Establishment of a Multiplex Detection Method for Common Bacteria in Blood Based on Human Mannan-Binding Lectin Protein-Conjugated Magnetic Bead Enrichment Combined with Recombinase-Aided PCR Technology

Objective Recombinase-aided polymerase chain reaction(RAP)is a sensitive,single-tube,two-stage nucleic acid amplification method.This study aimed to develop an assay that can be used for the early diagnosis of three types of bacteremia caused by Staphylococcus aureus(SA),Pseudomonas aeruginosa(PA),and Acinetobacter baumannii(AB)in the bloodstream based on recombinant human mannanbinding lectin protein(M1 protein)-conjugated magnetic bead(M1 bead)enrichment of pathogens combined with RAP.Methods Recombinant plasmids were used to evaluate the assay sensitivity.Common blood influenza bacteria were used for the specific detection.Simulated and clinical plasma samples were enriched with M1 beads and then subjected to multiple recombinase-aided PCR(M-RAP)and quantitative PCR(qPCR)assays.Kappa analysis was used to evaluate the consistency between the two assays.Results The M-RAP method had sensitivity rates of 1,10,and 1 copies/μL for the detection of SA,PA,and AB plasmids,respectively,without cross-reaction to other bacterial species.The M-RAP assay obtained results for<10 CFU/mL pathogens in the blood within 4 h,with higher sensitivity than qPCR.M-RAP and qPCR for SA,PA,and AB yielded Kappa values of 0.839,0.815,and 0.856,respectively(P<0.05).Conclusion An M-RAP assay for SA,PA,and AB in blood samples utilizing M1 bead enrichment has been developed and can be potentially used for the early detection of bacteremia.

Application of Tranexamic Acid in Shoulder Arthroscopic Surgery:A Randomised Controlled Trial

Objective To explore the optimal administration route of tranexamic acid(TXA)in shoulder arthroscopic surgery.Methods Patients undergoing arthroscopic rotator cuff repair were randomly divided into four groups:control group(without TXA treatment),intravenous group(TXA was intravenously administered 10 minutes before surgery),irrigation group(TXA was added to the irrigation fluid during subacromial decompression and acromioplasty),and intravenous plus irrigation group(TXA was applied both intravenously and via intra-articular irrigation).The primary outcome was visual clarity assessed with visual analog scale(VAS)score,and the secondary outcomes included irrigation fluid consumption and time to subacromial decompression and acromioplasty procedure.Results There were 134 patients enrolled in the study,including 33 in the control group,35 in the intravenous group,32 in the irrigation group,and 34 in the intravenous plus irrigation group.The median and interquartile range of VAS scores for the intravenous,irrigation,and intravenous plus irrigation groups were 2.70(2.50,2.86)(Z=-3.677,P=0.002),2.67(2.50,2.77)(Z=-3.058,P<0.001),and 2.91(2.75,3.00)(Z=-6.634,P<0.001),respectively,significantly higher than that of the control group[2.44(2.37,2.53)].Moreover,the control group consumed more irrigation fluid than the intravenous group,irrigation group,and intravenous plus irrigation group(all P<0.05).The intravenous plus irrigation group consumed less irrigation fluid than either the intravenous group or the irrigation group(both P<0.001).There was no difference in subacromial decompression and acromioplasty operative time among the four groups.Conclusion TXA applied both topically and systematically can improve intraoperative visual clarity,and the combined application is more effective.

Acute pancreatitis as initial presentation of acute myeloid leukemia-M2 subtype:A case report

BACKGROUND Direct infiltration of the pancreas by acute myeloid leukemia(AML)with acute pancreatitis(AP)as an initial symptom is extremely rare.Only once in the literature,the leukemia cells in AML have been implicated as the cause of AP.Pancreatitis caused by a rare predisposing factor is often misdiagnosed as idiopathic pancreatitis or pancreatitis of other common causes.Severe AP(SAP)progresses rapidly with a high fatality rate.Therefore,it is important to identify the predisposing factors in the early stage of SAP,evaluate the condition,determine prognosis,formulate treatment plans,and prevent a recurrence.Here,we describe a case of SAP due to AML.CASE SUMMARY A 61-year-old man presented to the hospital with fever and persistent abdominal pain.Blood analysis presented significantly elevated serum amylase and severe thrombocytopenia.Computed tomography examination of the abdomen revealed peripancreatic inflammatory effusion.The patient had no common etiologies and risk factors for AP,but the concurrent severe thrombocytopenia could not be explained by pancreatitis.Finally,the bone marrow aspirate and biopsy inspection revealed the underlying reason for pancreatitis,AML(M2 type based on the French-American-British classifications system).CONCLUSION Direct infiltration of the pancrease by acute leukemia,particularly AML cells,is an infrequent cause of AP.Therefore,although AP is a rare extramedullary infilt-ration characteristic for AML patients,it should be considered when determining the etiology of AP.

Iris metastasis from clear cell renal cell carcinoma: A case report

BACKGROUND Clear cell renal cell carcinoma(ccRCC)is a common type of tumor that can metastasize to any organs and sites.However,it is extremely rare for ccRCC to metastasize to the iris.Here,we describe a rare case of iris metastasis from ccRCC with a history of left nephrectomy in 2010.CASE SUMMARY A 62-year-old male was admitted to the hospital due to blurred vision and red eyes,and a mass was found on the iris in the right eye.B-scan ultrasonography revealed a well-bounded high-density lesion at the corner of the anterior chamber at the 3-4 o’clock position.Phacoemulsification with simultaneous intraocular lens implantation and iridocyclectomy was performed in the right eye.The lesion was confirmed to be metastatic ccRCC by histological and immunohistochemical analyses.The patient was still alive at 9 mo after surgical treatment.Ocular metastasis can be an initial sign with a poor prognosis.Timely detection and treatment may improve survival.Clinicians should pay attention to similar metastatic diseases to prevent misdiagnosis leading to missed treatment oppor-tunities.CONCLUSION This report of the characteristics and successful management of a rare case of iris metastasis from ccRCC highlights the importance of a comprehensive medical history,histopathology,immunohistochemistry,and clinical manifestation for successful disease diagnosis.

Tongxinluo promotes endothelium-dependent arteriogenesis to attenuate diabetic peripheral arterial disease

BACKGROUND Peripheral arterial disease(PAD)has become one of the leading causes of disability and death in diabetic patients.Restoring blood supply to the hindlimbs,especially by promoting arteriogenesis,is currently the most effective strategy,in which endothelial cells play an important role.Tongxinluo(TXL)has been widely used for the treatment of cardio-cerebrovascular diseases and extended for diabetes-related vascular disease.AIM To investigate the effect of TXL on diabetic PAD and its underlying mechanisms.METHODS An animal model of diabetic PAD was established by ligating the femoral artery of db/db mice.Laser Doppler imaging and micro-computed tomography(micro-CT)were performed to assess the recovery of blood flow and arteriogenesis.Endothelial cell function related to arteriogenesis and cellular pyroptosis was assessed using histopathology,Western blot analysis,enzyme-linked immunosorbent assay and real-time polymerase chain reaction assays.In vitro,human vascular endothelial cells(HUVECs)and human vascular smooth muscle cells(VSMCs)were pretreated with TXL for 4 h,followed by incubation in high glucose and hypoxia conditions to induce cell injury.Then,indicators of HUVEC pyroptosis and function,HUVECVSMC interactions and the migration of VSMCs were measured.RESULTS Laser Doppler imaging and micro-CT showed that TXL restored blood flow to the hindlimbs and enhanced arteriogenesis.TXL also inhibited endothelial cell pyroptosis via the reactive oxygen species/nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3/Caspase-1/GSDMD signaling pathway.In addition,TXL restored endothelial cell functions,including maintaining the balance of vasodilation,acting as a barrier to reduce inflammation,and enhancing endothelial-smooth muscle cell interactions through the Jagged-1/Notch-1/ephrin-B2 signaling pathway.Similar results were observed in vitro.CONCLUSION TXL has a pro-arteriogenic effect in the treatment of diabetic PAD,and the mechanism may be related to the inhibition of endothelial cell pyroptosis,restoration of endothelial cell function and promotion of endothelial cell-smooth muscle cell interactions.

Neuropeptide Y gene transfection inhibits post-epileptic hippocampal synaptic reconstruction

Exogenous neuropeptide Y has antiepileptic effects; however, the underlying mechanism and optimal administration method for neuropeptide Y are still unresolved. Previous studies have used intracerebroventricular injection of neuropeptide Y into animal models of epilepsy. In this study, a recombinant adeno-associated virus expression vector carrying the neuropeptide Y gene was injected into the lateral ventricle of rats, while the ipsilateral hippocampus was injected with kainic acid to establish the epileptic model. After transfection of neuropeptide Y gene, mossy fiber sprouting in the hippocampal CA3 region of epileptic rats was significantly suppressed, hippocampal synaptophysin （p38） mRNA and protein expression were inhibited, and epileptic seizures were reduced. These experimental findings indicate that a recombinant adeno-associated virus expression vector carrying the neuropeptide Y gene reduces mossy fiber sprouting and inhibits abnormal synaptophysin expression, thereby suppressing post-epileptic synaptic reconstruction.

Neuropeptide Y protects cerebral cortical neurons by regulating microglial immune function

Neuropeptide Y has been shown to inhibit the immunological activity of reactive microglia in the rat cerebral cortex, to reduce N-methyl-D-aspartate current（INMDA） in cortical neurons, and protect neurons. In this study, after primary cultured microglia from the cerebral cortex of rats were treated with lipopolysaccharide, interleukin-1β and tumor necrosis factor-α levels in the cell culture medium increased, and mRNA expression of these cytokines also increased. After primary cultured cortical neurons were incubated with the lipopolysaccharide-treated microglial conditioned medium, peak INMDA in neurons increased. These effects of lipopolysaccharide were suppressed by neuropeptide Y. After addition of the neuropeptide Y Y1 receptor antagonist BIBP3226, the effects of neuropeptide Y completely disappeared. These results suggest that neuropeptide Y prevents excessive production of interleukin-1β and tumor necrosis factor-α by inhibiting microglial reactivity. This reduces INMDA in rat cortical neurons, preventing excitotoxicity, thereby protecting neurons.

The Observation on Risk of Ventilator Failure Weaning by Ultrasound bedside Monitoring of Inferior Vena Cava and Lung B Line

Objective: This study was designed to investigate risk of ventilator weaning by ultrasound bedside monitoring of the width of inferior vena cava (IVC) and the number of lung B-lines (B-lines). Methods: This study was conducted on 106 patients from January 2019 to January 2020 who had mechanical ventilation for more than 48 hours in an emergency care unit. They were clinically stable and had the criteria for weaning from the ventilator. Before Spontaneous Breathing Test (SBT) and 30 min or 120 min after SBT, the width of IVC and the number of B-lines in patients were monitored via bedside ultrasound. There were 87 cases of successful weaning as a control group and 19 cases of ventilator failure weaning as a study group. Changes of the width of IVC and the number of B-lines were compared in the different stages of SBT. Results: A total of 106 patients were included in this study. There were 87 cases of ventilator successful weaning and 19 cases failure weaning. The weaning success rate was 82.08%. The width of IVC and the number of B-lines in the study group were higher than those in the control group in same stage of SBT, the difference was statistically significant (P < 0.05), and which increased significantly with time. There was no significant difference in the width of IVC and the number of B-lines on the different stage of SBT in the control group (P > 0.05), and significant difference in the study group. Conclusion: The width of IVC and the number of B-lines monitored by bedside ultrasound can assess the risk of ventilator weaning, it may be caused by cardiopulmonary interaction.

Application of Etiology List in Differential Diagnosis of Acute Abdominal Pain^#

Objective: To use the etiology list of abdominal pain to help identify acute abdominal pain. Methods: to design a list of causes of acute abdominal pain as per the concept of system thinking, determine the five differential diagnosis directions of “local organ disease, adjacent organ disease, systemic disease, psychogenic disease, and female reproductive system disease”, and elaborate the application effect of the checklist in the diagnosis of acute abdominal pain by virtue of the analysis of one case of acute abdominal pain. Results: according to the list of causes of abdominal pain, the causes of acute abdominal pain were screened, and patients suffering from acute renal infarction (ARI) who presented with simple abdominal pain were diagnosed and treated timely. Conclusion: the etiology list is helpful to guide the diagnosis direction of acute abdominal pain, and make a rapid clinical diagnosis, so as to form a systematic thinking mode.

A Dietary Supplement Jinghuosu Ameliorates Reproductive Damage Induced by Tripterygium Glycosides

Objective To determine the possible protective effects of Jinghuosu,a dietary supplement(DS),on tripterygium glycosides(TG)-induced reproductive system injury in rats and its underlying mechanisms.Methods A reproductive damage model was established in rats by feeding of TGs.Twenty-eight male Sprague Dawley rats were randomly divided into 4 groups using a random number table(n=7 in each):control(C)group,model(M)group,DS group and L-carnitine(LC)group.Rats in M,DS and LC groups received 40 mg/kg TGs orally.Starting from the 5th week,after administration of TGs for 4 h every day,rats in DS and LC groups were administered with 2.7 g/kg DS and 0.21 g/kg LC,respectively,for protective treatment over the next 4 weeks.Rats in Group C continued to receive the control treatment.Hematoxylin-eosin staining was used for histopathological analysis of rat testicular tissues.Enzyme-linked immunosorbent assay was performed to measure alkaline phosphatase(ALP),lactate dehydrogenase,alcohol dehydrogenase,total antioxidant capacity(T-AOC),superoxide dismutase,glutathione peroxidase(GSH-Px),and malondialdehyde(MDA)concentrations.Chemiluminescence assay was used to determine the serum testosterone content.Quantitative real-time PCR and Western blotting were conducted to analyze the expression of genes and proteins related to the testosterone synthesis pathway and the nuclear factor erythroid 2-related factor 2/heme oxygenase 1 antioxidant pathway.Results Oral administration of TGs induced significant increases in the testicular levels of zinc transporter 1 and MDA(P<0.05).On the other hand,sperm concentration,sperm motility,and serum testosterone,serum zinc,testicular zinc,Zrt-,Irt-like protein 1,ALP,luteinizing hormone(LH)receptor,steroidogenic acute regulatory protein,Cytochrome P450 family 11 subfamily A member 1,3β-hydroxysteroid dehydrogenase 1 T-AOC,GSH-Px,nuclear factor erythroid 2-related factor 2,heme oxygenase-1 and NAD(P)H:quinone oxidoreductase 1 levels decreased following TGs exposure(P<0.05).All of these phenotypes were evidently reversed by DS(P<0.05).Conclusion DS Jinghuosu protects against TG-induced reproductive system injury in rats,probably by improving zinc homeostasis,enhancing the testosterone synthesis and attenuating oxidative stress.

Effects of NLRP3 Inflammasome Mediated Pyroptosis on Cardiovascular Diseases and Intervention Mechanism of Chinese Medicine

Activation of the NOD-like receptor protein 3(NLRP3)inflammasome signaling pathway is an important mechanism underlying myocardial pyroptosis and plays an important role in inflammatory damage to myocardial tissue in patients with cardiovascular diseases(CVDs),such as diabetic cardiomyopathy,ischemia/reperfusion injury,myocardial infarction,heart failure and hypertension.Noncoding RNAs(nc RNAs)are important regulatory factors.Many Chinese medicine(CM)compounds,including their effective components,can regulate pyroptosis and exert myocardium-protecting effects.The mechanisms underlying this protection include inhibition of inflammasome protein expression,Toll-like receptor 4–NF-κB signal pathway activation,oxidative stress,endoplasmic reticulum stress(ERS),and mixed lineage kinase 3 expression and the regulation of silent information regulator 1.The NLRP3 protein is an important regulatory target for CVD prevention and treatment with CM.Exploring the effects of the interventions mediated by CM and the related mechanisms provides new ideas and perspectives for CVD prevention and treatment.

Hypertension-Induced Cerebral Small Vessel Disease Leading to Cognitive Impairment

Objective： Alzheimer＇s disease and vascular dementia are responsible for more than 80% of dementia cases. These two conditions share common risk factors including hypertension. Cerebral small vessel disease （CSVD） is strongly associated with both hypertension and cognitive impairment. In this review, we identify the pathophysiological changes in CSVD that are caused by hypertension and further explore the relationship between CSVD and cognitive impairment. Data Sources： We searched and scanned the PubMed database for recently published literatures up to December 2017. We used the keywords of＂hypertension＂, ＂cerebral small vessel disease＂, ＂＇white matter lesions＂, ＂enlarged perivascular spaces＂, ＂lacunar infarcts＂, ＂cerebral microbleeds＂, and ＂cognitive impairment＂ in the database of PubMed. Study Selection： Articles were obtained and reviewed to analyze the hypertension-induced pathophysiological changes that occur in CSVD and the correlation between CSVD and cognitive impairment. Results： In recent years, studies have demonstrated that hypertension-related changes （e.g., small vascular lesions, inflarnmator3, reactions, hypoperfusion, oxidative stress, damage to autoregulatory processes and the blood-brain barrier, and cerebral amyloid angiopathy） can occur over time in cerebral small vessels, potentially leading to lower cognitive function when blood pressure （BP） control is poor or lacking. Both isolated and co-occurrent CSVD can lead to cognitive deterioration, and this effect may be attributable to a dysfunction in either the cholinergic system or the functionality of cortical and subcortical tracts. Conclusions： We explore the currently available evidence about the hypertensive vasculopathy and inflammatory changes that occur in CSVD. Both are vital prognostic indicators of the development of cognitive impairment. Future studies should be performed to validate the relationship between BP levels and CSVD progression and between the nunabers, volumes, and anatomical locations of CSVD and cognitive impairment.

Carotid Atherosclerosis and Cognitive Impairment in Nonstroke Patients

Objective： As a vascular risk factor, carotid atherosclerosis is crucial to cognitive impairment. While carotid intima-media thickness, carotid artery plaque, and carotid stenosis can reflect carotid atherosclerosis in different stages, this review aimed to explore researches on the role of carotid intima-media thickness, carotid artery plaque, and carotid stenosis in the progress of cognitive impairment in nonstroke patients and tried to illustrate the possible mechanisms. Data Sources： We searched the PubMed database for recently published research articles up to July 2017, with the key words of ＂carotid atherosclerosis,＂ ＂carotid intima-media thickness,＂ ＂carotid plaque,＂ ＂carotid stenosis,＂ ＂nonstroke,＂ and ＂cognitive impairment.＂Study Selection： Articles were obtained and reviewed to analyze the role of carotid atherosclerosis such as carotid intima-thickness, carotid plaque, and carotid stenosis in the progress of cognitive impairment in nonstroke patients and the possible mechanisms. Results： In recent years, most studies proved that by evaluating carotid atherosclerosis with ultrasonography, carotid atherosclerosis accounts for the development of cognitive decline in nonstroke patients. Carotid atherosclerosis not only impairs the subtle general cognitive function but also decreases the specific domains of cognitive function, such as memory, motor function, visual perception, attention, and executive function. But, it is still controversial. The possible mechanisms of cognitive impairment in nonstroke patients with carotid atherosclerosis can be classified as systemic global cerebrovascular function, small-vessel diseases, and the mixed lesions. Conclusions： Carotid atherosclerosis can be used to predict the risk of cognitive impairment. Furthermore, diagnosing and treating carotid atherosclerosis at early stage might help clinicians prevent and treat vascular cognitive impairment in nonstroke patients.

Effects of Plasma Lipids and Statins on Cognitive Function

Objective： Dementia is the fourth most common cause of death in developed countries. The relationship between plasma lipids and cognitive function is complex and controversial. Due to the increasing life expectancy of the population, there is an urgent need to control vascular risk factors and to identify therapies to prevent and treat both cognitive impairment and dementia. Here, we reviewed the eff＇ects of plasma lipids and statins on cognitive function. Data Sources： We searched the PubMed database for research articles published through November 2017 with key words including ＂plasma lipids,＂ ＂hyperlipidemia,＂ ＂hypercholesterolemia,＂ ＂statins,＂ and ＂cognition function.＂ Study Selection： Articles were retrieved and reviewed to analyze the effects of plasma lipids and statins on cognitive function and the mechanisms underlying these effects. Results： Many studies have examined the relationship between plasma lipids and cognitive function, but no definitive conclusions can be drawn. The mechanisms involved may include blood-brain barrier injury, the influence on small blood vessels in the brain, the influence on amyloid deposition, and a neuroprotective effect. To date, most studies of statins and cognition have been observational, with few randomized controlled trials. Therefore, finn conclusions regarding whether mid- or long-term statin use affects cognition function and dementia remain elusive. However, increasing concern exists that statins may be a causative factor for cognitive problems. These adverse eff＇ects appear to be rare and likely represent a yet-to-be-defined vulnerability in susceptible individuals. Conclusions： The association between plasma lipids and cognition, the mechanism of the influence of plasma lipids on cognitive function, and the association between statins and cognitive function are complex issues and currently not fully understood. Future research aimed at identifying the mechanisms that underlie the effects of plasma lipids and statins on cognition will not only provide important insight into the causes and interdependencies of cognitive impairment and dementia, but also inspire novel strategies for treating and preventing these cognitive disorders.

调督通脑针刺法治疗中风后抑郁疗效观察（英文）

目的:观察调督通脑针刺法治疗中风后抑郁的临床疗效。方法:共纳入70例中风后抑郁患者,采用随机数字表法随机分为观察组和对照组。观察组患者接受调督通脑针刺法治疗,对照组患者口服草酸艾司西酞普兰片(Escitalopram Oxalate tablet)治疗,共治疗8星期。分别在治疗前、治疗4星期及8星期后进行汉密尔顿抑郁量表(Hamilton depression scale,HAMD)、蒙哥马利抑郁评定量表(Montgomery Asberg depression rating scale,MADRS)、Barthel指数(Barthel Index,BI)评价,同时统计不良反应。结果:治疗4星期后,两组HAMD及MADRS评分均较本组治疗前显著降低(P<0.05),BI评分较治疗前明显提高(P<0.05);组间比较,两组HAMD评分没有统计学差异(P>0.05),观察组MADRS评分明显低于对照组(P<0.05),观察组BI评分明显高于对照组(P<0.05)。治疗8星期后,两组各项评分均无统计学差异(P>0.05),但观察组不良反应发生情况明显低于对照组。结论:调督通脑针刺法治疗中风后抑郁安全有效,与艾斯西酞普兰总体疗效相当,但能较快改善抑郁核心症状及日常生活活动(activities of daily living,ADL)能力,且不良反应少。

Correlativity between blood measures related to blood stasis blocking collaterals and gene expression of angiotensin-converting enzyme of renal cortex in diabetic rats and effect of stasis removing and collaterals dredging

OBJECTIVE: To investigate the correlativity between the changes of blood measures related to blood stasis blocking collaterals and gene expression levels of angiotensin-converting enzyme(ACE)and ACE2 ofrenal cortex in diabetic rats with stasis blocking collaterals syndrome, as well as the effectof stasis removing and collaterals dredging.METHODS: Male Sprague-Dawley rats were divided randomly into normal control group(C group),high-carbohydrate-fat control group(H group) and streptozotocin(STZ)-injecting group. The diabeticrats were induced from rats in the STZ-injecting groupby high-carbohydrate-fat diet combined with STZ intraperitoneal injection, with sustained high-carbohydrate-fat diet fed afterwards, and were further divided into model group(M group)and Chinese medicine of stasis removing and collaterals dredging group(Z group). Rats in the Z group were fed with stasis-removing-and-collaterals-dredging herbal granule suspension intragastrically daily for 16 weeks, while drinking water of corresponding volume was administrated to the rats in other groups. At the end of the 16 th week after successful establishment of models, the ultrastructures of glomeruli in different groups were detected by a transmission electron microscopy; and blood measures related to blood stasis blocking collaterals, including lipid profile and blood viscosity measures, were tested, as well as the relative gene expressions of ACE and ACE2.RESULTS: Changes in ultrastructures of glomeruli in the M group were characterized by lack of clarity in structure and occasional thickening of glomerular basement membrane and extensive fusion in foot processes. The correlation analysis showed that there were positive correlations between lipid profile, blood viscosity, and the ACE mRNA expression levels in the M group(P<0.05), except for cholesterol. And except for triglyceride, the blood measures were in negative correlation with the ACE2 mRNA expression levels in the M group(P<0.05).Compared with the C and H groups, the lipid profile, plasma viscosity and blood viscosity were significantly higher(P<0.01). All the above-mentioned measures were significantly improved in the Z group rats(P<0.05). ACE mRNA expression was significantly higher in the M group thanin the C group(P<0.05). ACE2 mRNA level was significantly lower in the M group than in the C and H groups(P<0.01)and its levelin the Z group was higher than that in the M group(P<0.01).CONCLUSION: Blood measuresrelated to blood stasis blocking collaterals had positive linear correlations with ACE mRNAexpression and negative linear correlations with ACE2 mRNA expression in the M group. Chinese recipe of stasis removing and collaterals dredging could play a renal protecting role for diabetic rats by reducing lipid profile and blood viscosity, down-regulating ACE mRNA expression and up-regulating ACE2 mRNA expression.

A 42-year-old woman with 4H leukodystrophy caused by a homozygous mutation in POLR3A gene

A 42-year-old woman,born to non-consanguineous parents with no family history of neurological diseases,suffered from ataxia for 3 years.After a normal psychomotor development,the patient first presented dental eruption at 1-year-old and with absence at 5 years of age.She stopped growing when she was 15 years old,and remained heights under 150 cm.Intellectual impairment became evident at 35 years old.Approximately 4 years ago (38 years old),she appeared secondary amenorrhea.Ataxia aggravated in the following 3 years and gradually affected daily life.On examinations,she has short stature [Supplementary Figure 1,http://links.lww.com/CM9/A61],tooth dysplasia and ataxia-related syndrome.There were no nystagmus,papilla atrophy or other visual problems.Her Mini-Mental State Examination (MMSE) score was 19,indicating mild intellectual disability.No contraceptives were used.She gave birth to a boy by making a cesarean section at 23-year-old,and her son was without any neurological symptom so far.Her parents died of other internal medicine diseases.Their gonads developed normally when they were alive.Only one brother who showed normal appearance and cognition was in her family.

Hypoglycemic encephalopathy caused by overdose of metformin in an adolescent

To the Editor:Hypoglycemic encephalopathy is an acute brain dysfunction caused by hypoglycemia.Its clinical manifestations are complex,and sometimes its symptoms are not typical.Therefore,it can be misdiagnosed.This article shares a case of hypoglycemic encephalopathy caused by excessive ingestion of metformin for a suicide attempt in an adolescent.

Calcium Receptor and Nitric Oxide Synthase Expression in Circular Muscle of Lower Esophagus from Patients with Achalasia

To the Editor:Achalasia is a primary esophageal motility disorder.[l] The etiology ofachalasia remains unknown,but it is associated with degeneration,reduction,or absence of neurons in the esophageal muscular layer (Auerbach's plexus),leading to nerve-muscle conduction abnormalities.[2]

Bilateral thalamic lesions caused by a complex intracranial dural arteriovenous fistula: a rare case report

To the Editor:Bilateral thalamic lesions are uncomm on,but the different types of pathogenesis can be classified into metabolic processes,toxic exposures,infection,vascular lesions,and tumors.111 Among the possible forms of pathogenesis,intracranial dural arteriovenous fistula(dAVF)is extremely rare.