Liumotang comes from the Yuan dynasty's Effective Prescription Handed Down for Generations of Physicians. It is composed of six medicinal materials： Arecae Semen， Aquilariae Lignum Resinatum， Aucklandiae Radix， Linderae Radix， Rhei Radix et Rhizoma， and Aurantii Fructus. It is a classical formula for treating abdominal pain due to Qi stagnation and constipation accompanied by heat. This study systematically collated the records of Liumotang in ancient medical books and modern clinical literature and conducted in-depth analysis and textual research on its formula source， main diseases， composition， dosage， medical books， container capacity， processing， preparation method， usage， drug basis， formula meaning， and other key information， so as to provide a powerful reference for the development and clinical application of compound preparations of the classical formula Liumotang. The results show that Liumotang was first seen in Effective Prescription Handed Down for Generations of Physicians， and many medical books of the past dynasties have imitated this. In terms of drug basis， the dried and mature seeds of the palm plant Areca catechu， resin-containing wood of the Daphneaceae plant Aquilaria sinensis， the dried roots of the Asteraceae plant woody Aucklandia lappa， the dried tuber root of the Lauraceae plant Lindera aggregata， the dried roots and rhizomes of the knotweed plant， R. palmatum， R.tangutikum， and R. officinale， and the dried and unripe fruits of the citrus genus C. aurantium and its cultivated varieties from the family Rutaceae were selected. In terms of dosage， through the textual research on bowls in the Ming and Qing dynasties， combined with the conversion of medicines and bowl capacity in the Qing dynasty， it was estimated that the dosage of each drug in the Yuan dynasty was 10.86 g. In the Ming and Qing dynasties， the dosage of drugs was mostly equal， but the dosage of drugs was somewhat different. In terms of processing， preparation method， and usage， in the medical books of the past dynasties， the processing of drugs has slightly changed， but raw drugs are used in all preparations. The preparation method and usage did not change much during the Yuan， Ming， and Qing dynasties， except for certain differences in dosage. In terms of syndrome， Liumotang was first used to treat abdominal pain due to Qi stagnation and constipation accompanied by heat. Medical books of the past dynasties often omit the symptoms of heat. In modern clinical practice， Liumotang is mainly used in the digestive system and urinary system diseases and is mostly used to treat constipation-predominant irritable bowel syndrome， biliary reflux gastritis， functional constipation， slow transit constipation， and other diseases， with no adverse reactions found yet. The above results provide a reliable scientific basis for the development and clinical treatment of Liumotang compound preparations.

ObjectiveTo develop a nomogram-based risk prediction model for chronic obstructive pulmonary disease (COPD) incidence among the community-dwelling population aged 40 years old and above, so as to provide targeted references for the screening and prevention of COPD. MethodsBased on a natural population cohort in suburban Shanghai, a total of 3 381 randomly selected participants aged ≥40 years underwent pulmonary function tests between July and October 2021. Cox stepwise regression analysis was used to develop overall and gender-specific risk prediction models, along with the construction of corresponding risk nomograms. Model predictive performance was evaluated using the C-indice, area under the curve (AUC) values, and Brier score. Stability was assessed through 10-fold cross-validation and sensitivity analysis. ResultsA total of 3 019 participants were included, with a median follow-up duration of 4.6 years. The COPD incidence density was 17.22 per 1 000 person-years, significantly higher in males (32.04/1 000 person-years) than that in females (7.38/1 000 person-years) (P<0.001). The overall risk prediction model included the variables such as gender, age, education level, BMI, smoking, passive smoking, and respiratory comorbidities. The male-specific model incorporated the variables such as age, BMI, respiratory comorbidities, and smoking, while the female-specific model included age, marital status, respiratory comorbidities, and pulmonary tuberculosis history. The C-indices for the overall, male-specific, and female-specific models were 0.829, 0.749, and 0.807, respectively. The 5-year AUC values were 0.785, 0.658, and 0.811, with Brier scores of 0.103, 0.176, and 0.059, respectively. Both 10-fold cross-validated C-indices and sensitivity analysis (excluding participants with a follow-up duration of <6 months) yielded C-indices were above 0.740. ConclusionThis study developed concise and practical overall and gender-specific COPD risk prediction models and corresponding nomograms. The models demonstrated robust performance in predicting COPD incidence, providing a valuable reference for identifying high-risk populations and formulating targeted screening and personalized management strategies.

Lacking therapeutic targets highlights the crucial roles of chemotherapy and radiotherapy in the clinical management of triple-negative breast cancer (TNBC). To relieve the side effects of the chemoradiotherapy combination regimen, we design and develop a self-assembled micelle nanosystem consisting of perfluorocarbon chain-modified cisplatin prodrug. By incorporating perfluorodecalin, this nanosystem can effectively carry ozone and promote irradiation-derived reactive oxygen species (ROS) production. By leveraging the perfluorocarbon sidechain, the nanosystem exhibits efficient internalization by TNBC cells and effectively escapes from lysosomal entrapment. Under X-ray irradiation, ozone-generated ROS disrupts the intracellular redox balance, thereby facilitating the release of cisplatin in a reduction-responsive manner mediated by reduced glutathione. Moreover, oxygen derived from ozone decomposition enhances the efficacy of radiotherapy by alleviating tumor hypoxia. Notably, the combination of irradiation with ozone-loaded cisplatin prodrug nano system synergistically prompts antitumor efficacy and reduces cellular/systemic toxicity in vitro and in vivo. Furthermore, the combo regimen remodels the tumor microenvironment into an immune-favored state by triggering immunogenic cell death and relieving hypoxia, which provides a promising foundation for a combination regimen of immunotherapy. In conclusion, our nanosystem presents a novel strategy for integrating chemotherapy and radiotherapy to optimize the efficacy and safety of TNBC clinical treatment.

Cerebral edema is characterized by fluid accumulation, and the glymphatic system (GS) plays a pivotal role in regulating fluid transport. Using the Tenecteplase system, magnesium salt of salvianolic acid B/ginsenoside Rg1 (SalB/Rg1) was injected intravenously into mice 4.5 h after middle cerebral artery occlusion and once every 24 h for the following 72 h. GS function was assessed by Evans blue imaging, near-infrared fluorescence region II (NIR-II) imaging, and magnetic resonance imaging (MRI). SalB/Rg1 had significant effects on reducing the infarct volume and hemorrhagic transformation score, improving neurobehavioral function, and protecting tissue structure, especially inhibiting cerebral edema. Meanwhile, the influx/efflux drainage of GS was enhanced by SalB/Rg1 according to NIR-II imaging and MRI. SalB/Rg1 inhibited matrix metalloproteinase-9 (MMP-9) activity, reduced cleaved β-dystroglycan (β-DG), and stabilized aquaporin-4 (AQP4) polarity, which was verified by colocalization with CD31. Our findings indicated that SalB/Rg1 treatment enhances GS function and attenuates cerebral edema, accompanying the regulation of the MMP9/β-DG/AQP4 pathway.
Animals ; Ginsenosides/administration & dosage* ; Brain Edema/etiology* ; Male ; Benzofurans/administration & dosage* ; Glymphatic System/diagnostic imaging* ; Mice ; Infarction, Middle Cerebral Artery/drug therapy* ; Aquaporin 4/metabolism* ; Disease Models, Animal ; Mice, Inbred C57BL ; Matrix Metalloproteinase 9/metabolism* ; Neuroprotective Agents/pharmacology* ; Depsides

Background and purpose:Chimeric antigen receptor T(CAR-T)cell therapy has shown remarkable efficacy in treating hematological and lymphatic system tumors,but its effectiveness in solid tumors is relatively poor,which is partly attributed to target selection.For Ewing sarcoma(ES),CD99 can be a potential target for CAR-T cells.However,due to T cells'endogenous expression of CD99 protein,CAR-T cells targeting CD99 face limitations in their expansion capacity in vitro.This study aimed to identify the optimal conditions for preparing CD99 CAR-T cells by incorporating CD99 knockdown short hairpin RNA(shRNA),optimizing the multiplicity of infection(MOI)for lentiviral transduction,and screening for the best culture medium and container for CAR-T cell expansion.Methods:shRNA sequences were screened to enhance the expansion capacity of CD99 CAR-T cells.Different MOI,culture media,and containers were used to assess CAR-T cell transduction efficiency,cell viability,proliferation capacity,specific killing ability,and interferon-γ(IFN-γ)release levels under various conditions,in order to identify the optimal cell preparation conditions.Results:The expansion level of KO-CD99 CAR-T cells obtained through shRNA knockdown was significantly higher than that of CD99 CAR-T cells[(16.40±0.40)vs(6.33±1.53),P<0.01].The optimal expansion effect was observed when the transduction MOI was between 0.25 and 1.0,and OptiVitro was used as the culture medium.CAR-T cells cultured in ventilated flasks exhibited significantly higher expansion rates compared to cells cultured in bags[MOI=0.25:(50.23±3.32)vs(13.02±4.82);MOI=0.50:(49.96±0.83)vs(18.25±2.88);MOI=1.00:(48.27±5.08)vs(13.16±6.26);P<0.01],with better cell phenotype and higher specific killing ability.Conclusion:KO-CD99 CAR-T cells obtained through shRNA technology can achieve stable expansion.Based on the optimization of expansion conditions,KO-CD99 CAR-T cells exhibit superior expansion capacity and a higher proportion of memory T cells when the MOI is between 0.25 and 1.00,OptiVitro is used as the culture medium,and ventilated flasks are used as the culture container.These findings lay a solid foundation for further clinical trials of CD99 CAR-T cell therapy for ES.

Anterior cruciate ligament (ACL) injury of knee is a common sports injury.The hypofunc-tion of the knee joint appears after ACL injury,which seriously affects the overall stability,coordination and balance ability of the knee joint,meanwhile also increases the risk of ACL injury again.Proprioception training can not only enhance the balance ability of the knee joint,but also enhance the control ability of the knee joint.This article reviews the changes of proprioception after ACL injury and the related contents of proprioception rehabilitation after ACL injury in order to provide reference for further improving the functional recovery of the patients with ACL injury.

Objective:To explore the effect of knee arthroscopic operation training simulation system in clinical teaching of traditional Chinese medicine osteomatology resident doctor standardized training students.Methods:A total of 40 trainees were selected in Department of Orthopedics and Traumatology of the First Affiliated Hospital of Tianjin University of Chinese Medicine from January 2023 to September 2023. The trainees were divided into an experimental group and a control group according to the random number table method, with 20 in each group. Trainees in the control group was taught by presentations and video demonstrations. Trainees in the experimental group was taught by knee arthroscopic operation training simulation system. Trainees in each group were taught by a same teacher for a total of 2 weeks, with 2 class hours per week. After the teaching, the results of the assessment of theoretical knowledge, the results of the questionnaire survey on the mastery of teaching content and the results of the questionnaire survey on the evaluation of teaching methods were recorded. Then compared the results between the two groups.Results:Compared with the control group, there was no significant difference in the initial theoretical assessment scores between the two groups ( P > 0.05). The improvement rate of the test group was higher than that of the control group, with statistical significance ( P < 0.05). In terms of the mastery of teaching content, the experimental group was higher than the control group in three aspects: whether the teaching method was beneficial to the study of knee anatomy, imaging and surgical procedure, the difference was statistically significant ( P < 0.05); whether the teaching method was beneficial to the study of the selection of surgical indications, there was no statistically significant difference between the two groups ( P > 0.05). In the evaluation of teaching methods, there was no significant difference in the scores of teaching participation between the two groups ( P > 0.05), and the scores of the experimental group in six aspects of teaching interest, teaching effectiveness, teaching understanding, learning initiative, teaching course evaluation and course satisfaction were higher than those of the control group, with statistical significance ( P < 0.05). Conclusions:The application of knee arthroscopic operation training simulation operating system can significantly improve the theoretical achievements of traditional Chinese medicine bone injury training students, which is beneficial to master clinical teaching content and improve clinical teaching satisfaction.

Objective To explore the impact of macrophage-to-myofibroblast transition(MMT)on pulmonary fibro-sis induced by acute lung injury by LPS.Methods Totally 21 male mice were randomly classified into 7 groups:control group,model group(LPS-PF)at different time points and intervention group of clodronate-liposomes(CL-LIP)treatement at different time points(n=3).Pulmonary fibrosis was identified by HE and Masson staining microscopy.The immuno-fluorescence technology was used for the evaluation of numbers of macrophage-to-myofi-broblast transition cells(MMT cell which co-expressed CD68 and α-SMA).Bone marrow-derived macrophages(BMDMs)were randomly classified into two group:control(Ctrl)group and TGF-β1-treated group induced by transforming growthfactor-β1.α-SMA,FN and Col1 were detected by RT-qPCR.The expression of α-SMA,Smad3 and p-Smad3 protein was evaluated by Western blot.Results At day 7,the Ashcroft score of lung tissue in LPS-PF mouse model was significantly increased when compared with the Ctrl group(P＜0.01);While the score signifi-cantly declined when the model was pretreated with CL-LIP(P＜0.05).As detected by immuno-fluorescence stai-ning,in CL-LIP group the number of CD68-positive cells co-labeled with α-SMA was obviously less then that of LPS-PF group of the corresponding time point(P＜0.01).When the BMDMs were stimulated by TGF-β1 at 24 h,48 h and 96 h respectively,a higher expression of α-SMA,FN,Col1,were found in TGF-β1-treated group than that in Ctrl group at the corresponding time point(P＜0.01).The expression of Smad3,p-Smad3 significantly higher in LPS-PF group(at both day 7 and day 10)and TGF-β1-treated group(at both 48 h and 96 h)as compared to cor-responding control group(P＜0.01).Conclusions MMT promotes pulmonary fibrosis induced by ALI via LPS.Smad3 is proved to be involved in the MMT process.