Fine mapping and candidate gene analysis of CaFCD1 affecting cuticle biosynthesis in Capsicum annuum L.

KEY MESSAGE: CaFCD1 gene regulates pepper cuticle biosynthesis. Pepper (Capsicum annuum L.) is an economically important vegetable crop that easily loses water after harvesting, which seriously affects the quality of its product. The cuticle is the lipid water-retaining layer on the outside of the fruit epidermis, which regulates the biological properties and reduces the rate of water-loss. However, the key genes involved in pepper fruit cuticle development are poorly understood. In this study, a pepper fruit cuticle development mutant fcd1 (fruit cuticle deficiency 1) was obtained by ethyl methanesulfonate mutagenesis. The mutant has great defects in fruit cuticle development, and the fruit water-loss rate of fcd1is significantly higher than that of the wild-type '8214' line. Genetic analysis suggested that the phenotype of the mutant fcd1 cuticle development defect was controlled by a recessive candidate gene CaFCD1 (Capsicum annuum fruit cuticle deficiency 1) on chromosome 12, which is mainly transcribed during fruit development. In fcd1, a base substitution within the CaFCD1 domain resulted in the premature termination of transcription, which affected cutin and wax biosynthesis in pepper fruit, as revealed by the GC-MS and RNA-seq analysis. Furthermore, the yeast one-hybrid and dual-luciferase reporter assays verified that the cutin synthesis protein CaCD2 was directly bound to the promoter of CaFCD1, suggesting that CaFCD1 may be a hub node in the cutin and wax biosynthetic regulatory network in pepper. This study provides a reference for candidate genes of cuticle synthesis and lays a foundation for breeding excellent pepper varieties.

Effect of acupuncture combined with low frequency rTMS on comorbid mild-to-moderate depressive disorder and insomnia: a randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the impacts of acupuncture on depressive mood and sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia, and explore its effect mechanism.@*METHODS@#A total of 60 patients with comorbid mild-to-moderate depressive disorder and insomnia were randomly divided into an observation group (30 cases, 1 case dropped off) and a control group (30 cases, 2 cases dropped off). In the observation group, acupuncture and low frequency repeated transcranial magnetic stimulation (rTMS) were combined for the intervention. Acupuncture was applied to Baihui (GV 20), Yintang (GV 24+), Neiguan (PC 6) and Yanglingquan (GB 34), etc., the needles were retained for 30 min; and the intradermal needles were embedded at Xinshu (BL 15) and Danshu (BL 19) for 2 days. After acupuncture, the rTMS was delivered at the right dorsolateral prefrontal cortex (R-DLPFC), with 1 Hz and 80% of movement threshold, lasting 30 min in each treatment. In the control group, the sham-acupuncture was adopted, combined with low frequency rTMS. The acupoint selection and manipulation were the same as the observation group. In the two groups, acupuncture was given once every two days, 3 times weekly; while, rTMS was operated once daily, for consecutive 5 days a week. The duration of treatment consisted of 4 weeks. Hamilton depression scale-17 (HAMD-17) and Pittsburgh sleep quality index (PSQI) scores were observed before and after treatment, as well as 1 month after the treatment completion (follow-up period) separately. Besides, the levels of nerve growth factor (BDNF) and γ-aminobutyric acid (GABA) in the serum were detected before and after treatment in the two groups.@*RESULTS@#After treatment and in follow-up, the HAMD-17 scores were lower than those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than the control group (P<0.05). After treatment, the total scores and the scores of each factor of PSQI were reduced in the two groups in comparison with those before treatment except for the score of sleep efficiency in the control group (P<0.05); the total PSQI score and the scores for sleep quality, sleep latency, sleep efficiency and daytime dysfunction in the observation group were all lower than those in the control group (P<0.05). In the follow-up, except for the scores of sleep duration and sleep efficiency in the control group, the total PSQI score and the scores of all the other factors were reduced compared with those before treatment in the two groups (P<0.05); the total PSQI score and the scores of sleep quality, sleep latency, sleep duration, sleep efficiency and daytime dysfunction in the observation group were lower than the control group (P<0.05). After treatment, the levels of serum BDNF and GABA were increased in comparison with those before treatment in the observation group (P<0.05), and the level of serum BDNF was higher than that in the control group (P<0.05).@*CONCLUSION@#Acupuncture relieves depressive mood and improves sleep quality in patients with comorbid mild-to-moderate depressive disorder and insomnia. The effect mechanism may be related to the regulation of BDNF and GABA levels and the promotion of brain neurological function recovery.

Recent Advance of Newly Therapy for Chronic Myeloid Leukemia with BCR-ABLT315I Mutation--Review / 中国实验血液学杂志

BCR-ABLT315I mutation is the main mechanism of resistance to the first and second generation tyrosine kinase inhibitor (TKI) for patients with chronic myeloid leukemia (CML). Ponatinib as the third generation TKI has been found that can significantly improve the prognosis of CML patients with T315I mutation. However, the latest report has discovered that the T315I compound mutant is even resistant to ponatinib, which aroused the enthusiasm of research on the mechanism of CML resistance and targeted therapy once again. Previous studies have shown that TKI combined with other targeted drugs is effective to CML patients with drug resistance or relapse due to T315I mutation. The latest research has found that the allosteric inhibitor asciminib combined with TKI therapy is equally effective to CML patients with T315I compound mutant, but the specific mechanism is not yet clarified. This review will focus on the latest research progress of therapy for CML with BCR-ABLT315I mutation, hoping to provide reference for researching new drugs and improve therapy for treating CML with T315I mutation.

Regulations for the Manufacture and Control of Live Poliovirus Vaccine: International Experience and China's Path / 中国医学科学杂志(英文版)

The eradication of poliomyelitis is a landmark achievement in the history of public health, providing strong protection for children's health. The introduction of the Chinese Regulations for the Manufacture and Control of Live Poliovirus Vaccine is a prerequisite and safeguard for the large-scale production and use of domestically produced live poliovirus vaccines, serving as an indispensable component of vaccine safety. This article, based on archival documents, letters, collections of essays, and oral interviews, examines the historical experience of the development of Chinese Regulations for the Manufacture and Control of Live Poliovirus Vaccine. It contends that the emphasis on localization and the active engagement in international cooperation are critical factors in the swift introduction of Chinese Regulations for the Manufacture and Control of Live Poliovirus Vaccine.

Quality analysis of surgical specimens of rectal cancer in the Chinese taTME registry coll-aborative database: a nationwide registered study / 中华消化外科杂志

Objective:To analyze the quality of surgical specimens of rectal cancer in the Chinese transanal total mesorectal excision (taTME) registry collaborative (CTRC) database.Methods:The retrospective and descriptive study was conducted. Based on the concept of real-world research, the clinicopathological data of 1 761 patients with rectal cancer in the CTRC database who underwent taTME in 40 medical centers, including the Beijing Friendship Hospital of Capital Medical University et al, from November 15, 2017 to December 31, 2022 were collected. There were 1 212 males and 549 females, aged 62(range, 53-68)years. Observation indicators: (1) preoperative examinations; (2) neoadjuvant therapy; (3) postoperative examinations. Measurement data with skewed distri-bution were represented as M(range). Count data were described as absolute numbers. Results:(1) Preoperative examinations. Of the 1 761 patients, 1 324 patients underwent preoperative pelvic magnetic resonance imaging examination, and the results showed that 4 cases as clinical T0 stage, 30 cases as clinical T1 stage, 250 cases as clinical T2 stage, 828 cases as clinical T3 stage, 141 cases as clinical T4 stage, 11 cases as clinical Tx stage, 60 cases missing clinical T staging data, 490 cases as clinical N0 stage, 373 cases as clinical N1 stage, 311 cases as clinical N2 stage, 86 cases as clinical Nx stage, 64 cases missing clinical N staging data, 156 cases with mesorectal fascia invasion, 223 cases with extraintestinal blood vessels invasion. The distance from lower margin of tumor to anal margin of 1 324 patients was 50(range, 40-60)mm. (2) Neoadjuvant therapy. Of the 1 761 patients, 873 patients underwent neoadjuvant therapy, including 17 cases receiving radiotherapy alone, 155 cases receiving chemotherapy alone, 43 cases receiving short-course simultaneous chemoradiotherapy, 26 cases receiving short-course simultaneous chemoradiotherapy and delayed surgery, 1 case receiving contact radiotherapy, 277 cases receiving long-course simultaneous chemoradiotherapy, 9 cases receiving other treatments, and 345 cases missing neoadjuvant therapy data. (3) Postoperative examinations. Of the 1 761 patients, 1 584 cases achieved R 0 resection, 23 cases achieved R 1 resection, 1 case achieved R 2 resection, and there were 153 cases missing surgical margin data. The tumor diameter, number of lymph nodes harvest and positive rate of intravascular tumor thrombus were 30(range, 20-45)cm, 13(range, 10-17) and 20.794%(330/1 587) in 1 761 patients. There were 1 647 patients with circumferential margin records, which showed positive in 51 cases, and the minimum distance from deep part of tumor to circumferential margin was 5(rang, 3-13)mm in 1 647 patients. There were 547 cases with distal margin records, which showed positive in 4 cases, and the distance from lower margin of tumor to distal margin was 20(10-25)mm in 547 cases. There were 1 698 patients with specimen integrity records, which showed intact specimen in 1 436 cases, fair specimen in 233 cases, poor specimen in 8 cases, unevaluated specimen in 21 cases, and there were 20 cases with rectal tube perforation. Of the 1 761 patients, cases as pathological T0 stage, Tis stage, T1 stage, T2 stage, T3 stage, T4 stage was 103, 23, 145, 515, 712, 179, respectively, and there were 4 cases of pathology that could not be evaluated and 80 cases missing pathological T staging data. Of the 1 761 patients, cases as pathological N0 stage, N1a stage, N1b stage, N1c stage, N2a stage, N2b stage was 1 117, 189, 133, 66, 109, 68, respectively, and there were 79 cases missing pathological N staging data. Of the 1 761 patients, there were 79 cases with distant metastasis, 1 591 cases without distant metastasis, and 91 cases without data of tumor metastasis. Of the 873 patients undergoing neoadjuvant therapy, there were 405 patients with tumor regression grade records including 105 cases as grade 1, 142 cases as grade 2, 91 cases as grade 3, 43 cases as grade 4, 24 cases as grade 5. Conclusions:In China, the quality of surgical specimens of taTME for rectal cancer is good with low positive rate of resection margin. It is recommended that using a formatted postoperative pathological report for good quality control of pathological report of surgical specimen.

Effect of Shugan Tiaoshen acupuncture combined with western medication on depression-insomnia comorbidity due to COVID-19 quarantine: a multi-central randomized controlled trial / 中国针灸

OBJECTIVE@#To observe the effect of Shugan Tiaoshen acupuncture (acupuncture for soothing the liver and regulating the mentality) combined with western medication on depression and sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, and investigate the potential mechanism from the perspective of cortical excitability.@*METHODS@#Sixty patients with depression-insomnia comorbidity due to COVID-19 quarantine were randomly divided into an acupuncture group and a sham-acupuncture group, 30 cases in each one. The patients of both groups were treated with oral administration of sertraline hydrochloride tablets. In the acupuncture group, Shugan Tiaoshen acupuncture was supplemented. Body acupuncture was applied to Yintang (GV 24+), Baihui (GV 20), Hegu (LI 4), Zhaohai (KI 6), Qihai (CV 6), etc. The intradermal needling was used at Xin (CO15), Gan (CO12) and Shen (CO10). In the sham-acupuncture group, the sham-acupuncture was given at the same points as the acupuncture group. The compensatory treatment was provided at the end of follow-up for the patients in the sham-acupuncture group. In both groups, the treatment was given once every two days, 3 times a week, for consecutive 8 weeks. The self-rating depression scale (SDS) and insomnia severity index (ISI) scores were compared between the two groups before and after treatment and 1 month after the end of treatment (follow-up) separately. The cortical excitability indexes (resting motor threshold [rMT], motor evoked potential amplitude [MEP-A], cortical resting period [CSP]) and the level of serum 5-hydroxytryptamine (5-HT) were measured before and after treatment in the two groups.@*RESULTS@#After treatment and in follow-up, SDS and ISI scores were decreased in both groups compared with those before treatment (P<0.05), and the scores in the acupuncture group were lower than those in the sham-acupuncture group (P<0.05), and the decrease range in the acupuncture group after treatment was larger than that in the sham-acupuncture group (P<0.05). After treatment, rMT was reduced (P<0.05), while MEP-A and CSP were increased (P<0.05) in the acupuncture group compared with that before treatment. The levels of serum 5-HT in both groups were increased compared with those before treatment (P<0.05). The rMT in the acupuncture group was lower than that in the sham-acupuncture group, while MEP-A and CSP, as well as the level of serum 5-HT were higher in the acupuncture group in comparison with the sham-acupuncture group (P<0.05).@*CONCLUSION@#Shugan Tiaoshen acupuncture combined with western medication can relieve depression and improve sleep quality in the patients with depression-insomnia comorbidity due to COVID-19 quarantine, which is probably related to rectifying the imbalanced excitatory and inhibitory neuronal functions.

Case report: Successful treatment of acute generalized pustular psoriasis of puerperium with secukinumab.

Generalized pustular psoriasis (GPP) is a rare and severe form of psoriasis presenting with erythematous, aseptic pustules. Common systemic symptoms include fever and myalgias. The presentation of GPP resembles acute generalized exanthematous pustulosis (AGEP). However, the treatment of these two pathologies differs. While AGEP is self-limiting and treated with topical corticosteroids and constrain of systemic steroids. GPP treatment avoids corticosteroid, choosing acitretin, methotrexate, and cyclosporine as first-line agents. In this case report, a 27-year-old female with a medical history of AGEP presented to the hospital with extensive erythema and pustules. Complete blood count acute phase reactant analysis revealed an elevated white blood cell count and C-reactive protein (CRP). Two histopathological examinations revealed psoriatic hyperplasia of the epidermis with keratosis, along with Kogoj and Munro micro abscesses above the spina layer. Lymphocytic and neutrophilic infiltrate was present in the superficial derma layer along with vasodilation. The patient was diagnosed with GPP according to pathological and clinical criteria. Treatment was initiated with secukinumab because of the patient's failure to respond to systemic treatment with Acitretin, methotrexate, and cyclosporin. Following 2 weeks of therapy with 300 mg of secukinumab, the pustular lesions had resolved. This study indicates the potential efficacy of secukinumab as an effective therapy that can rapidly improve the clinical symptoms of GPP.

Comprehensive Proteome and Lysine Acetylome Analysis Reveals the Widespread Involvement of Acetylation in Cold Resistance of Pepper (Capsicum annuum L.).

Pepper is a typical warmth-loving vegetable that lacks a cold acclimation mechanism and is sensitive to cold stress. Lysine acetylation plays an important role in diverse cellular processes, but limited knowledge is available regarding acetylation modifications in the resistance of pepper plants to cold stress. In this study, the proteome and acetylome of two pepper varieties with different levels of cold resistance were investigated by subjecting them to cold treatments of varying durations followed by recovery periods. In total, 6,213 proteins and 4,574 lysine acetylation sites were identified, and this resulted in the discovery of 3,008 differentially expressed proteins and 768 differentially expressed acetylated proteins. A total of 1,988 proteins were identified in both the proteome and acetylome, and the functional differences in these co-identified proteins were elucidated through GO enrichment. KEGG analysis showed that 397 identified acetylated proteins were involved in 93 different metabolic pathways. The dynamic changes in the acetylated proteins in photosynthesis and the "carbon fixation in the photosynthetic organisms" pathway in pepper under low-temperature stress were further analyzed. It was found that acetylation of the PsbO and PsbR proteins in photosystem II and the PsaN protein in photosystem I could regulate the response of pepper leaves to cold stress. The acetylation levels of key carbon assimilation enzymes, such as ribulose bisphosphate carboxylase, fructose-1,6-bisphosphatase, sedoheptulose-1,7-bisphosphatase, glyceraldehyde 3-phosphate dehydrogenase, phosphoribulokinase, and triosephosphate isomerase decreased, leading to decreases in carbon assimilation capacity and photosynthetic efficiency, reducing the cold tolerance of pepper leaves. This study is the first to identify the acetylome in pepper, and it greatly expands the catalog of lysine acetylation substrates and sites in Solanaceae crops, providing new insights for posttranslational modification studies.

Incidence and risk factors of anastomotic leak after transanal total mesorectal excision in China: a retrospective analysis based on national database / 中华胃肠外科杂志

Objective: Transanal total mesorectal excision (taTME) was a very hot topic in the first few years since its appearance, but now more introspections and controversies on this procedure have emerged. One of the reasons why the Norwegian Ministry of Health stopped taTME was the high incidence of postoperative anastomotic leak. In current study, the incidence and risk factors of anastomotic leak after taTME were analyzed based on the data registered in the Chinese taTME Registry Collaborative (CTRC). Methods: A case-control study was carried out. Between November 15, 2017 and December 31, 2020, clinical data of 1668 patients undergoing taTME procedure registered in the CTRC database from 43 domestic centers were collected retrospectively. After excluding 98 cases without anastomosis and 109 cases without complete postoperative complication data, 1461 patients were finally enrolled for analysis. There were 1036 males (70.9%) and 425 females (29.1%) with mean age of (58.2±15.6) years and mean body mass index of (23.6±3.8) kg/m(2). Anastomotic leak was diagnosed and classified according to the International Study Group of Rectal Cancer (ISREC) criteria. The risk factors associated with postoperative anastomotic leak cases were analyzed. The impact of the cumulative number of taTME surgeries in a single center on the incidence of anastomotic leak was evaluated. As for those centers with the number of taTME surgery ≥ 40 cases, incidence of anastomic leak between 20 cases of taTME surgery in the early and later phases was compared. Results: Of 1461 patients undergoing taTME, 103(7.0%) developed anastomotic leak, including 71 (68.9%) males and 32 (31.1%) females with mean age of (59.0±13.9) years and mean body mass index of (24.5±5.7) kg/m(2). The mean distance between anastomosis site and anal verge was (2.6±1.4) cm. Thirty-nine cases (37.9%) were classified as ISREC grade A, 30 cases (29.1%) as grade B and 34 cases (33.0%) as grade C. Anastomotic leak occurred in 89 cases (7.0%,89/1263) in the laparoscopic taTME group and 14 cases (7.1%, 14/198) in the pure taTME group. Multivariate analysis showed that hand-sewn anastomosis (P=0.004) and the absence of defunctioning stoma (P=0.013) were independently associated with anastomotic leak after taTME. In the 16 centers (37.2%) which performed ≥ 30 taTME surgeries with cumulative number of 1317 taTME surgeries, 86 cases developed anastomotic leak (6.5%, 86/1317). And in the 27 centers which performed less than 30 taTME surgeries with cumulative number of 144 taTME surgeries, 17 cases developed anastomotic leak (11.8%, 17/144). There was significant difference between two kinds of center (χ(2)=5.513, P=0.019). Thirteen centers performed ≥ 40 taTME surgeries. In the early phase (the first 20 cases in each center), 29 cases (11.2%, 29/260) developed anastomotic leak, and in the later phase, 12 cases (4.6%, 12/260) developed anastomotic leak. The difference between the early phase and the later phase was statistically significant (χ(2)=7.652, P=0.006). Conclusion: The incidence of anastomotic leak after taTME may be reduced by using stapler and defunctioning stoma, or by accumulating experience.

Cognitive impairment in two subtypes of a single subcortical infarction / 中华医学杂志(英文版)

BACKGROUND@#Single subcortical infarction (SSI) is caused by two main etiological subtypes, which are branch atheromatous disease (BAD) and cerebral small vessel disease (CSVD)-related SSI. We applied the Beijing version of the Montreal Cognitive Assessment (MoCA-BJ), the Shape Trail Test (STT), and the Stroop Color and Word Test (SCWT) to investigate the differences in cognitive performance between these two subtypes of SSI.@*METHODS@#Patients with acute SSIs were prospectively enrolled. The differences of MoCA-BJ, STT, and SCWT between the BAD group and CSVD-related SSI group were analyzed. A generalized linear model was used to analyze the associations between SSI patients with different etiological mechanisms and cognitive function. We investigated the correlations between MoCA-BJ, STT, and SCWT using Spearman's correlation analysis and established cut-off scores for Shape Trail Test A (STT-A) and STT-B to identify cognitive impairment in patients with SSI.@*RESULTS@#This study enrolled a total of 106 patients, including 49 and 57 patients with BAD and CSVD-related SSI, respectively. The BAD group performances were worse than those of the CSVD-related SSI group for STT-A (83 [60.5-120.0] vs. 68 [49.0-86.5], P = 0.01), STT-B (204 [151.5-294.5] vs. 153 [126.5-212.5], P = 0.015), and the number of correct answers on Stroop-C (46 [41-49] vs. 49 [45-50], P = 0.035). After adjusting for age, years of education, National Institutes of Health Stroke Scale and lesion location, the performance of SSI patients with different etiological mechanisms still differed significantly for STT-A and STT-B.@*CONCLUSIONS@#BAD patients were more likely to perform worse than CSVD-related SSI patients in the domains of language, attention, executive function, and memory. The mechanism of cognitive impairment after BAD remains unclear.

Comparative study of simultaneous three scopes surgery and staged two scopes surgery in the treatment of choledocholithiasis with cholecystolithiasis / 国际外科学杂志

Objective:To compare the clinical efficacy of the Simultaneous three scopes combined surgery [laparoscopic cholecystectomy(LC)+ choledochoscopy exploration + choledochectomy and removal of the common bile duct + primary suture of the common bile duct + endoscopic guided nasobiliary duct placement] and staged two scopes surgery[endoscopic retrograde cholangiopancreatography (ERCP) combined with LC] in the treatment of choledocholithiasis and cholecystolithiasis.Methods:From January 2018 to June 2020, we retrospectively analyzed the clinical data of 83 patients with choledocholithiasis and choledocholithiasis, who underwent minimally invasive treatment in our center. According to the different surgical procedures, the patients were divided into three-mirror group ( n=42) and two-mirror group ( n=41). All patients in the three-mirror group underwent three-scopy combined surgery. The patients in two-mirror group received endoscopic retrograde cholangiopancreatography (ERCP) combined with laparoscopic cholecystectomy (LC). In this study we compared the relevant clinical indicators of the two groups, in terms of the operation time, intraoperative blood loss, one-time stone clearance rate, postoperative exhaust time, postoperative defecation time, total hospitalization cost, incidence of postoperative acute pancreatitis, postoperative stone recurrence rate, incidence of postoperative cholangitis, and incidence of postoperative biliary fistula, total hospitalization time, postoperative bile duct stricture rate. Use SPSS 26.0 software to statistically analyze various indexes such as intraoperative, postoperative, follow-up, etc. Normally distributed measurement data were described by the mean±standard deviation ( Mean± SD), the comparison between groups was by t test, and measurement data with skewed distribution were destribed as M( P25, P75), Pairwise comparisons were analyzed using nonparametric test. The comparison of count data between groups was by the chi-square test. Results:No death was observed in both two groups. The operation time, intraoperative blood loss, one-time stone clearance rate, postoperative exhaust time, and postoperative defecation time of the three-mirror groupwere (167.98±47.37) min, 50(50, 100) mL, 100%(42/42), (2.10±0.76) days, 3(3, 4) days, the two-mirror group were (143.80±34.47) min, 50(50, 50) mL, 85.4%(35/41), (1.53±0.99) days and 2(1, 3) days. Compared with the two groups, the three-mirror group was higher than the two-mirror group, and the difference was statistically significant ( P<0.05). The total hospitalization expenses, postoperative acute pancreatitis incidence, and postoperative calculus recurrence rate in the three-mirror group were (3.46±0.77) ten thousand yuan, 0(0/42), 2.38%(1/42), the two-mirror group were (4.22±1.50) ten thousand yuan, 9.8%(4/41), 19.5%(8/41). Compared with the two groups, the three-mirror group was lower than the two-mirror group, and the difference was statistically significant ( P<0.05). No postoperative cholangitis or biliary fistula occurred in the two groups. There was no statistically significant difference in the total hospital stay and incidence of postoperative bile duct stenosis between the two groups ( P>0.05). Conclusions:For choledocholithiasis combined with cholecystolithiasis patients, simultaneous three-scopes combined surgery and elective LC after ERCP are safe and effective, and each has its own advantages. It should be selected reasonably according to the patient′s condition and combined with the technical advantages of the treatment team.

Annexin A1-derived peptide Ac2-26 facilitates wound healing in diabetic mice.

Impaired wound healing is a common complication of diabetes. In diabetic wounds, macrophages present dysfunctional efferocytosis and abnormal phenotypes, which could result in excessive neutrophil accumulation and prolonged inflammation, thereby eventually hindering wound repair. ANXA1 N-terminal peptide Ac2-26 exhibits a high potential in mitigating inflammation and improving repair; however, its efficacy in diabetic wound repair remains unclear. In this study, a cutaneous excisional wound model was built in genetically diabetic mice. Ac2-26 or a vehicle solution was employed locally in wound sites. Subsequently, wound zones were measured and sampled at different time intervals post-wounding. Using hematoxylin-eosin and Masson's trichrome staining, we observed the histopathological variations and collagen deposition in wound samples. Based on immunohistochemistry and immunofluorescence, the numbers of neutrophils, macrophages, and CD206-positive macrophages in the wound samples were determined. Cytokine expression in wound samples was studied by immunoblot assay. Results showed that Ac2-26 treatment could facilitate diabetic wound closure, down-regulate the number of neutrophils, and improve angiogenesis and collagen deposition. In addition, Ac2-26 application expedited macrophage recruitment and up-regulated the percentage of macrophages expressing CD206, which is a marker for M2 macrophages. Moreover, Ac2-26 inhibited the expressions of TNF-α and IL-6 and up-regulated the expressions of IL-10, TGF-ß, and VEGFA during diabetic wound healing. Hence, based on the aforementioned findings, Ac2-26 application in diabetic wounds could exert anti-inflammatory and pro-repair effects by reducing neutrophil accumulation and facilitating M2 macrophage development.

Correlation between serum cathepsin S level and severity of coronary heart disease in elderly patients / 中华老年医学杂志

Objective To study the expression level of cathepsin S in elderly patients with different degree of coronary heart disease(CHD),and to evaluate the correlation between cathepsin S level and the severity of CHD.Methods A total of 126 elderly patients with CHD were enrolled,including 36 cases with acute myocardial infarction(group AMI),48 cases with unstable angina(group UAP),and 42 cases with stable angina(group SAP).During the same period,40 healthy subjects were selected as controls.Venous blood was collected immediately after admission.Arterial blood was taken through radial/femoral artery sheath in AMI patients who underwent primary percutaneous coronary intervention,and coronary arterial blood was taken in AMI patients undergoing intracoronary thrombus aspiration.SYNTAX score was assessed in patients undergoing coronary angiography.Serum levels of high sensitivity C reactive protein(hs-CRP),matrix metalloproteinase-9 (MMP-9) and cathepsin S were determined in all specimens and compared between groups.Results Serum levels of cathepsin S,MMP-9 and hs-CRP were higher in CHD patients than in the control group(P＜0.05).Among CHD patients,group AMI had the highest serum levels of cathepsin S,MMP-9 and hs-CRP,followed by group UAP and group SAP(F =106.830,197.035 and 310.442,all P =0.000).Spearman's rank correlation test suggested that cathepsin S level was positively correlated with serum levels of MMP-9 (r=0.816,P =0.000)and hs-CRP(r =0.827,P =0.000).SYNTAX score was positively correlated with serum levels of cathepsin S(r=0.581,P=0.000),MMP-9(r=0.511,P=0.000),and hs-CRP (r=0.557,P =0.000).Among the 24 patients with AMI who underwent intracoronary thrombus aspiration,the levels of cathepsin S,MMP-9 and hs-CRP were higher in coronary artery blood than in peripheral artery blood (t =217.288,3.177 and 681.479,all P =0.000).Cathepsin S and hs-CRP levels in peripheral arterial blood had positive correlations with those in coronary arterial blood respectively(r =0.962 and 0.494,P =0.000 and 0.014),but such correlation between in peripheral arterial blood versus in coronary artery blood was not found in MMP-9 levels (r =-0.188,P =0.380).Conclusions Serum cathepsin S level is higher in elderly CHD patients than in healthy people,increases along with the increased severity of CHD,and positively correlates with the degree of coronary stenosis.

Association of polycyclic aromatic hydrocarbon exposure and CYP1A1 gene and enzyme activity of peripheral blood monocyte cells in coke oven workers / 中华劳动卫生职业病杂志

Objective@#To explore the association between polycyclic aromatic hydrocarbons (PAHs) exposure and cytochrome P450 CYP1A1 expression at gene and enzyme activity levels in the peripheral blood monocyte cells in coke oven workers, and to provide a certain basis for the biological monitoring of health damage in coke oven workers.@*Methods@#We surveyed 118 coke oven workers and 63 controls (energy power workers in the same company) using self-designed questionnaire, determined their post-shift urinary 1-hydroxypyrene (1-OH-Py) concentration using high performance liquid chromatography (HPLC)-fluorescence detector method. We also isolated the peripheral blood mononuclear cell (PBMC) from fasting venous blood, and detected DNA damage using comet assay, CYP1A1 mRNA level using the real-time fluorescent quantitative PCR (FQ-PCR), and EROD activity using spectrophotometry. Statistical analyses including one-way analysis of variance and multiple linear regressions were used to analyze the association of urinary 1-OH-Py and CYP1A1 mRNA level and EROD activity.@*Results@#Compared to the control group, the urinary 1-OH-Py concentration and PBMC DNA tail moment were significantly increased in coke oven workers (P<0.05), and CYP1A1 gene level and EROD activity in PBMC were significantly decreased (P<0.05). Multiple linear regression showed that a ten-fold increase of urinary 1-OH-Pycon centration was associated with a decrease of 0.77 (95%CI: -1.33--0.21) in CYP1A1 gene level, and a decline of 0.15 (95%CI: -0.76--0.16) in EROD activity of PBMC in coke oven workers (P<0.05).@*Conclusion@#Occupational PAHs exposure induced DNA damage, which was associated with the decreased level in CYP1A1 gene cavel and EROD activity in PBMC of coke oven workers.

Effects of Acupuncture on Alzheimer's Disease: Evidence from Neuroimaging Studies / 中国结合医学杂志

As the worldwide population ages, the prevalence of Alzheimer's disease (AD) increases. However, the results of promising medications have been unsatisfactory. Chinese acupuncture has a long history of treating dementia, but lack of evidence from well-designed randomized controlled trials that validate its efficacy and safety, as well as its lack of clear underlying mechanisms, contribute to its limited application in clinical practice. In recent years, brain imaging technologies, such as functional magnetic resonance imaging and positron emission tomography, have been used to assess brain responses to acupuncture in a dynamic, visual, and objective way. These techniques are frequently used to explore neurological mechanisms of responses to acupuncture in AD and provide neuroimaging evidence as well as starting points to elucidate the possible mechanisms. This review summarizes the existing brain imaging evidence that explains the effects of acupuncture for AD and analyzes brain responses to acupuncture at cognitive-related acupoints [Baihui (GV 20), Shenmen (HT 7), Zusanli (ST 36), Neiguan (PC 6), and Taixi (KI 3)] from perspectives of acupoint specificity and acupoint combinations. Key issues and directions to consider in future studies are also put forward. This review should deepen our understanding of how brain imaging studies can be used to explore the underlying mechanisms of acupuncture in AD.

Effect of pre-acupuncture at Neiguan (PC 6) and Zusanli (ST 36) on exercise-induced fatigue / 中国针灸

OBJECTIVE@#To observe the therapeutic effect of pre-acupuncture at Neiguan (PC 6) and Zusanli (ST 36) on exercise-induced fatigue.@*METHODS@#A total of 50 subjects were divided into an observation group and a control group by random number table method, 25 cases in each one. In the observation group, acupuncture was applied at Neiguan (PC 6) and Zusanli (ST 36) before exercise, once a day, consecutive 5-day treatment was required. In the control group, there was no intervention. The subjective fatigue perception score, serum levels of lactate and lactate dehydrogenase, heart rate and oxygen saturation before and after exercise were observed in the two groups.@*RESULTS@#Compared before exercise, the subjective fatigue perception scores, serum levels of lactate and lactate dehydrogenase and heart rates after exercise were increased in the two groups (0.05).@*CONCLUSION@#Pre-acupuncture at Neiguan (PC 6) and Zusanli (ST 36) can effectively reduce the subjective fatigue perception score，serum levels of lactate and lactate dehydrogenase and heart rate to improve exercise-induced fatigue.

Laparoscopic spleen-preserving splenic hilar lymph nodes dissection through retropancreatic and extruded approach in radical gastrectomy for advanced gastric carcinoma / 局解手术学杂志

Objective To investigate the feasibility and safety of laparoscopic spleen-preserving splenic hilar lymph nodes dissection through retropancreatic and extruded approach in radical gastrectomy for proximal gastric carcinoma,and to preliminarily analyzed the anatom-ical features.Methods Adopted a retrospective cohort study.The clinical data of 84 patients with proximal gastric carcinoma who underwent radical resection in our hospital from June 2014 to January 2017 were collected.Among the 84 patients,44 case who underwent spleen extru-ded-retroperitoneal approach were regarded as the observation group,and the other 40 patients underwent conventional left approach were allo-cated into the control group.All the patients underwent laparoscopic D 2 radical total gastrectomy and spleen-preserving N0.10 nodes dissec-tion by the same operation team.The clinical situation of the two groups before operation,after operation and during the follow-up were ob-served.Results All the 84 patients successfully completed the radical gastrectomy without conversion to open surgery.In the observation group and the control group,the volume of intraopertative blood loss were respectively(107.9 ±52.9)mL and(153.1 ±72.2)mL;the opera-tion time were respectively(228.8 ±27.7)min and(244.7 ±31.3)min;the number of dissected N0.10 lymph node were respectively(5.0 ± 2.2)and(2.9 ±1.3).There were statistically significant differences in all the above indexs(P<0.05).In the observation group and the control group,the time for initial out-of-bed activity were respectively(1.6 ±0.4)days and(1.5 ±0.4)days;the time of initial anal exsuffla-tion were respectively(2.9 ±0.8)days and(2.6 ±0.5)days;the duration of hospital stay were respectively(7.5 ±1.4)days and(7.0 ± 1.3)days.Postoperative complications occured 4 cases in the observation group and 5 cases in the control group.There was no statistically significant difference in terms of time for initial out-of-bed activity,time of initial anal exsufflation,duration of hospital stay and postoperative complications(P>0.05).A total of 82 patients were followed up for 6 to 36 months,with a median time of 15.5 months.Conclusion Compared with the conventional left approach,laparoscopic spleen-preserving splenic hilar lymph nodes dissection through retropancreatic and extruded approach is safe and feasible for laparoscopic radical resection of proximal gastric carcinoma.And it can shorten the operation time, reduce the volume of intraopertative blood loss,and increase the clearance of N0.10 lymph nodes.

Detection of RAGE expression and its application to diabetic wound age estimation.

With the prevalence of diabetes, it is becoming important to analyze the diabetic wound age in forensic practice. The present study investigated the time-dependent expression of receptor for advanced glycation end products (RAGE) during diabetic wound healing in mice and its applicability to wound age determination by immunohistochemistry, double immunofluorescence, and Western blotting. After an incision was created in genetically diabetic db/db mice and control mice, mice were killed at posttraumatic intervals ranging from 6 h to 14 days, followed by the sampling of wound margin. Compared with control mice, diabetic mice showed the delayed wound healing. In control and diabetic wound specimens, RAGE immunoreactivity was observed in a small number of polymorphonuclear cells (PMNs), a number of macrophages, and fibroblasts. Morphometrically, the positive ratios of RAGE in macrophages or fibroblasts considerably increased in diabetic wounds during late repair, which exceeded 60% at 7 and 10 days post-injury. There were no control wound specimens to show a ratio of >60% in macrophages or fibroblasts. By Western blotting analysis, the ratios of RAGE to GAPDH were >1.4 in all diabetic wound samples from 7 to 10 days post-injury, which were >1.8 at 10 days after injury. By comparison, no control wound specimens indicated a ratio of >1.4. In conclusion, the expression of RAGE is upregulated and temporally distributed in macrophages and fibroblasts during diabetic wound healing, which might be closely involved in prolonged inflammation and deficient healing. Moreover, RAGE is promising as a useful marker for diabetic wound age determination.

The application and research progress of plasma heparin-binding protein in septic shock / 中华检验医学杂志

Septic shock is the most serious stage of sepsis and the main cause of the high mortality.So far,the scientists have paid more attentions on biomarkers for the early diagnosis and therapy monitoring of septic shock.As a kind of acute phase proteins, heparin-binding protein (HBP)has functions with increasing vascular permeability, sterilization, chemotaxis and regulating cell apoptosis.When the level of plasma HBP is high, it suggests that the patient has severe sepsis with edema and vascular collapse and can beapplied as a valuable biomarker for early diagnosis and therapy monitoring of septic shock.This review focuses on common inflammatory biomarkers for clinical application of sepsis, as well the structure and function of HBP and its clinical application of septic shock.

Activation of α7nAChR Promotes Diabetic Wound Healing by Suppressing AGE-Induced TNF-α Production.

Diabetes frequently presents accumulation of advanced glycation end products (AGEs), which might induce excessive TNF-α production from macrophages to cause impaired wound healing. Recent studies have shown that activation of α7 nicotinic acetylcholine receptor (α7nAChR) on macrophages efficiently suppressed TNF-α synthesis. The aim of this study was to investigate the accumulation of AGEs in the wounds and determine whether PNU282987, an α7nAChR agonist, can improve wound repair by inhibiting AGE-mediated TNF-α production in a streptozotocin (STZ)-induced diabetic mouse model. Animals were assigned into four groups: wounded control group, wounded diabetic group, wounded diabetic group treated intraperitoneally with PNU282987, or wounded diabetic group treated intraperitoneally with vehicle. Compared with the non-diabetic control mice, the diabetic mice exhibited delayed wound healing that was characterized by elevated accumulation of AGEs, increased TNF-α level and macrophage infiltration, and decreased fibroblast number and collagen deposition at the late stage of repair. Besides, macrophages of diabetic wounds showed expression of α7nAChR. During late repair, PNU282987 treatment of diabetic mice significantly reduced the level of TNF-α, accelerated wound healing, and elevated fibroblast number and collagen deposition. To investigate the cellular mechanism of these observations, RAW 264.7 cells, a macrophage cell line, were incubated with AGEs in the presence or absence of PNU282987. TNF-α production from AGE-stimulated macrophages was significantly decreased by PNU282987 in a dose-dependent manner. Furthermore, PNU282987 significantly inhibited AGE-induced nuclear factor-κB (NF-κB) activation and receptor for AGE (RAGE) expression. These results strongly suggest that activating α7nAChR can promote diabetic wound healing by suppressing AGE-induced TNF-α production, which may be closely associated with the blockage of NF-κB activation in macrophages.