ObjectiveTo investigate the mechanism of Buzhong Yiqitang in attenuating cisplatin resistance in non-small cell lung cancer by observing the effects of Buzhong Yiqitang on endoplasmic reticulum stress-related molecules in human lung adenocarcinoma cells （A549） and cisplatin-resistant cells in human lung adenocarcinoma cells （A549/DDP） via the nuclear factor E₂-related factor 2（Nrf2）/reactive oxygen species（ROS） pathway. MethodsThe serum containing Buzhong Yiqitang was prepared and A549 cells and A549/DDP cells were cultured. The cells were randomized into groups A （A549 cells+blank serum）， B （A549 cells+20 mg·L^-1 cisplatin+blank serum）， C （A549 cells+20 mg·L^-1 cisplatin+10% Buzhong Yiqitang-containing serum）， D （A549/DDP cells+blank serum）， E （A549/DDP cells+20 mg·L^-1 cisplatin+blank serum）， and F （A549/DDP cells+20 mg·L^-1 cisplatin+10% Buzhong Yiqitang-containing serum）. The cell counting kit-8 （CCK-8） method was used to detect the half maximal inhibitory concentration （IC₅₀） of cisplatin. The protein levels of Nrf2 and p-Nrf2 were determined by Western blotting. The DCFH-DA fluorescent probe was used to measure the content of reactive oxygen species （ROS） in each group. The protein levels of glucose-regulated protein 78 （GRP78）， activated transcription factor 6 （ATF6）， and C/EBP-homologous protein （CHOP） were determined by Western blot. ResultsCompared with group B， group C showed a reduction in IC₅₀ of cisplatin （P<0.05）， which held true in group E compared with group F （P<0.05）. Moreover， the IC₅₀ of cisplatin to A549/DDP cells was higher than that to A549 cells before and after Buzhong Yiqitang intervention （P<0.05）. Compared with group A， group B showed up-regulated protein levels of Nrf2 and p-Nrf2 （P<0.05）. Compared with group B， group C showed down-regulated protein levels of Nrf2 and p-Nrf2 （P<0.05）. Compared with group D， group E showed up-regulated protein levels of Nrf2 and p-Nrf2 （P<0.05）， which， however， were significantly down-regulated in group F （P<0.05）. The ROS content and the protein levels of GRP78， ATF6， and CHOP followed a descending trend of group C > group B > group A in A549 cells and group F > group E > group D in A549/DDP cells （P<0.05）. Moreover， the ROS content and the protein levels of GRP78， ATF6， and CHOP in A549 cells were higher than those in A549/DDP cells before and after Buzhong Yiqitang intervention （P<0.05）. ConclusionBuzhong Yiqitang may regulate endoplasmic reticulum stress via the Nrf2/ROS pathway to attenuate cisplatin resistance in non-small cell lung cancer.

Objective To establish a HPLC method for determining thimerosal compounds in eye drops. Methods A gradient HPLC system was used in the quantitative analysis of thimerosal compounds on Shiseido MGII C₁₈ column （4.6 mm×250 mm，5 μm）, using 1% triethylamine solution （pH adjusted to 3.0 with phosphate） as mobile phase A, the methanol as mobile phase B, gradient elution, The column temperature was 40 ℃, the detection wavelength was 222 nm, the flow rate was 1 ml/min and the injection volume was 20 µl. Results The established method had good linearity within the concentration range of 4.3-216.7 μg/ml （r>0.999） for thimerosal, with average recoveries was 102.1%, RSD2.7%. Conclusion This method was simple, accurate and highly specific, and could be used for determination of thimerosal compound in eye drops.

The immunomodulatory， repair， and regeneration-promoting functions of mesenchymal stem cells make them one of the potential treatment methods for liver diseases. At present， viral and non-viral delivery methods have been developed to genetically modify mesenchymal stem cells， and gene modification can promote the survival， homing， and cytokine secretion of mesenchymal stem cells， thereby enhancing the ability of mesenchymal stem cells to treat liver diseases. This article mainly summarizes the research advances in gene-modified mesenchymal stem cells in the treatment of liver diseases， in order to provide new insights and strategies for the clinical treatment of liver diseases.

Objective To systematically evaluate the predictive models for re-admission in patients with heart failure (HF) in China. Methods Studies related to the risk prediction model for HF patient re-admission published in The Cochrane Library, PubMed, EMbase, CNKI, and other databases were searched from their inception to April 30, 2024. The prediction model risk of bias assessment tool was used to assess the risk of bias and applicability of the included literature, relevant data were extracted to evaluate the model quality. Results Nineteen studies were included, involving a total of 38 predictive models for HF patient re-admission. Comorbidities such as diabetes, N-terminal pro B-type natriuretic peptide/brain natriuretic peptide, chronic renal insufficiency, left ventricular ejection fraction, New York Heart Association cardiac function classification, and medication adherence were identified as primary predictors. The area under the receiver operating characteristic curve ranged from 0.547 to 0.962. Thirteen studies conducted internal validation, one study conducted external validation, and five studies performed both internal and external validation. Seventeen studies evaluated model calibration, while five studies assessed clinical feasibility. The presentation of the models was primarily in the form of nomograms. All studies had a high overall risk of bias. Conclusion Most predictive models for HF patient re-admission in China demonstrate good discrimination and calibration. However, the overall research quality is suboptimal. There is a need to externally validate and calibrate existing models and develop more stable and clinically applicable predictive models to assess the risk of HF patient re-admission and identify relevant patients for early intervention.

ObjectiveTo investigate the pharmacodynamic effects of Houshihei San （HSHS） recorded with the effects of treating wind and limb heaviness on muscle tissue injury after middle cerebral artery occlusion （MCAO） in rats through the ferroptosis pathway. MethodsThirty SD male rats were selected and randomly grouped as follows： sham， MCAO， deferoxamine mesylate， high-dose HSHS （HSHS-H， 0.54 g·kg^-1）， and low-dose HSHS （HSHS-L， 0.27 g·kg^-1）， with 6 rats in each group. A laser scattering system was used to evaluate the stability of the MCAO model， and rats were administrated with corresponding agents by gavage for 7 days. During the administration period， behavioral， imaging and other methods were used to systematically evaluate the skeletal muscle tissue injury after MCAO and the therapeutic effect in each administration group. Hematoxylin-eosin staining was employed to evaluate the cross-section of muscle cells. Subsequently， immunohistochemistry was used to detect tumor suppressor p53 and glutathione peroxidase 4 （GPX4） in the soleus tissue. Western blot was employed to determine the protein levels of p53， GPX4， myogenic differentiation 1 （MyoD1）， nuclear factor E₂-related factor 2 （Nrf2）， Myostatin， solute carrier family 7 member 11 （SLC7A11）， muscle ring-finger protein-1 （MuRF1）， and muscle atrophy F-box protein （MAFbx） to verify the therapeutic effect in each group. ResultsCompared with the MCAO group， HSHS enhanced the locomotor ability and promoted muscle regeneration， which suggested that the pharmacological effects of HSHS were related to the inhibition of muscle tissue ferroptosis to reduce the expression of muscle atrophy factors. Behavioral and imaging results suggested that compared with the MCAO group， HSHS ameliorated neurological impairments in rats on day 7 （P<0.01）， enhanced 5-min locomotor distance and postural control （P<0.01）， strengthened grasping power and promoted muscle growth （P<0.01）， stabilized skeletal muscle length and weight （P<0.01）， and increased the cross-section of muscle cells （P<0.01）. Compared with the MCAO group， HSHS promoted the increases in glutathione and superoxide dismutase content and inhibited the increase in malondialdehyde content （P<0.05，P<0.01）. Ferroptosis pathway-related assays suggested that HSHS reduced the p53-positive cells and increased the GPX4-positive cells （P<0.01）. HSHS ameliorated muscle function decline after stroke by promoting the expression of GPX4， Nrf2， SLC7A11， and MyoD1 and inhibiting the expression of p53， Myostatin， MurRF1， and MAFbx to reduce ferroptosis in the muscle （P<0.01）. ConclusionHSHS， prepared with reference to the method in the Synopsis of Golden Chamber， can simultaneously reduce the myolysis and increase the protein synthesis in the skeletal muscle tissue after ischemic stroke by regulating the ferroptosis pathway.

OBJECTIVE To analyze chemical components of Yao ethnic medicine Pittosporum pauciflorum， establish its fingerprint and investigate the spectrum-effect relationship of its anti-inflammatory effect. METHODS UHPLC-Q-Orbitrap-MS technology was used to analyze the chemical components of P. pauciflorum （batch S6）. The fingerprints for 10 batches of P. pauciflorum from different producing areas in Guangxi Province （batches S1-S10） were established by HPLC， and similarity assessment and chemometric pattern recognition analysis were conducted. RAW264.7 inflammatory cell model was induced by lipopolysaccharide， and the anti-inflammatory activity of P. pauciflorum was investigated. Using inhibition rates of nitric oxide （NO）， tumor necrosis factor-α （TNF-α）， interleukin-6 （IL-6） and IL-1β as efficacy indicators， grey relational analysis and partial least squares regression analysis were adopted to evaluate the spectrum-effect relationship of the anti-inflammatory effect of P. pauciflorum. RESULTS There were 60 chemical components， including flavonoids， phenolic acids， lipids， etc.， identified in P. pauciflorum. The fingerprints for 10 batches of P. pauciflorum showed 14 common peaks，with similarity values ranging from 0.883 to 0.991. Three common peaks were assigned neochlorogenic acid （peak 5）， chlorogenic acid （peak 7）， and syringaldehyde （peak 10）. The classification results of the systematic clustering analysis and the principal component analysis were basically consistent. Batches S1 to S10 of P. pauciflorum significantly reduced the levels of NO， TNF-α， IL-6 （except for batch S5） and IL-1β in the cell supernatant （P＜0.05 or P＜0.01）. Inhibition rates of above inflammatory indexes were 10.26%-39.96%， 14.96%-31.36%， 1.38%-21.27%， 18.54%-28.00%， respectively. The contents of neochlorogenic acid， syringaldehyde， as well as the components corresponding to peaks 1， 3， 9， 12 and 14，exhibited a strong correlation with the anti-inflammatory effects of P. pauciflorum. CONCLUSIONS The present study has analyzed the chemical components of P. pauciflorum and established HPLC fingerprints for 10 batches of P. pauciflorum. Each batch of medicinal herbs demonstrates certain anti- inflammatory activities， among which neochlorogenic acid， syringaldehyde， and the components corresponding to peaks 1， 3， 9， 12 and 14 are likely to be the active anti-inflammatory components.

ObjectiveTo improve the quality standard of Yuanhu Zhitong oral liquid in order to strengthen the quality control of this oral liquid. MethodThin layer chromatography（TLC） was used for the qualitative identification of Corydalis Rhizoma and Angelicae Dahuricae Radix in Yuanhu Zhitong oral liquid by taking tetrahydropalmatine， corydaline reference substances and Corydalis Rhizoma reference medicinal materials as reference， and cyclohexane-trichloromethane-methanol（5∶3∶0.5） as developing solvent， Corydalis Rhizoma was identified using GF254 glass thin layer plate under ultraviolet light（365 nm）. And taking petroleum ether（60-90 ℃） -ether-formic acid（10∶10∶1） as developing solvent， Angelicae Dahuricae Radix was identified using a silica gel G TLC plate under ultraviolet light（305 nm）. High performance liquid chromatography（HPLC） was performed on a Waters XSelect HSS T3 column（4.6 mm×250 mm， 5 μm） with acetonitrile（A）-0.1% glacial acetic acid solution（adjusted pH to 6.1 by triethylamine）（B） as the mobile phase for gradient elution（0-10 min， 20%-30%A； 10-25 min， 30%-40%A； 25-40 min， 40%-50%A； 40-60 min， 50%-60%A）， the detection wavelength was set at 280 nm， then the fingerprint of Yuanhu Zhitong oral liquid was established， and the contents of tetrahydropalmatine and corydaline were determined. ResultIn the thin layer chromatograms， the corresponding spots of Yuanhu Zhitong oral liquid， the reference substances and reference medicinal materials were clear， with good separation and strong specificity. A total of 12 common peaks were identified in 10 batches of Yuanhu Zhitong oral liquid samples， and the peaks of berberine hydrochloride， dehydrocorydaline， glaucine， tetrahydropalmatine and corydaline. The similarities between the 10 batches of samples and the control fingerprint were all >0.90. The results of determination showed that the concentrations of corydaline and tetrahydropalmatine had good linearity with paek area in the range of 0.038 6-0.193 0， 0.034 0-0.170 0 g·L^-1， respectively. The methodological investigation was qualified， and the contents of corydaline and tetrahydropalmatine in 10 batches of Yuanhu Zhitong oral liquid samples were 0.077 5-0.142 9、0.126 1-0.178 2 g·L^-1， respectively. ConclusionThe established TLC， fingerprint and determination are simple， specific and reproducible， which can be used to improve the quality control standard of Yuanhu Zhitong oral liquid.

Aim To explore the efficacy of levosimendan on hypoxia pulmonary hypertension through animal experiments, and to further explore the potential mechanism of action using network pharmacological methods and molecular docking technique. Methods The rat model of hypoxia pulmonary hypertension was constructed to detect right heart systolic pressure and right heart remodeling index. HE , Masson, and VG staining were core targets were screened out. GO and KEGG pathway enrichment analysis were performed using the DAVID database. Molecular docking of the core targets was performed with the AutoDock software. Results The results of animal experiments showed that levosimendan had obvious therapeutic effect on hypoxia pulmonary hypertension. The network pharmacology results showed that SRC, HSP90AA1, MAPK1, PIK3R1, AKT1, HRAS, MAPK14, LCK, EGFR and ESR1 used to analyze the changes of rat lung histopathology. Search the Swiss Target Prediction, DrugBank Online, BatMan, Targetnet, SEA, and PharmMapper databases were used to screen for drug targets. Disease targets were retrieved from the GeneCards, OMIM databases. The "drug-target-disease" network was constructed after identification of the two intersection targets. The protein interaction network was constructed and the were the key targets to play a therapeutic role. Molecular docking showed good docking of levosimendan with all the top five core targets with degree values. Conclusions Levosimendan may exert a therapeutic effect on hypoxia-induced pulmonary hypertension through multiple targets.

ObjectiveTo investigate the efficacy， safety， and cost-effectiveness of endoscopic ultrasound （EUS）-guided coil placement combined with tissue adhesive injection in the treatment of gastric varices with spontaneous shunt. MethodsA retrospective analysis was performed for the patients with acute gastric variceal bleeding and spontaneous portosystemic shunt who were hospitalized and received balloon-occluded retrograde transvenous obliteration （BRTO） combined with endoscopic tissue adhesive injection or EUS-guided coil placement combined with tissue adhesive injection in Xiangyang Central Hospital from March 2019 to September 2022. The two surgical procedures were compared in terms of efficacy （technical success rate， 5-day rebleeding rate， 1-year rebleeding rate， and time to rebleeding）， safety （the incidence rate of ectopic embolism， the amount of tissue adhesive used， and the amount of lauromacrogol used）， and cost-effectiveness （hospital costs and length of hospital stay）. The t-test was used for comparison of normally distributed continuous data between two groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups. The Kaplan-Meier method was used to estimate the rebleeding. The chi-square test was used for comparison of categorical data between two groups. ResultsA total of 25 patients received successful EUS-guided coil placement and tissue adhesive injection， with a technical success rate of 100%， a median amount of 2.5 mL tissue adhesive used， a median amount of 11.0 mL lauromacrogol used， a mean length of hospital stay of 14.88±3.21 days， a mean hospital cost of 32 660.00±4 602.07 yuan， and a 5-day rebleeding rate of 0%； among these patients， 2 were lost to follow-up， and 23 patients with complete follow-up data had an incidence rate of ectopic embolism of 0% and a median time to rebleeding of 689 days. A total of 14 patients underwent modified BRTO combined with endoscopic tissue adhesive injection， with a technical success rate of 100%； a median amount of 5.0 mL tissue adhesive used during surgery， which was significantly higher than that used in EUS （U=39.000， P<0.001）； a median amount of 10.5 mL lauromacrogol used during surgery； a mean length of hospital stay of 15.38±4.94 days； a mean hospital cost of 57 583.47±18 955.40 yuan， which was significantly higher than that used in EUS （t=-6.310， P<0.001）； a 5-day rebleeding rate of 0%. No patient was lost to follow-up， and all 14 patients had an incidence rate of ectopic embolism of 0% and a median time to rebleeding of 244.50 days， with no significant difference between the two groups （χ²=1.448， P=0.229）. ConclusionEUS-guided coil placement combined with tissue adhesive injection is a relatively safe and effective technique for the treatment of gastric variceal bleeding and has a high technical success rate， a low incidence rate of serious adverse events， and similar efficacy to BRTO， with higher safety and cost-effectiveness.

ObjectiveTo improve the response capabilities to disasters and prevent major epidemics， it is of practical use to study the capability evaluation system of the national emergency medical rescue team that combines theoretical training and practical exercises， to enhance the overall quality of the teams. MethodsFirst， a capability assessment system for the national emergency medical rescue team was constructed based on the INSARAG External Classification （IEC） standards of the national emergency medical rescue team. Then， based on the outcome based education （OBE） concept， we conducted innovative research on the curriculum design and exercise programs for team building and member training. Finally， an empirical analysis was conducted on the effectiveness of the evaluation system and training exercises based on the statistical analysis of the comprehensive quality evaluation of the Shanghai national emergency medical rescue team from 2020 to 2023， as well as the empirical analysis of the rescue exercise on the Cruise of spectrum. ResultsBased on the linear regression analysis of each core competency indicators， the five core competencies in the evaluation system， including rescue skills， medical and health knowledge， disaster coping ability， team cooperation ability， and mental resilience training， were positively correlated with the cumulative number of trainings （r=0.71， r=0.76， r=0.81， r=0.84， r=0.96，all P<0.05）， indicating that the training was effective and the course design was reasonable. Empirical cases showed that the three-dimensional rescue drill model had remarkable results in the actual combat application and ability improvement of team members. ConclusionThe training courses and drills designed based on the three-level assessment system are effective in improving the comprehensive capabilities of the national emergency medical rescue team.