Objective To investigate the mechanism of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair in the treatment of hypertension based on the network pharmacology method and animal experiment verification.Methods(1)TCMSP,BATMAN and TCMIP databases were used to screen the active components and targets of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair.The hypertension-related targets were obtained by searching the Drugbank,Genecard,TTD and Disgenet databases.The intersection(common target)of the active component target and the target related to hypertension disease was taken,and the obtained intersection target was the potential target of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair for the treatment of hypertension.The active ingredients and their targets of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair were imported into Cytoscape 3.9.1 software to construct a'Chinese medicines-active ingredients-targets'network and screen key active ingredients.The protein-protein interaction(PPI)network of potential targets was constructed to screen potential core targets.The Metascape platform was used to analyze the GO function and KEGG pathway enrichment of potential targets.The key active components and potential core targets were selected for molecular docking verification.(2)Thirty male spontaneously hypertensive rats(SHR)were randomly divided into model group,western medicine group(Candesartan Cilexetil,0.72 mg·kg-1)and low-,medium-and high-dose groups of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma(2.25,4.50,9.00 g·kg-1).Another male WKY rats were selected as blank group,with 6 rats in each group,once a day for 8 weeks.The systolic blood pressure of rat tail artery was detected before administration and 2,4,6 and 8 weeks after drug intervention.The pathological changes of thoracic aorta were observed by HE staining.The protein expression levels of GRP78,CHOP and Caspase-12 in aorta abdominalis were detected by Western Blot.Results(1)A total of 83 active components of Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma were obtained,and 158 potential targets(intersection targets)for the treatment of hypertension were screened out.Five key active ingredients:p-hydroxybenzoic acid,4-hydroxybenzylamine,tanshinone I,tanshinone,γ-sitosterol;6 potential core targets:IL6,TNF,CASP3,JUN,PTGS2,IL1B;GO functional enrichment analysis obtained 1 826 biological process items,89 cell component items,and 199 molecular function items.KEGG pathway enrichment analysis obtained 186 pathways,mainly involving neuroactive ligand-receptor interaction,calcium signaling pathway,inflammatory response(such as TNF and MAPK signaling pathway),vascular protection(such as HIF-1 and cAMP signaling pathway),oxidative stress(such as PI3K-Akt signaling pathway)and other signaling pathways.Tanshinone I and tanshinone had strong binding force to 6 potential core targets,and γ-sitosterol had strong binding force to IL6,CASP3,JUN,PTGS2 and IL1B.(2)Compared with the blank group,the systolic blood pressure of the model group was significantly increased(P＜0.01).The thoracic aortic endothelial injury was obvious,the endothelial cell morphology was abnormal,swelling and exfoliated cells could be seen,the intima of the tissue was disordered,the intima structure was incomplete,and the intima was thickened.The protein expressions of GRP78,CHOP and Caspase-12 in abdominal aorta were significantly increased(P＜0.01).Compared with the model group,the systolic blood pressure of the rats in the administration group was significantly decreased(P＜0.01);the injury of thoracic aorta was alleviated,and the morphology,intima structure and thickness of endothelial cells were improved to varying degrees.The protein expressions of GRP78,CHOP and Caspase-12 in abdominal aorta were significantly decreased(P＜0.01).Conclusion Gastrodiae Rhizoma-Salviae Miltiorrhizae Radix et Rhizoma drug pair may act on core targets such as IL6,TNF,CASP3,JUN,PTGS2,and IL1B through key active components such as p-hydroxybenzoic acid,tanshinone,and γ-sitosterol,and regulate key signaling pathways such as TNF signaling pathway,MAPK signaling pathway,PI3K-Akt signaling pathway,and PERK signaling pathway to improve vascular endothelial dysfunction,inhibit endoplasmic reticulum stress,and lower blood pressure.

This article summarized the experience of Professor Xiong Jibai,a national TCM master,in treating pulmonary nodules based on the theory of"body fluids and blood stasis mixing"in Huang Di Nei Jing.Professor Xiong Jibai believes that the basic pathogenesis of pulmonary nodules is that"body fluids and blood stasis mixing"accumulate in lung collaterals,and the fundamental pathological factor is phlegm and blood stasis.Xiong's treatment is based on dissipating phlegm and activating qi,activating blood circulation and resolving masses,paying attention to syndrome differentiation and treatment,examining syndromes and seeking causes,flexibly selecting prescriptions and treating both symptoms and root causes;attaching importance to maintaining healthy qi,preventing both illness and change,and preventing recovery after illness.Clinical medical records were attached to prove the clinical thinking and medication characteristics.

Objective:This study aims to investigate the current application and the level of knowledge of intraoperative facial nerve monitoring among medical staff in China.Methods:A comprehensive online questionnaire was conducted among medical professionals across different regions in China from October 2022 to February 2023. The survey exclusively targeted departments specializing in otolaryngology, head and neck surgery, neurosurgery, and oral and maxillofacial surgery. The questionnaire covered various aspects including general information, intraoperative facial nerve monitoring practices, training history, indications for monitoring, parameters used during monitoring procedures, as well as factors influencing its implementation.Results:A total of 417 participants from 31 provincial, municipal, and autonomous regions were included. Intraoperative facial nerve monitoring was found to be implemented in 227 (54.4%,227/417) repondents of 53 institutions (24.9%, 53/213). The top three indications for implementing this technique were acoustic neuroma, parotid gland surgery, and modified middle ear surgery (mastoidectomy). Herein 81.1%(184/227) medical staff involved in intraoperative facial nerve monitoring had received relevant training, 57.3%(130/227)-92.1%(209/227) reported a lack of clear description regarding recording thresholds, stimulation currents/frequencies/wave widths.Conclusion:The majority of the institutions surveyed have not yet adopted intraoperative facial nerve monitoring. Furthermore, significant gaps concerning the procedure exist. It is imperative to establish standards or guidelines to promote its better development and application.

Objective To assess the efficacy and safety of ascending aorta banding technique combined with typeⅠhybrid aortic arch repair for the aortic arch diseases. Methods The clinical data of patients undergoing ascending aorta banding technique combined with type Ⅰ hybrid arch repair for aortic arch diseases from March 2019 to March 2022 in Beijing Anzhen Hospital were retrospectively analyzed. The technical success, perioperative complications and follow-up results were evaluated. Results A total of 44 patients were collected, including 35 males and 9 females, with a median age of 63.0 (57.5, 64.6) years. The average EuroSCORE Ⅱ score was 8.4%±0.7%. The technical success rate was 100.0%. All patients did not have retrograde type A aortic dissection and endoleaks. One patient died of multiple organ failure 5 days after operation, the in-hospital mortality rate was 2.3%, and the remaining 43 patients survived and were discharged from hospital. The median follow-up period was 14.5 (6-42) months with a follow-up rate of 100.0%. One patient with spinal cord injury died 2 years after hospital discharge. One patient underwent thoracic endovascular aortic repair at postoperative 3 months due to new entry tears near to the distal end of the stent. Conclusion Ascending aorta banding combined with typeⅠhybrid arch repair for the aortic arch diseases does not need cardio-pulmonary bypass. Ascending aorta banding technique strengthens the proximal anchoring area of the stent to avoid risks such as retrograde type A dissection, endoleak and migration. The operation owns small trauma, rapid recovery, low mortality and a low rate of reintervention, which may be considered as a safe and effective choice in the treatment of the elderly, high-risk patients with complex complications.

Arabidopsis thaliana is an important and long-established model species for plant molec-ular biology,genetics,epigenetics,and genomics.However,the latest version of reference genome still contains a significant number of missing segments.Here,we reported a high-quality and almost complete Col-0 genome assembly with two gaps(named Col-XJTU)by combining the Oxford Nanopore Technologies ultra-long reads,Pacific Biosciences high-fidelity long reads,and Hi-C data.The total genome assembly size is 133,725,193 bp,introducing 14.6 Mb of novel sequences compared to the TAIR1 0.1 reference genome.All five chromosomes of the Col-XJTU assembly are highly accurate with consensus quality(QV)scores＞60(ranging from 62 to 68),which are higher than those of the TAIR10.1 reference(ranging from 45 to 52).We completely resolved chro-mosome(Chr)3 and Chr5 in a telomere-to-telomere manner.Chr4 was completely resolved except the nucleolar organizing regions,which comprise long repetitive DNA fragments.The Chr1 cen-tromere(CEN1),reportedly around 9 Mb in length,is particularly challenging to assemble due to the presence of tens of thousands of CEN180 satellite repeats.Using the cutting-edge sequencing data and novel computational approaches,we assembled a 3.8-Mb-long CEN1 and a 3.5-Mb-long CEN2.We also investigated the structure and epigenetics of centromeres.Four clusters of CEN180 monomers were detected,and the centromere-specific histone H3-like protein(CENH3)exhibited a strong preference for CEN 180 Cluster 3.Moreover,we observed hypomethylation patterns in CENH3-enriched regions.We believe that this high-quality genome assembly,Col-XJTU,would serve as a valuable reference to better understand the global pattern of centromeric polymorphisms,as well as the genetic and epigenetic features in plants.

Complex structural variants(CSVs)are genomic alterations that have more than two breakpoints and are considered as the simultaneous occurrence of simple structural variants.How-ever,detecting the compounded mutational signals of CSVs is challenging through a commonly used model-match strategy.As a result,there has been limited progress for CSV discovery com-pared with simple structural variants.Here,we systematically analyzed the multi-breakpoint con-nection feature of CSVs,and proposed Mako,utilizing a bottom-up guided model-free strategy,to detect CSVs from paired-end short-read sequencing.Specifically,we implemented a graph-based pattern growth approach,where the graph depicts potential breakpoint connections,and pattern growth enables CSV detection without pre-defined models.Comprehensive evaluations on both simulated and real datasets revealed that Mako outperformed other algorithms.Notably,validation rates of CSVs on real data based on experimental and computational validations as well as manual inspections are around 70％,where the medians of experimental and computational breakpoint shift are 13 bp and 26 bp,respectively.Moreover,the Mako CSV subgraph effectively characterized the breakpoint connections of a CSV event and uncovered a total of 15 CSV types,including two novel types of adjacent segment swap and tandem dispersed duplication.Further analysis of these CSVs also revealed the impact of sequence homology on the formation of CSVs.Mako is publicly available at https://github.com/xjtu-omics/Mako.

Objective:To explore the application of cannulating the ischemic femoral and right axillary artery in Sun’s procedure for acute type A aortic dissection with lower extremity ischemia.Methods:Twelve patients of acute Stanford type A aortic dissection complicated by lower extremity ischemia were analyzed retrospectively between July 2017 and May 2019, and the right axillary and ischemic femoral artery were used for cardiopulmonary bypass. All the 12 patients were male and categorized as the complicated Stanford type A aortic dissection. The mean age was(48.4±8.4)years, and the median time from symptom onset to emergency operation was 24.00(18.50, 43.25)hours. Eleven patients presented with unilateral extremity ischemia, while bilateral extremity ischemia occurred in one. The prosthetic vessel, with a diameter of 8 mm, was anastomosed to the ischemic femoral artery via an end-to-side way. Both the right axillary artery and the prosthetic vessel were cannulated for CPB. For the proximal dissection in this cohort of patients, we performed Bentall procedure in 5 cases, ascending aortic replacement in 3, and the aortic valve commissure reconstruction with ascending aortic replacement in 4. Total arch replacement with stented elephant trunk implantation were carried out for arch and descending aortic lesion in 12 cases.Results:Early mortality was 8.3%(1/12). The time of CPB, aortic clamp, circulatory arrest, and selective cerebral perfusion averaged(204.6±26.3) min, (114.6±16.6) min, (23.4±8.5) min, and(33.5±11.0) min, respectively. Five patients underwent concomitant bypass procedures, including: ascending aorta-bilateral femoral artery bypass in 1, ascending aorta-right femoral artery bypass in 3, ascending aorta-left femoral artery bypass in 1. Acute renal failure with continuous renal replacement therapy occurred in 4 cases, re-thoratomy for hemaostsis in 1, and re-intubation in 1. One patient developed osteofascial compartment syndrome after aortic repair, and consequent left lower extremity compartment fasciotomy was performed. The mean follow-up time was(17.2±7.6)months, and no aortic-related adverse event was detected during follow up.Conclusion:To acute Stanford type A aortic dissection with lower extremity ischemia, cannulating the ischemic femoral and right axillary artery in Sun’s procedure were associated with lower perioperative mortality and better prognosis.

Objective:To evaluate the application of moderate hypothermia circulatory arrest(MHCA)with a higher temperature(29℃) and bilateral selective antegrade cerebral perfusion(bSACP) in acute Stanford type A aortic dissection(TAAD] treated by total arch replacement with stented elephant trunk implantation.Methods:From July 2019 to January 2020, fifteen patients of acute TAAD undergoing emergent operations via MHCA with a core temperature of 29℃ and bSACP were analyzed retrospectively(modified group), and 26 patients treated by MHCA(25℃) and unilateral selective antegrade cerebral perfusion(uSACP) during the same period were defined as the traditional group. All cases were complicated type A dissection. The mean age in this cohort was 49 years, and 32 patients(78%) were male. Thirty six patients(87.8%) suffered from arterial hypertension. The proximal manipulations included: aortic sinus repair in 13 cases(31.7%), ascending aortic replacement in 29(70.7%), Bentall in 12(29.3%). Total arch replacement with stented elephant trunk implantation was performed in all cases.Results:The in-hospital death occurred in 2(4.9%), and cerebral infarction in 3(7.3%), transient neurologic deficit in 5(12.2%), paraplegia in 2(4.9%). The ratios of above-mentioned adverse events in the traditional and modified group were[2(7.7%) vs. 0, P=0.524], [3(11.5%)vs. 0, P=0.287], [4(15.4%) vs. 1(6.7%), P=0.636], [1(3.8%) vs. 1(6.7%), P=1.000] respectively. The major adverse events in the modified group were transient neurologic deficit and paraplegia in 1 each. Compared with the traditional group, the time of operation, CPB, cardiac arrest, circulatory arrest of the lower part, anterograde low flow cerebral perfusion, mechanical ventilation and ICU stay was shorter. The drainage of 48 hours after surgery was less also. The differences in new acute renal failure requiring CRRT and re-sternotomy for bleeding between groups were not statistical significance. Conclusion:The early results of MHCA(29℃) and bSACP applied in total arch replacement with stented elephant trunk implantation for acute TAAD were satisfactory. The time of mechanical ventilation and ICU stay was shorter in the modified group, and the drainage of 48 hours after surgery was less also.

Objective To explore the relationship between single nucleotide polymorphism (SNP) locus rs1058587,rs1059519 and rs1059369 polymorphisms of growth differentiation factor-15 (GDF-15)gene and susceptibility to chronic Keshan disease in Gansu Province.Methods Using the case-control study method,56 individuals with chronic Keshan disease were taken as case group,and 53 individuals without chronic Keshan disease from the same villages were selected as control group in Gansu Keshan disease areas,venous blood samples were collected,and ethylenediamine tetraacetic acid disodium salt (EDTA) was used for anticoagulation,and the samples were sent for gene sequencing.Univariate and multivariate logistic regression analyses were conducted to analyze the influence of genotypes of rs1058587,rs1059519 and rs1059369 on the prevalence of chronic Keshan disease,and the risk factors for disease were expressed as odds ratio (OR).Results The age of the 56 patients in the case group was (60.93 + 21.99) years old,15 males and 41 females;the age of the 53 residents in control group was (47.49-+ 33.61) years old,26 males and 27 females.There was no significant difference in age between the two groups (t =46.16,P ＞ 0.05);the difference in gender was statistically significant (x2=5.76,P ＜ 0.05).The differences of allele frequencies of case group and control group rs1058587 (C:36.6％,32.1％,G:63.4％,67.9％),rs1059369 (A:61.6％,72.6％,T:38.4％,27.4％) between the two groups were not significantly different (x2 =0.50,3.00,P ＞ 0.05);the differences of allele frequencies of GDF-15 rs1059319 (C:25.0％,40.6％,G:75.0％,59.4％) between the two groups were significantly different (x2 =6.01,P ＜ 0.05).The genotype frequency distribution of GDF-15 gene rs1058587,rs1059519 and rs1059369 in the case group and the control group was not significantly different between the groups (P ＞ 0.05).However,in the case group,the mutant GG frequency of rs1059519 locus was higher than wild type CC (x2 =5.33,P ＜ 0.05).In multivariate logistic regression analysis,women were 3.81 times more likely to suffer from chronic Keshan disease than men,and people aged 45 or older were 5.30 times more likely to suffer from chronic Keshan disease than those younger than 45.The heterozygous and mutant types of GDF-15 gene rs1058587 and rs1059369 were compared with wild type,and the difference was not statistically significant (ORrs1058587 =0.46,0.50,ORrs1059369 =1.30,2.59,P ＞ 0.05);there was no significant difference between the heterozygous type of GDF-15 gene rs1059519 and wild type (OR =3.34,P ＞ 0.05),and the difference between the mutant and wild type was statistically significant (OR =8.58,P ＜ 0.05).Conclusions In this study,we find women of the study population are more likely to have chronic Keshan disease than men,and aged≥45 is a risk factor for chronic Keshan disease.Genetic polymorphisms of GDF-15 gene rs1058587,rs1059369 are not associated with susceptibility to chronic Keshan disease,and a certain correlation between genetic polymorphism of rs1059519 locus and susceptibility to chronic Keshan disease.

Objective To confirm the impact of renal malperfusion on early and late outcomes of patients undergoing sur-gery for type A aortic dissection(TAAD). Methods From June 2011 to July 2012,a total of 165 TAAD patients undergoing surgery in hospital were enrolled and divided into 2 groups based on the results:research group(complicated with renal malper-fusion),control group(without renal malperfusion). A cohort follow-up project was conducted among these patients. The pri-mary outcome was all-cause death. Baseline and operative characteristics,early and late outcomes were analyzed to assess difference between 2 groups. Cumlative survival rates within 72 months among the 2 groups was described with Kaplan-Meier curves. Cox proportional hazards model was used to estimate the hazard ratios(HR)and 95％ confidence intervals(95％ CI)of late mortality among the 2 groups. Results Renal malperfusion was detected in 38(23. 0％)of 165 TAAD patients. 30-day mortality was 15. 8％ and 3. 9％ in patients with and without renal malperfusion(P < 0. 05),respectively. The mean follow-up period was(67 ± 3)months,late survival was 68. 4％ in patients with renal malperfusion and 88. 2％ in patients without(P <0. 05). By Cox proportional hazards model,after adjusting forage,sex,group(acute or chronic),presence of cardiac tampon-ade,brachiocephalic vessels involvement,coronary arteries involvement,root replacement,total arch replacement,concomitant coronary artery bypass grafting(CABG)and other organ-malperfusion,when compared to the control group,the HR(95％ CI) of late mortality was 5. 18( 1. 07 - 5. 18)in the research group. Besides renal malperfusion,concomitant coronary artery bypass grafting was presented as an independent risk factor of long-term survival(HR = 10. 08,95％ CI:2. 28 - 44. 62,P = 0. 002). Conclusion Coexistence of renal malperfusion is associated with a substantially increased risk of death in patients undergoing surgery for TAAD. A more exact stratification that weight every malperfusion-affected organ but not base on the number of malp-erfusion-affected organ simply may be more helpful to TAAD patients with malperfusion syndrome.