ObjectiveTo evaluate the effects of Tongnaoyin on the blood-brain barrier status and neurological impairment in acute ischemic stroke （AIS） patients with the syndrome of phlegm-stasis blocking collaterals by dynamic contrast-enhanced magnetic resonance imaging （DCE-MRI）. MethodsA total of 63 patients diagnosed with AIS in the Jiangsu Province Hospital of Chinese Medicine from October 2022 to December 2023 were enrolled in this study. According to random number table method，the patients were assigned into a control group （32 cases） and an observation group （31 cases）. The control group received conventional Western medical treatment，and the observation group took 200 mL Tongnaoyin after meals，twice a day from day 2 of admission on the basis of the treatment in the control group. After 7 days of treatment，the patients were examined by DCE-MRI. The baseline data for two groups of patients before treatment were compared. The National Institute of Health Stroke Scale （NIHSS） score and modified Rankin Scale （mRS） score were recorded before treatment and after 90 days of treatment for both groups. The rKtrans，rKep，and rVe values were obtained from the region of interest （ROI） of the infarct zone/mirror area and compared between the two groups. ResultsThere was no significant difference in the NIHSS or mRS score between the two groups before treatment. After 90 days of treatment，the NIHSS and mRS scores declined in both groups，and the observation group had lower scores than the control group （P<0.05）. After treatment，the rKtrans and rVe in the observation group were lower than those in the control group （P<0.01）. ConclusionCompared with conventional Western medical treatment alone，conventional Western medical treatment combined with Tongnaoyin accelerates the repair of the blood-brain barrier in AIS patients，thereby ameliorating neurological impairment after AIS to improve the prognosis.

Ursodeoxycholic acid (UDCA) is a naturally occurring, low-toxicity, and hydrophilic bile acid (BA) in the human body that is converted by intestinal flora using primary BA. Solute carrier family 7 member 11 (SLC7A11) functions to uptake extracellular cystine in exchange for glutamate, and is highly expressed in a variety of human cancers. Retroperitoneal liposarcoma (RLPS) refers to liposarcoma originating from the retroperitoneal area. Lipidomics analysis revealed that UDCA was one of the most significantly downregulated metabolites in sera of RLPS patients compared with healthy subjects. The augmentation of UDCA concentration (≥25 μg/mL) demonstrated a suppressive effect on the proliferation of liposarcoma cells. [¹⁵N₂]-cystine and [¹³C₅]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione (GSH) synthesis. Mechanistically, UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis, leading to reactive oxygen species (ROS) accumulation and mitochondrial oxidative damage. Furthermore, UDCA can promote the anti-cancer effects of ferroptosis inducers (Erastin, RSL3), the murine double minute 2 (MDM2) inhibitors (Nutlin 3a, RG7112), cyclin dependent kinase 4 (CDK4) inhibitor (Abemaciclib), and glutaminase inhibitor (CB839). Together, UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity, and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA. More importantly, in combination with other antitumor chemotherapy or physiotherapy treatments, UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

Tic disorders in children refer to the neurodevelopmental disorders usually occurring in childhood and adolescence.Guided by the theory of five-zang-organ correlation,Professor Li Yirui approaches the treatment of tic disorders in children and comorbidities primarily from the perspective of liver-spleen disharmony,and points out that the pathogenesis is due to liver-spleen disharmony,wind-phlegm disturbance,and mutual involvement of the five zang organs.In clinical practice,Professor Li established the therapeutic principle of regulating the liver and spleen,extinguishing wind,and resolving phlegm,and adopted the four liver-regulating methods(calming liver,soothing liver,clearing liver,and softening liver)to extinguish wind and stop tics,as well as the four spleen-regulating methods(replenishing spleen,activating spleen,awakening spleen,and dredging spleen)to strengthen body resistance and support healthy qi.The self-formulated Fupi Xifeng Decoction(composed of Pseudostellariae Radix,Atractylodis Macrocephalae Rhizoma,Poria,Glycyrrhizae Radix et Rhizoma,Bupleuri Radix,Paeoniae Radix Alba,Uncariae Ramulus cum Uncis,Gastrodiae Rhizoma,Pinelliae Rhizoma Praeparatum,Citri Reticulatae Pericarpium,Os Draconis,etc.)serves as the basic formula,herbs directing to the affected regions were flexibly used,and insect drugs were occasionally adopted for refractory cases.The treatment for tic disorders in children focus on simultaneous regulation of the five zang-organs by modified use of herbs for dispersing wind and benefiting lung,tranquilizing heart and calming spirit,and supplementing liver and kidney to address comorbidities and secondary symptoms.Additionally,integrated internal-external treatment,relieving the discomforts physically and mentally,and family-centered comprehensive care are also taken into account to achieve optimal outcomes.

Objective To investigate the effects of Qizhi Zhoufei Granules on endoplasmic reticulum stress in rats with chronic obstructive pulmonary disease(COPD);To explore its mechanism.Methods COPD rat model was induced by lipopolysaccharide tracheal instillation and smoking.Totally 60 Wistar rats were divided into control group,model group,Bufei Huoxue Capsules group and Qizhi Zhoufei Granules low-,medium-and high-dosage groups using random number table method,with 10 rats in each group.Drug gavage intervention was carried out for the treatment group since the 29th day of modeling,and normal saline was given to the control group and model group for 28 d.Lung function tests were performed,HE staining was used to detect morphology of lung tissue,TUNEL staining was used to detect the degree of apoptosis in lung tissue,RT-qPCR and Western blot were used to detect the endoplasmic reticulum stress and apoptosis related molecular mRNA and protein expression in lung tissue.Results Compared with the control group,the lung function indexes of peak inspiratory flow(PIF),peak expiratory flow(PEF)and minute volume(MV)significantly decreased,and frequency of breathing(F)significantly increased in the model group(P＜0.05);the structural damage of the lung tissue was obvious,the lung injury score and apoptosis rate significantly increased(P＜0.05),the expressions of glucose regulated protein 78(GRP78),protein kinase R-like ER kinase(PERK),C/EBP-homologous protein(CHOP),Caspase-3 and Caspase-9 mRNA were increased(P＜0.05),the protein expressions of GRP78,p-PERK,activating transcription factor 4(ATF4),CHOP,Caspase-3 and Caspase-9 were significantly increased(P＜0.05).Compared with the model group,PIF,PEF and MV significantly increased in Qizhi Zhoufei Granules medium-and high-dosage groups and Bufei Huoxue Capsules group,and F significantly decreased(P＜0.05);the damage in lung tissue was improved,and the lung injury score and cell apoptosis rate significantly decreased(P＜0.05),the mRNA expressions of GRP78,PERK,CHOP,Caspase-3 and Caspase-9 in lung tissue decreased(P＜0.05),and the protein expressions of GRP78,p-PERK,ATF4,CHOP,Caspase-3 and Caspase-9 decreased(P＜0.05).Conclusion Qizhi Zhoufei Granules can prevent cell apoptosis and excessive damage by inhibiting the expression of endoplasmic reticulum stress related factors in COPD rats,thereby promoting unfolded protein response and improving endoplasmic reticulum folding ability,constraining endoplasmic reticulum stress state,and assisting in its regulation.

Objective To investigate the nebulization characteristics of human interferon α1b for injection.To characterize and compare the delivery rate,total drug substance and the aerodynamic characteristics between the two types of nebulizer.Methods Connect two types of nebulizers with a breathing simulator,respectively,and simulate the breathing patterns of an infant and child.Measure the delivery rate,total delivered dose,and delivery uniformity.The aerodynamic properties of human interferon α1b for injection were evaluated by the next generation impactor(NGI).The content of human interferon α1b was quantified by double antibody sandwich ELISA.Results In the three batches of samples in infant mode,the delivery rate and total delivered dose determind by A nebulizer were 0.45,0.49,0.44 μg·min-1,3.06,3.21,3.81 μg,respectcively;and 0.12,0.14,0.16 μg·min-1,0.73,0.73,0.75 μg,respectcively by B nebulizer.In child mode,the delivery rate and total delivered doses determined by A nebulizer were 1.36,1.49,1.20 μg·min-1,7.44,7.17,and 6.54 μg,respectcively;and 0.37,0.36,0.43 μg·min-1,1.66,1.59,and 1.41 μg,respectcively by B nebulizer.In child and infant mode,the ten results of the total drug substance delivered determined by nebulizer A were both between 65%to 135%of the average.The FPD,FPF,MMAD,and GSD determined by A neublizer of three batch samples were 2.48,2.92,2.35 μg,59.0%,57.4%,59.1%,4.18,4.34,4.15 μm,1.94,1.98,2.01,respectively.The FPD,FPF,MMAD and GSD determined by B neublizer of three batches samples were 2.70,3.38,3.06 μg,67.6%,66.4%,66.3%,3.55,3.65,3.68 μm,2.03,2.04,2.06,respectively.Conclusions The data obtained in this research characterized the in vitro nebulization characteristics of human interferon α1b for injection and provided a theoretical basis and reference for in vitro study and clinical practice.The influence of different types of nebulizers on nebulization characteristics was evaluated as well.It is suggested that the quality standard of nebulizers be strictly formulated and the use of nebulizers be standardized.

Objective To investigate the nebulization characteristics of human interferon α1b for injection.To characterize and compare the delivery rate,total drug substance and the aerodynamic characteristics between the two types of nebulizer.Methods Connect two types of nebulizers with a breathing simulator,respectively,and simulate the breathing patterns of an infant and child.Measure the delivery rate,total delivered dose,and delivery uniformity.The aerodynamic properties of human interferon α1b for injection were evaluated by the next generation impactor(NGI).The content of human interferon α1b was quantified by double antibody sandwich ELISA.Results In the three batches of samples in infant mode,the delivery rate and total delivered dose determind by A nebulizer were 0.45,0.49,0.44 μg·min-1,3.06,3.21,3.81 μg,respectcively;and 0.12,0.14,0.16 μg·min-1,0.73,0.73,0.75 μg,respectcively by B nebulizer.In child mode,the delivery rate and total delivered doses determined by A nebulizer were 1.36,1.49,1.20 μg·min-1,7.44,7.17,and 6.54 μg,respectcively;and 0.37,0.36,0.43 μg·min-1,1.66,1.59,and 1.41 μg,respectcively by B nebulizer.In child and infant mode,the ten results of the total drug substance delivered determined by nebulizer A were both between 65%to 135%of the average.The FPD,FPF,MMAD,and GSD determined by A neublizer of three batch samples were 2.48,2.92,2.35 μg,59.0%,57.4%,59.1%,4.18,4.34,4.15 μm,1.94,1.98,2.01,respectively.The FPD,FPF,MMAD and GSD determined by B neublizer of three batches samples were 2.70,3.38,3.06 μg,67.6%,66.4%,66.3%,3.55,3.65,3.68 μm,2.03,2.04,2.06,respectively.Conclusions The data obtained in this research characterized the in vitro nebulization characteristics of human interferon α1b for injection and provided a theoretical basis and reference for in vitro study and clinical practice.The influence of different types of nebulizers on nebulization characteristics was evaluated as well.It is suggested that the quality standard of nebulizers be strictly formulated and the use of nebulizers be standardized.

Objective To investigate the effects of Qizhi Zhoufei Granules on endoplasmic reticulum stress in rats with chronic obstructive pulmonary disease(COPD);To explore its mechanism.Methods COPD rat model was induced by lipopolysaccharide tracheal instillation and smoking.Totally 60 Wistar rats were divided into control group,model group,Bufei Huoxue Capsules group and Qizhi Zhoufei Granules low-,medium-and high-dosage groups using random number table method,with 10 rats in each group.Drug gavage intervention was carried out for the treatment group since the 29th day of modeling,and normal saline was given to the control group and model group for 28 d.Lung function tests were performed,HE staining was used to detect morphology of lung tissue,TUNEL staining was used to detect the degree of apoptosis in lung tissue,RT-qPCR and Western blot were used to detect the endoplasmic reticulum stress and apoptosis related molecular mRNA and protein expression in lung tissue.Results Compared with the control group,the lung function indexes of peak inspiratory flow(PIF),peak expiratory flow(PEF)and minute volume(MV)significantly decreased,and frequency of breathing(F)significantly increased in the model group(P＜0.05);the structural damage of the lung tissue was obvious,the lung injury score and apoptosis rate significantly increased(P＜0.05),the expressions of glucose regulated protein 78(GRP78),protein kinase R-like ER kinase(PERK),C/EBP-homologous protein(CHOP),Caspase-3 and Caspase-9 mRNA were increased(P＜0.05),the protein expressions of GRP78,p-PERK,activating transcription factor 4(ATF4),CHOP,Caspase-3 and Caspase-9 were significantly increased(P＜0.05).Compared with the model group,PIF,PEF and MV significantly increased in Qizhi Zhoufei Granules medium-and high-dosage groups and Bufei Huoxue Capsules group,and F significantly decreased(P＜0.05);the damage in lung tissue was improved,and the lung injury score and cell apoptosis rate significantly decreased(P＜0.05),the mRNA expressions of GRP78,PERK,CHOP,Caspase-3 and Caspase-9 in lung tissue decreased(P＜0.05),and the protein expressions of GRP78,p-PERK,ATF4,CHOP,Caspase-3 and Caspase-9 decreased(P＜0.05).Conclusion Qizhi Zhoufei Granules can prevent cell apoptosis and excessive damage by inhibiting the expression of endoplasmic reticulum stress related factors in COPD rats,thereby promoting unfolded protein response and improving endoplasmic reticulum folding ability,constraining endoplasmic reticulum stress state,and assisting in its regulation.

As a common clinical disease, fracture is often accompanied by pain, swelling, bleeding as well as other symptoms and has a high disability rate, even threatening life, seriously endangering patients' physical and psychological health and quality of life. Medical practitioners take many strategies for the treatment of fracture healing, including Traditional Chinese Medicine (TCM). In the early stage of fracture healing, the local fracture is often in a state of hypoxia, accompanied by the expression of hypoxia inducible factor-1α (HIF-1α), which is beneficial to wound healing. Through literature mining, we thought that hypoxia, HIF-1α and downstream factors affected the mechanism of fracture healing, as well as dominated this process. Therefore, we reviewed the local characteristics and related signaling pathways involved in the fracture healing process and summarized the intervention of TCM on these mechanisms, in order to inspirit the new strategy for fracture healing, as well as elaborate on the possible principles of TCM in treating fractures based on the HIF molecular mechanism.

ObjectiveTo investigate the changes in cerebral blood perfusion in patients with acute cerebral infarction after taking Tongnaoyin， a traditional Chinese medicine， based on head and neck computed tomography （CT） angiography （CTA） combined with brain CT perfusion imaging （CTP）. MethodA total of 240 patients with cerebral infarction of phlegm and blood stasis syndrome treated in Jiangsu Province Hospital of Traditional Chinese Medicine from March 2018 to September 2023 were randomly divided into a control group （99 cases） and a Tongnaoyin group （141 cases）. Based on the guidelines， the control group was treated with conventional treatment such as anti-aggregation， anticoagulation， lipid-lowering and plaque stabilization， brain protection， and supportive treatment. The Tongnaoyin group was treated with Tongnaoyin of 200 mL in warm conditions in the morning and evening on the basis of the control group. Both groups underwent CTA combined with CTP within 24 hours after admission， and they were reexamined by CTA and CTP in the sixth month after admission. The degree of intracranial artery stenosis was determined according to the North American Symptomatic Carotid Endarterectomy Trial （NASCET） method. The relative cerebral blood volume （rCBV）， relative cerebral blood flow （rCBF）， mean transit time （MTT）， and time to peak （TTP） of the lesion area before and after treatment were compared. The adverse outcomes of the two groups within six months after discharge were compared. ResultCompared with the group before treatment， the degree of vascular stenosis in the Tongnaoyin group was significantly reduced， and the difference was statistically significant （Z=105.369，P<0.05）. Compared with the control group after treatment， the improvement rate of vascular stenosis in the Tongnaoyin group was higher （χ²=84.179，P<0.01）， and the curative effect was better.After treatment， the rCBV and rCBF of patients in the Tongnaoyin group were significantly increased， and the difference was statistically significant （P<0.01）. MTT and TTP showed a trend of shortening， but the difference was not statistically significant. There was no statistically significant difference in rCBV， rCBF， MTT， and TTP in the control group. Compared with those in the control group after treatment， the rCBV and rCBF in the Tongnaoyin group were significantly increased， while MTT and TTP were significantly reduced （P<0.01）. After six months of discharge， the risk of poor prognosis in the Tongnaoyin group was significantly reduced compared with the control group （P<0.05）. ConclusionTongnaoyin has a good effect on improving cerebral blood perfusion in patients with acute cerebral infarction. It can be used as an effective supplement for the conventional treatment of ischemic stroke to improve clinical efficacy.

Objective To construct a nomogram to predict the prognosis of patients with gallbladder cancer(GBC).Methods The clinicopathological data of GBC patients were extracted from the SEER database,and the independent prognostic factors of GBC patients were analyzed by Cox regression,and a nomogram was constructed.Finally,the column diagrams in the training queue and validation queue are verified.Results Age,T stage,M stage,histological grade,radiotherapy,surgery and tumor size were independent prognostic factors in GBC patients,and the differences were statistically significant(P＜0.05).In the training cohort,the C index was 0.735(95％CI=0.721～0.749),and the AUC values at 1,3 and 5 years were 0.821,0.820 and 0.833,respectively.In the verification group,the C index was 0.733(95％CI=0.711～0.755),and the AUC values for 1,3 and 5 years were 0.816,0.807 and 0.827,respectively.The calibration curve shows that the predicted values of the nomogram are in good agreement with the observed values.The decision curve shows that the nomogram model has better prediction ability than TNM staging system.Conclusion The constructed dynamic prognosis nomogram of GBC patients has high accuracy and reliability.