Malignant tumors are one of the major diseases that endanger human life and health. Chinese medicine has unique advantages in clinical anti-tumor treatment. However， how to translate the anti-tumor effects of Chinese medicine into clinical practice is the core issue that must be addressed in the process of treating malignant tumors with traditional Chinese medicine （TCM）. Unlike modern chemical drugs， the compatibility application of Chinese medicine is the key factor that determines whether Chinese medicine can achieve optimal anti-tumor efficacy and realize the goal of "enhancing efficacy and reducing toxicity". The formulation structure based on this compatibility is the basic form for the safe， efficient， and rational clinical use of anti-tumor Chinese medicine， and it mainly includes three categories： herb pairs， tri-herbal combinations， and compound compatibility. Although herb pairs have the characteristics of a simple structure and strong targeting （enhancing efficacy and reducing toxicity）， they often have a single effect and cannot fully address the complex pathogenesis of tumors. As a result， herb pairs are rarely used alone in practice. Compared to herb pairs， tri-herbal combinations broaden the application scope of herbs in clinical treatment， but their therapeutic range remains limited. The traditional "sovereign， minister， assistant， and guide" compound prescription， which includes herb pairs and tri-herbal combinations， improves the efficacy of herbs in treating serious diseases， hypochondriasis， chronic diseases， and miscellaneous disorders. However， due to the limitations of its historical background， it has not been integrated with modern clinical practice and modern pharmacological research， which restricts the development of compound compatibility theory. With the emergence of modern medical technology， it has been combined with traditional compatibility theory of Chinese medicine to create an innovative modern compatibility theory. This includes the "aid medicine" theory derived from modern Chinese medicine pharmacology， which compensates for the inability of the "sovereign， minister， assistant， and guide" theory to accurately apply medicine. Additionally， the "state-targeted treatment based on syndrome differentiation" theory， developed from pharmacology and modern medicine， addresses the deficiency in disease cognition in the "sovereign， minister， assistant， and guide" theory. Under the guidance of these compatibility forms and theories， clinical anti-tumor Chinese medicine can exert its maximum anti-tumor efficacy， which is of great significance for the application of Chinese medicine in clinical tumor treatment.

OBJECTIVE: To precise classify sacral meningeal cysts, effective guide minimally invasive neurosurgery and postoperative personalized rehabilitation by multiple dimensions radiographic reconstruction MRI. METHODS: From March to December 2021, based on the original 3D-fast imaging employing steadystate acquisition (FIESTA) scanning sequence, 92 patients with sacral meningeal cysts were pre-operatively evaluated by multiple dimensional reconstruction MRI. The shape of nerve root and the leakage of cyst were reconstructed according to the direction of nerve root or leakage track showed on original MRI scans. Sacral canal cysts were accurately classified as including nerve root and without nerve root, so as to accurately design the incision of skin and formulate corresponding open range of the posterior wall of the sacral canal. Under the microscope intraoperation, the shape of the nerve roots inside cysts or leakage track of the cysts without nerve roots were verified and explored. After the reinforcement and shaping operation, several reexaminations of multiple dimensional reconstruction MRI were performed to understand the deformation of the nerve root and hydrops in the operation cavity, so as to formulate a persona-lized rehabilitation plan for the patients. RESULTS: Among the 92 patients with sacral mengingeal cyst, 58 (63.0%) cysts with nerve root cyst, 29 (31.5%) cysts without nerve root cyst, and 5 (5.4%) cysts with mixed sacral canal cyst. In 58 patients with nerve root cysts, the accuracy of preoperative clinical classification on MRI image reached 96.6% (56/58) through confirmation by operating microscope. Only 2 cases of large single cyst with nerve root on the head of cyst were mistaken for without nerve root type. In 29 patients with sacral cyst without nerve root, the accuracy of preoperative image reached 100% through confirmation by operating microscope. The accuracy of judging the internal nerve root and leakage of 12 cases with recurrent sacral cyst was also 100%. Two cases of delayed postoperative hydrops were found one month after operation. After rehabilitation treatment by moxibustion and bathing, the hydrops disappeared 4-6 months after operation. CONCLUSION Multiple dimensional reconstruction MRI can precisely make clinical classification of sacral meningeal cysts before operation, guide minimally invasive neurosurgery effectively, and improve the rehabilitation effect.
Humans ; Magnetic Resonance Imaging/methods* ; Male ; Female ; Sacrum/surgery* ; Adult ; Middle Aged ; Imaging, Three-Dimensional/methods* ; Cysts/rehabilitation* ; Aged ; Adolescent ; Young Adult ; Spinal Nerve Roots/diagnostic imaging* ; Minimally Invasive Surgical Procedures ; Neurosurgical Procedures/methods*

Idiopathic pulmonary fibrosis (IPF) is a progressive disease lacking effective therapy. Metformin, an antidiabetic medication, has shown promising therapeutic properties in preclinical fibrosis models; however, its precise cellular targets and associated mechanisms in fibrosis resolution remain incompletely defined. Most research on metformin's effects has focused on mesenchymal and inflammatory responses with limited attention to epithelial cells. In this study, we utilized Sftpc lineage-traced and Fgfr2b conditional knockout mice, along with BMP2/PPARγ and AMPK inhibitors, to explore metformin's impact on alveolar epithelial cells in a bleomycin-induced pulmonary fibrosis model and cell culture. We found that metformin increased the proliferation and differentiation of alveolar type 2 (AT2) cells, particularly the recently identified injury-activated alveolar progenitors (IAAPs)-a subpopulation characterized by low SFTPC expression but enriched for PD-L1. Single-cell RNA sequencing revealed a reduction in apoptosis among mature AT2 cells. Interestingly, metformin's therapeutic effects were not significantly affected by BMP2 or PPARγ inhibition, which blocked the lipogenic differentiation of myofibroblasts. However, Fgfr2b deletion in Sftpc lineage cells significantly impaired metformin's ability to promote fibrosis resolution, a process linked to AMPK signaling. In conclusion, metformin alleviates fibrosis by directly activating AT2 cells, especially the IAAPs, through a mechanism that involves AMPK and FGFR2b signaling, but is largely independent of BMP2/PPARγ pathways.

Computational approaches, encompassing both physics-based and machine learning (ML) methodologies, have gained substantial traction in drug repurposing efforts targeting specific therapeutic entities. The human dopamine (DA) transporter (hDAT) is the primary therapeutic target of numerous psychiatric medications. However, traditional hDAT-targeting drugs, which interact with the primary binding site, encounter significant limitations, including addictive potential and stimulant effects. In this study, we propose an integrated workflow combining virtual screening based on weighted holistic atom localization and entity shape (WHALES) descriptors with in vitro experimental validation to repurpose novel hDAT-targeting drugs. Initially, WHALES descriptors facilitated a similarity search, employing four benztropine-like atypical inhibitors known to bind hDAT's allosteric site as templates. Consequently, from a compound library of 4,921 marketed and clinically tested drugs, we identified 27 candidate atypical inhibitors. Subsequently, ADMETlab was employed to predict the pharmacokinetic and toxicological properties of these candidates, while induced-fit docking (IFD) was performed to estimate their binding affinities. Six compounds were selected for in vitro assessments of neurotransmitter reuptake inhibitory activities. Among these, three exhibited significant inhibitory potency, with half maximal inhibitory concentration (IC₅₀) values of 0.753 μM, 0.542 μM, and 1.210 μM, respectively. Finally, molecular dynamics (MD) simulations and end-point binding free energy analyses were conducted to elucidate and confirm the inhibitory mechanisms of the repurposed drugs against hDAT in its inward-open conformation. In conclusion, our study not only identifies promising active compounds as potential atypical inhibitors for novel therapeutic drug development targeting hDAT but also validates the effectiveness of our integrated computational and experimental workflow for drug repurposing.

Objective Explore the comprehensive emotion adjustment pattern that combines non-contact physiological and psychological detection methods in fasting and low metabolism scenarios.This study aims to verify the accuracy of non-contact physiological and psychological detection algorithms and evaluate the effectiveness of multimodal emotion adjustment schemes for addressing negative emotional states such as depression and anxiety.Methods Deploy non-contact physiological and psychological detection algorithms and emotion adjustment plans to build a multimodal emotion adjustment system.Collect physiological and psychological data from volunteers participating in the 15-days complete fasting human low metabolism experiment of"Green Star Travel Ⅷ".Utilize finger clip oximeters and scales to verify the accuracy of existing non-contact physiological and psychological methods within the system.Design an emotion adjustment experiment featuring four groups:sound adjustment,acupoints adjustment,magnetism adjustment,and combination adjustment.Compare the volunteers'scale scores before and after the adjustments to verify the effectiveness of the system's emotion adjustment capabilities.Results The experimental results demonstrate that the average difference in the Bland-Altman plot for the non-contact heart rate detection model is ﹣0.497 bpm,with 95.3%of the error values falling within the 95%consistency interval.The non-contact psychological detection model achieved an accuracy rate of over 80%in identifying stress,anxiety,and depression,and an accuracy rate of over 70%in identifying fatigue and anger.Following emotion adjustment,the stress levels of the subjects significantly improved(P?

Objective In the future,during the landing and exploration of near-Earth planets(e.g.,Mars,Jupiter,etc.),astronauts may take the initiative to start fasting to reduce the amount of load;and it is even more likely that astronauts will take the initiative to fast in the process of manned deep-space exploration in the future,or they may enter a dormant low-metabolism state to save the amount of load to enable the spaceship to fly for a longer period,and to locate in a deeper and farther position.The ability of an individual to maintain cognitive ability and respond appropriately over a period in a long-term fasting state is important for survival.Therefore,the present study focused on investigating the effects of 15 days of complete fasting on dual cognitive control function and its neural mechanisms.Methods Twenty-four healthy volunteers were recruited to participate in the fasting experiment.Behavioral and electroencephalographic data from the AX-CPT Task were collected with event-related potentials(ERP)to assess the effects of 15 days of complete fasting on dual cognitive control in 16 volunteers.Results(1)Behavioral outcomes had significant main effects on response time[F(1,15)=99.41,P?

As China's manned space missions gradually develop towards long-term residence and deep space exploration,astronauts will face increasingly severe psychological challenges.As a psychological adjustment method involving multiple disciplines such as music,psychology,and medicine,music therapy has the advantages of being convenient to implement,cost-effective,and highly personalized.This paper integrates the concept of music therapy and explores the research progress of music therapy in regulating psychological states in aspects such as physiology,emotional regulation,cognitive ability,and interpersonal relationships.Combined with the mechanism of action of music therapy and the practical situation in the field of manned spaceflight,it aims at the future development trends and problems to be solved,to construct a music therapy system for astronauts during on-orbit flight and ground daily training.This will help astronauts achieve healthy physical and mental development and promote the completion of missions.

Background::A phase II trial on recombinant human tenecteplase tissue-type plasminogen activator (rhTNK-tPA) has previously shown its preliminary efficacy in ST elevation myocardial infarction (STEMI) patients. This study was designed as a pivotal postmarketing trial to compare its efficacy and safety with rrecombinant human tissue-type plasminogen activator alteplase (rt-PA) in Chinese patients with STEMI.Methods::In this multicenter, randomized, open-label, non-inferiority trial, patients with acute STEMI were randomly assigned (1:1) to receive an intravenous bolus of 16 mg rhTNK-tPA or an intravenous bolus of 8 mg rt-PA followed by an infusion of 42 mg in 90 min. The primary endpoint was recanalization defined by thrombolysis in myocardial infarction (TIMI) flow grade 2 or 3. The secondary endpoint was clinically justified recanalization. Other endpoints included 30-day major adverse cardiovascular and cerebrovascular events (MACCEs) and safety endpoints.Results::From July 2016 to September 2019, 767 eligible patients were randomly assigned to receive rhTNK-tPA ( n = 384) or rt-PA ( n = 383). Among them, 369 patients had coronary angiography data on TIMI flow, and 711 patients had data on clinically justified recanalization. Both used a –15% difference as the non-inferiority efficacy margin. In comparison to rt-PA, both the proportion of patients with TIMI grade 2 or 3 flow (78.3% [148/189] vs. 81.7% [147/180]; differences: –3.4%; 95% confidence interval [CI]: –11.5%, 4.8%) and clinically justified recanalization (85.4% [305/357] vs. 85.9% [304/354]; difference: –0.5%; 95% CI: –5.6%, 4.7%) in the rhTNK-tPA group were non-inferior. The occurrence of 30-day MACCEs (10.2% [39/384] vs. 11.0% [42/383]; hazard ratio: 0.96; 95% CI: 0.61, 1.50) did not differ significantly between groups. No safety outcomes significantly differed between groups. Conclusion::rhTNK-tPA was non-inferior to rt-PA in the effect of improving recanalization of the infarct-related artery, a validated surrogate of clinical outcomes, among Chinese patients with acute STEMI.Trial registration::www.ClinicalTrials.gov (No. NCT02835534).

Objective To analyze the characteristics of platelet changes and their influencing factors during postoperative hospitalization in patients who underwent transcatheter aortic valve implantation (TAVI). Methods The patients who underwent TAVI at Beijing Anzhen Hospital Valve Surgery Center between March 2017 and October 2021 were retrospectively selected. The patients were divided into a self-limiting group and a non-self-limiting group according to the characteristics of postoperative platelet decline. In addition, the general preoperative data, preoperative and postoperative ultrasound data, intraoperative data, and the use of anticoagulant drugs during the postoperative stay in the hospital were compared between the two groups. Results A total of 249 patients were enrolled in this study. There were 175 (70.3%) patients in the self-limiting group, including 100 males and 75 females, and there were 74 (29.7%) patients in the non-self-limiting group, including 43 males and 31 females, with no statistical difference between the two groups (P=0.863). The mean age of patients was 73.11±8.88 years in the self-limiting group and 71.54±10.39 years in the non-self-limiting group (P=0.231). The decline of platelets in the self-limiting group generally occurred on the postoperative day 2 and reached the lowest count on the postoperative day 4, and returned to the baseline level on the postoperative day 5-7, while the platelets in the non-self-limiting group changed by simple rise, fall or irregular fluctuation. Patients in the self-limiting group had severer preoperative aortic stenosis (P<0.001) and used more extracorporeal circulation assistance during surgery (P<0.001). Postoperatively, patients in the self-limiting group were more likely to have periaortic valve leakage than those in the non-self-limiting group (P=0.013). Conclusion Platelet changes in most patients after TAVI show a self-limiting decline, which may be related to the severity of patients’ preoperative aortic stenosis, intraoperative extracorporeal circulation device use, and postoperative perivalvular leakage.

Mitral valve replacement is one of the most common heart valve surgeries in China. In recent years, with the increase in degenerative valve diseases, older patients, and the progress of anti-calcification technology of biological valves, the proportion of mitral valve biological valve replacement has been increasing year by year. After the damage of traditional mitral valve biological valves, re-operation of valve replacement with thoracotomy is required. However, the adhesion between the heart and sternum, as well as the damage caused by cardiopulmonary bypass and cardiac arrest, can cause significant trauma to elderly patients and those with multiple organ dysfunction, leading to increased mortality and complication rates. In recent years, interventional valve surgery, especially transcatheter valve-in-valve surgery, has developed rapidly. This procedure can correct the damaged mitral valve function without stopping the heart, but there are still many differences between its technical process and conventional aortic valve replacement surgery. Therefore, organizing and writing multicenter expert recommendations on the technical process of transcatheter valve-in-valve surgery for damaged mitral valve biological valves is of great significance for the training and promotion of this technology.