ObjectiveTo systematically evaluate the efficacy and safety of Qi-reinforcing and blood-activating/stasis-expelling Chinese patent medicines in the treatment of coronary microvascular disease （CMD）. MethodsPubMed， Cochrane Library， CNKI， Wanfang Data， and VIP were searched for the randomized controlled trials （RCTs） on the treatment of CMD with Chinese patent medicines for reinforcing Qi and activating blood/expelling stasis with the time interval from inception to December 31， 2023. The primary outcome indicators included the index of microcirculatory resistance （IMR）， coronary flow reserve （CFR）， and corrected TIMI flow frame count （cTFC）. The secondary outcome indicators included symptomatic efficacy， left ventricular ejection fraction （LVEF）， hypersensitive C-reactive protein （hs-CRP）， nitric oxide （NO）， and adverse events. Cochrane risk-of-bias assessment tool 2.0 （RoB 2.0） and Stata 17.0 were used for literature quality evaluation and meta-analysis of the included RCTs. The Grading of Recommendations， Assessment， Development and Evaluation （GRADE） was used to evaluate the quality of evidence. ResultsA total of 36 RCTs were included in this study， involving 3 029 patients. Compared with conventional Western medicine alone， the combined use of Chinese patent medicines for reinforcing Qi and activating blood/expelling stasis and Western medicine reduced the IMR ［mean difference （MD）=-5.93， 95% confidence interval （95%CI） ［-8.73，-3.14］， n=382， P<0.01］， cTFC （MD=-9.35， 95%CI ［-13.94，-4.76］， n=618， P<0.01）， and hs-CRP ［standard mean difference （SMD）=-1.50， 95%CI ［-1.90，-1.11］， n=1 483， P<0.01］， improved the CFR （SMD=1.14， 95%CI ［0.08，2.19］， n=304， P=0.03）， symptomatic efficacy ［relative risk （RR）=1.36， 95%CI ［1.21，1.53］， n=756， P<0.01］， LVEF （MD=4.39， 95%CI ［2.31，6.47］， n=533， P<0.01）， and NO （SMD=3.16， 95%CI ［2.07，4.25］， n=946， P<0.01） of CMD patients. In terms of safety， the combined therapy reduced the occurrence of adverse events in CMD patients （RR=0.49， 95%CI ［0.29，0.82］， n=591， P=0.01）. GRADE showed moderate quality evidence for adverse events， low quality evidence for cTFC， symptomatic efficacy， LVEF， and NO， and very low quality evidence for IMR， CFR， and hs-CRP. ConclusionBased on microcirculatory function indicators， the combined use of Qi-reinforcing and blood-activating/stasis-expelling Chinese patent medicines and Western medicine may further improve the coronary microvascular function in CMD patients with good safety. The above conclusions remain to be verified with high-quality clinical trials.

OBJECTIVE: To observe the effect of electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) on hippocampal neuronal ferritinophagy mediated by the nuclear receptor coactivator 4 (NCOA4)/ferritin heavy chain 1 (FTH1) signaling pathway in vascular dementia (VD) rats, and to explore the potential mechanisms of electroacupuncture for VD. METHODS: A total of 60 male rats of SPF grade were randomly divided into a blank group (12 rats), a sham surgery group (12 rats) and a modeling group (36 rats). In the modeling group, the modified 4-vessel occlusion method was used to establish the VD model. The 24 successfully modeled rats were randomly divided into a model group and an electroacupuncture group, with 12 rats in each group. In the electroacupuncture group, electroacupuncture was applied at left and right "Sishencong" (EX-HN1), and bilateral "Fengchi" (GB20), with continuous wave, in frequency of 2 Hz and current intensity of 1 mA, 30 min a time, once daily for 21 consecutive days. The learning and memory abilities were assessed using the Morris water maze test before modeling, after modeling and after intervention, as well as the novel object recognition test after intervention. After intervention, the neuronal morphology in the hippocampus was observed by Nissl staining; the iron deposition was observed by Prussian blue staining; the reactive oxygen species (ROS) level was detected by dihydroethidium (DHE) fluorescence staining; the levels of iron, malondialdehyde (MDA) and superoxide dismutase (SOD) in the hippocampal tissue were measured by the colorimetric assay, TBA method, and WST-1 method, respectively; the positive expression of NCOA4, FTH1 and glutathione peroxidase 4 (GPX4) was detected by immunohistochemistry; the protein expression of NCOA4, FTH1, GPX4, and the ratio of microtubule-associated protein 1 light chain 3B (LC3B) Ⅱ/Ⅰ in the hippocampus were detected by Western blot. RESULTS: Compared with the sham surgery group, in the model group, the escape latency was prolonged, and the number of platform crossings reduced (P<0.01), the recognition index (RI) was decreased (P<0.01); the hippocampal neurons displayed a blurred laminar structure, disorganized cellular arrangement, and the number of Nissl bodies was decreased (P<0.01); the percentage of iron deposition area in the hippocampus was increased (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were increased (P<0.01), the SOD level, and the protein expression of FTH1 and GPX4 were decreased (P<0.01). Compared with the model group, in the electroacupuncture group, the escape latency was shortened and the number of platform crossings was increased (P<0.01), the RI was increased (P<0.01); the hippocampal neurons exhibited more regular morphology, better-organized cellular structure, and the number of Nissl bodies was increased (P<0.05); the percentage of iron deposition area in the hippocampus reduced (P<0.01); in the hippocampus, the levels of ROS, iron, MDA, and the protein expression of NCOA4, as well as the LC3B Ⅱ/Ⅰ ratio were decreased (P<0.01, P<0.05), the SOD level, and the protein expression of FTH1 and GPX4 were increased (P<0.01). CONCLUSION Electroacupuncture at "Sishencong" (EX-HN1) and "Fengchi" (GB20) can improve learning and memory abilities in VD rats, and its mechanism may be associated with the regulation of the hippocampal NCOA4/FTH1 signaling pathway, inhibition of ferritinophagy, and alleviation of oxidative stress damage.
Animals ; Electroacupuncture ; Dementia, Vascular/genetics* ; Male ; Rats ; Signal Transduction ; Humans ; Memory ; Rats, Sprague-Dawley ; Nuclear Receptor Coactivators/genetics* ; Ferritins/genetics* ; Learning ; Hippocampus/metabolism* ; Acupuncture Points

ObjectiveTo explore whether the mechanism of Shuangshen Ningxin capsules （SSNX） in alleviating myocardial ischemia-reperfusion injury （MIRI） in rats is related to the regulation of mitochondrial fission and fusion. MethodThis study focused on Sprague Dawley （SD） rats and ligated the left anterior descending branch of the coronary artery to construct a rat model of MIRI. The rats were divided into the sham operation group， model group， SSNX group （90 mg·kg^-1） and trimetazidine group （5.4 mg·kg^-1）. The activity of superoxide dismutase （SOD） and the content of malondialdehyde （MDA） were detected by micro method. Changes in mitochondrial membrane potential （△Ψm） and the degree of mitochondrial permeability transition pore （mPTP） opening were detected by the chemical fluorescence method. The intracellular adenosine triphosphate （ATP） level was detected by the luciferase assay. The messenger ribonucleic acid （mRNA） and protein expression levels of mitochondrial fission and fusion related factors dynamin-related protein 1 （DRP1）， mitochondrial fission 1 protein （FIS1）， optic atrophy protein 1 （OPA1）， mitochondrial outer membrane fusion protein 1 （MFN1）， and MFN2 were detected by real-time polymerase chain reaction （real-time PCR） and Western blot. ResultCompared with the sham operation group， the model group showed a decrease in serum SOD activity and an increase in MDA content. The opening level of mPTP， the level of △Ψm and ATP content decreased， the protein expressions of mitochondrial fission factors DRP1 and FIS1 increased， and the protein expressions and mRNA transcription levels of fusion related factors OPA1 and MFN1 decreased. Compared with the model group，SSNX significantly increased serum SOD activity， reduced MDA content， increased intracellular ATP level and △Ψm， reduced the opening level of mPTP， downregulated the protein expressions of mitochondrial fission factors DRP1 and FIS1， and increased the mRNA transcription levels and protein expressions of fusion related factors OPA1 and MFN1. ConclusionSSNX inhibits the expressions of mitochondrial fission factors DRP1 and FIS1， and increases the expressions of fusion related factors OPA1 and MFN1， inhibiting mitochondrial fission and increasing mitochondrial fusion， thereby alleviating MIRI.

Medical and pharmaceutical research laboratories encompass a wide range of study areas.They utilize diverse materials ranging from animals and microorganisms to nanoparticles and other substances.However,as laboratory waste increases,more biosafety risks are created.In this context,we outlined the safety risks associated with gene amplification,gene recombination,research involving pathogenic microorganisms,nanotechnology,animal experiments,genetically modified animals,and experimental waste.Additionally,we here in propose preventive measures to mitigate laboratory biosafety risks.These measures primarily involve the development of strict legal frameworks,improvement of hardware infrastructure,strengthening of safety awareness,and enhancement of education and training programs.

Despite decades of laboratory and clinical trials,breast cancer remains the main cause of cancer-related disease burden in women.Considering the metabolism destruction effect of metformin(Met)and cancer cell starvation induced by glucose oxidase(GOx),after their efficient delivery to tumor sites,GOx and Met may consume a large amount of glucose and produce sufficient hydrogen peroxide in situ.Herein,a pH-responsive epigallocatechin gallate(EGCG)-conjugated low-molecular-weight chitosan(LC-EGCG,LE)nanoparticle(Met-GOx/Fe@LE NPs)was constructed.The coordination between iron ions(Fe3+)and EGCG in this nanoplatform can enhance the efficacy of chemodynamic therapy via the Fenton reaction.Met-GOx/Fe@LE NPs allow GOx to retain its enzymatic activity while simultaneously improving its stability.Moreover,this pH-responsive nanoplatform presents controllable drug release behavior.An in vivo biodistribution study showed that the intracranial accumulation of GOx delivered by this nano-platform was 3.6-fold higher than that of the free drug.The in vivo anticancer results indicated that this metabolism destruction/starvation/chemodynamic triple-combination therapy could induce increased apoptosis/death of tumor cells and reduce their proliferation.This triple-combination therapy approach is promising for efficient and targeted cancer treatment.

Objective To investigate the effect of early combined use of liraglutide on cardiometa-bolic risk factors and prognosis in patients with T2DM and CMVD.Methods A total of 124 T2DM patients with concomitant CMVD admitted in our hospital from May 2021 to June 2023 were enrolled,and divided into the liraglutide group(n=59)and the non-liraglutide group(n=65)according to taking liraglutide or not.The main observation indicators were compared between the two groups,including cardiometabolic risk factors,such as Hcy,UA,FPG,eGFR,HbA1c,hs-CRP,WC,BMI,WWI,and echocardiographic indicators,such as LAD,LVEDD,LVPWT,IVST,E/e',e',LVEF,LAVI,LVMI,and RWT.And the incidence of adverse reactions and read-mission rates were recorded during follow-up.Results After treatment,in the liraglutide group,Hcy,UA,FPG,HbA1c,hs-CRP,WC,BMI,WWI,E/e',LAVI,LVMI,RWT,IVST and LVPWT values,and anteroposterior,transverse and long diameters of left atrium were all lower than before treatment,and eGFR and e'value were increased(P＜0.05,P＜0.01),and no significant difference was seen in LVEF and LVEDD(P＞0.05).The non-liraglutide group obtained lower HbA1c,FPG,BMI,E/e'and LAVI values,and transverse diameter of left atrium,elevated LVPWT and e'value(P＜0.05,P＜0.01),and no obvious changes in Hcy,UA,eGFR,hs-CRP,WC,WWI,BMI,LVEF,LVMI,RWT,LVEDD,IVST,and anteroposterior and long diameters of left atrium when compared with the indicators before treatment(P＞0.05).At the end of the fol-low-up,when compared with the non-liraglutide group,the liraglutide group had more significant decreases in E/e',LAVI,LVMI and RWT values and increase in e'value(P＜0.05,P＜0.01),and higher total effective rates(94.92％vs 72.31％,P＜0.01).What's more,the readmission rate due to adverse cardiovascular events was notably lower in the liraglutide group and the non-liraglutide group(3.39％vs 15.38％,P＜0.05).Conclusion Compared with BMI,WWI may be more sensi-tive in reflecting changes in cardiometabolic risk factors in T2DM patients with CMVD;Early combined application of liraglutide has good efficacy and safety,and exerts multiple cardiovascular protective effects,including reducing cardiometabolic risk factors,improving cardiac diastolic function and renal function,inhibiting chronic inflammation and decreasing the occurrence of ad-verse cardiovascular events in the patients.

OBJECTIVE: To explore the mechanism of electroacupuncture (EA) at "Fengchi" (GB 20) and "Sishencong" (EX-HN 1) on learning and memory impairment in vascular dementia (VD) rats by observing the influences on the N-methyl-D-aspartate receptor (NMDAR)/cyclic adenosine monophosphate response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling pathway and the excitotoxicity induced by hippocampal calcium overload. METHODS: Thirty-two male SD rats of SPF grade were selected and randomized into a normal group (6 rats), a sham-operation group (6 rats) and an operation group (20 rats). VD model was established with the modified Pulsinelli's four-vessel occlusion (4-VO) method. Twelve rats after successfully modeled were assigned randomly into a model group and an EA group, 6 rats in each one. In the EA group, EA was delivered at bilateral "Fengchi" (GB 20) and "Sishencong" (EX-HN 1), with the continuous wave, the frequency of 2 Hz and the electric current of 1 mA. Stimulation intensity was adjusted depending on the slightly trembling of rat head. EA was given once daily, 30 min each time; and EA intervention was delivered for 21 days continuously. Using Morris water maze test, the learning and memory function was assessed. The neuronal morphology in the hippocampal CA1 was observed with HE staining; the level of glutamate (GLU) in serum and hippocampal tissue, as well as the activity of calcium pump (Ca²⁺-ATP) in the hippocampus were detected using colorimetric method. The protein expression of NMDAR, calmodulin-dependent protein kinase Ⅱ (CaMKⅡ), phosphorylated calmodulin-dependent protein kinase Ⅱ (p-CaMKⅡ), phosphorylated cyclic phosphoradenosine effector element binding proteins (p-CREB), CREB, and BDNF in the hippocampal CA1 was detected using immunohistochemistry. The protein expression of NMDAR, CREB, p-CREB and BDNF in the hippocampal tissue was detected using Western blot method. RESULTS: Compared to the sham-operation group, in the model group, the escape latency was prolonged and the platform crossing times of rats were reduced (P<0.01), the hippocampal neuron structure was damaged to different degrees, the structure in hippocampal CA1 was loosened, the arrangement disorganized, with clear grid-like structure; the neuronal morphology was irregular, pyknosis and even dissolution occurred, glial cells increased, blood capillary was dilated and the inflammatory cells were infiltrated and scattered. The level of GLU in the serum and hippocampal tissue and the protein expression of hippocampal NMDAR were elevated (P<0.01), the activity of Ca²⁺-ATP and the protein expression of CaMKⅡ, p-CaMKⅡ, CREB, p-CREB and BDNF were reduced (P<0.01, P<0.05); and the ratio of p-CaMKⅡ/CaMKⅡ and that of p-CREB/CREB were dropped (P<0.05). In comparison with the model group, in the EA group, the escape latency was shortened and the platform crossing times of rats rose (P<0.01), the arrangement was improved in the hippocampal CA1, the neuronal morphology was intact, the nucleoli were clear relatively and the pyknosis or dissolution were attenuated, the numbers of glial cells reduced relatively, the dilation of blood capillary was alleviated. The level of GLU in the serum and hippocampal tissue and the protein expression of NMDAR were reduced in the hippocampal tissue (P<0.01), the activity of Ca²⁺-ATP and the protein expression of CaMKⅡ, p-CaMKⅡ, CREB, p-CREB and BDNF were elevated (P<0.05, P<0.01); and the ratio of p-CaMKⅡ/CaMKⅡ and that of p-CREB/CREB increased (P<0.05). CONCLUSION EA at "Fengchi" (GB 20) and "Sishencong" (EX-HN 1) can attenuate learning and memory impairment in VD rats, which may be obtained by reducing GLU level in hippocampal tissue, inhibiting hippocampal excitotoxicity, mediating protein expression related to the NMDAR/CREB/BDNF signaling pathway, and maintaining neuronal survival and growth.
Electroacupuncture ; Male ; Animals ; Rats, Sprague-Dawley ; Learning ; Memory ; Signal Transduction ; Cyclic AMP Response Element-Binding Protein/metabolism* ; Memory Disorders/therapy* ; Brain-Derived Neurotrophic Factor/metabolism* ; Receptors, N-Methyl-D-Aspartate/metabolism* ; Dementia, Vascular/therapy*

Objective:To explore the effect of oxidative stress on cognitive function following chest blast injury in mice.Methods:Sixty male C57BL/6 mice were divided into control group ( n=15) and chest blast group ( n=45) according to a random number table. The chest blast group was subgrouped at 1, 3, 7 days after injury for subsequent experiments. A self-developed blast injury device was used to prepare the mouse model of chest blast injury. Toklu score was used to evaluate the behavior changes in mice. Morris water maze test was used to evaluate the changes in spatial memory. HE staining was used to observe the pathological changes in the frontal cortex and hippocampus. Tissue reactive oxygen species (ROS) assay kit was used to detect ROS expression in the frontal cortex and hippocampus. Western blotting was used to assess changes of malondialdehyde (MDA) and cyclooxygenase-2 (COX2) in the frontal cortex and hippocampus. Results:The Toklu score of the chest blast group at 1 day after injury was (6.7±2.1)points, significantly higher than that of the control group [(2.0±0.0)points], as well as those of the chest blast group at 3 and 7 days after injury [(2.7±1.2)points and (2.0±0.0)points] (all P<0.01). There was no significant difference in the Toklu score between the control group and the chest blast group at 3 and 7 days after injury (all P>0.05). The Morris water maze test showed that the latency periods at 1 and 3 days after injury were 60.1(60.1, 60.1)seconds and 60.1(56.3, 60.1)seconds, significantly longer than that of the control group [10.1(3.9, 18.3)seconds] (all P<0.01). The latency period of the chest blast group at 7 days after injury was 60.1(30.5, 60.1)seconds, with no difference from the control group ( P>0.05). No significant differences were found in the latency periods of the chest blast group at 1, 3 and 7 days after injury (all P>0.05). In the control group, the pyramidal cells in the frontal cortex and hippocampus were regular in shape, with intensely-stained and clearly visible nuclei as well as uniform cytoplasm. In the chest blast group, diflerent degree of necrosis of pyramidal cells in the frontal cortex and strong cytoplasmic eosinophilia in the hippocampus were observed at different time points after injury. The levels of ROS in the frontal cortex of the chest blast group were (10.43±0.36)RFU/mg and (2.91±0.35)RFU/mg at 3 and 7 days after injury, which were significantly higher than that of the control group [(0.70±0.01)RFU/mg] ( P<0.05 or 0.01). The level of ROS in the frontal cortex of the chest blast group at 3 days after injury was significantly higher than that at 1 day [(2.13±0.65)RFU/mg] and that at 7 days after injury (all P<0.01). There were no statistical differences in the levels of ROS in the frontal cortex of the chest blast group at 1 and 7 days after injury ( P>0.05). The levels of ROS in the hippocampus of the chest blast group were (5.39±0.79)RFU/mg and (5.65±1.17)RFU/mg at 3 and 7 days after injury, which were significantly higher than those of the control group and of the chest blast group at 1 day after injury [ (0.73±0.06)RFU/mg and (2.33±0.02)RFU/mg] (all P<0.01). No significant differences were found between the levels of ROS in the hippocampus of the chest blast group at 3 and 7 days after injury and between the ROS levels of the control group and of the chest blast group at 1 day after injury (all P>0.05). The levels of ROS in the frontal cortex and hippocampus showed significant differences between the chest blast group at 3 and 7 days after injury (all P<0.01) but no significant differences between the control group and the chest blast group at 1 day after injury (all P>0.05). Western blotting showed that the levels of MDA in the frontal cortex of the chest blast group were 0.73±0.04, 0.83±0.04 and 0.99±0.06 at 1, 3 and 7 days after injury, which were significantly higher than that of the control group (0.56±0.04) ( P<0.05 or 0.01). The level of MDA in the frontal cortex of the chest blast group was significantly higher at 7 days after injury compared with that at 1 and 3 days after injury ( P<0.05 or 0.01), but there was no statistical difference between 1 day and 3 days after injury ( P>0.05). The levels of COX2 in the frontal cortex of the chest blast group were 2.93±0.02, 4.82±0.15 and 4.76±0.06 at 1, 3 and 7 days after injury, which were significantly higher than that of the control group (1.93±0.06) (all P<0.01). There were statistical differences in the levels of COX2 in the frontal cortex of the chest blast group at 3 and 7 days after injury compared with that at 1 day after injury (all P<0.01), but no statistical significance was found between 3 and 7 days after injury ( P>0.05). The levels of MDA in the hippocampus of the chest blast group were 0.92±0.11, 0.83±0.03 and 0.68±0.03 at 1, 3 and 7 days after injury, which were significantly higher than that of the control group (0.49±0.03) (all P<0.01). There was a significant difference in the level of MDA in the hippocampus of the chest blast group at 7 days after injury compared with those at 1 and 3 days after injury ( P<0.05 or 0.01), but the difference was not statistically significant among other groups (all P>0.05). The levels of COX2 in the hippocampus of the chest blast group were 0.88±0.06, 0.87±0.06 and 0.80±0.06 at 1, 3 and 7 days after injury, which were significantly higher than that of the control group (0.37±0.04) (all P<0.01). There were significant differences in the levels of COX2 of the chest blast group among 1, 3 and 7 days after injury (all P>0.05). Statistically significant differences were found between the levels of MDA in the frontal cortex and hippocampus of the chest blast group at 1 and 7 days after injury (all P<0.01), but no statistical significant difference between the control group and the chest blast group at 1 day after injury ( P>0.05). The levels of COX2 in the frontal cortex and hippocampus were significantly different among all groups (all P<0.01). Conclusions:In the short term after chest blast injury, there will be cognitive dysfunction in mice. Oxidative stress is one of the important contributing factors, and the cognitive damage in the frontal cortex is more serious than that in the hippocampus.

Objective:To establish an animal model of acute systemic cold injury in mice.Methods:There were 98 C57BL/6 mice, half male and half female, with body weight of 22-27 g and age of 10 weeks. The mice were randomly divided into 7 groups ( n=14) according to the changes of anal temperature in cold environment, namely, group A (38.5 ± 1) ℃, group B (35 ± 1) ℃, group C (30 ± 1) ℃, group D (25 ± 1) ℃, group E (20 ± 1) ℃, group F (15 ± 1) ℃, and group G (10 ± 1) ℃, among which, group A was the blank control group, and the rest groups were the experimental group. The mice in the blank control group were placed in the normal environment (20 ± 5) ℃, and the mice in the experimental group were placed in the low temperature artificial climate box at - 20℃. The anal temperature of the mice was measured intermittently (as the core temperature), and the time required for the core temperature of the mice to drop to groups B, C, D, E, F and G was recorded. The righting reflex was used to evaluate the consciousness state, the action ability and the general state of each organ of mice were observed, and the blood routine and HE staining of each organ were detected. Results:The lower the core temperature of the experimental group, the longer the time required. The consciousness state, action ability, general state of organs, blood routine, and HE staining of organs in groups B, C, and D were basically the same as those in group A, and there was no acute systemic cold injury. Therefore, the blood routine, general observation of organs, and HE staining of organs in groups B, C, and D were no longer displayed compared with those in group A. Compared with group A, mice in group E began to suffer from disturbance of consciousness and action ability. With the decrease of core body temperature, the damage was aggravated, and mice in group G died. Compared with group A, the indices of blood routine test (WBC, RBC, HGB, PLT) of mice in group E began to decrease, and the univariate variance calculation showed that only WBC changes had statistical significance ( P<0.05). Compared with groups A and E, the indices of blood routine test (WBC, RBC, HGB, PLT) of mice in group F were further reduced, and the changes of each index in univariate variance calculation were statistically significant ( P<0.05). The general observation results showed that compared with group A, the lung, liver and spleen surfaces of mice in group E began to darken, and compared with groups A and E, the lung, liver, spleen, kidney and heart of mice in group F were further deepened and darkened, with irregular edges. HE staining results of various organs showed that compared with group A, the mice in group E began to have partial alveolar structure destruction and a small amount of inflammatory cell infiltration, the central vein of the liver was slightly congested, and the red and white pulp of the spleen were indistinct. Compared with groups A and E, the pathological structure damage of the lung, liver, spleen, kidney, heart and brain tissues of the mice in group F was further aggravated. Conclusions:Detection of consciousness state, action ability, general state of organs, blood routine and HE staining indices of organs in mice under low temperature can simulate the progress of clinical acute cold injury, and the animal model of acute systemic cold injury was successfully prepared.

Objective    To investigate effectiveness and safety of transcatheter aortic valve replacement in the treatment of aortic regurgitation. Methods     PubMed, EMbase, The Cochrane Library, Web of Science, CNKI, Wanfang Data and VIP were searched from inception to August 2021. According to the criteria of inclusion and exclusion, two reviewers independently screened the literature, extracted the data and evaluated the quality of the included studies. Then, Stata 16.0 software was used for meta-analysis. Subgroup meta-analysis of valve type used and study type was performed. Results    Twenty-five studies (12 cohort studies and 13 single-arm studies) were included with 4 370 patients. Meta-analysis results showed that an incidence of device success was 87% (95%CI 0.81-0.92). The success rate of the new generation valve subgroup was 93% (95%CI 0.89-0.96), and the early generation valve subgroup was 66% (95%CI 0.56-0.75). In addition, the 30-day all-cause mortality was 7% (95%CI 0.05-0.10), the 30-day cardiac mortality was 4% (95%CI 0.01-0.07), the incidence of pacemaker implantation was 10% (95%CI 0.08-0.13), and the incidence of conversion to thoraco-tomy was 2% (95%CI 0.01-0.04). The incidence of moderate or higher paravalvular aortic regurgitation was 6% (95%CI  0.03-0.09). Conclusion     Transcatheter aortic valve replacement for aortic regurgitation is safe and yields good results, but some limitations can not be overcome. Therefore, multicenter randomized controlled trials are needed to confirm our results.