Total flavonoids of Astragalus membranaceus protect against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice by inhibiting ferroptosis through SLC7A11/GPX-4 signaling pathway

Parkinson’s disease(PD)is a common neurodegenerative disorder with no cure.Astragalus membranaceus is used in Chinese culture as a food supplement to boost immunity.The present study aimed to explore the neuroprotective effects of total flavonoids extracted from A.membranaceus(TFA)and their protective mechanisms.TFA offered neuroprotection against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)in the mouse model of Parkinsonism,by improving behavior performance in the gait analysis and pole test,and inhibiting the decline of tyrosine hydroxylase(TH)positive neurons and TH protein expression in substantia nigra of mice.TFA also prevented 1-methyl-4-phenylpyridinium(MPP+)induced neurotoxicity in SHSY5Y cells,by increasing GSH and GSH/GSSG ratio,and reducing reactive oxygen species.In addition,the neuroprotective effects of TFA were associated with its ability to restore MPTP/MPP+induced downregulation of SLC7A11 and glutathione peroxidase 4(GPX-4).In conclusion,we demonstrated that TFA exerted significant neuroprotection against MPTP/MPP+induced neurodegeneration by inhibiting ferroptosis through the regulation of SLC7A11/GPX-4 axis,suggesting the use of TFA as a possible food supplement in the prevention of PD.

Granulomatous mastitis in a 50-year-old male:A case report and review of literature

BACKGROUND Granulomatous mastitis(GM)an inflammatory disease of the breast that usually affects women of childbearing age,occurs very rarely in males.CASE SUMMARY We present a case study of a 50-year-old male patient with GM.The patient developed a breast lump following the cleaning of a previously embedded dirtfilled nipple.While an initial improvement was noted with antibiotic therapy,a recurrence occurred a year later,showing resistance to the previously effective antibiotics.Subsequently,the lesion was excised.The histopathological examination confirmed the diagnosis of GM.CONCLUSION GM should be considered a possible diagnosis of male breast masses.

Colonoscopy-assisted removal of an impaction foreign body at the rectosigmoid junction: A case report

BACKGROUND When an anorectal foreign body is found,its composition and shape should be evaluated,and a timely and effective treatment plan should be developed based on the patient's symptoms to avoid serious complications such as intestinal perforation caused by displacement of the foreign body.CASE SUMMARY A 54-year-old male was admitted to our outpatient clinic on June 3,2023,due to a rectal foreign body that had been embedded for more than 24 h.The patient reported using a glass electrode tube to assist in the recovery of prolapsed hemorrhoids,however,the electrode tube was inadvertently inserted into the anus and could not be removed by the patient.During hospitalization,the patient underwent surgery,and the foreign body was dragged into the rectum with the aid of colonoscopy.The anus was dilated with a comb-type pulling hook and an anal fistula pulling hook to widen the anus and remove the foreign body,and the local anal symptoms were then relieved with topical drugs.The patient was allowed to eat and drink,and an entire abdominal Computed tomography(CT)and colonoscopy were reviewed 3 d after surgery.CT revealed no foreign body residue and colonoscopy showed no metal or other residues in the colon and rectum,and no apparent intestinal tract damage.CONCLUSION The timeliness and rationality of the surgical and therapeutic options for this patient were based on a literature review of the clinical signs and conceivable conditions in such cases.The type,material and the potential risks of rectal foreign bodies should be considered.

Heyingwuzi formulation alleviates diabetic retinopathy by promoting mitophagy via the HIF-1α/BNIP3/NIX axis

BACKGROUND Diabetic retinopathy(DR)is the primary cause of visual problems in patients with diabetes.The Heyingwuzi formulation(HYWZF)is effective against DR.AIM To determine the HYWZF prevention mechanisms,especially those underlying mitophagy.METHODS Human retinal capillary endothelial cells(HRCECs)were treated with high glucose(hg),HYWZF serum,PX-478,or Mdivi-1 in vitro.Then,cell counting kit-8,transwell,and tube formation assays were used to evaluate HRCEC proliferation,invasion,and tube formation,respectively.Transmission electron microscopy was used to assess mitochondrial morphology,and Western blotting was used to determine the protein levels.Flow cytometry was used to assess cell apoptosis,reactive oxygen species(ROS)production,and mitochondrial membrane potential.Moreover,C57BL/6 mice were established in vivo using streptozotocin and treated with HYWZF for four weeks.Blood glucose levels and body weight were monitored continuously.Changes in retinal characteristics were evaluated using hematoxylin and eosin,tar violet,and periodic acid-Schiff staining.Protein levels in retinal tissues were determined via Western blotting,immunohistochemistry,and immunostaining.RESULTS HYWZF inhibited excessive ROS production,apoptosis,tube formation,and invasion in hg-induced HRCECs via mitochondrial autophagy in vitro.It increased the mRNA expression levels of BCL2-interacting protein 3(BNIP3),FUN14 domain-containing 1,BNIP3-like(BNIP3L,also known as NIX),PARKIN,PTEN-induced kinase 1,and hypoxia-inducible factor(HIF)-1α.Moreover,it downregulated the protein levels of vascular endothelial cell growth factor and increased the light chain 3-II/I ratio.However,PX-478 and Mdivi-1 reversed these effects.Additionally,PX-478 and Mdivi-1 rescued the effects of HYWZF by decreasing oxidative stress and apoptosis and increasing mitophagy.HYWZF intervention improved the symptoms of diabetes,tissue damage,number of acellular capillaries,and oxidative stress in vivo.Furthermore,in vivo experiments confirmed the results of in vitro experiments.CONCLUSION HYWZF alleviated DR and associated damage by promoting mitophagy via the HIF-1α/BNIP3/NIX axis.

Differences and Correlations of Morphological and Hemodynamic Parameters between Anterior Circulation Bifurcation and Side-wall Aneurysms

Objective:The objective of this research was to explore the difference and correlation of the morphological and hemodynamic features between sidewall and bifurcation aneurysms in anterior circulation arteries,utilizing computational fluid dynamics as a tool for analysis.Methods:In line with the designated inclusion criteria,this study covered 160 aneurysms identified in 131 patients who received treatment at Union Hospital of Tongji Medical College,Huazhong University of Science and Technology,China,from January 2021 to September 2022.Utilizing follow-up digital subtraction angiography(DSA)data,these cases were classified into two distinct groups:the sidewall aneurysm group and the bifurcation aneurysm group.Morphological and hemodynamic parameters in the immediate preoperative period were meticulously calculated and examined in both groups using a three-dimensional DSA reconstruction model.Results:No significant differences were found in the morphological or hemodynamic parameters of bifurcation aneurysms at varied locations within the anterior circulation.However,pronounced differences were identified between sidewall and bifurcation aneurysms in terms of morphological parameters such as the diameter of the parent vessel(Dvessel),inflow angle(θF),and size ratio(SR),as well as the hemodynamic parameter of inflow concentration index(ICI)(P<0.001).Notably,only the SR exhibited a significant correlation with multiple hemodynamic parameters(P<0.001),while the ICI was closely related to several morphological parameters(R>0.5,P<0.001).Conclusions:The significant differences in certain morphological and hemodynamic parameters between sidewall and bifurcation aneurysms emphasize the importance to contemplate variances in threshold values for these parameters when evaluating the risk of rupture in anterior circulation aneurysms.Whether it is a bifurcation or sidewall aneurysm,these disparities should be considered.The morphological parameter SR has the potential to be a valuable clinical tool for promptly distinguishing the distinct rupture risks associated with sidewall and bifurcation aneurysms.

Global epidemiology of mental disorder in atrial fibrillation between 1998-2021:A systematic review and meta-analysis

BACKGROUND As the burden of mental disorders among patients with atrial fibrillation(AF)increases,researchers are beginning to pay close attention to the risk and prevalence of these comorbidities.Although studies have independently analyzed the risk of comorbidity with depression and anxiety in patients with AF,no study has systematically focused on the global epidemiology of these two mental disorders.AIM To explore the prevalence of depression and anxiety in patients with AF.METHODS Five databases were searched from their date of establishment until January 2023.Observational studies reporting the comorbidity of AF with depression and anxiety,were included in this study.Basic information,such as the first author/publication year,study year,study type,and prevalence of depression and anxiety,were extracted.STATA SE 15.1 was used to analyze the data.Subgroup,meta-regression,and sensitivity analyses were performed to estimate study heterogeneity.RESULTS After a thorough search,26 studies were identified and included in this metaanalysis.The prevalence rates of depression and anxiety in adults with AF were 24.3%and 14.5%,respectively.Among adult males with AF,the prevalence was 11.7%and 8.7%,respectively,whereas in females it was 19.8%and 10.1%,respectively.In older adults with AF,the prevalence rates of depression and anxiety were 40.3%and 33.6%,respectively.The highest regional prevalence of depression and anxiety was observed in European(30.2%)and North American(19.8%)patients with AF.CONCLUSION In this study,we found that the prevalence of depression and anxiety among patients with AF varies with sex,region,and evaluation scales,suggesting the need for psychological interventions for patients with AF in clinical practice.

Mechanisms of myeloid-derived suppressor cell-mediated immunosuppression in colorectal cancer and related therapies

Severe immunosuppression is a hallmark of colorectal cancer(CRC).Myeloid-derived suppressor cells(MDSCs),one of the most abundant components of the tumor stroma,play an important role in the invasion,metastasis,and immune escape of CRC.MDSCs create an immunosuppressive microenvironment by inhibiting the proliferation and activation of immunoreactive cells,including T and natural killer cells,as well as by inducing the proliferation of immunosuppressive cells,such as regulatory T cells and tumor-associated macrophages,which,in turn,promote the growth of cancer cells.Thus,MDSCs are key contributors to the emergence of an immunosup-pressive microenvironment in CRC and play an important role in the breakdown of antitumor immunity.In this narrative review,we explore the mechanisms through which MDSCs contribute to the immunosuppressive microenvironment,the current therapeutic approaches and technologies targeting MDSCs,and the therapeutic potential of modulating MDSCs in CRC treatment.This study provides ideas and methods to enhance survival rates in patients with CRC.

Effect of the traditional Chinese medicine fumigation combined with the meibomian gland squeezer for treatment of dry eye associated with meibomian gland dysfunction

Background:To observe the effect of traditional Chinese medicine fumigation combined with the meibomian gland squeezer for the treatment of dry eye associated with meibomian gland dysfunction(MGD).Methods:This is a randomized,controlled,non-masked,single-center study.Seventy-four cases(74 eyes)of dry eye associated with MGD were randomly divided into two groups.Thirty-seven patients were chosen as the treatment group was treated by the traditional Chinese medicine fumigation 3 times a week combined with the meibomian gland squeezer once a week for one month.The other 37 cases were sorted as the control group and only treated with the meibomian gland squeezer once a week for one month.Both groups received the primary treatment for 1 month,including Tobradex eye ointment once a day and 0.1%sodium hyaluronate eye drops 4-6 times daily.Patients were evaluated at baseline and 2-week and 1-month visits for the ocular symptom scores,international ocular surface disease index(OSDI),fluorescein tear break-up time(TBUT),corneal fluorescein staining test(CFS),Schirmer I test,meibum quality and meibum expressibility.Results:Sixty-seven patients were followed in the study,and the mean age was 57(±12.6)years.Thirty-three patients(11 males)in the treatment group and 34 patients(8 males)in the control group were followed in the study,and the mean age of the two groups was 45.36±15.02 years and 43.68±13.43 years,respectively.Before treatment,there was no significant difference between the two groups in gender,age,ocular symptom scores,OSDI,TBUT,CFS,Schirmer I test,meibum quality,and meibum expressibility(P>0.05).Compared with baseline,the 2 groups had different degrees of improvement in the ocular symptom scores,OSDI,TBUT,CFS,meibum quality,and meibum expressibility at the 2-week and 1-month visits(P<0.05),and the treatment group showed a more significant improvement in the ocular symptom scores,OSDI,TBUT,CFS,meibum quality and meibum expressibility compared with the control group(P<0.05).In addition,no serious adverse events were observed in each group.Conclusions:The traditional Chinese medicine fumigation combined with the meibomian gland squeezer may be safe,effective,and helpful for the treatment of dry eye associated with MGD.

The Role of Pharmacists in Perioperative Antibiotic Application in a Hospital of Traditional Chinese Medicine (TCM)

Objective: To determine adherence to Chinese guidelines for perioperative antibiotic use in our hospital of TCM and discuss the role of pharmacists on antibiotic management. Methods: 2844 operative cases between May 2011 and December 2011 in our hospital were investigated by pharmacists and relative data were collected, including demographic data, type of surgery, wound classification (clean and clean contaminated) and parameters of antibiotic application (antibiotic choice, route, dose, time of first dose, time of operative re-dosing and duration of prophylaxis). The rationality of antibiotic administration in these cases was respectively evaluated based on Chinese guidelines for perioperative antibiotic use. Results: After intervention of pharmacists, perioperative antibiotic application in our hospital was obviously improved from May to December of 2011: the rates of antibiotic application in operative cases and antibiotic prophylaxis in clean operation were both decreased. However, there was no significant improvement for the rate of rationality. In detail, TCM surgery was well compliant with the guidelines: the rate of antibiotic application was less than 30%, regimen of antibiotic prophylaxis and therapy was reasonable;in the breast ward, antibiotic application was improved after pharmacists’ intervention: the rate of antibiotic prophylaxis in clean operation significantly decreased from 100% to 30%;however, in the anorectal ward, some troubles were resolved while other new problems came out;in other ward such as general surgery and orthopedics, old problems still existed. Conclusions: Protocol violations were frequent to perioperative antibiotic application in our hospital due to considerable over prescription. Intervention was effective but not enough. Further educational strategies are essential for reducing costs and antibiotic resistance rates.

Chronic spinal cord compression associated with intervertebral disc degeneration in SPARC-null mice

Chronic spinal cord compression(CSCC)is induced by disc herniation and other reasons,leading to movement and sensation dysfunction,with a serious impact on quality of life.Spontaneous disc herniation rarely occurs in rodents,and therefore establishing a chronic spinal cord compression(CSCC)animal model is of crucial importance to explore the pathogenesis and treatment of CSCC.The absence of secreted protein,acidic,and rich in cysteine(SPARC)leads to spontaneous intervertebral disc degeneration in mice,which resembles human disc degeneration.In this study,we evaluated whether SPARC-null mice may serve as an animal model for CSCC.We performed rod rotation test,pain threshold test,gait analysis,and Basso Mouse Scale score.Our results showed that the motor function of SPARC-null mice was weakened,and magnetic resonance images revealed compression at different spinal cord levels,particularly in the lumbar segments.Immunofluorescence staining and western blot assay showed that the absence of SPARC induced apoptosis of neurons and oligodendrocytes,activation of microglia/macrophages with M1/M2 phenotype and astrocytes with A1/A2 phenotype;it also activated the expression of the NOD-like receptor protein 3 inflammasome and inhibited brain-derived neurotrophic factor/tyrosine kinase B signaling pathway.Notably,these findings are characteristics of CSCC.Therefore,we propose that SPARC-null mice may be an animal model for studying CSCC caused by disc herniation.

Oncogenic BRAF^(V600E) induces microglial proliferation through extracellular signal-regulated kinase and neuronal death through c-Jun N-terminal kinase

Activating V600E in v-Raf murine sarcoma viral oncogene homolog B(BRAF)is a common driver mutation in cancers of multiple tissue origins,including melanoma and glioma.BRAF^(V600E) has also been implicated in neurodegeneration.The present study aims to characterize BRAF^(V600E) during cell death and proliferation of three major cell types of the central nervous system:neurons,astrocytes,and microglia.Multiple primary cultures(primary cortical mixed culture)and cell lines of glial cells(BV2)and neurons(SH-SY5Y)were employed.BRAF^(V600E) and BRAF^(WT) expression was mediated by lentivirus or retrovirus.Blockage of downstream effectors(extracellular signal-regulated kinase 1/2 and JNK1/2)were achieved by siRNA.In astrocytes and microglia,BRAF^(V600E) induces cell proliferation,and the proliferative effect in microglia is mediated by activated extracellular signal-regulated kinase,but not c-Jun N-terminal kinase.Conditioned medium from BRAF^(V600E)-expressing microglia induced neuronal death.In neuronal cells,BRAF^(V600E) directly induces neuronal death,through c-Jun N-terminal kinase but not extracellular signal-regulated kinase.We further show that BRAF-related genes are enriched in pathways in patients with Parkinson’s disease.Our study identifies distinct consequences mediated by distinct downstream effectors in dividing glial cells and in neurons following the same BRAF mutational activation and a causal link between BRAF-activated microglia and neuronal cell death that does not require physical proximity.It provides insight into a possibly important role of BRAF in neurodegeneration as a result of either dysregulated BRAF in neurons or its impact on glial cells.

Microneedle-based interstitial fluid extraction for drug analysis:Advances,challenges,and prospects

Similar to blood,interstitial fluid(ISF)contains exogenous drugs and biomarkers and may therefore substitute blood in drug analysis.However,current ISF extraction techniques require bulky instruments and are both time-consuming and complicated,which has inspired the development of viable alternatives such as those relying on skin or tissue puncturing with microneedles.Currently,microneedles are widely employed for transdermal drug delivery and have been successfully used for ISF extraction by different mechanisms to facilitate subsequent analysis.The integration of microneedles with sensors enables in situ ISF analysis and specific compound monitoring,while the integration of monitoring and delivery functions in wearable devices allows real-time dose modification.Herein,we review the progress in drug analysis based on microneedle-assisted ISF extraction and discuss the related future opportunities and challenges.

Promising way to address massive intragastric clotting in patients with acute upper gastrointestinal bleeding:A case report

BACKGROUND Massive intragastric clotting(MIC) makes endoscopic therapy difficult in patients with acute upper gastrointestinal bleeding. Literature data on how to address this problem are limited. Here, we report on a case of massive stomach bleeding with MIC that was successfully treated endoscopically using an overtube of singleballoon enteroscopy.CASE SUMMARY A 62-year-old gentleman with metastatic lung cancer was admitted to the intensive care unit due to tarry stools and hematemesis of 1500 mL of blood during hospitalization. Emergent esophagogastroduodenoscopy revealed massive blood clots and fresh blood in the stomach with evidence of active bleeding.Bleeding sites could not be observed even by changing the patient’s position and aggressive endoscope suction. The MIC was successfully removed using an overtube connected with a suction pipe, which was inserted into the stomach with an overtube of a single-balloon enteroscope. An ultrathin gastroscope was also introduced through the nose into the stomach to guide the suction. A massive blood clot was successfully removed, and an ulcer with oozing bleeding at the inferior lesser curvature of the upper gastric body was revealed, facilitating endoscopic hemostatic therapy.CONCLUSION This technique appears to be a previously unreported method to suction MIC out of the stomach in patients with acute upper gastrointestinal bleeding. This technique could be considered when other methods are not available or if they fail to remove massive blood clots in the stomach.

Danggui Niantong decoction ameliorates joint inflammation and cardiopulmonary injury in TNF-Tg mice

Objective:Rheumatoid arthritis(RA)is a common autoimmune disease characterized by multiple joint lesions and systemic complications.Danggui Niantong decoction(DGNTT)has been clinically used for RA treatment;however,its beneficial effect on cardiopulmonary complications has not been reported.Methods:Female tumor necrosis factor-transgenic(TNF-Tg)mice were used to evaluate the therapeutic effects of DGNTT on arthritis and cardiopulmonary complications.Methotrexate(MTX)served as a positive control.Histopathological assessment of the joint sections was performed using hematoxylin and eosin(HE),Alcian Blue/Orange G,and tartrate-resistant acid phosphatase staining.Bone mass was assessed by micro-computed tomography,inflammatory infiltrates in the heart and lungs were evaluated by HE staining,cardiopulmonary fibrotic injury was identified by Masson’s trichrome staining,and hypertrophy of mouse cardiomyocytes was measured by wheat germ agglutinin(WGA)staining.Results:DGNTT mitigated the inflammation of the ankle joint synovium,decreased the number of osteoclasts,and increased the area of cartilage and bone mass in TNF-Tg mice.In addition,DGNTT decreased the infiltration of inflammatory cells into the lung and heart tissues,accompanied by a reduction in cardiopulmonary fibrosis and myocardial cell hypertrophy in TNF-Tg mice.As a positive control drug,MTX attenuated the pathological changes in joints,but had no beneficial effect on cardiopulmonary inflammation and fibrosis in TNF-Tg mice.Conclusions:DGNTT improved joint lesions and alleviated cardiopulmonary complications in TNF-Tg mice.

Rare rectal gastrointestinal stromal tumor case:A case report and review of the literature

BACKGROUND Gastrointestinal stromal tumors(GISTs)are rare tumors of the gastrointestinal tract accounting for less than 1%of all gut tumors.GISTs occurring in the rectum are extremely rare,and these usually present at an advanced stage compared with other sites.CASE SUMMARY A 60-year-old male who presented with features of sensations of rectal tenesmus was referred to our department with a mass in the lower rectum that was detected during a routine checkup.Colonoscopy,transrectal ultrasound,perianal magnetic resonance imaging and ultrasonic contrast were used to diagnose the rectum GIST,and then the patient underwent complete transanal resection using the ultrasonic scalpel.The patient was discharged ten days after the operation and was defined as low risk.Therefore,he had no need to receive subsequent adjuvant therapies,and he had not suffered any anal dysfunction or had any evidence of recurrence at follow up.CONCLUSION Surgical resection with histologically negative margins is the standard curative treatment for rectal GISTs.Appropriate surgical techniques based on the location,size,and resectability of the tumor should attract great attention from clinicians.

Clinicopathological features and expression of regulatory mechanism of the Wnt signaling pathway in colorectal sessile serrated adenomas/polyps with different syndrome types

BACKGROUND Colorectal cancer(CRC)is the third most common cancer worldwide,with the fourth highest mortality among all cancers.Reportedly,in addition to adenomas,serrated polyps,which account for 15%-30%of CRCs,can also develop into CRCs through the serrated pathway.Sessile serrated adenomas/polyps(SSAs/Ps),a type of serrated polyps,are easily misdiagnosed during endoscopy.AIM To observe the difference in the Wnt signaling pathway expression in SSAs/Ps patients with different syndrome types.METHODS From January 2021 to December 2021,patients with SSAs/Ps were recruited from the Endoscopy Room of Shanghai Traditional Chinese Medicine-Integrated Hospital,affiliated with Shanghai University of Traditional Chinese Medicine.Thirty cases each of large intestine damp-heat(Da-Chang-Shi-Re,DCSR)syndrome and spleen-stomach weakness(Pi-Wei-Xu-Ruo)syndrome were reported.Baseline comparison of the general data,typical tongue coating,colonoscopy findings,and hematoxylin and eosin findings was performed in each group.The expression of the Wnt pathway-related proteins,namelyβ-catenin,adenomatous polyposis coli,and mutated in colorectal cancer,were analyzed using immunohistochemistry.RESULTS Significant differences were observed with respect to the SSAs/Ps size between the two groups of patients with different syndrome types(P=0.001).The other aspects did not differ between the two groups.The Wnt signaling pathway was activated in patients with SSAs/Ps belonging to both groups,which was manifested asβ-catenin protein translocation into the nucleus.However,SSAs/Ps patients with DCSR syndrome had more nucleation,higherβ-catenin expression,and negative regulatory factor(adenomatous polyposis coli and mutated in colorectal cancer)expression(P<0.0001)than SSA/P patients with Pi-Wei-Xu-Ruo syndrome.In addition,the SSA/P size was linearly correlated with the related protein expression.CONCLUSION Patients with DCSR syndrome had a more obvious Wnt signaling pathway activation and a higher risk of carcinogenesis.A high-quality colonoscopic diagnosis was essential.The thorough assessment of clinical diseases can be improved by combining the diseases of Western medicine with the syndromes of traditional Chinese medicine.

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.

Bibliometric analysis and visual atlas of mercury-containing Chinese medicine:Hongfen(hydrargyrum oxydatum crudum)

Objectives In order to provide theoretical support for clinical standardization and promotion of the use of Hongfen(hydrargyrum oxydatum crudum),a mercury-containing Chinese medicine,as well as to make it easier to apply traditional Chinese topical preparations in a more contemporary manner.Methods We screened the topical research literature on Hongfen.Firstly,we analyzed the current research status of Hongfen statistically in terms of disciplinary distribution,research institutions,funding,publication volume,research types,and research focus of the literature;secondly,we analyzed the research status of Hongfen by MeSH term analysis,abstract and combined with the herbal literature,the indications,usage,dosage,and adverse effects of Hongfen were statistically analyzed,and keyword co-occurrence analysis and data visualization were performed using python+pyecharts.Results Early studies on Hongfen were mainly on the evaluation of the formulation process,while the current studies are mainly focused on clinical effectiveness and safety,with a considerable part of the studies also focused on drug toxicology,metabolism of mercury components target organ toxicity studies,while the basic studies on its mechanism of action are less.The clinical application is mainly focused on chronic ulcerated sores,refractory sinus fistula,and other surgical sore diseases,the use of which is mostly in the form of compounding and adding excipients,the use of which requires consideration of the accumulation of drug toxicity and attention to drug dosage and duration of use in order to reduce the occurrence of clinical side effects.Conclusion Hongfen is a type of mineral medicine that is extremely toxic but has a known curative effect.Its clinical use is low-risk,and its advantages greatly outweigh its drawbacks.Molecular biology technology should be actively carried out to analyze the pharmacological mechanism of Hongfen,which will play a positive role in the transmission and promotion of traditional Chinese medicine topical preparations.

Chinese herbal medicine combined with cognitive–behavioural therapy for avoidant paruresis:a controlled trial

Background Avoidant paruresis is a common clinical condition in urology and psychosomatic medicine.However,it has limited treatment options that are safe and effective with few side effects.Aims Our study aimed to investigate the effectiveness and safety of the Chinese herbal Yangxin Tongquan decoction combined with cognitive-behavioural therapy(CBT)for avoidant paruresis.Methods Sixty-eight patients with avoidant paruresis were divided into a treatment group(33 patients)and a control group(35 patients).The control group was assigned 10 weeks of CBT and systematic desensitisation.In addition to CBT and systematic desensitisation,the treatment group was given the Chinese herbal Yangxin Tongquan decoction during the 10-week study.The Shy Bladder Syndrome Scale(SBS)and the Self-rating Anxiety Scale(SAS)were administered before and after treatment to measure any change.Results The overall efficacy in the treatment group(n=30)was 80.0%vs 62.5%in the control group(n=33).Comparing pretreatment and post-treatment measures,both groups showed improvement in SBS scores and SAS scores(treatment group:t_((SBS))=8.397,p_((SBS))<0.001,t_((SAS))=8.216,p_((SAS))<0.001;control group:t_((SBS))=6.802,p_((SBS))<0.001,t_((SAS))=5.171,p_((SAS))<0.001).Moreover,both groups’SBS and SAS scores changed significantly over time(SBS scores:F_(time)=118.299,p<0.001;SAS scores:F_(time)=92.114,p<0.001).However,the treatment group performed better than the control group(SBS scores:F_(time*group)=5.709,p=0.020;SAS scores:F_(time*group)=7.235,p=0.009).Conclusions The Chinese herbal Yangxin Tongquan decoction combined with cognitive-behavioural psychotherapy positively affects the treatment of avoidant paruresis without significant adverse effects.

Characterization of SHARPIN knockout Syrian hamsters developed using CRISPR/Cas9 system

Background : SHARPIN (SHANK- associated RH domain interactor) is a component ofthe linear ubiquitination complex that regulates the NF- κB signaling pathway. To betterunderstand the function of SHARPIN, we sought to establish a novel geneticallyengineered Syrian hamster with SHARPIN disruption using the CRISPR/Cas9 system.Methods : A single- guide ribonucleic acid targeting exon 1 of SHARPIN gene was designedand constructed. The zygotes generated by cytoplasmic injection of the Cas9/gRNA ribonucleoprotein were transferred into pseudopregnant hamsters. Neonatalmutants were identified by genotyping. SHARPIN protein expression was detectedusing Western blotting assay. Splenic, mesenteric lymph nodes (MLNs), and thymicweights were measured, and organ coefficients were calculated. Histopathologicalexamination of the spleen, liver, lung, small intestine, and esophagus was performedindependently by a pathologist. The expression of lymphocytic markers and cytokineswas evaluated using reverse transcriptase- quantitative polymerase chain reaction.Results : All the offspring harbored germline- transmitted SHARPIN mutations.Compared with wild- type hamsters, SHARPIN protein was undetectable in SHARPIN −/−hamsters. Spleen enlargement and splenic coefficient elevation were spotted inSHARPIN −/− hamsters, with the descent of MLNs and thymuses. Further, eosinophilinfiltration and structural alteration in spleens, livers, lungs, small intestines, and esophagiwere obvious after the deletion of SHARPIN. Notably, the expression of CD94 and CD22 was downregulated in the spleens of knockout (KO) animals. Nonetheless,the expression of CCR3, CCL11, Il4 , and Il13 was upregulated in the esophagi. Theexpression of NF- κB and phosphorylation of NF- κB and IκB protein significantly diminishedin SHARPIN −/− animals.Conclusions : A novel SHARPIN KO hamster was successfully established using theCRISPR/Cas9 system. Abnormal development of secondary lymphoid organs andeosinophil infiltration in multiple organs reveal its potential in delineating SHARPINfunction and chronic inflammation.