Traditional Chinese medicine nursing protocols for COVID-19

In order to facilitate nurses to understand the key points of COVID‑19’s common syndromes,master the key points of nursing with syndrome differentiation,use the advantages of traditional Chinese medicine(TCM)nursing characteristics,standardize TCM nursing behavior,and improve the TCM nursing effect,through the search of relevant information,combined with the clinical practice experience of more than 1 month of front‑line anti‑epidemic nursing staff,the TCM nursing protocols for COVID‑19(draft)were formed.After four rounds of expert consultation and discussion,and 15 times of collation and revision,the final version of TCM nursing protocols for COVID‑19 was formed.The TCM nursing protocols for COVID‑19 include the following five parts:key points of common syndromes,nursing for common symptoms/syndromes,TCM special nursing,healthy guidance,and difficulties in nursing;it is scientific and practical,and can provide clinical guidance for nursing of patients with COVID‑19.

“Buyi Ganshen”,a traditional Chinese medicine treatment,combined with dopa preparation for Parkinson’s disease therapy:a meta-analysis of randomized controlled trials

Traditional Chinese medicine Buyi Ganshen therapy combined with dopa preparation in the therapy of Parkinson’s disease could enhance the clinical safety and efficacy compared with dopa preparation along.The exact mechanism of how Buyi Ganshen works combined with dopa preparation still unknown and the enrolled articles quality was relatively inadequate,yet it could provide the reference in the clinical application and further studies.Background:To research the influence of“Buyi Ganshen”,a traditional Chinese medicine that commonly used in“Tonifying the Liver and the Kidney”,added dopa preparation for the therapy of Parkinson’s disease.Methods:This meta-analysis examined existing literature by searching 7 electronic databases(CNKI,WanFang,EMBASE,PubMed,Medline,the Cochrane Library,and the VIP database)from inception to December 2019.Randomized controlled trials evaluating the influence of“Buyi Ganshen”combined with dopa preparation for Parkinson’s disease were identified.The main results were clinical efficacy,UPDRS I(mental score),total unified Parkinson’s disease ratingscale score,UPDRS III(motor score),UPDRS II(activities of daily life),and UPDRS IV(complications of treatment).The subordinate results were the SPOCA-AUT scores,traditional Chinese medicine syndromes and other adverse reactions.The Review Manager 5.3 software was used to calculate the pooled estimate effect.The outcomes were showed as relative ratio with 95%confidence interval.The fixed or random model was elected based on the level of homogeneity among researches.The I2 was used to detected heterogeneity.The quality of the researches was also assessed.Results:The meta-analysis include 2,241 individuals from a total of 30 studies.These data suggested that the therapy of Parkinson’s disease with the combination of“Buyi Ganshen”and dopa preparation were more effective compared to dopa preparation alone.Conclusion:“Buyi Ganshen”combined with dopa preparation exists,in some degree,to enhance clinical safety and effectiveness in the cure of Parkinson’s disease,compared with dopa preparation along.As most of the studies included were with low quality,this conclusion must be considered with caution.Thus,more multi-center,high-quality,prospective randomized controlled trials with large enough sample sizes are required to further illuminate the influence of“Buyi Ganshen”combined with dopa preparation for Parkinson’s disease.

The effects of Chinese herbal medicines on Madopar dose and adverse reaction during the maintenance phase of Parkinson's disease:a systematic review with meta-analysis

Background:Parkinson’s disease is a progressive neurodegenerative disease,and is usually treated with levodopa combined with dopa decarboxylase inhibitor like Madopar.In order to improve the efficacy and reduce adverse reactions,Chinese herbal medicines are usually applied with Madopar to treat Parkinson’s disease in clinic.According to the results of certain randomized controlled trials,levodopa drugs combined with Chinese herbal medicines could achieve better effects like the improvement of clinical symptoms,the reduced incidence of adverse reactions,and the reduced dose of levodopa drugs(especially in the maintenance phase).However,not all the randomized controlled trials showed favorable effect on Parkinson’s disease.Therefore,it is necessary to find out how to effectively combine Chinese herbal medicines with Madopar.In order to evaluate the effects of Chinese herbal medicines on Madopar dose and adverse reaction during the maintenance phase of Parkinson’s disease,a meta-analysis was conducted.Methods:A systematic research was carried out for randomized controlled trials of combined Chinese herbal medicines and Madopar treatment for Parkinson’s disease during the maintenance phase published till August 2019.The primary outcome was the Madopar dose and secondary outcome was the incidence of adverse reaction.Data were pooled and analyzed with RevMan 5.3.Results:A total of 18 studies were included with 1,169 cases.However,study quality evaluation showed low methodological quality.Meta-analyses showed that the dose of Madopar in the treatment group was significantly lower than that in the control group,and the incidence of adverse reactions in the treatment group was also significantly lower than that in the control group.However,the correlation analysis showed that the reduction of Madopar dose was not related to the reduction of incidence of adverse reactions(P>0.05).There existed publication bias on the primary outcome and secondary outcome.Conclusions:Chinese herbal medicines could reduce the Madopar dose and adverse reaction during the maintenance phase of Parkinson’s disease treatment.This conclusion must be considered cautiously,for lack of studies of high quality.

To set up a logistic regression prediction model for hepatotoxicity of Chinese herbal medicines based on the efficacy of Chinese herbal medicines

In our previous research,a logistic regression prediction model for hepatotoxicity of Chinese herbal medicines based on the four properties,five flavors and channel tropism has been successfully established.However,could Chinese herbal medicines efficacy also be applied to predict the hepatotoxicity of Chinese herbal medicines?Therefore,a logistic regression prediction model for hepatotoxicity of Chinese herbal medicines based on Chinese herbal medicines efficacy has been tentatively set up to study the correlations of hepatotoxic and nonhepatotoxic Chinese herbal medicines with efficacy by using a chi-square test for two-way unordered categorical data.Logistic regression prediction model was established and the accuracy of the prediction by this model was evaluated.It has been found that the hepatotoxicity and nonhepatotoxicity of Chinese herbal medicines were weakly related to the efficacy,and the coefficient was 0.295.There were 20 variables from Chinese herbal medicines efficacy analyzed with unconditional logistic regression,and 6 variables,rectifying Qi and relieving pain,clearing heat and disinhibiting dampness,invigorating blood and stopping pain,invigorating blood and relieving swelling,killing worms and relieving fright were chosen to establish the logistic regression prediction model,with the optimal cutoff value being 0.250.Dissipating cold and relieving pain(DCRP),clearing heat and disinhibiting dampness,invigorating blood and relieving pain(IBRP),invigorating blood and relieving swelling,killing worms,and relieving fright were the variables to affect the hepatotoxicity and the established logistic regression prediction model had predictive power for hepatotoxicity of Chinese herbal medicines to a certain degree.

Efficacy of a Chinese herbal formula on hepatitis B e antigenpositive chronic hepatitis B patients

BACKGROUND No guideline recommends antiviral therapy for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus(HBV)DNA viral load.AIM To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV infection.METHODS In total,395 patients(30–65 years old)with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 wk.Endpoints to evaluate therapeutic efficacy included:(1)HBV DNA levels decreased to less than 4 log10 IU/mL at weeks 48 and 96;and(2)HBeAg clearance and seroconversion rates at weeks 48 and 96.RESULTS HBV DNA levels≤4 log10 IU/mL were 10.05%at week 48 and 18.59%at week 96 in the treatment group.The HBeAg clearance and conversion rates were 8.54%and 8.04%at week 48 and 16.08%and 14.57%at week 96,respectively.However,HBV DNA levels≤4 log10 IU/mL were 2.55%and 2.55%at weeks 48 and 96,respectively,and the HBeAg clearance rates were 3.06%and 5.61%at weeks 48 and 96,respectively,in the control group.The quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 12 and 24 were strong predictors of HBeAg clearance.CONCLUSION High rates of HBV DNA reduction,HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments,and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine aminotransferase.The ability of the compound to modulate host immune function probably contributed to this effect.

Caveolin‑1 is critical for hepatic iron storage capacity in the development of nonalcoholic fatty liver disease

Background:Nonalcoholic fatty liver disease(NAFLD)is associated with disordered lipid and iron metabolism.Our previous study has substantiated the pivotal role of Caveolin-1(Cav-1)in protecting hepatocytes and mediating iron metabolism in the liver.This study aimed to explore the specific mechanisms underlying the regulation of iron metabolism by Cav-1 in NAFLD.Methods:Hepatocyte-specific Cav-1 overexpression mice and knockout mice were used in this study.Cav-1-knockdown of RAW264.7 cells and mouse primary hepatocytes were performed to verify the changes in vitro.Moreover,a high-fat diet and palmitic acid plus oleic acid treatment were utilized to construct a NAFLD model in vivo and in vitro,respectively,while a high-iron diet was used to construct an in vivo iron overload model.Besides,iron concentration,the expression of Cav-1 and iron metabolism-related proteins in liver tissue or serum were detected using iron assay kit,Prussian blue staining,Western blotting,immunofluorescence staining,immunohistochemical staining and ELISA.The related indicators of lipid metabolism and oxidative stress were evaluated by the corresponding reagent kit and staining.Results:Significant disorder of lipid and iron metabolism occurred in NAFLD.The expression of Cav-1 was decreased in NAFLD hepatocytes(P<0.05),accompanied by iron metabolism disorder.Cav-1 enhanced the iron storage capacity of hepatocytes by activating the ferritin light chain/ferritin heavy chain pathway in NAFLD,subsequently alleviating the oxidative stress induced by excess ferrous ions in the liver.Further,CD68^(+) CD163^(+) macrophages expressing Cav-1 were found to accelerate iron accumulation in the liver,which was contrary to the effect of Cav-1 in hepatocytes.Positive correlations were also observed between the serum Cav-1 concentration and the serum iron-related protein levels in NAFLD patients and healthy volunteers(P<0.05).Conclusions:These findings confirm that Cav-1 is an essential target protein that regulates iron and lipid metabolic homeostasis.It is a pivotal molecule for predicting and protecting against the development of NAFLD.

Ileal collision tumor associated with gastrointestinal bleeding: A case report and review of literature

BACKGROUND Collision tumors involving the small intestine,specifically the combination of a hamartomatous tumor and a lipoma,are extremely rare.To our knowledge,no previous case report has described a collision tumor composed of two benign tumors of different origins in the small intestine.CASE SUMMARY Here,we present the case of an 82-year-old woman who presented with hemorrhagic shock and was found to have a mass measuring approximately 50 mm×32 mm×30 mm in the terminal ileum.Based on computed tomography scan findings,the mass was initially suspected to be a lipoma.A subsequent colonoscopy revealed a pedunculated submucosal elevation consisting of two distinct parts with a visible demarcation line.A biopsy of the upper portion suggested a juvenile polyp(JP).Owing to the patient’s advanced age,multiple comorbidities,and poor surgical tolerance,a modified endoscopic submucosal dissection was performed.Histopathological examination of the excised mucosal mass revealed a lipoma at the base and a JP at the top,demonstrating evidence of rupture and associated bleeding.The patient’s overall health remained satisfactory,with no recurrence of hematochezia during the six-month follow-up period.CONCLUSION This case report provides new evidence for the understanding of gastrointestinal collision tumors,emphasizing their diverse clinical presentations and histopathological characteristics.It also offers diagnostic and therapeutic insights as well as an approach for managing benign collision tumors.

Electroacupuncture Alleviates Memory Deficits in APP/PS1 Mice by Targeting Serotonergic Neurons in Dorsal Raphe Nucleus

Objective Alzheimer’s disease(AD)has become a significant global concern,but effective drugs able to slow down AD progression is still lacked.Electroacupuncture(EA)has been demonstrated to ameliorate cognitive impairment in individuals with AD.However,the underlying mechanisms remains poorly understood.This study aimed at examining the neuroprotective properties of EA and its potential mechanism of action against AD.Methods APP/PS1 transgenic mice were employed to evaluate the protective effects of EA on Shenshu(BL 23)and Baihui(GV 20).Chemogenetic manipulation was used to activate or inhibit serotonergic neurons within the dorsal raphe nucleus(DRN).Learning and memory abilities were assessed by the novel object recognition and Morris water maze tests.Golgi staining,western blot,and immunostaining were utilized to determine EA-induced neuroprotection.Results EA at Shenshu(BL 23)and Baihui(GV 20)effectively ameliorated learning and memory impairments in APP/PS1 mice.EA attenuated dendritic spine loss,increased the expression levels of PSD95,synaptophysin,and brain-derived neurotrophic factor in hippocampus.Activation of serotonergic neurons within the DRN can ameliorate cognitive deficits in AD by activating glutamatergic neurons mediated by 5-HT1B.Chemogenetic inhibition of serotonergic neurons in the DRN reversed the effects of EA on synaptic plasticity and memory.Conclusion EA can alleviate cognitive dysfunction in APP/PS1 mice by activating serotonergic neurons in the DRN.Further study is necessary to better understand how the serotonergic neurons-related neural circuits involves in EA-induced memory improvement in AD.

Efficacy and Safety of Chinese Herbal Medicines Combined with Chemical Drugs for Alzheimer's Disease:A Systematic Review and Meta-Analysis

Objective:To evaluate the efficacy and safety of Chinese herbal medicines(CHMs)combined with chemical drugs for the treatment of Alzheimer's disease(AD).Materials and Methods:Databases were searched to retrieve randomized controlled trials(RCTs)of CHMs combined with tacrine,galantamine,rivastigmine,donepezil,or memantine,following strict inclusion and exclusion criteria.Only research papers published in English,Chinese,and Japanese were considered.The primary outcome was the mini-mental state examination(MMSE)score and the secondary outcomes were AD assessment scale cognitive subscale(ADAS-Cog)score and safety evaluation.Meta-analysis was carried out using Rev Man 5.3 and subgroup analysis was conducted to identify the sources of heterogeneity.Results:A total of 15 RCTs with 1386 participants were included in this study.Only donepezil was used in the retrieved literature.Meta-analyses showed that the combination of CHMs with donepezil led to significant improvement in the MMSE score(Z=9.45;P<0.00001;weighted mean difference[WMD]=2.68,95%confidence interval[CI]:2.12-3.24)and a significant decrease in the ADAS-Cog score(Z=5.53;P<0.00001;WMD=-3.79;95%CI:-5.13--2.44).Safety evaluation demonstrated that these combination treatments relieved adverse events such as insomnia(risk ratio[RR]=0.20,95%CI:0.06-0.68;P=0.01)and hive(RR=0.10;95%CI:0.01-0.73;P=0.02).Conclusions:The combination of CHMs with a chemical drug like donepezil led to significant improvements in patient cognition as well as a better safety profile when compared to the application of a chemical drug alone.

Effects of Traditional Chinese Medicine on the survival of patients with stage Ⅰ gastric cancer and high-risk factors:a real-world retrospective study

OBJECTIVE:To investigate the benefits of Traditional Chinese Medicine(TCM) therapy for improving the survival of patients with stage I gastric cancer(GC) and high-risk factors in a real-world setting.METHODS:The clinical data of patients who were diagnosed with stage I GC from March 1,2012 to October 31,2020 were collected.Prognostic analysis was performed to explore the high-risk factors that affected the survival of the patients.A Cox multivariate regression model was used to compare the hazard ratios for the mortality risk of patients,especially those with high-risk factors.Kaplan-Meier survival curve and log-rank test were utilized to assess the survival time.RESULTS:Prognostic analysis demonstrated that female sex,tumor invasion into blood vessels,and Ib stage were independent risk factors.The 1-,3-,and 5-year survival rates of the TCM group vs those of the non-TCM group were 100.0% vs 91.0%,97.6% vs 64.5%,and 81.4% vs 55.5%,respectively.A significant difference in median overall survival(m OS) was found between the two groups(χ2 = 7.670,P = 0.006).Subgroup analysis showed that the m OS of female patients and stage Ib patients in the TCM group were longer than those in the non-TCM group (P ≤ 0.001 and 0.001,respectively).CONCLUSIONS:TCM treatment can improve the survival of patients with stage I GC and high-risk factors.

The relationship between the distribution of HBcAg in liver cells and the pathological manifestations of the liver in 429 HBeAg-positive chronic HBV-infected individuals

Background:The natural history of chronic HBV infection is typically characterized by four stages:the immune tolerance period,the immune clearance period,the immune control period,and the immune escape period.These stages are associated with the distribution of HBcAg in liver cells;however,this relationship remains a topic of broad debate within the field of liver disease.To objectively and quantitatively measure the intracellular distribution of HBcAg,this paper aims to design a method referred to as the“layered evaluation method”and to examine its validation.Methods:The distribution of HBcAg in liver cells is assessed using Image Pro Plus image processing software,along with calculations of cytoplasmic and nuclear positive staining rates.Results:The findings indicate that the highest proportion of patients exhibited a positive cytoplasmic expression rate ranging from 0-2.5%.More than 40% of the total sample was categorized within the 0-2.5% positive nuclear expression range.The HBcAg cytoplasmic positive staining rates were classified into five levels:a cytoplasmic HBcAg positive staining rate of less than 0.05% is designated as level 0,indicating negative expression;a staining rate between 0.05% and 5% is classified as level 1;a rate from 5% to less than 10% is classified as level 2;a rate from 10% to less than 20% is classified as level 3;and a nuclear positivity rate exceeding 20% is classified as level 4.Conclusion:The inflammatory activity grade in these patients was positively correlated with the cytoplasmic distribution of HBcAg.Furthermore,the nuclear distribution rate of HBcAg was significantly higher in the G3 group compared to the other groups.

Electro-acupuncture at Conception and Governor vessels and transplantation of umbilical cord bloodderived mesenchymal stem cells for treating cerebral ischemia/reperfusion injury

Mesenchymal stem cell transplantation is a novel means of treating cerebral ischemia/reper- fusion, and can promote angiogenesis and neurological functional recovery. Acupuncture at Conception and Governor vessels also has positive effects as a treatment for cerebral ischemia/ reperfusion. Therefore, we hypothesized that electro-acupuncture at Conception and Governor vessels plus mesenchymal stem cell transplantation may have better therapeutic effects on the promotion of angiogenesis and recovery of neurological function than either treatment alone. In the present study, human umbilical cord blood-derived mesenchymal stem cells were isolated, cultured, identified and intracranially transplanted into the striatum and subcortex of rats at 24 hours following cerebral ischemia/reperfusion. Subsequently, rats were electro-acupunctured at Conception and Governor vessels at 24 hours after transplantation. Modified neurological severity scores and immunohistochemistry findings revealed that the combined interventions of electro-acupuncture and mesenchymal stem cell transplantation clearly improved neurological impairment and up-regulated vascular endothelial growth factor expression around the isch- emic focus. The combined intervention provided a better outcome than mesenchymal stem cell transplantation alone. These findings demonstrate that electro-acupuncture at Conception and Governor vessels and mesenchymal stem cell transplantation have synergetic effects on promot- ing neurological function recovery and angiogenesis in rats after cerebral ischemia/reperfusion.

Bariatric surgery in patients with non-alcoholic fatty liver disease-from pathophysiology to clinical effects

Non-alcoholic fatty liver disease(NAFLD) is increasingly recognized as a significant liver disease,and it covers the disease spectrum from simple steatosis with a risk of development of non-alcoholic steatohepatitis(NASH) to fibrosis,subsequent cirrhosis,end-stage liver failure,and liver cancer with a potential need for liver transplantation.NAFLD and NASH are closely related to obesity,metabolic syndrome,and type 2 diabetes(T2 D).The role of gut hormones,especially glucagon-like peptide 1(GLP-1),is important in NAFLD.Bariatric surgery has the potential for inducing great weight loss and may improve the symptoms of metabolic syndrome and T2 D.Recent data demonstrated significant effects of bariatric surgery on GLP-1 and other gut hormones and important lipid metabolic and inflammatory abnormalities in the pathophysiology of NAFLD.Therefore,bariatric surgery may reverse the pathological liver changes in NAFLD and NASH patients.In the present review,we describe NAFLD and NASH pathophysiology and the primary effects of bariatric surgery on metabolic pathways.We performed a systematic review of the beneficial and harmful effects and focused on changes in liver disease severity in NAFLD and NASH patients.The specific focus was liver histopathology as assessed by the invasive liver biopsy.Additionally,we reviewed several non-invasive methods used for the assessment of liver disease severity following bariatric surgery.

Long-term follow-up of cumulative incidence of hepatocellular carcinoma in hepatitis B virus patients without antiviral therapy

BACKGROUND China has a high prevalence of hepatitis B virus(HBV),but most chronic hepatitis B(CHB)patients do not receive standardized antiviral therapy.There are few relevant reports addressing the outcomes of the large number of CHB patients who do not receive antiviral therapy.AIM To observe the outcomes of long-term follow-up of patients with CHB without antiviral treatment.METHODS This study included 362 patients with CHB and 96 with hepatitis B cirrhosis without antiviral treatment and with only liver protection and anti-inflammatory treatment from 1993 to 1998.The median follow-up times were 10 and 7 years,respectively.A total of 203 CHB and 129 hepatitis B cirrhosis patients receiving antiviral therapy were selected as the control groups.The median follow-up times were 8 and 7 years,respectively.Kaplan-Meier curves were used to analyze the cumulative incidence of hepatocellular carcinoma(HCC),and the Cox regression model was used to analyze the risk factors for HCC.RESULTS Among the patients in the non-antiviral group,16.9%had spontaneous decreases(HBeAg)seroconversion.In the antiviral group,87.2%of patients had undetectable HBV DNA,and 52%showed HBeAg seroconversion.Among CHB and hepatitis B cirrhosis patients,the cumulative incidence rates of HCC were 14.9%and 53.1%,respectively,in the non-antiviral group and were 10.7%and 31.9%,respectively,in the antiviral group.There was no difference between the two groups regarding the CHB patients(P=0.842),but there was a difference between the groups regarding the hepatitis B cirrhosis patients(P=0.026).The cumulative incidence rates of HCC were 1.6%and 22.3%(P=0.022)in the groups with and without spontaneous HBeAg seroconversion,respectively.The incidence rates of HCC among patients with and without spontaneous declines in HBV DNA to undetectable levels were 1.6%and 19.1%,respectively(P=0.051).There was no difference in the cumulative incidence of HCC between the two groups regarding the patients with drug-resistant CHB(P=0.119),but there was a significant difference between the two groups regarding the patients with cirrhosis(P=0.004).The Cox regression model was used for regression of the corrected REACH-B score,which showed that alanine aminotransferase>400 U/L,history of diabetes,and family history of liver cancer were risk factors for HCC among men aged>40 years(P<0.05).Multifactorial analysis showed that a family history of HCC among men was a risk factor for HCC.CONCLUSION Antiviral therapy and non-antiviral therapy with liver protection and antiinflammatory therapy can reduce the risk of HCC.Antiviral therapy may mask the spontaneous serological response of some patients during CHB.Therefore,the effect of early antiviral therapy on reducing the incidence of HCC cannot be overestimated.

Preventive electroacupuncture reduces cognitive deficits in a rat model of D-galactose-induced aging

Acupuncture can reduce cognitive deficits in Alzheimer’s disease.However,whether electroacupuncture can prevent or alleviate the cognitive deficits in animal models of aging remains poorly understood.Studies have shown that disordered epigenetic modifications play a critical role in age-related cognitive decline.Therefore,we hypothesized that preventive electroacupuncture might improve cognitive functions during aging by regulating epigenetic modifications.A rat model of aging was produced by intraperitoneal injection of 120 mg/kg D-galactose for 8 weeks.Baihui and Shenshu acupoints were stimulated by electroacupuncture for 8 weeks from the first day of D-galactose administration.Preventive electroacupuncture alleviated memory impairment,decreased tau hyperphosphorylation,and reduced glycogen synthase kinase-3βprotein and mRNA expression levels in the brainstem dorsal raphe nucleus,where intracellular neurofibrillary tangle lesions first occur.In addition,the DNA methylation level in the promoter region of the glycogen synthase kinase-3βgene was increased.The effects of preventive electroacupuncture were stronger than those of preventive acupuncture.Intraperitoneal injection of 0.4 mg/kg 5-aza-2ʹ-deoxycytidine,an inhibitor of DNA methyltransferase that blocks epigenetic modifications,antagonized the effects of preventive electroacupuncture.Our results suggest that preventive electroacupuncture treatment alleviates cognitive impairment in aging rats probably by affecting the epigenetic modification of the glycogen synthase kinase-3βgene in the dorsal raphe nucleus.This study was approved by the Animal Ethics Committee of Hubei University of Chinese Medicine,China(approval No.HUCMS201712001)on November 28,2017.

New tight junction protein 2 variant causing progressive familial intrahepatic cholestasis type 4 in adults: A case report

BACKGROUND Progressive familial intrahepatic cholestasis(PFIC)encompasses a group of autosomal recessive disorders with high morbidity and mortality.Variants in the gene encoding tight junction protein-2(TJP2)have been linked to PFIC type 4(PFIC4),which predominantly presents in childhood.However,there are only limited data from adults with TJP2-related PFIC4.We report a family with an autosomal recessive disorder with a novel variant in the TJP2 gene in adults with very variable expression of PFIC4.CASE SUMMARY The index patient presented at 19 years old with liver cirrhosis and variceal bleeding and was treated with endoscopic banding and beta-blockers.In 2018,he developed primary liver cancer that was treated with radiofrequency ablation followed by liver transplantation in 2019.Genetic testing revealed a novel homozygous TJP2 variant causing PFIC4(TJP2([NM_004817.3]:c.[3334C>T];[3334C>T])).The consanguineous family consists of the father and mother(both heterozygous)and their 12 children,of which five carry the variant in a homozygous state;however,these five siblings have highly variable expression of PFIC4.Two homozygous brothers had cirrhosis and portal hypertension at diagnosis at the ages of 19 and 36.Two other homozygous brothers,age 23 and 19,and the homozygous sister,age 21,have elevated liver enzymes but presently no cirrhosis,which may suggest an age-dependent penetrance.In addition,five sisters had severe and mild intrahepatic cholestasis of pregnancy and carry the TJP2 variant in a homozygous and heterozygous state,respectively.CONCLUSION This novel TJP2 variant is associated with PFIC4 causing severe liver disease with cirrhosis and primary liver cancer in adolescents/adults.

Neuroprotective Effects of Dexmedetomidine Preconditioning on Oxygen-glucose Deprivation-reoxygenation Injury in PC12 Cells via Regulation of Ca^2+-STIM1/Orail Signaling

Summary:Dexmedetomidine(DEX),a potent and highly selective agonist for a2-adrenergic receptors(a2AR),exerts neuroprotective effects by reducing apoptosis through decreased neuronal Ca^2+influx.However,the exact action mechanism of DEX and its effects on oxygen-glucose deprivation-reoxygenation(OGD/R)injury in vitro are unknown.We demonstrate that DEX pretreatment reduced OGD/R injury in PC12 cells,as evidenced by decreased oxidative stress,autophagy,and neuronal apoptosis.Specifically,DEX pretreatment decreased the expression levels of stromal interaction molecule 1(STIM1)and calcium release-activated calcium channel protein 1(Orail),and reduced the concentration of intracellular calcium pools.In addition,variations in cytosolic calcium concentration altered apoptosis rate of PC12 cells after exposure to hypoxic conditions,which were modulated through STIM 1/Orail signaling.Moreover,DEX pretreatment decreased the expression levels of Beclin-1 and microtubule-associated protein 1A/1B-light chain 3(LC3),hallmark markers of autophagy,and the formation of autophagosomes.In conclusion,these results suggested that DEX exerts neuroprotective effects against oxidative stress,autophagy,and neuronal apoptosis afier OGD/R injury via modulation of Caf-STIM1/Orai1 signaling.Our results offer insights into the molecular mechanisms of DEX in protecting against neuronal ischemia-reperfusion injury.

Epigenetic Regulation of Amyloid-beta Metabolism in Alzheimer’s Disease

Senile plaques(SPs)are one of the pathological features of Alzheimer’s disease(AD)and they are formed by the overproduction and aggregation of amyloid-beta(Aβ)peptides derived from the abnormal cleavage of amyloid precursor protein(APP).Thus,understanding the regulatory mechanisms during Aβ metabolism is of great importance to elucidate AD pathogenesis.Recent studies have shown that epigenetic modulation-including DNA methylation,non-coding RNA alterations,and histone modifications-is of great significance in regulating Aβ metabolism.In this article,we review the aberrant epigenetic regulation of Aβ metabolism.

Chinese Herbal Medicine Combined with Entecavir for HBeAg Positive Chronic Hepatitis B:Study Protocol for a Multi-Center,Double-Blind Randomized-Controlled Trial

Background： The domestic prevalence of chronic hepatitis B （CHB） in China is 7.18% in 2006, imposing great societal healthcare burdens. Nucleot（s）ide analogues （NUCs） anti-hepatitis B virus （HBV） therapies are widely applied despite the relatively low rate of seroconversion and high risk of drug-resistant mutation. More effective treatments for CHB deserve further explorations. Combined therapy of NUCs plus Chinese herbal medicine （CHM） is widely accepted in China, which is recognized as a prospective alternative approach. The study was primarily designed to confirm the hypothesis that Tiaogan-Yipi Granule （调肝益脾颗粒, TGYP） or Tiaogan-Jianpi-Jiedu Granule （调肝健脾解毒颗粒, TGJPJD） plus entecavir tablet （ETV） was superior over ETV monotherapy in enhancing HBeAg loss rate. Methods： The study was a nationwide, large-scale, multi-center, double-blind, randomized, placebo-controlled trial with a designed duration of 108 weeks. A total of 16 hospitals and 596 eligible Chinese HBeAg positive CHB patients were enrolled from November 2012 to September 2013 and randomly allocated into 2 groups in 1：1 ratio via central randomization system： experimental group （EG） and control group （CG）. Subjects in EG received CM formulae （TGYP or TGJPJD, 50 g per dose, twice daily） plus ETV tablet （or ETV placebo） 0.5 mg per day in the first 24 weeks （stage 1）, and CHM granule plus ETV tablet （0.5 mg per day） from week 25 to 108 （stage 2）. Subjects in CG received CHM Granule placebo plus E＇IV tablet （0.5 mg per day） for 108 weeks throughout the trial. The assessments of primary outcomes （HBV serum markers and HBV-DNA） were conducted by a third-party College of American Pathologists （CAP） qualified laboratory. Adverse effects were observed in the hospitals of recruitment. Discussion： The study was designed to compare the curative effect of CM plus E＇IV and ETV monotherapy in respect of HBeAg loss, which is recognized by the European Association for the Study of the Liver as ＂a valuable endpoint＂. We believe this trial could provide a reliable status for patients＇ ＂joumey＂ towards durable responses after treatment discontinuation. The trial was registered before recruitment on Chinese Clinical trial registry （No. ChiCTR-TRC-12002784, Version 1.0, 2015/12/23）.

Overexpression of mitogen-activated protein kinase phosphatase-1 in endothelial cells reduces blood-brain barrier injury in a mouse model of ischemic stroke

Ischemic stroke can cause blood-brain barrier(BBB)injury,which worsens brain damage induced by stroke.Abnormal expression of tight junction proteins in endothelial cells(ECs)can increase intracellular space and BBB leakage.Selective inhibition of mitogen-activated protein kinase,the negative regulatory substrate of mitogen-activated protein kinase phosphatase(MKP)-1,improves tight junction protein function in ECs,and genetic deletion of MKP-1 aggravates ischemic brain injury.However,whether the latter affects BBB integrity,and the cell type-specific mechanism underlying this process,remain unclear.In this study,we established an adult male mouse model of ischemic stroke by occluding the middle cerebral artery for 60 minutes and overexpressed MKP-1 in ECs on the injured side via lentiviral transfection before stroke.We found that overexpression of MKP-1 in ECs reduced infarct volume,reduced the level of inflammatory factors interleukin-1β,interleukin-6,and chemokine C-C motif ligand-2,inhibited vascular injury,and promoted the recovery of sensorimotor and memory/cognitive function.Overexpression of MKP-1 in ECs also inhibited the activation of cerebral ischemia-induced extracellular signal-regulated kinase(ERK)1/2 and the downregulation of occludin expression.Finally,to investigate the mechanism by which MKP-1 exerted these functions in ECs,we established an ischemic stroke model in vitro by depriving the primary endothelial cell of oxygen and glucose,and pharmacologically inhibited the activity of MKP-1 and ERK1/2.Our findings suggest that MKP-1 inhibition aggravates oxygen and glucose deprivation-induced cell death,cell monolayer leakage,and downregulation of occludin expression,and that inhibiting ERK1/2 can reverse these effects.In addition,co-inhibition of MKP-1 and ERK1/2 exhibited similar effects to inhibition of ERK1/2.These findings suggest that overexpression of MKP-1 in ECs can prevent ischemia-induced occludin downregulation and cell death via deactivating ERK1/2,thereby protecting the integrity of BBB,alleviating brain injury,and improving post-stroke prognosis.