group （χ²=45.498， P<0.01）. In terms of skeletal muscle mass and function， the TCM group demonstrated a significant increase in handgrip strength （P<0.01） and a significant reduction in the 5-time sit-to-stand duration （P<0.05）. However， although body fat percentage increased， leading to a decrease in skeletal muscle mass and the ratio of skeletal muscle to fat， these changes were not statistically significant. For pancreatic islet function， the TCM group showed significant reductions in fasting insulin （FINS） and homeostasis model assessment of insulin resistance （HOMA-IR） （P<0.01）. Additionally， the TCM syndrome score in the TCM group was significantly reduced （P<0.01）. ConclusionJianpi Qinghua granules may reduce blood glucose fluctuations in newly diagnosed overweight/obese T2DM patients with Qi-Yin deficiency syndrome by enhancing skeletal muscle function， improving pancreatic islet function， and ameliorating related TCM syndromes.

BACKGROUND:Abutment screw loosening is one of the most common mechanical complications in implant restoration.Mechanical wear,as a potential cause of thread loosening,warrants attention due to its impact on mechanical performance and long-term stability.However,studies on the mechanical effects of thread wear in abutment screws remain limited,and no definitive conclusions have been reached.OBJECTIVE:To investigate the effect of different degrees of mechanical wear on the spatial stress distribution of the Morse taper connection implant system,with a view to providing a theoretical basis for the clinical assessment of the long-term stability of dental implants.METHODS:Three-dimensional finite element models of Morse taper implants with central screw thread wear levels of 0,0.1,1,10,and 100 μm were established using SolidWorks software,and simulation analysis with Ansys Workbench software was performed.The implant models were inserted into artificial bone blocks(simulating type Ⅱ bone,with a cortical bone thickness of 2 mm on the outer layer and cancellous bone inside).An alternating load of 300 N in the buccolingual direction was applied at the centroid of the abutment(forming an angle of 30° with the long axis of the implant).The von Mises stress,principal stress,displacement,and fatigue life of the abutment,central screw,implant,and bone tissue in the five groups of models were analyzed.RESULTS AND CONCLUSION:(1)As the degree of mechanical wear on the central screw thread increased,the von Mises stress,principal stress,and strain in the implant and abutment also increased.The stress in the model was concentrated at the top of the implant,at the shoulder level of the implant,at the neck of the abutment,and at the bottom edge of the abutment.(2)Under moderate wear conditions(≥ 10 μm),the fatigue life of the implant system decreased by 30％,and the maximum von Mises stress of the central screw decreased by 37％,with the stress still primarily concentrated at the transition area between the head and the body of the central screw.(3)Under significant wear conditions(≥ 100 μm),the von Mises stress of the central screw decreased by 98％,with the stress concentrated at the screw head,and the fatigue life of the implant system decreased by 63％.Therefore,when the wear level of the central screw thread reaches ≥ 10 μm,the risk of screw loosening is significantly increased,and the fatigue life of the implant system is markedly reduced,warranting clinical attention.

BACKGROUND:Abutment screw loosening is one of the most common mechanical complications in implant restoration.Mechanical wear,as a potential cause of thread loosening,warrants attention due to its impact on mechanical performance and long-term stability.However,studies on the mechanical effects of thread wear in abutment screws remain limited,and no definitive conclusions have been reached.OBJECTIVE:To investigate the effect of different degrees of mechanical wear on the spatial stress distribution of the Morse taper connection implant system,with a view to providing a theoretical basis for the clinical assessment of the long-term stability of dental implants.METHODS:Three-dimensional finite element models of Morse taper implants with central screw thread wear levels of 0,0.1,1,10,and 100 μm were established using SolidWorks software,and simulation analysis with Ansys Workbench software was performed.The implant models were inserted into artificial bone blocks(simulating type Ⅱ bone,with a cortical bone thickness of 2 mm on the outer layer and cancellous bone inside).An alternating load of 300 N in the buccolingual direction was applied at the centroid of the abutment(forming an angle of 30° with the long axis of the implant).The von Mises stress,principal stress,displacement,and fatigue life of the abutment,central screw,implant,and bone tissue in the five groups of models were analyzed.RESULTS AND CONCLUSION:(1)As the degree of mechanical wear on the central screw thread increased,the von Mises stress,principal stress,and strain in the implant and abutment also increased.The stress in the model was concentrated at the top of the implant,at the shoulder level of the implant,at the neck of the abutment,and at the bottom edge of the abutment.(2)Under moderate wear conditions(≥ 10 μm),the fatigue life of the implant system decreased by 30％,and the maximum von Mises stress of the central screw decreased by 37％,with the stress still primarily concentrated at the transition area between the head and the body of the central screw.(3)Under significant wear conditions(≥ 100 μm),the von Mises stress of the central screw decreased by 98％,with the stress concentrated at the screw head,and the fatigue life of the implant system decreased by 63％.Therefore,when the wear level of the central screw thread reaches ≥ 10 μm,the risk of screw loosening is significantly increased,and the fatigue life of the implant system is markedly reduced,warranting clinical attention.

The study focuses on the concept of multifunctional traditional Chinese medicine (TCM) formulas and aims to evaluate the efficacy of the classical formula Xiaoyao San (逍遥散). Study employs the integrated evidence chain (Eff-iEC) method to organize, integrate, and evaluate its therapeutic efficacy in treating different diseases with the same therapy, and to investigate the feasibility of using Eff-iEC to evaluate the multifunctionality of TCM formulas. The evaluation covered Xiaoyao San's therapeutic effects on depression, premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Concurrently, the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) system was used for evaluation, and authoritative medical documents were incorporated to corroborate the recognition of Xiaoyao San within the medical community. Depression and menopausal syndrome received higher ratings than other conditions in the Eff-iEC, GRADE, and Medical Community Recognition assessments. The Eff-iEC evidence grade for Xiaoyao San was rated as "High" or above for chronic hepatitis, irritable bowel syndrome, dyspepsia, and menopausal syndrome. Premenstrual syndrome received a "Moderate ⁺" rating. The GRADE evidence level was "Low-〇〇⨁⨁" for depression, premenstrual syndrome, and chronic hepatitis; "Moderate-〇⨁⨁⨁" for dyspepsia and menopausal syndrome; and "Very Low-〇〇〇⨁" for irritable bowel syndrome. Depression and menopausal syndrome had the highest inclusion frequency, appearing in all 4 categories. Premenstrual syndrome, chronic hepatitis, and dyspepsia are not recommended in Western medical guidelines, but they are included in TCM guidelines, the China National Basic Medical Insurance Drug List, and the China National Essential Drug List. Irritable bowel syndrome appears only in the China National Basic Medical Insurance Drug List and China National Essential Drug List. The evaluation results obtained using the Eff-iEC method align with Medical Community Recognition, providing an objective and comprehensive assessment of Xiaoyao San's efficacy. The findings suggest that Xiaoyao San has strong evidence for treating depression and menopausal syndrome. However, further experimental and clinical trials are needed to assess its efficacy in treating premenstrual syndrome, chronic hepatitis, irritable bowel syndrome, and dyspepsia. These results support the clinical efficacy and rational use of Xiaoyao San, expand the application scope of the Eff-iEC method, and offer valuable insights and methodological references for the comparative evaluation of multifunctional TCM formulas.

ObjectiveTranscranial magneto-acoustic stimulation (TMAS) is an emerging non-invasive neuromodulation technique that may provide a novel non-pharmacological intervention strategy for Parkinson's disease (PD). PD is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to motor impairments such as bradykinesia, tremor, and rigidity. Increasing evidence indicates that mitochondrial dysfunction and impaired mitochondrial quality control are central mechanisms underlying dopaminergic neuronal loss. In particular, abnormalities in mitophagy and mitochondrial fission-fusion balance contribute substantially to oxidative stress, energy metabolic failure, and neuronal injury. At present, most clinical treatments for PD mainly alleviate symptoms but do not effectively halt disease progression. Therefore, exploring new interventions targeting the core pathological mechanisms is of considerable significance. This study aims to investigate whether TMAS can improve neural damage and motor dysfunction in PD mice by regulating mitophagy and the fission/fusion dynamic balance, thereby providing theoretical and experimental support for its application in PD treatment. MethodsMale C57BL/6 mice were used in this study. A PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days. After model induction, mice in the intervention group received TMAS once daily for 14 consecutive days, whereas the corresponding control group received sham stimulation. The stimulation target was positioned over the primary motor cortex (M1). Motor performance was evaluated using the pole test and the open-field test. To verify the activation effect of TMAS on the target cortical region, c-Fos immunohistochemistry was performed in the M1. To assess nigral dopaminergic neuronal injury, tyrosine hydroxylase (TH) immunohistochemistry was used to quantify TH-positive neurons in the SNc. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels and adenosine triphosphate (ATP) content in the SNc. Western blot was further performed to determine the expression of mitophagy-related proteins, including PINK1, Parkin, LC3-II, and p62, as well as mitochondrial dynamics-related proteins, including Drp1 and Opa1. ResultsTMAS significantly increased the number of c-Fos-positive cells in M1 (P<0.000 1), indicating effective activation of neurons in the targeted cortical region. Compared with the control group, MPTP-treated mice exhibited marked motor dysfunction, including a significant reduction in total distance traveled in the open-field test (P<0.000 1) and mean speed (P=0.000 1), as well as significant prolongation of turn time and total climbing time in the pole test (P<0.000 1). These behavioral impairments were accompanied by a substantial loss of TH-positive dopaminergic neurons in the SNc, whereas TMAS significantly increased TH-positive neuron survival (P<0.000 1). In parallel, MPTP induced a pronounced increase in ROS levels and a significant reduction in ATP content, indicating severe mitochondrial dysfunction and energy metabolism impairment (P<0.01). TMAS treatment significantly improved motor performance, as reflected by the reversal of MPTP-induced impairment in the open-field and pole tests, and significantly reduced ROS accumulation (P<0.01) while restoring ATP production (P<0.001). At the molecular level, MPTP markedly downregulated PINK1 and Parkin, decreased p62 expression, increased LC3-II accumulation, elevated Drp1 expression, and reduced Opa1 expression, whereas TMAS significantly reversed these abnormalities, suggesting restoration of mitophagy-related mitochondrial quality control and re-establishment of mitochondrial fission-fusion balance. Collectively, these findings indicate that TMAS ameliorates MPTP-induced neurotoxicity and restores mitochondrial homeostasis and energy metabolism. ConclusionTMAS effectively attenuates neural damage and improves motor dysfunction in MPTP-induced PD mice. Its neuroprotective effects are closely associated with multidimensional regulation of the mitochondrial quality control system, including restoration of PINK1/Parkin-mediated mitophagy and rebalancing of Drp1/Opa1-related mitochondrial dynamics. Rather than acting only as a symptomatic neuromodulatory intervention, TMAS may influence a key pathological axis of PD by improving mitochondrial homeostasis in SNc and protecting nigral dopaminergic neurons. These findings provide experimental evidence supporting TMAS as a promising non-invasive physical intervention for PD.

ObjectiveTranscranial magneto-acoustic stimulation (TMAS) is an emerging non-invasive neuromodulation technique that may provide a novel non-pharmacological intervention strategy for Parkinson's disease (PD). PD is characterized by the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNc), leading to motor impairments such as bradykinesia, tremor, and rigidity. Increasing evidence indicates that mitochondrial dysfunction and impaired mitochondrial quality control are central mechanisms underlying dopaminergic neuronal loss. In particular, abnormalities in mitophagy and mitochondrial fission-fusion balance contribute substantially to oxidative stress, energy metabolic failure, and neuronal injury. At present, most clinical treatments for PD mainly alleviate symptoms but do not effectively halt disease progression. Therefore, exploring new interventions targeting the core pathological mechanisms is of considerable significance. This study aims to investigate whether TMAS can improve neural damage and motor dysfunction in PD mice by regulating mitophagy and the fission/fusion dynamic balance, thereby providing theoretical and experimental support for its application in PD treatment. MethodsMale C57BL/6 mice were used in this study. A PD model was established by intraperitoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 consecutive days. After model induction, mice in the intervention group received TMAS once daily for 14 consecutive days, whereas the corresponding control group received sham stimulation. The stimulation target was positioned over the primary motor cortex (M1). Motor performance was evaluated using the pole test and the open-field test. To verify the activation effect of TMAS on the target cortical region, c-Fos immunohistochemistry was performed in the M1. To assess nigral dopaminergic neuronal injury, tyrosine hydroxylase (TH) immunohistochemistry was used to quantify TH-positive neurons in the SNc. Mitochondrial function was evaluated by measuring reactive oxygen species (ROS) levels and adenosine triphosphate (ATP) content in the SNc. Western blot was further performed to determine the expression of mitophagy-related proteins, including PINK1, Parkin, LC3-II, and p62, as well as mitochondrial dynamics-related proteins, including Drp1 and Opa1. ResultsTMAS significantly increased the number of c-Fos-positive cells in M1 (P<0.000 1), indicating effective activation of neurons in the targeted cortical region. Compared with the control group, MPTP-treated mice exhibited marked motor dysfunction, including a significant reduction in total distance traveled in the open-field test (P<0.000 1) and mean speed (P=0.000 1), as well as significant prolongation of turn time and total climbing time in the pole test (P<0.000 1). These behavioral impairments were accompanied by a substantial loss of TH-positive dopaminergic neurons in the SNc, whereas TMAS significantly increased TH-positive neuron survival (P<0.000 1). In parallel, MPTP induced a pronounced increase in ROS levels and a significant reduction in ATP content, indicating severe mitochondrial dysfunction and energy metabolism impairment (P<0.01). TMAS treatment significantly improved motor performance, as reflected by the reversal of MPTP-induced impairment in the open-field and pole tests, and significantly reduced ROS accumulation (P<0.01) while restoring ATP production (P<0.001). At the molecular level, MPTP markedly downregulated PINK1 and Parkin, decreased p62 expression, increased LC3-II accumulation, elevated Drp1 expression, and reduced Opa1 expression, whereas TMAS significantly reversed these abnormalities, suggesting restoration of mitophagy-related mitochondrial quality control and re-establishment of mitochondrial fission-fusion balance. Collectively, these findings indicate that TMAS ameliorates MPTP-induced neurotoxicity and restores mitochondrial homeostasis and energy metabolism. ConclusionTMAS effectively attenuates neural damage and improves motor dysfunction in MPTP-induced PD mice. Its neuroprotective effects are closely associated with multidimensional regulation of the mitochondrial quality control system, including restoration of PINK1/Parkin-mediated mitophagy and rebalancing of Drp1/Opa1-related mitochondrial dynamics. Rather than acting only as a symptomatic neuromodulatory intervention, TMAS may influence a key pathological axis of PD by improving mitochondrial homeostasis in SNc and protecting nigral dopaminergic neurons. These findings provide experimental evidence supporting TMAS as a promising non-invasive physical intervention for PD.

In 2025， the European Liver and Intestine Transplant Association released the guidelines on the utilization and evaluation of deceased donor livers. The guidelines focus on the definition of high-risk donor livers and the strategies and criteria for dynamic liver assessment， aiming to provide standardized guidance for clinicians. This article gives an excerpt of the key recommendations in the guidelines.

Mycophenolic acid (MPA), the active moiety of both mycophenolate mofetil (MMF) and enteric-coated mycophenolate sodium (EC-MPS), serves as a primary immunosuppressant for maintaining solid organ transplants. Therapeutic drug monitoring (TDM) enhances treatment outcomes through tailored approaches. This study aimed to develop an evidence-based guideline for MPA TDM, facilitating its rational application in clinical settings. The guideline plan was drawn from the Institute of Medicine and World Health Organization (WHO) guidelines. Using the Delphi method, clinical questions and outcome indicators were generated. Systematic reviews, Grading of Recommendations Assessment, Development, and Evaluation (GRADE) evidence quality evaluations, expert opinions, and patient values guided evidence-based suggestions for the guideline. External reviews further refined the recommendations. The guideline for the TDM of MPA (IPGRP-2020CN099) consists of four sections and 16 recommendations encompassing target populations, monitoring strategies, dosage regimens, and influencing factors. High-risk populations, timing of TDM, area under the curve (AUC) versus trough concentration (C₀), target concentration ranges, monitoring frequency, and analytical methods are addressed. Formulation-specific recommendations, initial dosage regimens, populations with unique considerations, pharmacokinetic-informed dosing, body weight factors, pharmacogenetics, and drug‍-‍drug interactions are covered. The evidence-based guideline offers a comprehensive recommendation for solid organ transplant recipients undergoing MPA therapy, promoting standardization of MPA TDM, and enhancing treatment efficacy and safety.
Mycophenolic Acid/administration & dosage* ; Drug Monitoring/methods* ; Humans ; Organ Transplantation ; Immunosuppressive Agents/administration & dosage* ; Delphi Technique

Debates persist regarding the efficacy and safety of azvudine, particularly its real-world outcomes. This study involved patients aged ≥60 years who were admitted to 25 hospitals in mainland China with confirmed SARS-CoV-2 infection between December 1, 2022, and February 28, 2023. Efficacy outcomes were all-cause mortality during hospitalization, the proportion of patients discharged with recovery, time to nucleic acid-negative conversion (T _NANC), time to symptom improvement (T _SI), and time of hospital stay (T _HS). Safety was also assessed. Among the 5884 participants identified, 1999 received azvudine, and 1999 matched controls were included after exclusion and propensity score matching. Azvudine recipients exhibited lower all-cause mortality compared with controls in the overall population (13.3% vs. 17.1%, RR, 0.78; 95% CI, 0.67-0.90; P = 0.001) and in the severe subgroup (25.7% vs. 33.7%; RR, 0.76; 95% CI, 0.66-0.88; P < 0.001). A higher proportion of patients discharged with recovery, and a shorter T _NANC were associated with azvudine recipients, especially in the severe subgroup. The incidence of adverse events in azvudine recipients was comparable to that in the control group (2.3% vs. 1.7%, P = 0.170). In conclusion, azvudine showed efficacy and safety in older patients hospitalized with COVID-19 during the SARS-CoV-2 omicron wave in China.