OBJECTIVE To form an expert consensus on the clinical application of parenteral direct thrombin inhibitors （DTIs） in patients during the perioperative period. METHODS Led by Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital （the Affiliated Hospital of UESTC）， a multidisciplinary working group was established. Through literature review and the Delphi method， clinical questions related to the rational perioperative use of parenteral DTIs were identified. A structured design was adopted using the “Population-Intervention-Comparison-Outcome” framework； systematic searches were conducted in CNKI， Medline， Embase and other databases. Relevant evidence from randomized controlled trials and cohort studies was included and synthesized. Evidence quality was assessed using the Grades of Recommendations Assessment，Development and Evaluation （GRADE） approach， and recommendations were formulated through multiple rounds of Delphi surveys and expert consensus meetings. RESULTS &CONCLUSIONS Seven recommendations （each with an expert consensus rate exceeding 90%） on the use of parenteral DTIs in perioperative patients were developed. These recommendations specify drug selection， dosing ranges， key monitoring points， and safety management strategies for parenteral DTIs in various scenarios， including the perioperative period of ventricular assist device implantation， the perioperative period of cardiac surgery， perioperative patients with lower-extremity atherosclerotic disease， the perioperative period of percutaneous coronary intervention in patients with acute coronary syndrome， the perioperative period of carotid artery stenting in patients with carotid stenosis， the perioperative period of patients with right heart thrombosis， and patients who develop related thrombosis and dysfunction after a central venous catheter insertion. In addition， warning and management pathways for perioperative bleeding and thrombotic events were proposed. This expert consensus， which is formulated based on the best available evidence， provides evidence-based guidance for standardized and individualized use of parenteral DTIs in perioperative period.

OBJECTIVE To analyze the characteristics and influencing factors of disposal behavior of expired medicines among Chinese residents across regional divisions， and to provide references for regional classification management and precise policy implementation regarding expired medicines. METHODS A stratified random sampling method was employed to conduct a questionnaire survey among residents across sample provinces and cities， utilizing a combination of online and offline approaches. Binary Logistic regression analysis was used to systematically explore the regional （eastern， central and western regions） and urban-rural disparities in the recycling of expired medicines among Chinese residents， identify the core driving factors influencing standardized disposal behaviors， and propose corresponding recommendations. RESULTS A total of 2 200 ques tionnaires were collected， with 2 159 deemed valid， yielding an effective response rate of 98.1%. The surveyed residents commonly stored medicines at home （67.7%）， yet the rate of regular medicine clearance was low （only 57.7%）. Nearly half of the residents （49.7%） had expired medicines in their households， with improper disposal of expired medicines remaining the predominant behavior. Insufficient convenience in recycling was identified as the primary reason for improper disposal of expired medicines （50.1%）. Statistically significant differences were observed between residents in the eastern， central and western regions， as well as between urban and rural residents， in terms of household medicine storage rates and the prevalence of expired medicine possession （ P ＜0.05）. However， no statistically significant difference was found in the standardized disposal rates across regional divisions （ P ＞0.05）. Furthermore， the residents demonstrated a higher level of awareness regarding the health hazards of expired medicines compared to their awareness of environmental hazards， with 46.0% and 32.1% indicating they were “relatively familiar” and “very familiar”， respectively. The participation rate in standardized recycling was only 37.6%. Among non-participating residents， the three primary barriers were “recycling points being too far away” （46.6%）， “unawareness of recycling channels” （46.1%） and “lack of incentives” （48.1%）. The surveyed residents showed relatively high trust in pharmaceutical regulatory authorities and on-site recycling personnel， with “high trust” accounting for 31.2% and 34.7%， respectively. Binary Logistic regression analysis results indicated that the awareness of environmental hazards and the accessibility of recycling points were the core driving factors for proper disposal. CONCLUSIONS Significant issues exist in the recycling of expired medicines among Chinese residents， characterized by “improper behavior， cognitive bias， and unbalanced system”. It is recommended to construct a tiered recycling network focusing on “quality improvement in the eastern region， expansion in the central region， and basic coverage in the western region”， implement targeted educational campaigns and differentiated incentive policies. Moreover， the specific needs of groups such as the elderly should be addressed to achieve spatial equalization and service optimization of the recycling system.

OBJECTIVE To evaluate the clinical comprehensive value of four Chinese patent medicines （Xuezhikang， Zhibitai， Zhibituo， Jiangzhiling） in the treatment of hyperlipidemia， and provide a reference for rational clinical drug use. METHODS A clinical comprehensive evaluation index system was established in accordance with the Evidence and Value： Impact on Decision-Making （EVIDEM） framework and Technical Guideline for Clinical Comprehensive Evaluation of Cardiovascular Drugs （2022 edition， trial implementation）. CNKI， Wanfang data， VIP， PubMed， ScienceDirect， Embase and official websites were retrieved to collect the literature such as drug instructions， guidelines and consensus statements， and systematic reviews/meta-analyses for the four Chinese patent medicines. A comprehensive evaluation was conducted from seven dimensions： effectiveness， safety， economy， suitability， accessibility， innovation and characteristics of traditional Chinese medicine. RESULTS This evaluation index system included 7 first-level indicators， 15 second-level indicators and 30 third-level indicators. Xuezhikang achieved the highest comprehensive evaluation score of 81.4 points， and was classified as class Ⅰ recommendation. Zhibitai with 76.0 points and Zhibituo with 60.9 points were both classified as class Ⅱ recommendation. Jiangzhiling with 48.8 points was classified as class Ⅳ recommendation. CONCLUSIONS Xuezhikang demonstrates the optimal clinical comprehensive value for treating hyperlipidemia. Zhibitai exhibits certain advantages in terms of safety and characteristics of traditional Chinese medicine； Zhibituo shows a moderate performance in all aspects； Jiangzhiling has a relatively low score. Appropriate medicines can be selected clinically according to actual conditions and patients’ characteristics.

OBJECTIVE To investigate the effect and mechanism of self-assembled nanoparticles from Shaoyao gancao decoction （SGD-SAN） on the intestinal absorption behavior of its main active components. METHODS SGD-SAN was prepared and characterized. Using an in-situ single-pass intestinal perfusion model in rats， the absorption characteristics of five active components （albiflorin， paeoniflorin， liquiritin apioside， liquiritin， glycyrrhizic acid） from SGD-SAN in the jejunum and ileum were studied， with the absorption rate constant （ K a ） and apparent permeability coefficient （ P eff ） as indicators， and compared with free drugs. In the intestinal segment with optimal absorption， the effects of drug concentration and efflux transporter inhibitors （P-glycoprotein inhibitor verapamil， multidrug resistance-associated protein 2 inhibitor indomethacin， breast cancer resistance protein inhibitor reserpine） on the intestinal absorption characteristics of these components were examined. RESULTS The obtained SGD-SAN exhibited a spherical shape with uniform sizes， an average particle diameter of （155.57±2.65） nm， a polydispersity index of 0.34±0.03， and a Zeta potential of （－9.30±1.12） mV. The average total content of five active components， including albiflorin， was 12.26%， and remained unaffected by enzymatic degradation and intestinal physical absorption. Compared with the free drug group， the five active components in the SGD-SAN group exhibited higher absorption rates in the ileal segment， with significantly elevated K a and P eff values （except for the P eff value of glycyrrhizic acid in the ileal segment） （ P ＜0.05 or P ＜0.01）. Their absorption demonstrated a concentration-dependent trend. In the free drug groups， the absorption of each component was regulated by corresponding inhibitors （ P ＜0.05 or P ＜0.01）； whereas in the SGD-SAN groups， except for albiflorin and paeoniflorin， the absorption of the remaining components was not affected by the inhibitors （ P ＞0.05）. CONCLUSIONS SGD-SAN significantly enhances the intestinal absorption efficiency of active components. The above absorption-enhancing effect may be related to the avoidance of efflux transporter influence and the presence of a mixed absorption mode.

OBJECTIVE To observe the effects of endogenous metabolite mesaconate combined with Sodium lactate Ringer’s injection （LR） on prolonging the golden treatment time window and its resuscitation efficacy in rats with hemorrhagic shock under high-altitude conditions. METHODS Rats were divided into the shock group， LR group， and 5， 20， 50 mg/kg mesaconate+LR groups， with 20 rats in each group， to investigate the effect of additional use of mesaconate on the golden treatment time window. After establishing a model of uncontrolled hemorrhagic shock under high-altitude conditions in all groups by housing in a hypobaric hypoxia chamber combined with splenic artery transection， rats in the shock group received no resuscitation， while rats in the LR group and mesaconate+LR groups underwent low-pressure resuscitation with LR or mesaconate combined with LR. Blood pressure control， fluid infusion volume， blood loss rate and survival status were observed in each group. Rats were further divided into the normal group， shock group and mesaconate （50 mg/kg）+LR group， with 10 or 20 rats in each group， to evaluate the resuscitation effects after extending the golden treatment time window by additionally using mesaconate. Except for the normal group， the other groups underwent the same procedure to establish an uncontrolled hemorrhagic shock model under high-altitude conditions. Rats in the shock group received no resuscitation. In the mesaconate+LR group， after 3 h of low-pressure resuscitation， bleeding control was performed by ligation of the spleen artery， and the infusion volume and blood loss rate were recorded； subsequently， the rats received LR resuscitation with twice the volume of blood loss. Then， blood gas indicators of the mesaconate+LR group were measured at different time points. Survival rates， indicators related to sublingual microcirculatory perfusion， liver and kidney blood flow， indicators related to the function of vital organs， and lung and brain water content were observed in all groups. RESULTS LR infusion alone could effectively maintain mean arterial pressure （MAP） within 50-60 mmHg for approximately 1 h. The administration of mesaconate combined with LR during hypotensive resuscitation could maintain MAP within 50-60 mmHg for over 3 h， with significantly reduced fluid infusion volume and blood loss rate in 50 mg/kg mesaconate+LR group， compared to the LR group （ P ＜0.05）. In the LR group， rats maintained low pressure for up to 1 hour with a survival rate of 52.94%， and no rats survived beyond 2 h. In the 5， 20 and 50 mg/kg mesaconate+LR groups， rats maintained low pressure for up to 1 h with a survival rate exceeding 80%； in the 20 and 50 mg/kg mesaconate+LR groups， rats maintained low pressure for up to 3 h with a survival rate exceeding 70%. After complete resuscitation with mesaconate combined with LR， the 72 h survival rate of rats was 43.75%， and significant improvements in blood gas parameters were observed compared to the end of the shock phase （ P ＜0.05）. Compared to the shock group， the mesaconate+LR group showed significant recovery in sublingual microcirculatory indicators， and liver/kidney blood flow after complete resuscitation （ P ＜0.05）， with significant reductions in heart， liver and kidney function-related indicators and lung water content （ P ＜0.05）. CONCLUSIONS Mesaconate combined with LR significantly extends the golden treatment time window for hemorrhagic shock in rats under high-altitude conditions， improves blood gas parameters， sublingual microcirculatory perfusion， and liver/kidney blood flow， mitigates vital organ impairment and pulmonary edema， and increases the survival rate of shocked rats.

OBJECTIVE To establish the method for determining the contents of five active components in raw and charred herb pairs of Gardenia jasminoides-Scutellaria baicalensis ， construct their fingerprints， and investigate the effects of G. jasminoides processing on chemical constituents in the h erb pairs. METHODS The HPLC method was used to determine the contents of genipin 1- β -D-gentiobioside， geniposide， crocin Ⅰ， crocin Ⅱ and baicalin in ten batches of raw G. jasminoides-S. baicalensis herb pairs and ten batches of charred G. jasminoides-S. baicalensis herb pairs. Using the same HPLC method， chromatographic fingerprints for the ten batches of raw herb pairs and ten batches of processed herb pairs were established with the Similarity Evaluation System for Chromatographic Fingerprints of Traditional Chinese Medicine （2012 edition）. Principal component analysis and orthogonal partial least squares-discriminant analysis were performed. RESULTS Compared with the raw G. jasminoides-S. baicalensis herb pair， the average content of genipin 1- β -D-gentiobioside in the charred G. jasminoides-S. baicalensis herb pair increased by 12.65%； while the average contents of geniposide， crocin Ⅰ， crocin Ⅱ and baicalin decreased by 7.86%， 60.62%， 62.07% and 0.15%， respectively. Chromatographic fingerprints of ten batches of raw herb pairs and ten batches of processed herb pairs shared 18 common peaks with similarities ranging from 0.997 to 1.000 and 0.988 to 1.000， respectively. Five common peaks were identified： genipin 1- β -D-gentiobioside （peak 2）， geniposide （peak 3）， crocin Ⅰ （peak 6）， crocin Ⅱ （peak 9） and baicalin （peak 10）. Principal component analysis and orthogonal partial least squares-discriminant analysis results showed that the raw G. jasminoides-S. baicalensis herb pair and the charred G. jasminoides-S. baicalensis herb pair could be clearly distinguished. Variable importance in the projection （VIP） values for crocin Ⅰ and crocin Ⅱ were both greater than one. CONCLUSIONS A method has been successfully developed for the determination of five active c omponents， including genipin 1- β -D-gentiobioside， in the G. jasminoides-S. baicalensis herb pair， and its fingerprint has been drawn. Processing is found to increase the content of genipin 1- β -D-gentiobioside， while decreasing the levels of geniposide， crocin Ⅰ， crocin Ⅱ and baicalin in the herb pair. Furthermore， crocin Ⅰ and crocin Ⅱ could serve as potential quality markers for the quality control of this herb pair.

OBJECTIVE To identify the quality markers （Q-Markers） of Hyssopus cuspidatus against airway remodeling in bronchial asthma （referred to as “asthma”）， an d to provide a reference for the quality control research of H. cuspidatus based on pharmacodynamic activity. METHODS Potential active components and action targets of H. cuspidatus were screened by network pharmacology method. Using human airway smooth muscle cells （HASMCs） as objects， airway remodeling cell model was induced by platelet-derived growth factor-BB （PDGF-BB）； validation test was then performed for anti-asthmatic effects of H. cuspidatus and the potential active components. HPLC method was employed to establish the fingerprints of 14 batches of H. cuspidatus samples， and chemometric analysis was also conducted. Combined with the results of pharmacodynamic experiments and fingerprint analysis， the Q-Markers of H. cuspidatus against airway remodeling in asthma were determined. RESULTS&CONCLUSIONS Network pharmacology analysis showed that the potential active components of H. cuspidatus against asthma might be flavonoids and phenolic acids such as luteolin， quercetin and rosmarinic acid， and the core anti-asthmatic targets were interleukin-6， mitogen-activated protein kinase， etc. In vitro experimental results confirmed that 25， 50， 100 μg/mL of H. cuspidatus ， as well as neochlorogenic acid （80 μmol/L）， acacetin （80 μmol/L）， salvianolic acid B （40 μmol/L） and quercetin-3- O - β -D-glucuronide （80 μmol/L）， significantly reduced the cell viability induced by PDGF-BB， inhibited cell proliferation， migration， and the phosphorylation level of extracellular signal-regulated protein kinase 1/2， decreased the levels of interleukin-6， tumor necrosis factor-α and reactive oxygen species， and generally arrested cells in the G 0 /G 1 phase （ P ＜0.05）. Fingerprint analysis showed that there were 27 common peaks in the fingerprints of the 14 batches of H. cuspidatus samples， with 15 compounds （including luteolin） identified， and the similarities of fingerprints were all greater than 0.8. The 14 batches of samples could be divided into three categories： S1-S7 as one category， S8-S13 as one category， and S14 as one category. The variable importance in the projection values of rosmarinic acid， chlorogenic acid， caffeic acid， salvigenin， luteolin， ferulic acid， quercetin-3- O - β -D-glucuronide， and the components corresponding to peaks 5 and 8 were greater than 1， indicating they were potential differential markers affecting quality. Integrating network pharmacology， in vitro experimental validation， and chemometric analysis， rosmarinic acid， neochlorogenic acid， caffeic acid， salvigenin， luteolin， ferulic acid， quercetin-3- O - β -D-glucuronide， acacetin， salvianolic acid B and chlorogenic acid may be the Q-Markers of H. cuspidatus against asthma.

OBJECTIVE To systematically evaluate the quality of the Heat-clearing and symptom-relieving formula and screen potential marker components that influence the quality of the formula. METHODS The contents of 11 components （calycosin-7- O - β -D-glucoside， ononin， hyperoside， isoquercitrin， baicalin， baicalein， cryptotanshinone， tanshinone Ⅱ A ， tanshinone Ⅰ， senkyunolide A， ferulic acid） in the Heat-clearing and symptom-relieving formula were determined by high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS）. Using the contents of the aforementioned components as variables， cluster analysis （CA）， principal component analysis （PCA）， and orthogonal partial least squares-discriminant analysis （OPLS-DA） were conducted using OriginPro 2024 software and SIMCA 14.1 software； marker components affecting the quality of the Heat-clearing and symptom-relieving formula were then screened based on the criteria of variable importance in the projection （VIP） value＞1 and P ＜0.05. The comprehensive evaluation of 20 batches of samples was carried out using the entropy weight-technique for order preference by similarity to ideal solution（TOPSIS） and grey correlation analysis （GCA） methods. RESULTS The contents of the above 11 components were 7.993-72.866， 4.542-31.228， 727.666-1 901.884， 496.846-1 293.279， 1 995.501-6 779.150， 54.500-241.280， 150.302-304.339， 79.698-189.206， 257.118-682.418， 5.498-21.687， 7.524-26.935 μg/g. CA， PCA and OPLS-DA results showed that 20 batches of samples were grouped into 2 categories. Q1， Q3， Q4， Q7-Q9， Q12， Q15， Q16 were grouped into one category， and the rest were grouped into another category； VIP values of ferulic acid， tanshinone Ⅱ A ， baicalin， cryptotanshinone， calycosin-7- O - β -D-glucoside and ononin were all greater than 1 （ P ＜0.05）. Both the entropy weight-TOPSIS and GCA methods showed that the samples ranked in the top 11 according to the euclidean distance and relative correlation degree were Q2， Q5， Q6， Q10， Q11， Q13， Q14， Q17-Q20. CONCLUSIONS The established HPLC-MS/MS method is rapid， accurate and highly sens itive. Combined with chemical pattern recognition analysis， entropy weight-TOPSIS and GCA methods， this method can be used to evaluate the quality of the Heat-clearing and symptom-relieving formula. Ferulic acid， tanshinone Ⅱ A ， baicalin， cryptotanshinone， calycosin-7- O - β -D-glucoside and ononin may be the marker components that affect the quality of this formula. The overall quality of 11 batches of the Heat-clearing and symptom-relieving formula， including Q17， is relatively superior.

OBJECTIVE To prepare the β -cyclodextrin （ β -CD） inclusion complex with volatile oil from Qianghuo qushi qingwen granules， and to characterize and quantitatively analyze the inclusion complex. METHODS The comprehensive scores calculated by inclusion rate and inclusion compound yield were used as indicators for screening the inclusion method. The single-factor experiments and Box-Behnken response surface experiments were used to op timize the inclusion conditions， with the above comprehensive score as response value， and taking the ratio of β -CD to volatile oil， inclusion temperature and inclusion time as indexes. The volatile oil inclusion complex of Qianghuo qushi qingwen granules was prepared according to the determined optimal process， followed by validation. Ultraviolet （UV）-visible spectroscopy， thin-layer chromatography （TLC）， and microscopic imaging were also performed. Ultra-high performance liquid chromatography was used to determine the contents of perillaldehyde， pogostone and atractylodin. RESULTS The saturation aqueous solution method was adopted. The optimal inclusion process conditions were as follows： the ratio of β -CD to volatile oil was 7.5∶1， the inclusion temperature was 40 ℃， and the inclusion time was 2.2 h. In three verification experiments， the average inclusion rate was 72.32%， the average yield of inclusion compound was 74.45%， the average comprehensive score was 72.96 points， and the relative error with the predicted value （74.15 points） of the model was 1.61%. UV-visible spectroscopy， TLC and microscopic imaging showed that β -CD and volatile oil successfully formed a new inclusion complex. The average contents of perillaldehyde， pogostone and atractylodin were 4.498 2， 0.814 9， 0.905 7 mg/g， respectively， with RSDs of 0.31%， 0.56% and 0.63% （ n ＝3）. CONCLUSIONS A stable and feasible preparation process of the volatile oil inclusion complex of Qianghuo qushi qingwen granules is successfully established.

OBJECTIVE To investigate the protective effects and potential mechanism of alisol B 23-acetate on acute alcoholic liver injury in mice. METHODS Fifty male Kunming mice were divided into the blank group， model group， and alisol B 23-acetate low-， medium- and high-dose groups （10， 20， 40 mg/kg）， with 10 mice in each group. Each group was given relevant drug solution or normal saline intragastrically， once a day， for 2 consecutive weeks. On the 15th day， mice in the blank group were given normal saline intragastrically， while the other four groups were given 12 mL/kg white wine intragastrically， twice at six-hour intervals， to establish an acute alcoholic liver injury model. On the 16th day of the experiment， the liver indexes of mice in each group were calculated； the serum levels of alanine transaminase （ALT）， aspartate transaminase （AST）， total cholesterol （TC）， triglycerides （TG）， malondialdehyde （MDA） and glutathione （GSH） were also determined. The histopathological morphology of their liver tissues was observed and scored. The protein expressions of cytochrome P450 2E1 （CYP2E1）， Kelch-like ECH-associated protein 1 （Keap1）， nuclear factor erythroid 2-related factor 2 （Nrf2） and NAD（P）H： quinone oxidoreductase 1 （NQO1） were measured in liver tissue. RESULTS Compared with model group， mice in each dosage group of alisol B 23-acetate showed varying degrees of recovery in body weight， along with improvements in pathological changes in liver tissues such as inflammatory cell infiltration and fatty vacu oles. Their liver indexes， histopathological scores of liver tissue， serum levels of ALT， AST， TC， TG and MDA， as well as the protein expressions of CYP2E1 and Keap1 in liver tissue， were all significantly decreased （ P ＜0.05 or P ＜0.01）. The serum GSH levels and the protein expressions of Nrf2 （except for the alisol B 23-acetate low-dose group） and NQO1 in liver tissue were significantly increased （ P ＜0.05 or P ＜0.01）， and the changes in the above quantitative indicators showed a dose-dependent pattern. CONCLUSIONS Alisol B 23-acetate can ameliorate acute alcoholic liver injury in mice， and its mechanism may be related to improving antioxidant capacity by regulating the Keap1/Nrf2/NQO1 signaling pathway while simultaneously improving liver lipid metabolism-related indexes.