Protocol for the FACE study:frailty and comorbidity in elderly patients—a multicenter,Chinese observational cohort study

The present protocol describes an observational cohort study that was designed to propose a therapeutic scheme and formulate an individualized treatment strategy for frail elderly patients diagnosed with multiple diseases in a Chinese,multicenter setting.Over a 3-year period,we will recruit 30,000 patients from 10 hospitals and collect baseline data including patient demographic information,comorbidity characteristic,FRAIL scale,age-adjusted Charlson comorbidity index(aCCI),relevant blood tests,the results of imaging examination,prescription of drugs,length of hospital stay,number of overall re-hospitalizations and death.Elderly patients(≥65 years old)with multimorbidity and receiving hospital care are eligible for this study.Data collection is being performed at baseline and 3,6,9 and 12 months after discharge.Our primary analysis was all-cause death,readmission rate and clinical events(including emergency visits,stroke,heart failure,myocardial infarction,tumor,acute chronic obstructive pulmonary disease,etc).The study is approved by the National Key R&D Program of China(2020YFC2004800).Data will be disseminated in manuscripts submitted to medical journals and in abstracts submitted to international geriatric conferences.Clinical Trial Registration:[www.ClinicalTrials.gov],identifier[ChiCTR2200056070].

腹腔镜和开腹手术治疗胃间质瘤的安全性及肿瘤学疗效比较

目的对比腹腔镜与开腹术治疗胃间质瘤的临床疗效及安全性。方法选取2009年1月-2012年12月丰南区医院门诊确诊且进行手术治疗的连续胃间质瘤患者为研究对象,按手术方式分为腹腔镜组(58例)及开腹术组(47例)。对比两组的围手术期情况、术后恢复情况及随访期生存情况。结果两组的手术方式大致相同(P>0.05),但腹腔镜组的手术时间、术中出血量、恢复肛门排气时间、恢复全流食、半流食的时间、住院时间低于开腹组(P<0.05),其术中风险等级也优于开腹组(P<0.05);腹腔镜组均快于开腹组(P<0.05);术后并发症的Clavien-Dinbo评级,腹腔镜组以I、II级为主,开腹组以II、III级为主,开腹组的并发症情况较腹腔镜组更为严重(P<0.05);此外,开腹组术后进行辅助治疗者的比例高于腹腔镜组(P<0.05);腹腔镜组复发率6.7%,低于开腹组10.6%,两组相比差异无统计学意义(P>0.05);3年无瘤生存率94.5%,高于开腹组,两组相比差异无统计学意义(P<0.05)。结论腹腔镜手术相对于开腹术具备更好的手术安全性与更低的术中风险,有利于促进恢复。其近期肿瘤学疗效与开腹术相当,今后的研究应注重其远期肿瘤学疗效。

黄芪桂枝五物汤联合悬吊训练治疗不完全性脊髓损伤患者的康复效果分析

目的探讨黄芪桂枝五物汤联合悬吊训练治疗不完全性脊髓损伤患者的康复效果及对血清胶质纤维酸性蛋白(GFAP)、神经生长因子(NGF)的影响。方法选取2018年2月—2019年12月河北北方学院附属第一医院收治的32例不完全性脊髓损伤患者为研究对象,随机分为对照组、研究组,每组16例。对照组给予常规综合康复训练联合悬吊训练治疗,研究组在对照组基础上另给予黄芪桂枝五物汤,两组均持续治疗8周后评价效果。记录两组中医症状积分及临床疗效,统计两组肌力、肌张力及下肢运动功能情况,对比两组平衡能力及日常生活活动功能的变化,记录两组血清NGF、GFAP及不良事件发生情况。结果研究组治疗前后的主症、次症中医证候评分,以及徒手肌力评定评分、改良Ashworth痉挛量表评分的下降程度大于对照组(P<0.05)。研究组总有效率高于对照组(P<0.05)。研究组治疗前后下肢运动评分、功能性步行能力量表评分、Berg平衡量表评分、Barthel指数(BI)评分、NGF、GFAP的差值高于对照组(P<0.05)。两组治疗期间无不良事件发生。结论黄芪桂枝五物汤治疗不完全性脊髓损伤患者可提高康复效果,改善肌力、肌张力、下肢运动功能、日常生活能力及神经营养因子,且安全性良好。

Characteristics and prognosis of gastric cancer in patients aged ≥ 70 years

AIM:To elucidate the prognostic value of age for gastric cancer and identify the optimal treatment for elderly gastric cancer patients.METHODS:We enrolled 920 patients with gastric cancer who underwent gastrectomy between January 2003and December 2007 in our center.Patients were categorized into three groups:younger group(age<50years),middle-aged group(50-69 years),and elderly group(≥70 years).Clinicopathological features were compared among the three groups and potential prognostic factors were analyzed.The log-rank test was used to assess statistical differences between curves.Independent prognostic factors were identified by the Cox proportional hazards regression model.Stratified analysis was used to investigate the impact of age on survival at each stage.Cancer-specific survival was also compared among the three groups by excluding deaths due to reasons other than gastric cancer.We analyzed the potential prognostic factors for patients aged≥70years.Finally,the impact of extent of lymphadenectomy and postoperative chemotherapy on survival for each age group was evaluated.RESULTS:In the elderly group,there was a male predominance.At the same time,cancers of the upper third of the stomach,differentiated type,and less-invasive surgery were more common than in the younger or middle-aged groups.Elderly patients were more likely to have advanced tumor-node-metastasis(TNM)stage and larger tumors,but less likely to have distant metastasis.Although 5-year overall survival(OS)rate specific to gastric cancer was not significantly different among the three groups,elderly patients demonstrated a significantly lower 5-year OS rate than the younger and middle-aged patients(elderly vs middle-aged vs younger patients=22.0%vs 36.6%vs 38.0%,respectively).In the TNM-stratified analysis,the differences in OS were only observed in patients withⅡandⅢtumors.In multivariate analysis,only surgical margin status,pT4,lymph node metastasis,M1 and sex were independent prognostic factors for elderly patients.The5-year OS rate did not differ between elderly patients undergoing D1 and D2 lymph node resection,and these patients benefited little from chemotherapy.CONCLUSION:Age≥70 years was an independent prognostic factor for gastric cancer after gastrectomy.D1 resection is appropriate and postoperative chemotherapy is possibly unnecessary for elderly patients with gastric cancer.

Impact of intraoperative blood loss on survival after curative resection for gastric cancer

AIM:To elucidate the potential impact of intraoperative blood loss(IBL)on long-term survival of gastric cancer patients after curative surgery.METHODS:A total of 845 stageⅠ-Ⅲgastric cancer patients who underwent curative gastrectomy between January 2003 and December 2007 in our center were enrolled in this study.Patients were divided into 3groups according to the amount of IBL:group 1(<200mL),group 2(200-400 mL)and group 3(>400 mL).Clinicopathological features were compared among the three groups and potential prognostic factors were analyzed.The Log-rank test was used to assess statistical differences between the groups.Independent prognostic factors were identified by the Cox proportional hazards regression model.Stratified analysis was used to investigate the impact of IBL on survival in each stage.Cancer-specific survival was also compared among the three groups by excluding deaths due to reasons other than gastric cancer.Finally,we explored the possible factors associated with IBL and identified the independent risk factors for IBL≥200 mL.RESULTS:Overall survival was significantly influenced by the amount of IBL.The 5-year overall survival rates were 51.2%,39.4%and 23.4%for IBL less than 200mL,200 to 400 mL and more than 400 mL,respectively(<200 mL vs 200-400 mL,P<0.001;200-400 mL vs>400 mL,P=0.003).Age,tumor size,Borrmann type,extranodal metastasis,tumour-node-metastasis(TNM)stage,chemotherapy,extent of lymphadenectomy,IBL and postoperative complications were found to be independent prognostic factors in multivariable analysis.Following stratified analysis,patients staged TNMⅠ-Ⅱand those with IBL less than 200 mL tended to have better survival than those with IBL not less than 200mL,while patients staged TNMⅢ,whose IBL was less than 400 mL had better survival.Tumor location,tumor size,TNM stage,type of gastrectomy,combined organ resection,extent of lymphadenectomy and year of surgery were found to be factors associated with the amount of IBL,while tumor location,type of gastrectomy,combined organ resection and year of surgery were independently associated with IBL≥200 mL.CONCLUSION:IBL is an independent prognostic factor for gastric cancer after curative resection.Reducing IBL can improve the long-term outcome of gastric cancer patients following curative gastrectomy.

The bZIP transcription factor MdHY5 regulates anthocyanin accumulation and nitrate assimilation in apple

The basic leucine zipper(bZIP)transcription factor HY5 plays a multifaceted role in plant growth and development.Here the apple MdHY5 gene was cloned based on its homology with Arabidopsis HY5.Expression analysis demonstrated that MdHY5 transcription was induced by light and abscisic acid treatments.Electrophoretic mobility shift assays and transient expression assays subsequently showed that MdHY5 positively regulated both its own transcription and that of MdMYB10 by binding to E-box and G-box motifs,respectively.Furthermore,we obtained transgenic apple calli that overexpressed the MdHY5 gene,and apple calli coloration assays showed that MdHY5 promoted anthocyanin accumulation by regulating expression of the MdMYB10 gene and downstream anthocyanin biosynthesis genes.In addition,the transcript levels of a series of nitrate reductase genes and nitrate uptake genes in both wild-type and transgenic apple calli were detected.In association with increased nitrate reductase activities and nitrate contents,the results indicated that MdHY5 might be an important regulator in nutrient assimilation.Taken together,these results indicate that MdHY5 plays a vital role in anthocyanin accumulation and nitrate assimilation in apple.

B cell receptor signaling pathway involved in benign lymphoepithelial lesions of the lacrimal gland

AIM：To detect the expression of B cell receptor signaling pathway（BCRSP） in lacrimal gland benign lymphoepithelial lesions（LGBLEL）.METHODS：Gene microarray was used to compare whole-genome expression in lacrimal gland tissues from LGBLEL patients to tissues from orbital cavernous hemangioma（control tissues）. Expression of BCRSP was confirmed by polymerase chain reaction（PCR） and immunohistochemistry. RESULTS：The expression of 22 genes of the BCRSP increased significantly in LGBLEL patients. PCR analysis showed that CD22, CR2, and BTK were all highly expressed in LGBLEL tissues. Immunohistochemical analysis showed that CR2 protein was present in LGBLEL, but CD22 and BTK proteins were negative. CR2, CD22, and BTK were not observed in the orbital cavernous hemangiomas with either PCR or immunohistochemistry. CONCLUSION：BCRSP might be involved in the pathogenesis of LGBLEL.

Association of TCR-signaling pathway with the development of lacrimal gland benign lymphoepithelial lesions

·AIM: To identify the association of the T cell receptor(TCR) signaling with the development of benign lymphoepithelial lesions(BLEL) of the lacrimal gland.· METHODS: We collected affected lacrimal gland tissues from 9 patients who underwent dacryoadenectomy in the Capital Medical University Beijing Tongren Hospital Eye Center between August2010 and March 2013 and were confirmed to have lacrimal gland BLEL by histopathological analysis. Tumor tissues from 9 patients with orbital cavernous hemangioma were also collected and used as control.Whole genome gene expression microarray was used to compare gene expression profiles of affected lacrimal gland tissues from patients with lacrimal gland BLEL to those from of orbital cavernous hemangiomas.Differential expression of TCR pathway genes between these tissues was confirmed by polymerase chain reaction(PCR) and immunohistochemistry.·RESULTS: Microarray analysis showed that in lacrimal glands with BLEL, 32 signaling pathways were enriched in the upregulated genes, while 25 signaling pathways were enriched in the downregulated genes. In-depth analysis of the microarray data showed that the expression of 27 genes of the TCR signaling pathway increased significantly. To verify the differential expression of three of these genes, CD3, CD4, and interleukin(IL)-10, reverse transcription-PCR(RT-PCR)and immunohistochemistry assays were performed. RT-PCR analysis showed that CD3 and CD4 were expressed in the lacrimal glands with BLEL, but IL-10 was not expressed. Immunohistochemistry confirmed that CD3 and CD4 proteins were also present, but IL-10 protein was not. CD3, CD4, or IL-10 expression was not found in the orbital cavernous hemangiomas with either RT-PCR or immunohistochemistry.· CONCLUSION: TCR signaling pathway might be involved in the pathogenesis of lacrimal gland BLEL.

The antioxidant activity and hypolipidemic activity of the total flavonoids from the fruit of Rosa laevigata Michx

In the present work, the antioxidant activity in vitro and hypolipidemic activity of the total fla-vonoids (TFs) from the Rosa laevigata Michx fruit was evaluated, and the antioxidant effect in vivo was also discussed. The TFs exhibited a high scavenging effect on 2, 2-diphenyl-1- picrylhydrazyl (?DPPH) with IC50 values 0.01 mg/mL, and a stong reduce power in the test. Hyperli-pemic mice were intragastric administrated with TFs (25, 50 mg/kg/day) for 4 weeks, and fenofi-brate was used as the positive reference sub-stance. After the experiment, the levels of TC (total cholesterol), TG (triglyceride), LDL- C (low density lipoprotein-cholesterol) of the mice ad-ministrated with high-dose of TFs were mark-edly declined by 45.02%, 33.86% and 73.68%, re-spectively, while HDL-C (high density lipopro-tein-cholesterol) was significantly increased com-pared with model group. To investigate the hepatoprotective effect, histopathological assay, ALT (alanine aminotransferase), AST (aspartate aminotransefrase) and ALP (alkaline phosphatase) were also studied, and the results showed that TFs exhibited a favorable effect on liver protec-tion, of which the levels of ALT, AST and ALP were elevated by 55.85%, 29.15% and 25.68%, respectively. Furthermore, the TFs could sig-nificantly decrease the MDA (malondialdehyde) level and improve the levels of CAT (Catalas), SOD (superoxide dismutase), GSH (reduced glutathione), and GPX (glutathione peroxidase) compared with hyperlipemia mice. Our results suggested that TFs has a high antioxidant ac-tivity and hypolipidemic activity, which can be used as a potential medicine for cardiovascular diseases.

Effects of extended lymphadenectomy and postoperative chemotherapy on node-negative gastric cancer

AIM:To investigate the effects of extended lymphadenectomy and postoperative chemotherapy on gastric cancer without lymph node metastasis.METHODS:Clinical data of 311 node-negative gastric cancer patients who underwent potentially curative gastrectomy with more than 15 lymph nodes resected,from January 2002 to December 2006,were analyzed retrospectively.Patients with pT4 stage or distant metastasis were excluded.We analyzed the relationship between the D2 lymphadenectomy and the 5-year survival rate among different subgroups stratified by clinical features,such as age,tumor size,tumor location and depth of invasion.At the same time,the relationship between postoperative chemotherapy and the5-year survival rate among different subgroups were also analyzed.RESULTS:The overall 5-year survival rate of the entire cohort was 63.7%.The 5-year survival rate was poor in those patients who were:(1)more than 65 years old;(2)with tumor size larger than 4 cm;(3)with tumor located in the upper portion of the stomach;and(4)with pT3 tumor.The survival rate was improved significantly by extended lymphadenectomy only in patients with pT3 tumor(P=0.019),but not in other subgroups.Moreover,there was no significant difference in survival rate between patients with and without postoperative chemotherapy among all of the subgroups(P>0.05).CONCLUSION:For gastric cancer patients without lymph node metastasis,extended lymphadenectomy could improve the survival rate of those who have pT3-stage tumor.However,there was no evidence of a survival benefit from postoperative chemotherapy alone.

Chemistry and bioactivities of natural steroidal alkaloids

Steroidal alkaloids possess the basic steroidal skeleton with a nitrogen atom in rings or side chains incorporated as an integral part of the molecule.They have demonstrated a wide range of biological activities,and some of them have even been developed as therapeutic drugs,such as abiraterone acetate(Zytiga®),a blockbuster drug,which has been used for the treatment of prostate cancer.Structurally diverse natural steroidal alkaloids present a wide spectrum of biological activities,which are attractive for natural product chemistry and medicinal chemistry communities.This review comprehensively covers the structural classification,isolation and various biological activities of 697 natural steroidal alkaloids discovered from 1926 to October 2021,with 363 references being cited.

MdbHLH162 connects the gibberellin and jasmonic acid signals to regulate anthocyanin biosynthesis in apple

Anthocyanins are secondary metabolites induced by environmental stimuli and developmental signals.The positive regulators of anthocyanin biosynthesis have been reported,whereas the anthocyanin repressors have been neglected.Although the signal transduction pathways of gibberellin(GA)and jasmonic acid(JA)and their regulation of anthocyanin biosynthesis have been investigated,the cross-talk between GA and JA and the antagonistic mechanism of regulating anthocyanin biosynthesis remain to be investigated.In this study,we identified the anthocyanin repressor MdbHLH162 in apple and revealed its molecular mechanism of regulating anthocyanin biosynthesis by integrating the GA and JA signals.MdbHLH162 exerted passive repression by interacting with MdbHLH3 and MdbHLH33,which are two recognized positive regulators of anthocyanin biosynthesis.MdbHLH162 negatively regulated anthocyanin biosynthesis by disrupting the formation of the anthocyanin-activated MdMYB1-MdbHLH3/33complexes and weakening transcriptional activation of the anthocyanin biosynthetic genes MdDFR and MdUF3GT by MdbHLH3 and MdbHLH33.The GA repressor MdRGL2a antagonized MdbHLH162-mediated inhibition of anthocyanins by sequestering MdbHLH162 from the MdbHLH162-MdbHLH3/33 complex.The JA repressors MdJAZ1 and MdJAZ2 interfered with the antagonistic regulation of MdbHLH162 by MdRGL2a by titrating the formation of the MdRGL2a-MdbHLH162 complex.Our findings reveal that MdbHLH162 integrates the GA and JA signals to negatively regulate anthocyanin biosynthesis.This study provides new information for discovering more anthocyanin biosynthesis repressors and explores the cross-talk between hormone signals.

Antifungal alkaloids from Mahonia fortunei against pathogens of postharvest fruit

Postharvest pathogens can affect a wide range of fresh fruit and vegetables,including grapes,resulting in significant profit loss.Isoquinoline alkaloids of Mahonia fortunei,a Chinese herbal medicine,have been used to treat infectious microbes,which might be effective against postharvest pathogens.The phytochemical and bioactive investigation of this plant led to the isolation of 18 alkaloids,of which 9 compounds inhibited the growth of Botrytis cinerea and 4 compounds against Penicillium italicum.The antifungal alkaloids could change the mycelium morphology,the total lipid content,and leak the cell contents of B.cinerea.Furthermore,the two most potent antifungal alkaloids,berber-ine(13)completely inhibited effect on gray mold of table grape at 512 mg L^(−1),while jatrorrhizine(18)exhibited an inhibition rate>90%on grape rot at the same concentration,with lower cytotoxicity and residue than chlorothalonil,which suggested that ingredients of M.fortunei might be a low-toxicity,low-residue,eco-friendly botanical fungicide against postharvest pathogens.

Clinical Research on Benign Lymphoepithelial Lesions of Lacrimal Gland in 20 Chinese Patients

Background：Benign lymphoepithelial lesion （BLEL） is characterized by symmetric bilateral swelling of the lacrimal and salivary glands and considered a subtype of immunoglobulin G4 （IgG4）-related sclerosing disease,the etiology and pathogenesis of which has not been determined.The purpose of the present study was to analyze the clinical features of BLEL in the lacrimal gland and the relationship between the serum level of IgG4 and BLEL.Methods：Twenty consecutive patients with BLEL diagnosed in Department of Ophthalmology at Beijing Tongren Hospital,Capital Medical University between January 2012 and December 2013 were observed.The clinical features,imaging findings,laboratory tests,treatments and follow-up status of these 20 consecutive patients were analyzed.Results：In all 20 patients,the ratio of male to female was 1：4,the ages ranged from 28 to 57 years,the ratio of unilateral to bilateral eyes involvement was 1：4,and painless uncongested symmetrical swelling of the upper eyelid was the main clinical manifestation.Orbital magnetic resonance imaging （MRI） showed that all patients involved lacrimal gland,which were obviously enlarged with equal signals in T1W images and T2W images and obvious enhancement on contrast MRI.Extraocular muscles were involved in 5 patients,salivary gland in 8 patients,and frontal nerve in 3 patients.Serum IgG4 concentration was elevated in 18 patients.The treatment strategy mainly included surgery and steroid administration.Three patients were lost to follow-up,17 patients reached complete response,and no recurrence was observed.Conclusions：Eyelid swelling is the typical symptom of BLEL.Most of the patients involved bilateral lacrimal glands.High serum IgG4 level and abundant IgG4-positive plasma cell infiltration are the important features,which can be found in most of BLEL patients.Surgery combined with glucocorticoids is an efficient treatment strategy.

Daytime hypercapnia in adult patients with obstructive sleep apnea in China

To the Editor:Obstructive sleep apnea(OSA)is a common sleep-disordered breathing.Previous studies reported that the incidence of daytime hypercapnia in patients with OSA was 26.2%in China[1]and 14%in Japan.[2]However,Weitzenblum et al[3]demonstrated that daytime hypercapnia in patients with OSA might not be secondary to sleep apneas/hypopneas,but might due to the comorbidities,such as chronic obstructive pulmonary disease or severe obesity.Obesity hypoventilation syndrome(OHS)is defined as a conjunction of obesity(body mass index[BMI]≥30 kg/m^(2)),daytime hypercapnia(partial pressure of carbon dioxide in arterial blood[PaCO_(2)]≥45 mmHg)and sleep disordered breathing,after excluding other causes for alveolar hypoventilation.[4]Since patients with OHS were not completely excluded in previous studies,[1,2]we assumed that the incidence of daytime hypercapnia in Chinese patients with OSA might be low.

Percutaneous Endoscopic Lumbar Discectomy on L5-S1： Comparison of Modified Knee-Chest and Prone Position in Terms of Foraminal Height and Puncture Time

To the Editor： Percutaneous endoscopic lumbar discectomy （PELD） becomes increasingly popular among spine surgeries in recent years. PELD is one of the minimally invasive spine surgeries with significant advantages including small incision, less muscle stripping, and enhanced postoperative recovery.

Carbon nanomaterials： controlled growth and field-effect transistor biosensors

Carbon nanostructures, including carbon nanotubes （CNTs） and gra- phene, have been studied extensively due to their special structures, excellent electrical properties and high chemical stability. With the development of nanotechnology and nanoscience, various methods have been developed to synthesize CNTs/graphene and to assemble them into microelectroniclsensor devices. In this review, we mainly demon- strate the latest progress in synthesis of CNTs and graphene and their applications in field-effect transistors （FETs） for biological sensors.

Metal-free intramolecular hydroarylation of alkynes

An efficient metal-free intramolecular hydroarylation reaction of alkynes is described here.A series of aryl and N-group attached alkynes generated the intramolecular hydroarylation products in high yields.