OBJECTIVE To analyze and evaluate serious adverse drug reaction(SADR) and drug-drug interactions(DDIs) in the real-world, so as to obtain the clinical evidence of DDIs-related SADR, and to provide a reference for rational clinical use. METHODS The SADR reports reported to the National Adverse Drug Reaction Monitoring Center from January 2011 to December 2020 were collected, and Lexi-Interaction® software in UpToDate was used to analyze ≥2 drugs in SADR to evaluate whether there were potential DDIs. And the possible adverse drug reactions caused by DDIs were statistically analyzed. RESULTS Among the 360 cases of SADR, males were slightly more than females(50.83% vs 49.17%), the mean age was (65.27±14.71) years old, and 56.39% were ≥65 years old. Cardiovascular agents were the most common implicated pharmacological group, and the gastrointestinal system was the most frequently affected system, and aspirin was the most frequently reported drug. Among 150 cases of SADR with at least two suspected drugs, 64 cases had potential DDIs, while 42 cases had clinically significant DDIs, of which only 16 and 2 cases of SADR were caused by actual DDIs in category D and X, respectively. The majority of reports(71.43%) were caused by additive pharmacodynamic interactions. Aspirin was the most common drug in both potential DDIs and actual DDIs, while aspirin and clopidogrel was the most commonly involved drug pair in actual DDIs, with gastrointestinal bleeding being the most common SADR. CONCLUSION Attention should be paid to the influence of drug interactions on SADR, and prescription should be optimized, especially in the elderly population. According to the results of potential DDIs, therapeutic drugs should be rationally selected. Meanwhile, monitoring of cardiovascular drugs and key populations should be strengthened to ensure drug safety.

ObjectiveTo investigate the effect of Yiqi Tongxin formula （YQTM） on liver inflammation in apolipoprotein E^-∕- （ApoE^-∕-） mice by regulating the nuclear transcription factor-κB （NF-κB）/NOD-like receptor protein 3 （NLRP3） signaling pathway. MethodForty ApoE^-∕- mice were randomly divided into a model group， an atorvastatin group （positive drug group）， and low-， medium-， and high-dose YQTM groups （0.39， 0.78， 1.56 g·kg^-1）. Each drug administration group was given the corresponding concentration of the drug by gavage on the basis of high-fat feeding for 12 consecutive weeks. Eight C57BL/6J mice were used as a blank group and fed with normal chow. After 12 weeks， oil red O staining and Masson staining were used to observe the aortic lesions in mice and to determine whether the modeling was successful. Oil red O staining was used to observe the lipidosis in the livers of mice. Hematoxylin-eosin （HE） staining was used to observe the tissue lesions in the livers of mice. Masson staining was used to observe the distribution of collagen fibers in the livers of mice. Enzyme markers were used to detect the total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL-C）， aspartate aminotransferase （AST）， and alanine aminotransferase （ALT） in mouse serum， as well as total cholesterol （TC） and triglyceride （TG） in the liver. Interleukin-1β （IL-1β） and IL-18 were detected in mouse liver by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry （IHC） was utilized to observe the expression regions of NF-κB and NLRP3 in the livers of mice. Western blot was employed to detect the protein expression levels of NF-κB， NF-κB inhibitory protein （IκB）， IκB kinase β （IKKβ）， phosphorylated NF-κB （p-NF-κB）， phosphorylated IκB （p-IκB）， phosphorylated IKK β （p-IKKβ）， NLRP3， and Caspase-1 in the livers of mice. ResultCompared with the blank group， the model group showed severe aortic lipidosis， and the intracellular fat droplets in the livers aggregated in large quantities. The cytoplasm was filled with fat vacuoles（P<0.01）. The serum levels of TG， TC， LDL-C， AST， and ALT were significantly elevated in the mice（P<0.01）. TG and TC levels were elevated in the liver（P<0.01）. The levels of IL-1β and IL-18 in liver tissue， as well as the protein expression levels of NF-κB， IκB， IKKβ， p-NF-κB， p-IκB， p-IKKβ， NLRP3， and Caspase-1 in the liver were significantly elevated（P<0.01）. Compared with the model group， the aortic arch plaques of mice in each YQTM group were attenuated， and the fat aggregation in the liver was reduced. The inflammatory cell infiltration was alleviated（P<0.05，P<0.01）. The serum levels of TG， TC， LDL-C， AST， and ALT were significantly reduced（P<0.05，P<0.01）. TG and TC levels in the liver were reduced. The IL-1β and IL-18 levels in liver tissue， as well as protein expression levels of NF-κB， IκB， IKKβ， p-NF-κB， p-IκB， p-IKKβ， NLRP3， and Caspase-1 in the liver were significantly reduced（P<0.05，P<0.01）. ConclusionThe intervention mechanism of YQTM on liver inflammation in ApoE^-∕- mice may be related to the down-regulation of the NF-κB/NLRP3 signaling pathway.

OBJECTIVE To investigate the effects of Yiqi tongmai formula on atherosclerosis （AS） in ApoE－/－ mice and its mechanism. METHODS Forty ApoE－/－ mice were randomly divided into model group， positive control group [atorvastatin calcium， 2.6 mg/（kg·d）]， and low-dose， medium-dose and high-dose groups of Yiqi tongmai formula [0.46， 0.91， 1.82 g/（kg·d）， by raw material]， with 8 mice in each group. Eight C57BL/6J mice were selected as the normal group. Except for the normal group， the other groups were given a high-lipid diet and relevant drug or normal saline intragastrically， once a day， for 12 consecutive weeks. After the last medication， the serum levels of total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein cholesterol （LDL-C） and high-density lipoprotein cholesterol （HDL-C） as well as the contents of tumor necrosis factor-α （TNF-α）， interleukin-1β （IL-1β） and monocyte chemoattractant protein-1 （MCP-1） were measured in mice. The proportion of aortic plaque area in each group of mice was detected and calculated， and the pathological morphological changes of the aortic sinus were observed； the protein phosphorylation levels of aortic phosphoinositide 3-kinase （PI3K）， protein kinase B （aka Akt） and mammalian target of rapamycin （mTOR） were examined. RESULTS Compared with the model group， the serum levels of TC， TG and LDL-C and the contents of TNF-α， IL-1β and MCP-1 （including low-dose group） were decreased significantly in medium-dose and high-dose groups of Yiqi tongmai formula， while the content of HDL-C in high-dose group was increased significantly （P＜0.05 or P＜0.01）； aortic plaques of the mice were reduced in Yiqi tongmai formula groups to different extents， and pathological changes such as lipid deposition and inflammatory cell infiltration were relieved to different extents； the proportion of aortic plaque area， the protein phosphorylation levels of PI3K， Akt and mTOR in aortic tissue were significantly reduced in medium-dose and high-dose groups of Yiqi tongmai formula （P＜0.05 or P＜0.01）. CONCLUSIONS Yiqi tongmai formula can improve lipid metabolism， reduce inflammatory response， and delay plaque development in AS mice. Its effect may be related to the inhibition of PI3K/Akt/mTOR signaling pathway activation.

There has been a growing amount of evidence that a balanced blood component transfusion with roughly equal ratio of units of packed red blood cells,fresh frozen plasma,and platelets leads to better outcomes in massive transfusion re-suscitation of trauma victims.Therefore,the great interest of massive transfusion protocol(MTP)with whole blood was a-roused.Low titer group O whole blood(LTOWB)is implemented in routine use for civilian prehospital ambulance services in large trauma centers of most European and American countries nowadays.There is a growing body of evidence to date to support that early use of LTOWB in patients with life-threatening bleeding improve their survival.In view of the current situ-ation of whole blood supply in our country,most trauma resuscitation guidelines still recommend balanced component trans-fusion for MTPs in the early stage of resuscitation.The research and application of LTOWB abroad will be introduced in this article.

ObjectiveTo explore the molecular mechanism of Shuyuwan regulating polarization of tumor-associated macrophages （TAMs） to inhibit the progression of colorectal cancer （CRC）. MethodThe nude mouse model of orthotopic transplantation of colon cancer was established. Male BALB/c-nu nude mice （n=28， 4 weeks old） were randomly assigned into 4 groups （n=7）： Model group （normal saline） and low-， medium-， and high-dose （1.725， 2.310， 2.895 g·kg^-1·d^-1， respectively） Shuyuwan groups. On day 9 after the tumor block was inoculated， the mice were administrated by gavage with corresponding agents at a dose of 15 mL·kg^-1 once a day， 6 days a week， and no agent on the 7^th day. After two consecutive weeks of intervention， the nude mice were sacrificed and the tumor samples were collected. A part of the colon tissue and the tumor tissue was used to prepare sections， and hematoxylin-eosin （HE） staining was performed for pathological observation. The expression of inducible nitric oxide synthase （iNOS） and arginase-1 （Arg-1） in the tumor tissue was detected by immunohistochemistry （IHC）. The mRNA levels of interleukin-12 （IL-12）， epidermal growth factor （EGF）， and transforming growth factor-β₁ （TGF-β₁） in the tumor tissue were determined by Real-time polymerase chain reaction （PCR）. Western blot was employed to determine the protein levels of iNOS， IL-12， EGF， and TGF-β₁ in the tumor tissue. ResultCompared with the model group， Shuyuwan inhibited the growth of colon cancer cells in nude mice and caused the tumor cell necrosis in different degrees. The high-dose Shuyuwan group had the strongest inhibitory effect on the growth of tumor cells， which basically lost the normal morphology. Furthermore， Shuyuwan up-regulated the expression of iNOS and IL-12 in M1-type macrophages （P<0.05） and down-regulated the expression of Arg-1， EGF， and TGF-β₁ in M2-type macrophages （P<0.05）， which indicated the weakened polarization of macrophages toward M2 type and the enhanced polarization toward M1 type after treatment with Shuyuwan. ConclusionShuyuwan can inhibit the growth of orthotopically transplanted colon tumor by blocking the polarization of TAMs to M2 type and promoting the polarization of TAMs to M1 type.

In the context of non-alcoholic fatty liver disease (NAFLD), characterized by dysregulated lipid metabolism in hepatocytes, the quest for safe and effective therapeutics targeting lipid metabolism has gained paramount importance. Sanhuang Xiexin Tang (SXT) and Baihu Tang (BHT) have emerged as prominent candidates for treating metabolic disorders. SXT combined with BHT plus Cangzhu (SBC) has been used clinically for Weihuochisheng obese patients. This retrospective analysis focused on assessing the anti-obesity effects of SBC in Weihuochisheng obese patients. We observed significant reductions in body weight and hepatic lipid content among obese patients following SBC treatment. To gain further insights, we investigated the effects and underlying mechanisms of SBC in HFD-fed mice. The results demonstrated that SBC treatment mitigated body weight gain and hepatic lipid accumulation in HFD-fed mice. Pharmacological network analysis suggested that SBC may affect lipid metabolism, mitochondria, inflammation, and apoptosis-a hypothesis supported by the hepatic transcriptomic analysis in HFD-fed mice treated with SBC. Notably, SBC treatment was associated with enhanced hepatic mitochondrial biogenesis and the inhibition of the c-Jun N-terminal kinase (JNK)/nuclear factor-kappa B (NF-κB) and extracellular signal-regulated kinase (ERK)/NF-κB pathways. In conclusion, SBC treatment alleviates NAFLD in both obese patients and mouse models by improving lipid metabolism, potentially through enhancing mitochondrial biogenesis. These effects, in turn, ameliorate inflammation in hepatocytes.
Humans ; Mice ; Animals ; Non-alcoholic Fatty Liver Disease/metabolism* ; NF-kappa B/metabolism* ; Organelle Biogenesis ; Retrospective Studies ; Mice, Inbred C57BL ; Obesity/metabolism* ; Liver ; Inflammation/metabolism* ; Body Weight ; Lipid Metabolism ; Lipids ; Diet, High-Fat/adverse effects*

ObjectiveTo decipher the mechanism of modified Sanpiantang in the treatment of nitroglycerin-induced migraine in rats. MethodSeventy-two Wistar rats were randomized into the control， model （nitroglycerin， 10 mg·kg^-1）， positive control （rizatriptan， 0.89 mg·kg^-1）， and high- （12.96 g·kg^-1）， medium- （6.48 g·kg^-1）， and low-dose （3.24 g·kg^-1） modified Sanpiantang groups. The rat model of migraine was established by intraperitoneal injection of 10 mg·kg^-1 nitroglycerin. The behavioral test was carried out to measure the mechanical pain thresholds （MPT） of the periorbital region and hindpaw after successful modeling. The serum levels of nitric oxide （NO）， tumor necrosis factor-α （TNF-α）， interferon-γ （IFN-γ）， and interleukin-1β （IL-1β） in rats were determined by enzyme-linked immunosorbent assay （ELISA）. Immunohistochemistry （IHC） was employed to determine the expression of inducible nitric oxide synthase （iNOS） in the trigeminal nucleus caudalis （TNC）. Western blot was employed to determine the protein levels of iNOS and phospho-p38 mitogen-activated protein kinase （p-p38 MAPK） in the TNC. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was performed to measure the mRNA levels of iNOS， p38 MAPK， and IL-1β in the TNC. ResultCompared with the control group， the model group showed decreased MPT （P<0.01）， elevated serum levels of NO， TNF-α， IFN-γ， and IL-1β （P<0.01）， and up-regulated expression levels of p38 MAPK， iNOS， and IL-1β in the TNC （P<0.05， P<0.01）. Compared with the model group， modified Sanpiantang increased the MPT （P<0.05）， and the medium-dose group showed the most significant effect （P<0.01）. In addition， modified Sanpiantang down-regulated the mRNA levels of iNOS， p38 MAPK， and IL-1β and the protein levels of p-p38 MAPK and iNOS in the TNC of migraine rats （P<0.05， P<0.01） and lowered the serum levels of NO， TNF-α， IFN-γ， and IL-1β （P<0.05， P<0.01）. ConclusionModified Sanpiantang may treat migraine by down-regulating the expression of pro-inflammatory factors such as NO， TNF-α， IFN-γ， and IL-1β in the p38 MAPK/iNOS signaling pathway to reduce the neurogenic inflammation.

Purpose To investigate the diagnostic criteria and prognostic significance of squamous cell components in pa-pillary thyroid carcinoma(PTC).Methods Twenty-three cases of PTC containing squamous cell components were collect-ed,and pathological sections were reviewed.p40,CK5/6,Ki-67,BRAF V600E,p53,PD-L1(22C3),PAX8,and CD10,markers related to diagnosis,prognosis,and treatment,were de-tected by immunohistochemistry.Histological characteristics and immunophenotype of squamous cell components were comprehen-sively evaluated.The squamous cell components were classified histologically.The relationship between squamous cell classifica-tion and clinicopathological parameters,and their prognostic im-pact were analyzed.Results The squamous cell components were divided into squamous differentiation(19 cases)and ana-plastic carcinoma(4 cases).In the latter,the squamous cell components were diffusely distributed in sheets;the cell atypia was moderate to severe;and the Ki-67 index was at least 30%.High expression of p53 was found only in anaplastic carcinoma.Compared with squamous differentiation,anaplastic carcinoma had a larger diameter,higher BRAF V600E positive rate,high PD-L1 combined positive score,and extremely worse progression-free survival and overall survival.Squamous differentiation had inconspicuous impact on survival,and only one case relapsed af-ter secondary surgery.Conclusion The cell atypia,distribu-tion,maximum diameter,Ki-67 and p53 expression of squamous cell components are helpful in differentiating squamous compo-nents from anaplastic carcinoma.Positive BRAF V600E and PD-L1 expression suggest the feasibility of targeted therapy and im-munotherapy for anaplastic carcinoma.

Objective:To investigate the value of chain management of perioperative pressure injury in patients undergoing supine craniocerebral injury, so as to provide reference for the prevention of pressure injury and the application of chain management.Methods:In this retrospective study, a total of 116 patients with craniocerebral injury who underwent supine surgery in Shanxi Cardiovascular Hospital from December 2019 to December 2020 were included in the control group, using traditional perioperative pressure injury management protocol. And 124 patients admitted from January 2021 to December 2021 were included in the observation group, and were managed by the pressure injury chain management scheme. The risk assessment/judgment rate of pressure ulcers, the risk assessment/judgment accuracy rate of pressure ulcers, the implementation rate of intervention measures, the qualified rate of intervention records and the reported rate of high-risk patients with pressure ulcers in the two groups were analyzed. The occurrence of stress injury and medical expenses of the two groups of patients were investigated.Results:The risk assessment/judgment rate of pressure ulcers, the risk assessment/judgment accuracy rate of pressure ulcers, the implementation rate of intervention measures, the qualified rate of intervention records and the reported rate of high-risk patients with pressure ulcers were 100.00%(124/124), 96.77%(120/124), 92.74%(115/124), 93.55%(116/124), 100.00%(29/29) in the observation group, which were 77.59%(90/116), 72.41%(84/116), 68.97%(80/116), 68.97%(80/116), 83.33%(30/36) in the control group, the difference was statistically significant ( χ2 values were 22.24-31.17, all P<0.05). The overall incidence of stress injury in the observation group and the control group was 15.52%(18/116) and 3.23%(4/124), respectively, and the difference between the two groups was statistically significant ( χ2=10.88, P<0.05). There was no significant difference in the total hospitalization cost between the two groups ( P>0.05). The cost of stress-related consumables was (144.94 ± 47.28) yuan in the observation group and (194.21 ± 55.76) yuan in the control group, and the difference was statistically significant ( t=7.40, P<0.05). Conclusions:Perioperative stress injury chain management can reduce the incidence of pressure injury in patients with craniocerebral injury, improve service quality, and reduce medical costs, with good clinical application value.

【Objective】 To investigate the effect of leukocyte-depleted suspended red blood cells (lds-RBCs) storaged for different time on blood transfusion effect of patients with hematologic diseases and malignant tumors, as well as to evaluate the storage quality of lds-RBCs in blood stations. 【Methods】 Seven hospitals (4 tertiary-A hospitals and 3 secondary-A hospitals), applying for blood from our blood center, were selected. Blood transfusion cases (medical record) and related data (indicators) of patients with blood diseases and malignant tumors in those hospitals from December 2018 to May 2019 were collected, including disease diagnosis (type) before transfusion, demographic characteristics, date of solo transfusion of lds-RBCs, units of lds-RBCs [(1~2)U/bag, 1 U=200 mL whole blood], different storage duration (1~5 weeks) (bar code), and hemoglobin (Hb) 48 h before and after transfusion. The efficacy of lds-RBCs (storaged for different time) transfusion in patients with hematologic diseases and malignant tumors was evaluated by statistical analysis. 【Results】 A total of 3 557 patients with hematologic diseases and malignant tumors were enrolled in this study. No significant changes were noticed in transfusion efficacy by blood transfusion unit, gender and previous transfusion history (P > 0.05). The effective rate of lds-RBCs in patients with blood diseases and malignant tumors, stratified by storage duration, i. e. storaged for >1~2 weeks, >2~3 weeks, >3~4 weeks and more than >4~5 weeks, was 78.77% vs 77.68% vs 75.06% vs 70.37%, and 79.32% vs 76.73% vs 72.79% vs 67.65%, respectively(P<0.05), with lds-RBCs of 4-5 storage weeks presenting the lowest transfusion efficacy in both groups of patients. 【Conclusion】 The storage time of most lds-RBCs supplied by our center is moren than 3 weeks, and the transfusion effect of lds-RBCs stored for 5 weeks needs further observation. In order to ensure and improve the efficacy of blood transfusion, evidence-based medicine and information management are needed to help the clinical gasp the advantageous time of blood products and shorten the storage-to-transfusion time of red blood cells.