An investigation of the influence of intestinal flora in external traditional Chinese medicine therapy

External therapy,which has been used for millennia to treat disease,has now become the newest member of complementary and alternative therapies.A growing number of clinical studies and animal experiments have shown that external therapy exerts a positive effect on the intestinal flora.In this paper,we review the research related to external therapy on various systemic diseases and focus on changes in the intestinal flora.We found that studies on external therapy are dominated by acupuncture and tuina,primarily aimed at the treatment of digestive and neurological diseases.However,the deeper mechanism of regulation of the intestinal flora by external therapy has not yet been experimentally confirmed.

Feasibility and clinical benefits of the double-ProGlide technique for hemostasis after cryoballoon atrial fibrillation ablation with uninterrupted oral anticoagulants

OBJECTIVE To access the efficacy and safety of the double-ProGlide technique for the femoral vein access-site closure in cryoballoon ablation with uninterrupted oral anticoagulants(OAC),and its impact on the electrophysiology laboratory time as well as hospital stay after the procedure in this observational study.METHODS Patients with atrial fibrillation undergoing cryoballoon ablation with uninterrupted OAC at Department of Cardiology,Beijing Anzhen Hospital,Capital Medical University,Beijing,China from May 2019 to May 2021 were enrolled in this study.From October 2020,double-ProGlide technique was consistently used for hemostasis(ProGlide group),and before that conventional manual compression was utilized(manual compression group).The occurrence of vascular and groin complications was accessed during the hospital stay and until the three-month follow-up.RESULTS A total of 140 participants(69.30%of male,mean age:59.21±10.29 years)were evaluated,70 participants being in each group.Immediate hemostasis was achieved in all the patients with ProGlide closure.No major vascular complications were found in the ProGlide group while two major vascular complications were occurred in the manual compression group.The incidence of any groin complication was obviously higher in subjects with manual compression than patients with ProGlide devices(15.71%vs.2.86%,P=0.009).In addition,compared with the manual compression group,the ProGlide group was associated with significantly shorter total time in the electrophysiology laboratory[112.0(93.3–128.8)min vs.123.5(107.3–158.3)min,P=0.006],time from sheath removal until venous site hemostasis[3.8(3.4–4.2)min vs.8.0(7.6–8.5)min,P<0.001],bed rest time[8.0(7.6–8.0)h vs.14.1(12.0–17.6)h,P<0.001]and hospital stay after the procedure[13.8(12.5–17.8)h vs.38.0(21.5–41.0)h,P<0.001].CONCLUSIONS Utilization of the double-ProGlide technique for hemostasis after cryoballoon ablation with uninterrupted OAC is feasible and safe,which has the clinical benefit in reducing the total electrophysiology laboratory time and the hospital stay length after the procedure.

The Psychosomatic Traits of“People with the Five Elements in Traditional Chinese Medicine”:A Qualitative Study

Objective To identify the representative attributes of the five elements of a person with a qualitative methodology and provide the basis for the clinical diagnosis and treatment of“people with the five elements in traditional Chinese medicine(TCM).”Methods Data collected from the literature review,two sessions of brainstorming of experts with related experience in“people with the five elements in TCM”from October 2020 to December 2020,and six rounds of in-depth interviews with 30 participants who had various attributes of the five elements from March 2021 to October 2021 were analyzed.Triangulation was used in this study,and theming and synthesizing were used to analyze the data.Results A total of 31 experts and 30 interviewees participated in this study.The median age of the experts and interviewees were 48.0 and 38.5 years,respectively;51.66%and 54.8%of experts and interviewees,respectively,were men.The descriptors of facial diagrams of“people with the five elements in TCM”were complexion,shape,distribution state of facial bones,convergence trend of facial muscles,and facial expression.A theoretical model of“people with the five elements in TCM”was shaped based on these findings.Conclusion The study suggests a possibility for bridging the gap between personality and bodily state,identifying an avenue for personality research from the perspective of TCM.

Yiqi Qingre Xiaozheng formula protects against diabetic nephropathy by restoring autophagy in mice

Objective:To evaluate the protective effect of Yiqi Qingre Xiaozheng formula(YQQRXZF)via the regulation of autophagy in diabetic nephropathy(DN)mice induced by injection of streptozotocin(STZ)after high fat diet(HFD).Methods:The composition of YQQRXZF was analyzed by high performance liquid chromatographyelectrospray ionization/mass spectrometry(HPLC-ESI/MSn).The DN model was induced by intraperitoneally injection of 50 mg/kg STZ within 5 days,followed by HFD feeding for 8 weeks in C57BL/6J mice.Mice were randomly separated into DN group,YQQRXZF group,irbesartan group,and control group.Blood glucose was calculated,and body weight was measured every 2 weeks.An enzyme-linked immunosorbent assay was used to measure the urinary albumin-to-creatinine ratio(uACR)before and after treatment,and the serum concentrations of total cholesterol(TC),low-density lipoprotein(LDL),triglycerides(TG),high-density lipoprotein(HDL),blood urea nitrogen(BUN),and serum creatinine(Scr)were measured.In addition,hematoxylin-eosin(H&E)staining,periodic acid-Schiff(PAS)staining,Masson's trichrome staining,and transmission electron microscopy(TEM)were used to observe pathological changes in renal tissue.Autophagy levels were determined by immunofluorescence staining.Results:In this study,21 dominant chemical constituents were identified in YQQRXZF.The treatment group reduced u ACR in a more significant way than the DN group(P=.018).The treatment group reduced TC,TG,and LDL concentrations after YQQRXFF treatment(P=.021,P=.014 and P=.026,respectively).H&E,PAS,and Masson staining showed that pathological damage to mice kidneys improved,the volume of renal glomeruli was reduced,and glomerular sclerosis and fibrosis were reduced.Immunofluorescence analysis revealed that expressions of LC3-Ⅱprotein increased in the treatment group(P=.013).In contrast,the protein expressions of P62 were reduced after treatment(P=.025).

Infrared thermography in metabolic diseases

The prevalence of metabolic diseases,some diseases that are seriously harmful for human health and affect the quality of life,is increasing year by year.Early detection and intervention is the common strategy to deal with them.Infrared thermography(IRT)is a special medical imaging technology which can capture the changes of skin temperature associated with metabolic disorders.It might be a new method for early detection of metabolic diseases.The purpose of this review is to summarize advances of the use of IRT in evaluating single metabolic disorder such as obesity,hyperglycemia and hypertension,complex metabolic disorders such as metabolic syndrome and target organ damage such as coronary artery atherosclerosis and diabetic foot.The characteristic of thermograms of metabolic disease patients,the changes of thermal maps during the development of the disease,and the lacks in current studies are also discussed in the article.

Clinical efficacy of external treatment with Zi Cao Yang He Tang combined with hormone therapy for granulomatous mastitis and its effect on cellular pyroptosis proteins

Objective:To observe the clinical effect of external application of Zi Cao Yang He Tang combined with dexamethasone ointment in the treatment of granulomatous lobular mastitis in the mass stage and the effect on cellular pyroptosis-related proteins.Methods:Forty patients with granulomatous lobular mastitis were randomly divided into 20 cases in the observation group and 20 cases in the control group.Both groups were given dexamethasone ointment for treatment,and the observation group was treated with external application of Zi Cao Yang He Tang on the basis of the control group.Breast lump vol-ume changes,breast pain and pus symptoms,pathology and histology and immunohistochemistry,cellular death-related indicators expression were compared between the two groups.Results:After treatment,the difference in mass volume of the observation group was significantly greater than that of the control group(16.7±21.5 in the control group and 32.9±27.4 in the experimental group)and the difference between the two groups was statistically significant(P<0.05);the objective remission rate of the patients in the observation group(ORR=85%)was significantly higher than that of the treatment group(ORR=50%,P<0.05).In terms of pus formation rate and pain level,the breast pain score of the observation group was significantly lower than that of the control group after two weeks or three weeks of treatment(P<0.05);the pus formation rate of the observation group was 30%,and the pus formation rate of the control group was 20%,and the difference was not statistically significant(P>0.05).The immunohistochemical expression levels of caspase-1 and GSDMD in the observation group were significantly lower than those in the control group(P<0.05);and in terms of the expression of cellular pyroptosis-related indexes,the expression of GSDMD,cas-pase-1,and NLRP3 in the observation group was significantly lower compared with that in the control group(P<0.05).Conclusion:The efficacy of external application of Zi Cao Yang He Tang combined with dexamethasone ointment in treating granulomatous lobular mastitis in the mass stage is remarkable,which can effectively reduce breast pain,reduce the size of the mass,de-crease the expression of cellular pyroptosisrelated indexes,and have a good anti-inflammatory effect.

Meta-analysis of the impact of hyperuricemia on contrast agent-related acute kidney injury after percutaneous coronary intervention

Objective:To evaluate the impact of hyperuricemia on the occurrence of contrast agentrelated acute kidney injury after percutaneous coronary intervention.Methods:Retrieve PubMed,Embase,Cochrane Library,Web of Science,CNKI,Wanfang,and VIP databases,and publish articles on the correlation between hyperuricemia and contrast agent-related acute kidney damage after percutaneous coronary intervention from the establishment of the database to August 162023.Two researchers independently conducted literature screening and data extraction to evaluate the bias risk of inclusion in the study,and conducted metaanalysis using Review Manager 5.4 software.Results:A total of 12 articles were included,including 11676 patients.The meta-analysis results showed that compared with patients without hyperuricemia,patients with hyperuricemia had a higher risk of developing PC-AKI,with an incidence rate of 22.3%.Hyperuricemia was a risk factor for the occurrence of PCAKI(OR=2.03,95%CI:1.58-2.61);Patients with hyperuricemia have a higher risk of death after PC-AKI,with a mortality rate of 7.5%.Hyperuricemia is a risk factor for early death in PC-AKI patients(OR=2.33,95%CI:1.81-3.00);The probability of CRRT treatment after PCAKI in patients with hyperuricemia is higher,at 3.14%.Hyperuricemia is an influencing factor for CRRT treatment in PC-AKI patients(OR=7,95%CI:2.83-17.30).Conclusion:Existing research evidence suggests that the presence of hyperuricemia is an independent risk factor for the occurrence of PC-AKI,and it significantly increases the hospital mortality rate and the risk of renal replacement therapy in PC-AKI patients.

Online pharmaceutical process analysis of Chinese medicine using a miniature mass spectrometer: Extraction of active ingredients as an example

The automation of traditional Chinese medicine(TCM)pharmaceuticals has driven the development of process analysis from offline to online.Most of common online process analytical technologies are based on spectroscopy,making the identification and quantification of specific ingredients still a challenge.Herein,we developed a quality control(QC)system for monitoring TCM pharmaceuticals based on paper spray ionization miniature mass spectrometry(mini-MS).It enabled real-time online qualitative and quantitative detection of target ingredients in herbal extracts using mini-MS without chromatographic separation for the first time.Dynamic changes of alkaloids in Aconiti Lateralis Radix Praeparata(Fuzi)during decoction were used as examples,and the scientific principle of Fuzi compatibility was also investigated.Finally,the system was verified to work stably at the hourly level for pilot-scale extraction.This mini-MS based online analytical system is expected to be further developed for QC applications in a wider range of pharmaceutical processes.

Correlation analysis of anxiety with psoriasis severity, oxidative stress and inflammatory factors in patients with psoriasis vulgaris

Objective:To investigate the anxiety status of patients with psoriasis vulgaris,and analyze the correlation between anxiety and severity of the disease,oxidative stress factors and inflammatory factors.Methods:From August 2021 to February 2022,84 patients with psoriasis in the Dermatology Department of Dongzhimen Hospital of Traditional Chinese Medicine were recruited.Hamilton anxiety scale(HAMA),psoriasis lesion area and severity index(PASI),VAS pruritus scale(VAS)were collected to detect serum malondialdehyde(MDA),superoxide dismutase(SOD),glutathione peroxidase(GSH px),interleukin-6(IL-6),interleukin-17A(IL-17A),and tumor necrosis factor-α(TNF-α).Based on the HAMA score,a group controlled study and correlation analysis were conducted.In addition,the HAMA scores of 84 healthy people were collected for a controlled study.Results:HAMA score of patients with psoriasis vulgaris was higher than that of healthy people(Z=-7.730,P<0.05).There were differences in PASI,VAS scores,MDA,SOD,GSH px,IL-6,IL-17A secretion levels between psoriasis vulgaris patients with anxiety and psoriasis vulgaris patients without anxiety.HAMA score was positively correlated with PASI and VAS scores in patients with psoriasis vulgaris(r=0.564,0.513,P<0.05).It was positively correlated with MDA,IL-6,IL-17A in serum(r=0.390,0.355,0.248,P<0.05).It was negatively correlated with SOD and GSH px(r=-0.313,-0.502,P<0.05);and TNF-αnot relevant.Conclusion:The anxiety risk of psoriasis patients was higher than that of healthy people;anxiety is closely related to psoriasis,and is reflected in the skin lesions,itching,oxidative stress and inflammatory factor levels of psoriasis patients.The comorbidity mechanism of anxiety and psoriasis may be related to oxidative stress and up regulation of inflammatory factors.

Effectiveness and safety of traditional Chinese medicine for diabetic retinopathy:A systematic review and network meta-analysis of randomized clinical trials

BACKGROUND Diabetic retinopathy(DR)is currently recognized as one of the most serious diabetic microangiopathies and a major cause of adult blindness.Commonly used clinical approaches include etiological control,microvascular improvement,and surgical intervention,but they are ineffective and have many side effects.Oral Chinese medicine(OCM)has been used for thousands of years to treat DR and is still widely used today,but it is unclear which OCM is more effective for DR.AIM To estimate relative effectiveness and safety profiles for different classes of OCMs for DR,and provide rankings of the available OCMs.METHODS The search time frame was from the creation of the database to January 2023.RevMan 5.3 and Stata 14.0 software were used to perform the systematic review and Network meta-analyses(NMA).RESULTS A total of 107 studies and 9710 patients were included,including 4767 cases in the test group and 4973 cases in the control group.Based on previous studies and clinical reports,and combined with the recommendations of Chinese guidelines for the prevention and treatment of DR,9 OCMs were finally included in this study,namely Compound Xueshuantong Capsules,Qiming Granules,Compound Danshen Dripping Pills,Hexue Mingmu Tablets(HXMM),Qiju Dihuang Pills(QJDH),Shuangdan Mingmu Capsules(SDMM),Danggui Buxue Decoction(DGBX),Xuefu Zhuyu Decoction and Buyang Huanwu Decoction.When these nine OCMs were analyzed in combination with conventional western medicine treatment(CT)compared with CT alone,the NMA results showed that HXMM+CT has better intervention effect on the overall efficacy of DR patients,HXMM+CT has better effect on improving patients'visual acuity,SDMM+CT has better effect on inhibiting vascular endothelial growth factor,DGBX+CT has better effect on reducing fundus hemorrhage area,HXMM+CT has better effect on reducing fasting blood glucose,and QJDH+CT has better effect on reducing glycated hemoglobin.When there are not enough clinical indicators for reference,SDMM+CT or HXMM+CT treatments can be chosen because they are effective for more indicators and demonstrate multidimensional efficacy.CONCLUSION This study provides evidence that combining OCMs with CT leads to better outcomes in all aspects of DR compared to using CT alone.Based on the findings,we highly recommend the use of SDMM or HXMM for the treatment of DR.These two OCMs have demonstrated outstanding efficacy across multiple indicators.

Current status of outcome reporting in randomized controlled trials of traditional Chinese medicine for mammary gland hyperplasia: A systematic review

Objective:To assess outcome indicators in clinical trials and provide a reference for establishing a core outcome set to treat hyperplasia of mammary gland(HMG)with traditional Chinese medicine(TCM).Methods:Eight online databases were searched from their inception to December 31,2022,to assess outcomes reported in randomized controlled trials(RCTs)of HMG treated with TCM.The quality of the included studies was assessed according to the Cochrane Risk of Bias Assessment Tool.All outcomes were extracted,classified,and described.Results:A total of 8249 articles were initially retrieved.Of these,70 articles were eligible and involved 10618 participants with HMG.A total of 17 outcome indicators with a frequency of 271 times were involved and were collected according to six outcome domains.Conclusions:The core outcomes of RCTs of HMG treated with TCM are large and divergent.There are problems in evaluation standards,primary and secondary outcomes,TCM characteristic indicators,long-term prognosis,and standardization of reporting.It is recommended to strengthen the trial design and actively construct the core outcome sets with TCM characteristics for HMG.

Effectiveness and safety of seven oral Chinese patent medicines as adjuvant therapy for cancer-related anemia: A systematic review and network meta-analysis of randomized controlled trials

Objective:To evaluate the effectiveness and safety of seven oral Chinese patent medicines(CPMs)as adjuvant therapy for cancer-related anemia(CRA)by network meta-analysis(NMA).Methods:A literature search to obtain randomized controlled trials(RCTs)of seven oral CPMs in the adjuvant treatment of CRA was conducted in multiple databases from the inception to April 2022.The RevMan5.3 and R 4.1.1 software were used for NMA.Results:We ultimately included 29 RCTs with 2140 patients.Traditional meta-analysis showed that Fufang E'jiao syrup(FFEJS),Shengxuebao mixture(SXBM),Shengxuening tablets(SXNT),Jianpi Shengxue granules(JPSXG),and Yixuesheng capsule(YXSC)combined with basic Western treatment(BWT)could improve the hemoglobin(HGB)level.JPSXG combined with BWT could improve the red blood cell(RBC).FFEJS combined with BWT improved the Karnofsky performance status(KPS).NMA showed that FFEJS,JPSXG,SXBM,and SXNT plus BWT improved HGB better than Shengxue tablets(SXT)plus BWT,with top three ranking results being JPSXG plus BWT>SXNT plus BWT>FFEJS plus BWT.FFEJS plus BWT,JPSXG plus BWT,SXBM plus BWT,SXNT plus BWT,and SXT plus BWT improved RBC better than BWT,with top three ranking results being SXNT plus BWT>JPSXG plus BWT>FFEJS plus BWT.In terms of the KPS score,compared with SXT plus BWT,FFEJS,JPSXG,SXBM,SXNT,and Yizhong Shengxue capsule(YZSXC)plus BWT had higher KPS,with top three ranking results being SXBM plus BWT>JPSXG plus BWT>FFEJS plus BWT.Conclusions:Our NMA demonstrated that seven oral CPMs used as adjuvant treatment of CRA had a definite clinical effect.JPSXG not only increases the levels of HGB and RBC to enhance the clinical effect but also improves patients'quality of life.More accurate conclusions need to be verified by more high-quality RCTs.

Assessment of gastric cancer prognosis,immune infiltration based on cuproptosis-related LncRNAs and prediction of traditional Chinese medicine

Objective:Constructing a prognostic model for gastric cancer(GC)based on cuproptosisrelated LncRNAs(CRLs)and predict the traditional Chinese medicine that regulate cuproptosis-related genes(CRGs).Methods:Clinical data and RNA-seq of 443 GC cases were obtained from The Cancer Genome Atlas(TCGA)database,and CRLs were screened by Pearson analysis,Cox regression,and least absolute shrinkage and selection operator(LASSO)regression to construct a risk model to predict GC prognosis,and the nomogram was constructed by combining risk scores and clinical characteristics.The accuracy of the model was validated by the receiver operating characteristic curve,Kaplan-Meier curves and C-index.To assess the correlation of risk scores with immune infiltration,immune checkpoint gene expression and chemotherapy/targeted agents.The Coremine Medical database was applied to predict potential traditional Chinese medicine that regulate CRGs.Results:Risk models for GC were constructed based on the risk scores of seven CRLs(AP001107.9,VCAN-AS1,AC016394.2,LINC02675,AC100814.1,HAGLR,and LINC01094).The AUC of the risk model predicting 1-,3-,and 5-year survival in GC patients was 0.720,0.682,and 0.711,and its prognostic value was better than age,Grade classification,and TNM stage.The AUC of the risk model combining age and TNM stage to predict 1-year survival in GC patients was 0.793.The risk score correlated with the degree of enrichment of immune cells such as tumorinfiltrating lymphocytes and regulatory T cells and the expression of 22 immune checkpoint genes such as LAG3,ICOS,CD28,NRP1 and the sensitivity of 13 chemotherapeutic/targeted agents.There are 58 traditional Chinese medicine with potential regulatory effects on CRGs,mainly for clearing heat and detoxing,promoting blood circulation and relieving pain,which are mainly attributed to the liver,spleen and lung meridians.Spirulina and osthole have potential regulatory effects on FDX1,a key gene in the death mechanism of cuproptosis.Conclusions:A risk signature constructed based on seven CRLs could assess the prognosis and immunity of GC,and Spirulina and Serpentine may have important regulatory efficacy on the mechanism of copper cuproptosis.

Effect of Huoxue Yiqi recipe on proliferation,migration and tube formation of miR-484 overexpressed umbilical vein endothelial cells

Objective:To explore the possible mechanism of Huoxue Yiqi recipe promoting angiogenesis by targeting VEGF with miR-484.Methods:The model of miR-484 overexpressed in HUVEC was prepared and intervened with Huoxue Yiqi Recipe Freeze-dried powder.The effects of Huoxue Yiqi Recipe on proliferation,migration and tubular forming ability of HUVEC were separatly detected by CCK-8 method,cell scratch test and Matrigel three-dimensional forming test in vitro.The effect of Huoxue Yiqi Recipe on VEGFA mRNA expression was detected by real-time fluorescence quantitative PCR.Results:Compared with the control group,the proliferation and migration area of cells in miR-484 overexpression model group decreased,the length,number of branches and nodes involved in tube formation decreased,the tube formation ability decreased significantly,and the expression level of VEGFA mRNA decreased,with statistical significance.Compared with the model group,the cell proliferation ability,migration area,length,number of branches and nodes involved in tube formation,tube formation ability and expression level of VEGFA mRNA in the Huoxue Yiqi Prescription group were up-regulated,and the difference was statistically significant(P<0.05).Conclusion:MiR-484 inhibits the expression of VEGFA and the proliferation,migration and formation of HUVEC,and Huoxue Yiqi recipe has a certain negative regulation effect on this process,which may be a new target of Huoxue Yiqi recipe to promote angiogenesis.

Mechanism of Qiliqiangxin capsule on the regulation of IP3Rs/GRP75/VDAC1 gene in myocardial infarction rat heart

Objective:To investigate the regulatory effect of Qiliqiangxin Capsule on mitochondrial Ca^(2+)related genes in rats with myocardial infarction(MI).Methods:The rat model of MI was established by ligation of the left anterior descending coronary artery.After operation,the rats were randomly assigned to the model group,the Qiliqiangxin group and the captopril group;a sham-operated group was also available as a control.After four weeks of treatment,the extent of infarction in rats was observed by gross cardiac structure and the morphological changes of myocardial histopathology were observed by HE staining.Detection of mitochondrial Ca^(2+)transport-related genes such as inositol-1,4,5-trisphosphate receptor 2(IP3R2),glucose regulated protein 75(GRP75),voltage-dependent anion channel 1(VDAC1),and mitofusion 2(Mfn2)and mitochondrial apoptosis-related genes such as B-cell lymphoma-2(Bcl-2)and Bcl-2 related X protein(Bax)mRNA expression changes was measured by RT-PCR in the infarct margins of the heart;Western blot was used to detect changes in Bcl-2,Bax protein expression in myocardial tissue.The rate of apoptosis in cardiac myocardial tissue was detected by TUNEL staining.Results:Compared with the sham group,the anterior left ventricular wall of the model group showed a large area of infarction,and the structure of myocardial tissue was disordered.The mRNA expression level of mitochondrial Ca^(2+)transport-related genes such as IP3R2,GRP75,VDAC1,and Mfn2 were significantly increased(P<0.05,P<0.01);The mRNA and protein expression of Bcl-2,a molecule related to mitochondrial apoptosis,were significantly decreased(P<0.01),while the mRNA and protein expression of Bax were significantly increased(P<0.01);and apoptosis rate was significantly increased(P<0.01).Compared with the model group,the infarct size of cardiac gross specimens in the Qiliqiangxin group and the captopril group was reduced and myocardial fibers were relatively well ordered;The mRNA expression of mitochondrial Ca^(2+)transport-related genes such as IP3R2,GRP75,VDAC1,and Mfn2 were significantly reduced(P<0.01);the mRNA and protein expression of Bcl-2,a molecule related to mitochondrial apoptosis,were increased(P<0.05,P<0.01),and the mRNA and protein expression of Bax were significantly decreased(P<0.05,P<0.01).and apoptosis rate was significantly decreased(P<0.01).Conclusion:Qiliqiangxin Capsule can improve the morphological structure of the heart of rats with MI,and its mechanism is related to regulation of the gene expression of mitochondrial Ca^(2+)transport complex IP3R2/GRP75/VDAC1,thereby inhibiting apoptosis.

Optimizing diabetic kidney disease animal models:Insights from a meta-analytic approach

Diabetic kidney disease(DKD)is a prevalent complication of diabetes,often leading to end-stage renal disease.Animal models have been widely used to study the pathogenesis of DKD and evaluate potential therapies.However,current animal models often fail to fully capture the pathological characteristics of renal injury observed in clinical patients with DKD.Additionally,modeling DKD is often a time-consuming,costly,and labor-intensive process.The current review aims to summarize modeling strategies in the establishment of DKD animal models by utilizing meta-analysis related methods and to aid in the optimization of these models for future research.A total of 1215 articles were retrieved with the keywords of“diabetic kidney disease”and“animal experiment”in the past 10 years.Following screening,84 articles were selected for inclusion in the meta-analysis.Review manager 5.4.1 was employed to analyze the changes in blood glucose,glycosylated hemoglobin,total cholesterol,triglyceride,serum creatinine,blood urea nitrogen,and urinary albumin excretion rate in each model.Renal lesions shown in different models that were not suitable to be included in the metaanalysis were also extensively discussed.The above analysis suggested that combining various stimuli or introducing additional renal injuries to current models would be a promising avenue to overcome existing challenges and limitations.In conclusion,our review article provides an in-depth analysis of the limitations in current DKD animal models and proposes strategies for improving the accuracy and reliability of these models that will inspire future research efforts in the DKD research field.

Isoliquiritigenin regulated ox-LDL through activating the PPAR-γ signaling pathway to stabilize atherosclerosis plaques

Objective:To explore the molecular mechanisms of isoliquiritigenin in stabilizing atherosclerotic plaques by activating PPAR-γsignal pathway to regulate ox-LDL metabolism.Methods:The ApoE-/-mice AS carotid plaque model was prepared by using high fat diet and right perivascular carotid collar placement(PCCP).ApoE-/-mice were randomly divided into the model group and the isoliquiritigenin group after PCCP.C57BL/6J mice were used for the control group.High fat diet continued feeding for 8 weeks after PCCP to establish the AS model.Automatic biochemical analyzer was used to test levels of total cholesterol(TC),triacylglyceride(TG),low-density lipoprotein cholesterol(LDL-C)and high-density lipoprotein cholesterol(HDL-C).ELISA was used to measure oxidized low-density lipoprotein(ox-LDL)in serum.Hematoxylin-eosin(HE)staining was used to observe the pathological pattern of the carotid artery,and then calculated the carotid parameters.Oil red O staining was used for lipid determination,Masson staining was used to determine collagen content,MOMA-2 andα-SMA immunohistochemical staining were used to determine macrophages and smooth muscle cells,and to calculate the vulnerability index.Western blot was used to detected the expression of PPAR-γ,LXR-α,FABP-4,MMP-2 and MMP-9 in mice arteries.Results:Compared with the normal group,TC、TG、LDL-C、HDL-C and ox-LDL were increased in the model group.Compared with the model group,TC、TG、LDL-C and ox-LDL were reduced,and there was no significant change in HDL-C of the isoliquiritigenin group.Compared with the normal group,intima thickness(IT),intima/media thickness(IT/MT),plaque area(PA),and plaque area/lumen area(PA/LA)of carotid arteries were increased,the content of lipid and MOMA-2 in plaques was increased,collagen andα-SMA content decreased,and the vulnerability index was higher in the model group.The expression of PPAR-γand LXR-αwere reduced and the expression of FABP-4,MMP-2 and MMP-9 were increased in the model group.Compared with the model group,carotid IT,IT/MT,PA,and PA/LA were reduced,the content of lipid and MOMA-2 in plaques was decreased,collagen andα-SMA content were increased,and the vulnerability index was decreased in the isoliquiritigenin group.PPAR-γand LXR-αexpression were increased,FABP-4,MMP-2 and MMP-9 expression were decreased significantly in the isoliquiritigenin group.Conclusion:Isoliquiritigenin can exert anti-AS effects by activating PPAR-γ,up-regulating LXR-α,reducing FABP-4 expression,reducing ox-LDL,reducing the protein expression of MMP-2 and MMP-9,decreasing plaque vulnerability index,and increasing plaque stability.

Characteristic metabolic and microbial profiles in acute ischemic stroke patients with phlegm-heat pattern

Objective:To explore the characteristics of plasma metabolites,feces gut microbiota and the crosstalk between gut microbiota and host metabolism in patients with acute ischemic stroke and phlegm-heat pattern(AIS-PHP).Methods:The metabolic and microbiome profiles of 20 AIS-PHP patients and 20 healthy controls(HCs)were analyzed using liquid chromatography-tandem mass spectrometry(LC-MS/MS)-based metabolomics and 16s rDNA sequencing,respectively.The covariation between LC-MS/MS-based metabolite data and 16s rDNA sequence data was presented.Results:Distinct alterations in the plasma metabolic phenotype of AIS-PHP patients were found,in which 16 metabolites differed significantly between the AIS-PHP patients and the HCs.These metabolites represented 17 different metabolic pathways,including amino acid metabolism,lipid metabolism,and nucleotide metabolism.Additionally,significant alterations of gut microbiota composition and taxon were revealed at the phylum level between the AIS-PHP patients and the HCs.In AIS-PHP,Bacteroidetes,Firmicutes,and Proteobacteria dominated.Moreover,some microbes that differed between the 2 groups manifested a sole association with certain metabolites,such as the connection between Bacteroides and inosine and between Lachnospiraceae_unclassified and hypoxanthine.Conclusion:The present study preliminarily investigated the metabolomic and gut microbiome characteristics of AIS-PHP patient indicators.The link between metabolic and microbial dysbiosis in AIS-PHP sheds new light on the function of gut microbiota and associated metabolomics in the pathogenesis of the disease.

Scientific connotation of “treating different diseases with the same method” from the perspective of metabolic-immune dysregulation in inflammation-mediated carcinogenesis of digestive organs

Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system.In the chronic inflammation microenvironment,the metabolic activity of tissue cells undergoes extensive changes,which interfere with the normal function of immune cells.Dysregulation of cell metabolism and immune function has been identified as a key factor contributing to inflammation-mediated carcinogenesis within the major digestive organs,such as the stomach,liver,and colorectum.This metabolic-immune imbalance also corresponds to traditional Chinese medicine(TCM)theories of“yin-yang disharmony”and“disharmony between Ying-nutrients and Wei-defense.”The metabolic-immune imbalance has also been regarded as the key factor supporting“treatment of different diseases with the same method”,in which the same approach is adopted in the treatment of different conditions.In the TCM treatment process,it is necessary to first identify TCM patterns and then apply the corresponding TCM to correct the dysregulated metabolic and immune function,thereby blocking the progression from inflammation to malignancy.Our study findings deepen the TCM understanding of metabolic-immune dysregulation and the relationship between metabolic-immune dysregulation,pattern identification,and treatment method.They also provide new insights for the treatment of inflammation-mediated carcinogenesis in major digestive organs and help us further explore the scientific connotation of the TCM strategy of“treating different diseases with the same method”.

Comparison of external treatment of Acupuncture and moxibustion and intervention of Chinese and Western Medicine on postoperative pain of hemorrhoids:A systematic review and meta-analysis

Background To evaluate the clinical efficacy and safety of acupuncture and moxibustion in the treatment of postoperative pain of hemorrhoids compared with traditional Chinese medicine and western medicine.Methods CNKI,PubMed,Cochrane Library,Science Direct,Wan Fang,VIP,CBM,WOS,Bailian Yun Library and other databases were systematically retrieved from January 1,2017 to October 31,2022 for clinical randomized controlled trials of acupuncture versus traditional Chinese medicine and Western medicine for postoperative pain in hemorrhoids.The two evaluators independently retrieved,sifted through literature and extracted data for inclusion in a randomized controlled trial of acupuncture for the treatment of hemorrhoid pain that matched the study.Literature quality assessment was performed using RevMan5.4 for meta-analysis.Results A total of 540 related literature articles were retrieved,of which 139 were from CNKI,104 from Wan Fang,26 from VIP,7 from PubMed,9 from Cochrane Library,35 from WOS,173 from CMB,1 from Science Direct and 46 from the Bailian Yun Library,Screening resulted in inclusion of 10 RCTs including 870 patients.Meta analysis showed no statistically significant difference between the degree of pain in 2 hours[MD=-0.01,95%CI(-0.23,0.24),P=0.95].And it showed that the total effective rate of the two groups was[RR=1.14,95%CI(1.06,1.24),P=0.001],intervention for 2 days pain degree was[MD=0.41,95%CI(0.13,0.69),P=0.004],the length of hospital stay was[SMD=1.10,95%CI(0.73,1.48),P<0.00001],the incidence of adverse reaction was[RR=0.15,95%CI(0.03,0.79),P=0.03],the difference was statistically significant(P<0.05).Conclusion Drug treatment is effective quickly,analgesia effect is better than acupuncture in early treatment,but the effect is not lasting.Acupuncture treatment is slow to start but the effects of acupuncture will gradually become apparent at a later stage.However,due to the poor quality of collection,multicenter,large sample size and double-blind randomized controlled trials are still needed.